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Sample records for genetically increased antioxidative

  1. Antioxidants can increase melanoma metastasis in mice.

    PubMed

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-01

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. PMID:26446958

  2. The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

    PubMed Central

    Poggi, Chiara

    2014-01-01

    Abstract Significance: Oxidative stress is involved in the development of newborn lung diseases, such as bronchopulmonary dysplasia and persistent pulmonary hypertension of the newborn. The activity of antioxidant enzymes (AOEs), which is impaired as a result of prematurity and oxidative injury, may be further affected by specific genetic polymorphisms or an unfavorable combination of more of them. Recent Advances: Genetic polymorphisms of superoxide dismutase and catalase were recently demonstrated to be protective or risk factors for the main complications of prematurity. A lot of research focused on the potential of different antioxidant strategies in the prevention and treatment of lung diseases of the newborn, providing promising results in experimental models. Critical Issues: The effect of different genetic polymorphisms on protein synthesis and activity has been poorly detailed in the newborn, hindering to derive conclusive results from the observed associations with adverse outcomes. Therapeutic strategies that aimed at enhancing the activity of AOEs were poorly studied in clinical settings and partially failed to produce clinical benefits. Future Directions: The clarification of the effects of genetic polymorphisms on the proteomics of the newborn is mandatory, as well as the assessment of a larger number of polymorphisms with a possible correlation with adverse outcome. Moreover, antioxidant treatments should be carefully translated to clinical settings, after further details on optimal doses, administration techniques, and adverse effects are provided. Finally, the study of genetic polymorphisms could help select a specific high-risk population, who may particularly benefit from targeted antioxidant strategies. Antioxid. Redox Signal. 21, 1863–1880. PMID:24382101

  3. Vitamins, stress and growth: the availability of antioxidants in early life influences the expression of cryptic genetic variation.

    PubMed

    Kim, S-Y; Noguera, J C; Tato, A; Velando, A

    2013-06-01

    Environmental inputs during early development can shape the expression of phenotypes, which has long-lasting consequences in physiology and life history of an organism. Here, we study whether experimentally manipulated availability of dietary antioxidants, vitamins C and E, influences the expression of genetic variance for antioxidant defence, endocrine signal and body mass in yellow-legged gull chicks using quantitative genetic models based on full siblings. Our experimental study in a natural population reveals that the expression of genetic variance in total antioxidant capacity in plasma increased in chicks supplemented with vitamins C and E despite the negligible effects on the average phenotype. This suggests that individuals differ in their ability to capture and transport dietary antioxidants or to respond to these extra resources, and importantly, this ability has a genetic basis. Corticosterone level in plasma and body mass were negatively correlated at the phenotypic level. Significant genetic variance of corticosterone level appeared only in control chicks nonsupplemented with vitamins, suggesting that the genetic variation of endocrine system, which transmits environmental cues to adaptively control chick development, appeared in stressful conditions (i.e. poor antioxidant availability). Therefore, environmental inputs may shape evolutionary trajectories of antioxidant capacity and endocrine system by affecting the expression of cryptic genetic variation. PMID:23517061

  4. Isoflurane and Propofol Contribute to Increasing the Antioxidant Status of Patients During Minor Elective Surgery

    PubMed Central

    Braz, Mariana G.; Braz, Leandro G.; Freire, Cristiana M.M.; Lucio, Lorena M.C.; Braz, José R.C.; Tang, Guangwen; Salvadori, Daisy M.F.; Yeum, Kyung-Jin

    2015-01-01

    Abstract Isoflurane is a volatile halogenated anesthetic used especially for anesthesia maintenance whereas propofol is a venous anesthetic utilized for anesthesia induction and maintenance, and reportedly an antioxidant. However, there are still controversies related to isoflurane-induced oxidative stress and it remains unanswered whether the antioxidant effects occur in patients under propofol anesthesia. Taking into account the importance of better understanding the role of anesthetics on oxidative stress in anesthetized patients, the present study was designed to evaluate general anesthesia maintained with isoflurane or propofol on antioxidant status in patients who underwent minimally invasive surgeries. We conducted a prospective randomized trial in 30 adult patients without comorbidities who underwent elective minor surgery (septoplasty) lasting at least 2 h admitted to a Brazilian tertiary hospital. The patients were randomly allocated into 2 groups, according to anesthesia maintenance (isoflurane, n = 15 or propofol, n = 15). Peripheral blood samples were drawn before anesthesia (baseline) and 2-h after anesthesia induction. The primary outcomes were to investigate the effect of either isoflurane or propofol anesthesia on aqueous plasma oxidizability and total antioxidant performance (TAP) by fluorometry as well as several individual antioxidants by high-performance liquid chromatography. As secondary outcome, oxidized genetic damage (7,8-dihydro-8-oxoguanine, known as 8-oxo-Gua) was investigated by the comet assay. Both anesthesia techniques (isoflurane or propofol) for a 2-h period resulted in a significant decrease of plasma α-tocopherol, but not other antioxidants including uric acid, carotenoids, and retinol (P > 0.05). Propofol, in contrast to isoflurane anesthesia, significantly increased (P < 0.001) anti-inflammatory/antioxidant plasma γ-tocopherol concentration in patients. Both anesthesia types significantly enhanced

  5. A novel technology to increase antioxidant activity of an antioxidant by reducing volatility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During frying, an antioxidant is lost by reaction with radicals for its antioxidant activity, but it is also lost by decomposition and evaporation before it is able to exert antioxidant activity. Some low molecular weight antioxidants are often so volatile that they show much reduced antioxidant act...

  6. Increased oxidative stress and impaired antioxidant response in Lafora disease.

    PubMed

    Romá-Mateo, Carlos; Aguado, Carmen; García-Giménez, José Luis; Ibáñez-Cabellos, José Santiago; Seco-Cervera, Marta; Pallardó, Federico V; Knecht, Erwin; Sanz, Pascual

    2014-10-01

    Lafora Disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxirredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LD. PMID:26461389

  7. Genetic markers for antioxidant capacity in a reef-building coral

    PubMed Central

    Jin, Young K.; Lundgren, Petra; Lutz, Adrian; Raina, Jean-Baptiste; Howells, Emily J.; Paley, Allison S.; Willis, Bette L.; van Oppen, Madeleine J. H.

    2016-01-01

    The current lack of understanding of the genetic basis underlying environmental stress tolerance in reef-building corals impairs the development of new management approaches to confronting the global demise of coral reefs. On the Great Barrier Reef (GBR), an approximately 51% decline in coral cover occurred over the period 1985–2012. We conducted a gene-by-environment association analysis across 12° latitude on the GBR, as well as both in situ and laboratory genotype-by-phenotype association analyses. These analyses allowed us to identify alleles at two genetic loci that account for differences in environmental stress tolerance and antioxidant capacity in the common coral Acropora millepora. The effect size for antioxidant capacity was considerable and biologically relevant (32.5 and 14.6% for the two loci). Antioxidant capacity is a critical component of stress tolerance because a multitude of environmental stressors cause increased cellular levels of reactive oxygen species. Our findings provide the first step toward the development of novel coral reef management approaches, such as spatial mapping of stress tolerance for use in marine protected area design, identification of stress-tolerant colonies for assisted migration, and marker-assisted selective breeding to create more tolerant genotypes for restoration of denuded reefs. PMID:27386515

  8. Genetic markers for antioxidant capacity in a reef-building coral.

    PubMed

    Jin, Young K; Lundgren, Petra; Lutz, Adrian; Raina, Jean-Baptiste; Howells, Emily J; Paley, Allison S; Willis, Bette L; van Oppen, Madeleine J H

    2016-05-01

    The current lack of understanding of the genetic basis underlying environmental stress tolerance in reef-building corals impairs the development of new management approaches to confronting the global demise of coral reefs. On the Great Barrier Reef (GBR), an approximately 51% decline in coral cover occurred over the period 1985-2012. We conducted a gene-by-environment association analysis across 12° latitude on the GBR, as well as both in situ and laboratory genotype-by-phenotype association analyses. These analyses allowed us to identify alleles at two genetic loci that account for differences in environmental stress tolerance and antioxidant capacity in the common coral Acropora millepora. The effect size for antioxidant capacity was considerable and biologically relevant (32.5 and 14.6% for the two loci). Antioxidant capacity is a critical component of stress tolerance because a multitude of environmental stressors cause increased cellular levels of reactive oxygen species. Our findings provide the first step toward the development of novel coral reef management approaches, such as spatial mapping of stress tolerance for use in marine protected area design, identification of stress-tolerant colonies for assisted migration, and marker-assisted selective breeding to create more tolerant genotypes for restoration of denuded reefs. PMID:27386515

  9. Amphetamine exposure imbalanced antioxidant activity in the bivalve Dreissena polymorpha causing oxidative and genetic damage.

    PubMed

    Parolini, Marco; Magni, Stefano; Castiglioni, Sara; Binelli, Andrea

    2016-02-01

    Illicit drugs have been recognized as emerging aquatic pollutants due to their presence in aquatic ecosystems up to µg/L level. Among these, the synthetic psycho-stimulant drug amphetamine (AMPH) is commonly found in both surface and wastewaters worldwide. Even though the environmental occurrence of AMPH is well-known, the information on its toxicity towards non-target freshwater organisms is completely lacking. This study investigated the imbalance of the oxidative status and both oxidative and genetic damage induced by a 14-day exposure to two concentrations (500 ng/L and 5000 ng/L) of AMPH on the freshwater bivalve Dreissena polymorpha by the application of a biomarker suite. We investigated the activity of antioxidant enzymes (SOD, CAT and GPx), the phase II detoxifying enzyme GST, the lipid peroxidation level (LPO) and protein carbonyl content (PCC), as well as primary (Single Cell Gel Electrophoresis assay) and fixed (DNA diffusion assay and Micronucleus test) genetic damage. Our results showed that a current realistic AMPH concentration (500 ng/L) did neither cause notable imbalances in enzymatic activities, nor oxidative and genetic damage to cellular macromolecules. In contrast, the bell-shaped trend of antioxidants showed at the highest tested concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation. PMID:26363322

  10. Antioxidants

    MedlinePlus

    ... carotene Lutein Lycopene Selenium Vitamin A Vitamin C Vitamin E Vegetables and fruits are rich sources of antioxidants. There is good ... eating a diet with lots of vegetables and fruits is healthy and lowers risks ... smokers. High doses of vitamin E may increase risks of prostate cancer and ...

  11. Antioxidant compounds and their bioaccessibility in tomato fruit and puree obtained from a DETIOLATED-1 (DET-1) down-regulated genetically modified genotype.

    PubMed

    Talens, P; Mora, L; Bramley, Peter M; Fraser, Paul D

    2016-12-15

    The economic value, the ease of cultivation and processing, and the well-known health-promoting properties of tomato fruit, make the tomato an important target for genetic manipulation to increase its nutritional content. A transgenic variety, down-regulated in the DETIOLATED-1 (DET-1) gene, has been studied in comparison with the parental line, for antioxidant levels in fresh and hot break fruit, as well as the bioaccessibility of antioxidants from puree. Differences in the concentrations of antioxidants between the wild-type and the genetically modified raw tomatoes were confirmed, but antioxidant levels were maintained to a greater extent in the GM puree than in the parent. The bioaccessibility of the compounds, tested using an in vitro digestion model, showed an increase in the genetically modified samples. PMID:27451242

  12. Metabolic engineering of β-carotene in orange fruit increases its in vivo antioxidant properties.

    PubMed

    Pons, Elsa; Alquézar, Berta; Rodríguez, Ana; Martorell, Patricia; Genovés, Salvador; Ramón, Daniel; Rodrigo, María Jesús; Zacarías, Lorenzo; Peña, Leandro

    2014-01-01

    Orange is a major crop and an important source of health-promoting bioactive compounds. Increasing the levels of specific antioxidants in orange fruit through metabolic engineering could strengthen the fruit's health benefits. In this work, we have afforded enhancing the β-carotene content of orange fruit through blocking by RNA interference the expression of an endogenous β-carotene hydroxylase gene (Csβ-CHX) that is involved in the conversion of β-carotene into xanthophylls. Additionally, we have simultaneously overexpressed a key regulator gene of flowering transition, the FLOWERING LOCUS T from sweet orange (CsFT), in the transgenic juvenile plants, which allowed us to obtain fruit in an extremely short period of time. Silencing the Csβ-CHX gene resulted in oranges with a deep yellow ('golden') phenotype and significant increases (up to 36-fold) in β-carotene content in the pulp. The capacity of β-carotene-enriched oranges for protection against oxidative stress in vivo was assessed using Caenorhabditis elegans as experimental animal model. Golden oranges induced a 20% higher antioxidant effect than the isogenic control. This is the first example of the successful metabolic engineering of the β-carotene content (or the content of any other phytonutrient) in oranges and demonstrates the potential of genetic engineering for the nutritional enhancement of fruit tree crops. PMID:24034339

  13. Increased antioxidant capacity in tomato by ectopic expression of the strawberry D-galacturonate reductase gene.

    PubMed

    Amaya, Iraida; Osorio, Sonia; Martinez-Ferri, Elsa; Lima-Silva, Viviana; Doblas, Veronica G; Fernández-Muñoz, Rafael; Fernie, Alisdair R; Botella, Miguel A; Valpuesta, Victoriano

    2015-03-01

    Increasing L-ascorbic acid (AsA, vitamin C) content in fruits is a common goal in current breeding programs due to its beneficial effect on human health. Attempts to increase AsA content by genetic engineering have resulted in variable success likely due to AsA's complex regulation. Here, we report the effect of ectopically expressing in tomato the D-galacturonate reductase (FaGalUR) gene from strawberry, involved in AsA biosynthesis, either under the control of the constitutive 35S or the tomato fruit-specific polygalucturonase (PG) promoters. Although transgenic lines showed a moderate increase on AsA content, complex changes in metabolites were found in transgenic fruits. Metabolomic analyses of ripe fruits identified a decrease in citrate, glutamate, asparagine, glucose, and fructose, accompanied by an increase of sucrose, galactinol, and chlorogenic acid. Significant metabolic changes also occurred in leaves of 35S-FaGalUR lines, which showed higher non-photochemical fluorescence quenching (NPQ), indicative of a higher constitutive photo-protective capacity. Overall, overexpression of FaGalUR increased total antioxidant capacity in fruits and the results suggest a tight control of AsA content, probably linked to a complex regulation of cellular redox state and metabolic adjustment. PMID:25143316

  14. Antioxidants

    MedlinePlus

    Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods, including fruits and ... are also available as dietary supplements. Examples of antioxidants include Beta-carotene Lutein Lycopene Selenium Vitamin A ...

  15. Antioxidant strategies in genetic syndromes with high neoplastic risk in infant age.

    PubMed

    Anichini, Cecilia; Lotti, Federica; Longini, Mariangela; Felici, Cosetta; Proietti, Fabrizio; Buonocore, Giuseppe

    2014-01-01

    Oxidative stress plays a key role in carcinogenesis. Oxidative damage to cell components can lead to the initiation, promotion and progression of cancer. Oxidative stress is also a distinctive sign in several genetic disorders characterized by a cancer predisposition such as ataxia-telangiectasia, Fanconi anemia, Down syndrome, Beckwith-Wiedemann syndrome and Costello syndrome. Taking into account the link between oxidative stress and cancer, the capacity of antioxidant agents to prevent or delay neoplastic development has been tested in various studies, both in vitro and in vivo, with interesting and promising results. In recent years, research has been conducted into the molecular mechanisms linking oxidative stress to the pathogenesis of the genetic syndromes we consider in this review, with the resulting identification of possible new therapeutic targets. The aim of this review is to focus on the oxidative mechanisms intervening in carcinogenesis in cancer-prone genetic disorders and to analyze the current status and future prospects of antioxidants. PMID:25688491

  16. Genetic Instability in Lymphocytes is Associated With Blood Plasma Antioxidant Levels in Health Care Workers Occupationally Exposed to Ionizing Radiation.

    PubMed

    Kumar, Dayanidhi; Kumari, Sandhya; Salian, Sujith Raj; Uppangala, Shubhashree; Kalthur, Guruprasad; Challapalli, Srinivas; Chandraguthi, Shrinidhi Gururajarao; Kumar, Pratap; Adiga, Satish Kumar

    2016-05-01

    Earlier reports have suggested that exposure to radiation at workplace may induce cytogenetic abnormalities. However, the association between plasma antioxidants and the cytogenetic abnormalities in these patients has not been elucidated till now. Hence, the present study was undertaken to determine the relationship between the cytogenetic abnormalities, plasma antioxidant system, and the radiation exposure levels in men who were occupationally exposed to ionizing radiation. The study included 134 male volunteers, among whom 83 were occupationally exposed to ionizing radiation. Incidence of micronuclei and chromosomal aberration was assessed in lymphocytes. Total and reduced glutathione (GSH), total antioxidant capacity (TAC), superoxide dismutase (SOD), and lipid peroxidation were assessed in the plasma. The micronuclei frequency and chromosomal aberrations were significantly higher in the exposed group in comparison to the nonexposed group (P < 0.01-0.0001). Similarly, GSH, TAC, and SOD in the blood plasma were significantly higher in the exposed group than the nonexposed group (P < 0.01-0.0001). However, the level of malondialdehyde, which is an indicator of lipid peroxidation, did not differ significantly between both the groups. Importantly, radiation absorbed dose exhibited a positive correlation with the incidence of micronuclei in blood lymphocytes but not with chromosomal aberrations. This study shows that the susceptibility of peripheral blood lymphocytes to chromosomal damage is associated with plasma antioxidant levels. Furthermore, increased levels of blood plasma GSH, TAC, and SOD in occupationally exposed individuals could be an adaptive measure in response to oxidative stress to protect somatic cell genetic integrity. PMID:26758870

  17. Evaluation of Oxidative Stress Response Related Genetic Variants, Pro-oxidants, Antioxidants and Prostate Cancer

    PubMed Central

    Lavender, Nicole; Hein, David W.; Brock, Guy; Kidd, La Creis R.

    2015-01-01

    Background Oxidative stress and detoxification mechanisms have been commonly studied in Prostate Cancer (PCa) due to their function in the detoxification of potentially damaging reactive oxygen species (ROS) and carcinogens. However, findings have been either inconsistent or inconclusive. These mixed findings may, in part, relate to failure to consider interactions among oxidative stress response related genetic variants along with pro- and antioxidant factors. Methods We examined the effects of 33 genetic and 26 environmental oxidative stress and defense factors on PCa risk and disease aggressiveness among 2,286 men from the Cancer Genetic Markers of Susceptibility project (1,175 cases, 1,111 controls). Single and joint effects were analyzed using a comprehensive statistical approach involving logistic regression, multi-dimensionality reduction, and entropy graphs. Results Inheritance of one CYP2C8 rs7909236 T or two SOD2 rs2758331 A alleles was linked to a 1.3- and 1.4-fold increase in risk of developing PCa, respectively (p-value = 0.006–0.013). Carriers of CYP1B1 rs1800440GG, CYP2C8 rs1058932TC and, NAT2 (rs1208GG, rs1390358CC, rs7832071TT) genotypes were associated with a 1.3 to 2.2-fold increase in aggressive PCa [p-value = 0.04–0.001, FDR 0.088–0.939]. We observed a 23% reduction in aggressive disease linked to inheritance of one or more NAT2 rs4646247 A alleles (p = 0.04, FDR = 0.405). Only three NAT2 sequence variants remained significant after adjusting for multiple hypotheses testing, namely NAT2 rs1208, rs1390358, and rs7832071. Lastly, there were no significant gene-environment or gene-gene interactions associated with PCa outcomes. Conclusions Variations in genes involved in oxidative stress and defense pathways may modify PCa. Our findings do not firmly support the role of oxidative stress genetic variants combined with lifestyle/environmental factors as modifiers of PCa and disease progression. However, additional multi-center studies poised

  18. Increasing antioxidant levels in tomatoes through modification of the flavonoid biosynthetic pathway.

    PubMed

    Verhoeyen, M E; Bovy, A; Collins, G; Muir, S; Robinson, S; de Vos, C H R; Colliver, S

    2002-10-01

    Flavonoids are a diverse group of phenolic secondary metabolites that occur naturally in plants and therefore form an integral component of the human diet. Many of the compounds belonging to this group are potent antioxidants in vitro and epidemiological studies suggest a direct correlation between high flavonoid intake and decreased risk of cardiovascular disease, cancer and other age-related diseases. Enhancing flavonoid biosynthesis in chosen crops may provide new raw materials that have the potential to be used in foods designed for specific benefits to human health. Using genetic modification, it was possible to generate several tomato lines with significantly altered flavonoid content and to probe the role and importance of several key enzymatic steps in the tomato flavonoid biosynthetic pathway. Most notably an up to 78-fold increase in total fruit flavonols was achieved through ectopic expression of a single biosynthetic enzyme, chalcone isomerase. In addition, chalcone synthase and flavonol synthase transgenes were found to act synergistically to up-regulate flavonol biosynthesis significantly in tomato flesh tissues. PMID:12324533

  19. Genetic Diversity Increases Insect Herbivory on Oak Saplings

    PubMed Central

    Castagneyrol, Bastien; Lagache, Lélia; Giffard, Brice; Kremer, Antoine; Jactel, Hervé

    2012-01-01

    A growing body of evidence from community genetics studies suggests that ecosystem functions supported by plant species richness can also be provided by genetic diversity within plant species. This is not yet true for the diversity-resistance relationship as it is still unclear whether damage by insect herbivores responds to genetic diversity in host plant populations. We developed a manipulative field experiment based on a synthetic community approach, with 15 mixtures of one to four oak (Quercus robur) half-sib families. We quantified genetic diversity at the plot level by genotyping all oak saplings and assessed overall damage caused by ectophagous and endophagous herbivores along a gradient of increasing genetic diversity. Damage due to ectophagous herbivores increased with the genetic diversity in oak sapling populations as a result of higher levels of damage in mixtures than in monocultures for all families (complementarity effect) rather than because of the presence of more susceptible oak genotypes in mixtures (selection effect). Assemblages of different oak genotypes would benefit polyphagous herbivores via improved host patch location, spill over among neighbouring saplings and diet mixing. By contrast, genetic diversity was a poor predictor of the abundance of endophagous herbivores, which increased with individual sapling apparency. Plant genetic diversity may not provide sufficient functional contrast to prevent tree sapling colonization by specialist herbivores while enhancing the foraging of generalist herbivores. Long term studies are nevertheless required to test whether the effect of genetic diversity on herbivory change with the ontogeny of trees and local adaptation of specialist herbivores. PMID:22937168

  20. Increased antioxidant content in juice enriched with dried extract of pomegranate (Punica granatum) peel.

    PubMed

    Mastrodi Salgado, Jocelem; Baroni Ferreira, Tânia Rachel; de Oliveira Biazotto, Fúvia; Dos Santos Dias, Carlos Tadeu

    2012-03-01

    Antioxidants are compounds responsible for free radical scavenging in the body. They protect the organism from oxidative modification of cells and tissues. These modifications have been associated with degenerative diseases, atherosclerosis and carcinogenesis. Punica granatum displays high antioxidant potential due to the presence of phenolic compounds, which are capable of disease prevention. The present study showed the highest antioxidant activity in pomegranate peel than in seeds and pulp. Based on these results, pomegranate peel was used to produce dried extract that was added to commercial tomato juice and orange juice with strawberries. Analysis to determine the content of phenolic compounds and antioxidant activity was performed on pomegranate pulp, seeds and peel and in juices enriched with dried extract of pomegranate peel. The dried extract was responsible for a significant increase in antioxidant activity of the juices, proportional to the concentrations added. However, although both flavors of enriched juices displayed high antioxidant levels, the samples with higher dried extract concentrations received the lowest scores from sensory analysis participants due to the characteristic astringent flavor of pomegranate peels. Therefore, to obtain greater acceptance in the consumer market, we concluded that the maximum addition of dried pomegranate peel extract is 0.5% in tomato juice and orange juice with strawberries. PMID:22392496

  1. Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle

    NASA Technical Reports Server (NTRS)

    Lawler, John M.; Song, Wook; Demaree, Scott R.; Bloomfield, S. A. (Principal Investigator)

    2003-01-01

    Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.

  2. Tetraploidization of diploid Dioscorea results in activation of the antioxidant defense system and increased heat tolerance.

    PubMed

    Zhang, Xiao-Yi; Hu, Chun-Gen; Yao, Jia-Ling

    2010-01-15

    Polyploidy is reported to show increased tolerance to environmental stress. In this work, tetraploid plants of Dioscorea zingiberensis were obtained by colchicine treatment of shoots propagated in vitro. The highest tetraploid induction rate was achieved by treatment with 0.15% colchicine for 24h. Diploid and tetraploid plants were exposed to normal (28 degrees C) and high temperature (42 degrees C) for 5d during which physiological indices were measured. Compared with diploid plants, relative electrolyte leakage and contents of malondialdehyde, superoxide anions and hydrogen peroxide were lower in tetraploids, while activities of antioxidant enzymes, such as superoxide dismutase, peroxidase, catalase, ascorbate peroxidase and glutathione reductase, were stimulated and antioxidants (ascorbic acid and glutathione) were maintained at high concentrations. These results indicate that tetraploid plants possess a stronger antioxidant defense system and increased heat tolerance. PMID:19692145

  3. Increase of rutin antioxidant activity by generating Maillard reaction products with lysine.

    PubMed

    Zhang, Ru; Zhang, Bian-Ling; He, Ting; Yi, Ting; Yang, Ji-Ping; He, Bin

    2016-06-01

    Rutin exists in medicinal herbs, fruits, vegetables, and a number of plant-derived sources. Dietary sources containing rutin are considered beneficial because of their potential protective roles in multiple diseases related to oxidative stresses. In the present study, the change and antioxidation activity of rutin in Maillard reaction with lysine through a heating process were investigated. There is release of glucose and rhamnose that interact with lysine to give Maillard reaction products (MRPs), while rutin is converted to less-polar quercetin and a small quantity of isoquercitrin. Because of their high cell-membrane permeability, the rutin-lysine MRPs increase the free radical-scavenging activity in HepG2 cells, showing cellular antioxidant activity against Cu(2+)-induced oxidative stress higher than that of rutin. Furthermore, the MRPs significantly increased the Cu/Zn SOD (superoxide dismutase) activity and Cu/Zn SOD gene expression of HepG2 cells, consequently enhancing antioxidation activity. PMID:27106712

  4. In vivo Raman spectroscopy detects increased epidermal antioxidative potential with topically applied carotenoids

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Caspers, P. J.; van der Pol, A.; Richter, H.; Patzelt, A.; Zastrow, L.; Darvin, M.; Sterry, W.; Fluhr, J. W.

    2009-01-01

    In the present study, the distribution of the carotenoids as a marker for the complete antioxidative potential in human skin was investigated before and after the topical application of carotenoids by in vivo Raman spectroscopy with an excitation wavelength of 785 nm. The carotenoid profile was assessed after a short term topical application in 4 healthy volunteers. In the untreated skin, the highest concentration of natural carotenoids was detected in different layers of the stratum corneum (SC) close to the skin surface. After topical application of carotenoids, an increase in the antioxidative potential in the skin could be observed. Topically applied carotenoids penetrate deep into the epidermis down to approximately 24 μm. This study supports the hypothesis that antioxidative substances are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Subsequently they penetrate into the different layers of the SC.

  5. Green tea supplementation increases glutathione and plasma antioxidant capacity in adults with the metabolic syndrome.

    PubMed

    Basu, Arpita; Betts, Nancy M; Mulugeta, Afework; Tong, Capella; Newman, Emily; Lyons, Timothy J

    2013-03-01

    Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (α-carotene, β-carotene, lycopene) and tocopherols (α-tocopherol, γ-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively; P < .05) and whole blood glutathione (1783 to 2395 μg/g hemoglobin and 1905 to 2751 μg/g hemoglobin, respectively; P < .05) vs controls at 8 weeks. No effects were noted in serum levels of carotenoids and tocopherols and glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 μg/dL, P < .02), whereas copper, zinc, and selenium were not affected. These results support the hypothesis that green tea may provide antioxidant protection in the metabolic syndrome. PMID:23507223

  6. Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory

    PubMed Central

    Schrodi, Steven J.

    2016-01-01

    Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. PMID:27375680

  7. Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory.

    PubMed

    Schrodi, Steven J

    2016-01-01

    Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. PMID:27375680

  8. Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against Podocytopathy.

    PubMed

    Zhou, Sijie; Wang, Pei; Qiao, Yingjin; Ge, Yan; Wang, Yingzi; Quan, Songxia; Yao, Ricky; Zhuang, Shougang; Wang, Li Juan; Du, Yong; Liu, Zhangsuo; Gong, Rujun

    2016-08-01

    Evidence suggests that the glycogen synthase kinase 3 (GSK3)-dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3β (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3β in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3β mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3β by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3β-regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies. PMID

  9. Novel transgenic rice overexpressing anthocyanidin synthase accumulates a mixture of flavonoids leading to an increased antioxidant potential.

    PubMed

    Reddy, Ambavaram M; Reddy, Vaka S; Scheffler, Brian E; Wienand, Udo; Reddy, Arjula R

    2007-01-01

    In addition to their plant-associated functions, flavonoids act as antioxidants against harmful free radicals in animals. Genetic engineering of food crops for a mix of antioxidant flavonoids is highly beneficial in promoting human health. Anthocyanidin synthase (ANS) is one of the four dioxygenases (DOX) of the flavonoid biosynthetic pathway that catalyzes the formation of anthocyanidins from leucoanthocyanidins. To investigate whether ANS mediates different DOX reactions of the pathway and produces a mix of flavonoids, the rice ANS cDNA was cloned and overexpressed in a rice mutant Nootripathu (NP). This mutant accumulates proanthocyanidins exclusively in pericarp and absolutely no anthocyanins in any tissue. In silico sequence analysis revealed that ANS contains a double-stranded beta helix and shows high sequence similarity with other DOXs of the pathway including flavonol synthase, flavonone 3beta-hydroxylase and flavone synthase I. Bacterially expressed ANS protein converted dihydroquercetin to quercetin and Pro(35S):ANS complemented the maize a2 mutant in producing anthocyanins in aleurone, suggesting that ANS functions as a DOX with different flavonoid substrates. Similarly, transgenic NP plants overexpressing Pro(MAS):ANS channeled the proanthocaynidin precursors to the production of anthocyanins in pericarp. Transgenics showed approximately ten and four-fold increase in the ANS transcripts and enzyme activity, respectively. As a result, these plants showed an increased accumulation of a mixture of flavonoids and anthocyanins, with a concomitant decrease in proanthocyanidins, suggesting that ANS may act directly on different flavonoid substrates of DOX reactions. Thus, overexpression of ANS in a rice mutant resulted in novel transgenic rice with a mixture of flavonoids and an enhanced antioxidant potential. PMID:17157544

  10. Natural genetic variation in the expression regulation of the chloroplast antioxidant system among Arabidopsis thaliana accessions.

    PubMed

    Juszczak, Ilona; Rudnik, Radoslaw; Pietzenuk, Björn; Baier, Margarete

    2012-09-01

    Photosynthesis is the predominant source of reactive oxygen species in light. In order to prevent the negative influence of reactive oxygen species (ROS) on cell functionality, chloroplasts have evolved a highly efficient antioxidant protection system. Here, we present the first study on natural variation in this system. Comparison of temperature and developmental responses in seven accessions of Arabidopsis thaliana from northern habitats showed that the regulation is widely genetically manifested, but hardly correlates with geographic parameters. Transcript, polysomal RNA (pRNA) and protein data showed that the ecotypes use different strategies to adjust the chloroplast antioxidative defense system, either by regulating transcript abundance or initiation of translation. Comparison of mRNA and pRNA levels showed that Col-0 invests more into transcript accumulation, while Van-0, WS and C24 regulates the chloroplast antioxidant protection system more on the level of pRNA. Nevertheless, both strategies of regulation led to the expression of chloroplast antioxidant enzymes at sufficient level to efficiently protect plants from ROS accumulation in Col-0, WS, C24 and Van-0. On the contrary, Cvi-0, Ms-0 and Kas-1 accumulated high amounts of ROS. The expression of copper/zinc superoxide dismutase (Csd2), ascorbate peroxidases and 2-Cys peroxiredoxins was higher in Cvi-0 on the transcriptional level, while Csd2, peroxiredoxin Q, type II peroxiredoxin E and glutathione peroxidase 1 were induced in Ms-0 on the mRNA level. Similar to Kas-1, in which mRNA levels were less than or similar to Col-0 gene, specific support for translation was observed in Ms-0, showing that the ecotypes use different strategies to adjust the antioxidant system. PMID:22339086

  11. Antioxidant deficit in gills of Pacific oyster (Crassostrea gigas) exposed to chlorodinitrobenzene increases menadione toxicity.

    PubMed

    Trevisan, Rafael; Arl, Miriam; Sacchet, Cássia Lopes; Engel, Cristiano Severino; Danielli, Naissa Maria; Mello, Danielle Ferraz; Brocardo, Caroline; Maris, Angelica Francesca; Dafre, Alcir Luiz

    2012-02-01

    Disturbances in antioxidant defenses decrease cellular protection against oxidative stress and jeopardize cellular homeostasis. To knock down the antioxidant defenses of Pacific oyster Crassostrea gigas, animals were pre-treated with 1-chloro-2,4-dinitrobenzene (CDNB) and further challenged with pro-oxidant menadione (MEN). CDNB pre-treatment (10 μM for 18 h) was able to consume cellular thiols in gills, decreasing GSH (53%) and decrease protein thiols (25%). CDNB pre-treatment also disrupted glutathione reductase and thioredoxin reductase activity in the gills, but likewise strongly induced glutathione S-transferase activity (270% increase). Surprisingly, hemocyte viability was greatly affected 24 h after CDNB removal, indicating a possible vulnerability of the oyster immune system to electrophilic attack. New in vivo approaches were established, allowing the identification of higher rates of GSH-CDNB conjugate export to the seawater and enabling the measurement of the organic peroxide consumption rate. CDNB-induced impairment in antioxidant defenses decreased the peroxide removal rate from seawater. After showing that CDNB decreased gill antioxidant defenses and increased DNA damage in hemocytes, oysters were further challenged with 1 mM MEN over 24 h. MEN treatment did not affect thiol homeostasis in gills, while CDNB pre-treated animals recovered GSH and PSH to the control level after 24 h of depuration. Interestingly, MEN intensified GSH and PSH loss and mortality in CDNB-pre-treated animals, showing a clear synergistic effect. The superoxide-generating one-electron reduction of MEN was predominant in gills and may have contributed to MEN toxicity. These results support the idea that antioxidant-depleted animals are more susceptible to oxidative attack, which can compromise survival. Data also corroborate the idea that gills are an important detoxifying organ, able to dispose of organic peroxides, induce phase II enzymes, and efficiently export GSH

  12. Elucidating the genetic basis of antioxidant status in lettuce (Lactuca sativa)

    PubMed Central

    Damerum, Annabelle; Selmes, Stacey L; Biggi, Gaia F; Clarkson, Graham JJ; Rothwell, Steve D; Truco, Maria José; Michelmore, Richard W; Hancock, Robert D; Shellcock, Connie; Chapman, Mark A; Taylor, Gail

    2015-01-01

    A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases, but many of the most popular vegetables are low in phytonutrients. Wild relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients, and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional quality. In this study, lettuce recombinant inbred lines, generated from a cross between wild and cultivated lettuce (Lactuca serriola and Lactuca sativa, respectively), were analysed for antioxidant (AO) potential and important phytonutrients including carotenoids, chlorophyll and phenolic compounds. When grown in two environments, 96 quantitative trait loci (QTL) were identified for these nutritional traits: 4 for AO potential, 2 for carotenoid content, 3 for total chlorophyll content and 87 for individual phenolic compounds (two per compound on average). Most often, the L. serriola alleles conferred an increase in total AOs and metabolites. Candidate genes underlying these QTL were identified by BLASTn searches; in several cases, these had functions suggesting involvement in phytonutrient biosynthetic pathways. Analysis of a QTL on linkage group 3, which accounted for >30% of the variation in AO potential, revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase, an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol, which are known to have powerful AO activity. Follow-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents, providing further evidence of their potential involvement in determining the contrasting phenotypes. These results offer exciting opportunities to improve the nutritional

  13. Elucidating the genetic basis of antioxidant status in lettuce (Lactuca sativa).

    PubMed

    Damerum, Annabelle; Selmes, Stacey L; Biggi, Gaia F; Clarkson, Graham Jj; Rothwell, Steve D; Truco, Maria José; Michelmore, Richard W; Hancock, Robert D; Shellcock, Connie; Chapman, Mark A; Taylor, Gail

    2015-01-01

    A diet rich in phytonutrients from fruit and vegetables has been acknowledged to afford protection against a range of human diseases, but many of the most popular vegetables are low in phytonutrients. Wild relatives of crops may contain allelic variation for genes determining the concentrations of these beneficial phytonutrients, and therefore understanding the genetic basis of this variation is important for breeding efforts to enhance nutritional quality. In this study, lettuce recombinant inbred lines, generated from a cross between wild and cultivated lettuce (Lactuca serriola and Lactuca sativa, respectively), were analysed for antioxidant (AO) potential and important phytonutrients including carotenoids, chlorophyll and phenolic compounds. When grown in two environments, 96 quantitative trait loci (QTL) were identified for these nutritional traits: 4 for AO potential, 2 for carotenoid content, 3 for total chlorophyll content and 87 for individual phenolic compounds (two per compound on average). Most often, the L. serriola alleles conferred an increase in total AOs and metabolites. Candidate genes underlying these QTL were identified by BLASTn searches; in several cases, these had functions suggesting involvement in phytonutrient biosynthetic pathways. Analysis of a QTL on linkage group 3, which accounted for >30% of the variation in AO potential, revealed several candidate genes encoding multiple MYB transcription factors which regulate flavonoid biosynthesis and flavanone 3-hydroxylase, an enzyme involved in the biosynthesis of the flavonoids quercetin and kaempferol, which are known to have powerful AO activity. Follow-up quantitative RT-PCR of these candidates revealed that 5 out of 10 genes investigated were significantly differentially expressed between the wild and cultivated parents, providing further evidence of their potential involvement in determining the contrasting phenotypes. These results offer exciting opportunities to improve the nutritional

  14. A High Antioxidant Spice Blend Attenuates Postprandial Insulin and Triglyceride Responses and Increases Some Plasma Measures of Antioxidant Activity in Healthy, Overweight Men123

    PubMed Central

    Skulas-Ray, Ann C.; Kris-Etherton, Penny M.; Teeter, Danette L.; Chen, C-Y. Oliver; Vanden Heuvel, John P.; West, Sheila G.

    2011-01-01

    There is much interest in the potential of dietary antioxidants to attenuate in vivo oxidative stress, but little characterization of the time course of plasma effects exists. Culinary spices have demonstrated potent in vitro antioxidant properties. The objective of this study was to examine whether adding 14 g of a high antioxidant spice blend to a 5060-kJ (1200 kcal) meal exerted significant postprandial effects on markers of plasma antioxidant status and metabolism. Healthy overweight men (n = 6) consumed a control and spiced meal in a randomized crossover design with 1 wk between testing sessions. Blood was sampled prior to the meal and at 30-min intervals for 3.5 h (total of 8 samples). Mixed linear models demonstrated a treatment × time interaction (P < 0.05) for insulin and TG, corresponding with 21 and 31% reductions in postprandial levels with the spiced meal, respectively. Adding spices to the meal significantly increased the ferric reducing antioxidant power, such that postprandial increases following the spiced meal were 2-fold greater than after the control meal (P = 0.009). The hydrophilic oxygen radical absorbance capacity (ORAC) of plasma also was increased by spices (P = 0.02). There were no treatment differences in glucose, total thiols, lipophilic ORAC, or total ORAC. The incorporation of spices into the diet may help normalize postprandial insulin and TG and enhance antioxidant defenses. PMID:21697300

  15. Migratory refueling affects non-enzymatic antioxidant capacity, but does not increase lipid peroxidation.

    PubMed

    Eikenaar, Cas; Jönsson, Johanna; Fritzsch, Anna; Wang, Hong-Lei; Isaksson, Caroline

    2016-05-01

    All aerobic organisms are to some degree affected by oxidative stress, which is an imbalance between pro-oxidants and antioxidants in favor of the former. Pro-oxidants can damage DNA, proteins and lipids, and as such oxidative stress can carry considerably fitness costs. In mammals excessive calorie intake is a known cause of oxidative stress. We investigated whether in migrant birds, which typically engage in over-eating in between flights (refueling), high food intake causes oxidative stress. In an experiment we compared levels of plasmatic total non-enzymatic antioxidant capacity (AOX) and oxidative damage (lipid peroxidation) between migrants repeatedly fasted and refed (simulating the flight-refuel cycle of wild migrants), and migrants on ad libitum food. We found that refueling increased AOX, an effect mainly attributable to an increase in uric acid level, an antioxidant that is produced during protein metabolism. Accordingly, variation in AOX was mainly explained by the refueling birds' food intake. However, food intake in migrants on ad libitum food did not explain any variation in AOX. Refueling did not affect lipid peroxidation, nor were its levels explained by food intake. We propose that over-eating migrants retain uric acid, which might be a very low cost mechanism to forego oxidative damage. PMID:26921098

  16. Feed supplemented with byproducts from olive oil mill wastewater processing increases antioxidant capacity in broiler chickens.

    PubMed

    Gerasopoulos, Konstantinos; Stagos, Dimitrios; Kokkas, Stylianos; Petrotos, Konstantinos; Kantas, Dimitrios; Goulas, Panagiotis; Kouretas, Dimitrios

    2015-08-01

    In the present study, a ceramic membrane microfiltration method was used for the separation of two liquid products, the downstream permeate and the upstream retentate, from olive mill wastewater (OMWW). These liquid products were examined for their antioxidant activity by incorporating them into broilers' feed. Twenty four broilers 13 d old were divided into two feeding groups receiving supplementation with OMWW retentate or permeate for 37 d. Blood was drawn at 17, 27 and 37 d, while tissues (muscle, heart, liver) were collected at 37 d. The antioxidant effects were assessed by measuring oxidative stress biomarkers in blood and tissues. The results showed that broilers given feed supplemented with OMWW retentate or permeate had significantly lower protein oxidation and lipid peroxidation levels and higher total antioxidant capacity in plasma and tissues compared to control group. In both OMWW groups, catalase activity in erythrocytes and tissues was significantly increased compared to control group. OMWW retentate administration increased significantly GSH in erythrocytes in broilers with low GSH, although both OMWW products significantly reduced GSH in broilers with high GSH. Thus, it has been demonstrated for the first time that supplementation with OMWW processing residues could be used for enhancing broilers' redox status. PMID:25916917

  17. Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes.

    PubMed

    Zhou, Yan; Zhou, Lili; Ruan, Zheng; Mi, Shumei; Jiang, Min; Li, Xiaolan; Wu, Xin; Deng, Zeyuan; Yin, Yulong

    2016-05-01

    Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome c released were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases. PMID:26824685

  18. BDNF increases with behavioral enrichment and an antioxidant diet in the aged dog.

    PubMed

    Fahnestock, Margaret; Marchese, Monica; Head, Elizabeth; Pop, Viorela; Michalski, Bernadeta; Milgram, William N; Cotman, Carl W

    2012-03-01

    The aged canine (dog) is an excellent model for investigating the neurobiological changes that underlie cognitive impairment and neurodegeneration in humans, as canines and humans undergo similar pathological and behavioral changes with aging. Recent evidence indicates that a combination of environmental enrichment and antioxidant-fortified diet can be used to reduce the rate of age-dependent neuropathology and cognitive decline in aged dogs, although the mechanisms underlying these changes have not been established. We examined the hypothesis that an increase in levels of brain-derived neurotrophic factor (BDNF) is one of the factors underlying improvements in learning and memory. Old, cognitively impaired animals that did not receive any treatment showed a significant decrease in BDNF mRNA in the temporal cortex when compared with the young group. Animals receiving either an antioxidant diet or environmental enrichment displayed intermediate levels of BDNF mRNA. However, dogs receiving both an antioxidant diet and environmental enrichment showed increased levels of BDNF mRNA when compared with untreated aged dogs, approaching levels measured in young animals. BDNF receptor TrkB mRNA levels did not differ between groups. BDNF mRNA levels were positively correlated with improved cognitive performance and inversely correlated with cortical Aβ((1-42)) and Aβ((1-40)) levels. These findings suggest that environmental enrichment and antioxidant diet interact to maintain brain levels of BDNF, which may lead to improved cognitive performance. This is the first demonstration in a higher animal that nonpharmacological changes in lifestyle in advanced age can upregulate BDNF to levels approaching those in the young brain. PMID:20447733

  19. Antioxidant supplementation increases retinal responses and decreases refractive error changes in dogs.

    PubMed

    Wang, Wei; Hernandez, Jerome; Moore, Cecil; Jackson, Janet; Narfström, Kristina

    2016-01-01

    The objective of the study was to examine whether a nutritional antioxidant supplementation could improve visual function in healthy dogs as measured by electroretinography (ERG) and autorefraction. A total of twelve Beagles, 6 to 8 years of age, with normal eyes upon indirect ophthalmoscopy and slit lamp biomicroscopy, were age and sex matched and randomly assigned to receive a feeding regimen for 6 months with or without a daily antioxidant supplementation. Portable, mini-Ganzfeld ERG and a Welch Allyn hand-held autorefractor were used to test retinal response and refractive error in the dogs at baseline and at the end of the supplementation period. All ERG a-wave amplitudes obtained were increased in the treatment group compared with those of dogs in the control group, with significant improvements in the scotopic high and photopic single flash cone ERG responses (P < 0·05 for both). For the b-wave amplitudes, all responses were similarly increased, with significant improvements in responses for the scotopic high light intensity stimulation (P < 0·05), and for photopic single flash cone and 30 Hz flicker (P < 0·01 for both) recordings. Change in refractive error was significantly less in the treatment group compared with that of the control group during the 6-month study (P < 0·05). Compared with the control group, the antioxidant-supplemented group showed improvement to varying degrees for retinal function and significantly less decline in refractive error. Dogs, like humans, experience retinal and lens functional decline with age. Antioxidant supplementation as demonstrated may be beneficial and effective in the long-term preservation and improvement of various functions of the canine eye. PMID:27293555

  20. Reproducing butterflies do not increase intake of antioxidants when they could benefit from them.

    PubMed

    Beaulieu, Michaël; Bischofberger, Ines; Lorenz, Isabel; Scheelen, Lucie; Fischer, Klaus

    2016-02-01

    The significance of dietary antioxidants may be limited by the ability of animals to exploit them. However, past studies have focused on the effects of dietary antioxidants after 'antioxidant forced-feeding', and have overlooked spontaneous antioxidant intake. Here, we found that reproducing female Bicyclus anynana butterflies had higher antioxidant defences and enhanced fecundity when forced to consume antioxidants (polyphenols). Interestingly, these positive effects were not constant across the oviposition period. When given the choice between food resources with and without antioxidants, reproducing butterflies did not target antioxidants when they could have benefited the most from them. Moreover, they did not consume more antioxidants than non-reproducing butterflies. These results emphasize that, despite potential positive effects of dietary antioxidants, the ability of animals to exploit them is likely to restrict their ecological significance. PMID:26911341

  1. Manipulating the antioxidant capacity of halophytes to increase their cultural and economic value through saline cultivation.

    PubMed

    Boestfleisch, Christian; Wagenseil, Niko B; Buhmann, Anne K; Seal, Charlotte E; Wade, Ellie Merrett; Muscolo, Adele; Papenbrock, Jutta

    2014-01-01

    Halophytes, salt-tolerant plants, are a source of valuable secondary metabolites with potential economic value. The steady-state pools of many stress-related metabolites are already enhanced in halophytes when compared with glycophytes, but growth under conditions away from the optimum can induce stress and consequently result in changes to secondary metabolites such as antioxidants. However, direct evidence for increasing the concentration of valuable secondary metabolites as a consequence of altering the salinity of the growing environment still remains equivocal. To address this, we analysed a range of metabolites with antioxidant capacity (including total phenols, flavonoids, ascorbate, reduced/oxidized glutathione and reactive oxygen species scavenging enzymes) in seedlings and plants from different families (Amaranthaceae, Brassicaceae, Plantaginaceae and Rhizophoraceae) and habitats grown under different salt concentrations. We show that it is possible to manipulate the antioxidant capacity of plants and seedlings by altering the saline growing environment, the length of time under saline cultivation and the developmental stage. Among the species studied, the halophytes Tripolium pannonicum, Plantago coronopus, Lepidium latifolium and Salicornia europaea demonstrated the most potential as functional foods or nutraceuticals. PMID:25125698

  2. Manipulating the antioxidant capacity of halophytes to increase their cultural and economic value through saline cultivation

    PubMed Central

    Boestfleisch, Christian; Wagenseil, Niko B.; Buhmann, Anne K.; Seal, Charlotte E.; Wade, Ellie Merrett; Muscolo, Adele; Papenbrock, Jutta

    2014-01-01

    Halophytes, salt-tolerant plants, are a source of valuable secondary metabolites with potential economic value. The steady-state pools of many stress-related metabolites are already enhanced in halophytes when compared with glycophytes, but growth under conditions away from the optimum can induce stress and consequently result in changes to secondary metabolites such as antioxidants. However, direct evidence for increasing the concentration of valuable secondary metabolites as a consequence of altering the salinity of the growing environment still remains equivocal. To address this, we analysed a range of metabolites with antioxidant capacity (including total phenols, flavonoids, ascorbate, reduced/oxidized glutathione and reactive oxygen species scavenging enzymes) in seedlings and plants from different families (Amaranthaceae, Brassicaceae, Plantaginaceae and Rhizophoraceae) and habitats grown under different salt concentrations. We show that it is possible to manipulate the antioxidant capacity of plants and seedlings by altering the saline growing environment, the length of time under saline cultivation and the developmental stage. Among the species studied, the halophytes Tripolium pannonicum, Plantago coronopus, Lepidium latifolium and Salicornia europaea demonstrated the most potential as functional foods or nutraceuticals. PMID:25125698

  3. Increasing global participation in genetics research through DNA barcoding.

    PubMed

    Adamowicz, Sarah J; Steinke, Dirk

    2015-12-01

    DNA barcoding--the sequencing of short, standardized DNA regions for specimen identification and species discovery--has promised to facilitate rapid access to biodiversity knowledge by diverse users. Here, we advance our opinion that increased global participation in genetics research is beneficial, both to scientists and for science, and explore the premise that DNA barcoding can help to democratize participation in genetics research. We examine publication patterns (2003-2014) in the DNA barcoding literature and compare trends with those in the broader, related domain of genomics. While genomics is the older and much larger field, the number of nations contributing to the published literature is similar between disciplines. Meanwhile, DNA barcoding exhibits a higher pace of growth in the number of publications as well as greater evenness among nations in their proportional contribution to total authorships. This exploration revealed DNA barcoding to be a highly international discipline, with growing participation by researchers in especially biodiverse nations. We briefly consider several of the challenges that may hinder further participation in genetics research, including access to training and molecular facilities as well as policy relating to the movement of genetic resources. PMID:26642251

  4. Edible bird's nest enhances antioxidant capacity and increases lifespan in Drosophila Melanogaster.

    PubMed

    Hu, Q; Li, G; Yao, H; He, S; Li, H; Liu, S; Wu, Y; Lai, X

    2016-01-01

    In this study, we aims to investigate the effects of edible bird's nest (EBN) on anti-aging efficacy. In order to investigate lifespan and mortality rate of flies, we treated flies with various doses of EBN. Besides, fecundity, water content and food are determined and heat-stress test is conducted after flies treating with different medium. Effects of EBN on total antioxidant activity (T-AOC), super-oxide dismutase activity (SOD), catalase activity (CAT), and malondialdehyde (MDA) were examined in drosophila melanogaster. Results indicated that flies in EBN treated group illustrated significantly lower mortality rates and longer median and maximum lifespan compared to control group (P<0.05). The fecundity in EBN-treated group was increased compared to control group. SOD levels and CAT activity were significantly increased, and MDA levels decreased in EBN-treated group compared to control group (P<0.01). In conclusion, EBN can extend lifespan, decrease mortality rate and increase survival rate in heat-stress test, and which can also promote SOD and CAT activity and reduce MDA levels. EBN is able to delay drosophila melanogaster aging, attributing to the increasing antioxidant enzyme activities and decreasing content of lipid peroxidation products in drosophila melanogaster. PMID:27188745

  5. Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

    SciTech Connect

    Black, Adrienne T.; Gray, Joshua P.; Shakarjian, Michael P.; Laskin, Debra L. Heck, Diane E.; Laskin, Jeffrey D.

    2008-09-15

    Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which was greater in differentiated cells. Paraquat treatment also resulted in increased expression of HO-1, Cu,Zn-SOD, catalase, GSTP1, GSTA3 and GSTA4. However, no major differences in expression of these enzymes were evident between undifferentiated and differentiated cells. In contrast, expression of GSTA1-2 was significantly greater in differentiated relative to undifferentiated cells after paraquat treatment. No changes in expression of MT-2, Mn-SOD, GPx-1, GSTM1 or the microsomal GST's mGST1, mGST2 and mGST3, were observed in response to paraquat. These data demonstrate that paraquat induces oxidative stress in keratinocytes leading to increased expression of antioxidant genes. These intracellular proteins may be important in protecting the skin from paraquat-mediated cytotoxicity.

  6. Genetic Variants in Antioxidant Genes Are Associated With Diisocyanate-Induced Asthma

    PubMed Central

    Yucesoy, Berran

    2012-01-01

    Diisocyanates are a common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants of antioxidant defense genes, glutathione S-transferases (GSTM1, GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (SOD2), and microsomal epoxide hydrolase (EPHX1) are associated with increased susceptibility to diisocyanate-induced asthma (DA). The main study population consisted of 353 Caucasian French-Canadians from among a larger sample of 410 diisocyanate-exposed workers in three groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+, n = 95); symptomatic diisocyanate workers with a negative SIC (DA−, n = 116); and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5′-nuclease PCR assay. The SOD2 rs4880, GSTP1 rs1695, and EPHX1 rs2740171 variants were significantly associated with DA in both univariate and multivariate analyses. In the first logistic regression model comparing DA+ and DA− groups, SOD2 rs4880, GSTM1 (null), GSTP1 rs762803, and EPHX1 rs2854450 variants were associated with DA (p = 0.004, p = 0.047, p = 0.021, p <0.001, respectively). Genotype combinations GSTT1*GSTP1 rs762803, GSTM1*EPHX1 rs2854450, EPHX1 rs2740168*EPHX1 rs1051741, and GSTP1 rs762803*EPHX1 rs2740168 were also associated with DA in this model (p = 0.027, p = 0.002, p = 0.045, p = 0.044, respectively). The GSTP1 rs1695 and EPHX1 rs1051741 and rs2740171 variants showed an association with DA in the second model comparing DA+ and AW groups (p = 0.040, p = 0.019, p = 0.002, respectively). The GSTM3 rs110913*EPHX1 rs1051741 genotype combination was also associated with DA under this model (p = 0.042). The results suggest that variations in SOD2, GST, and EPHX1 genes and their interactions contribute to DA susceptibility. PMID:22610343

  7. Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities.

    PubMed

    Del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G; LeBlanc, Jean Guy

    2014-02-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti

  8. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti

  9. The wheat MAP kinase phosphatase 1 alleviates salt stress and increases antioxidant activities in Arabidopsis.

    PubMed

    Zaidi, Ikram; Ebel, Chantal; Belgaroui, Nibras; Ghorbel, Mouna; Amara, Imène; Hanin, Moez

    2016-04-01

    Mitogen-activated protein kinase phosphatases (MKPs) are important negative regulators in the MAPK signaling pathways, which play crucial roles in plant growth, development and stress responses. We have previously shown that the heterologous expression of a durum wheat MKP, TMKP1, results in increased tolerance to salt stress in yeast but its particular contribution in salt stress tolerance in plants was not investigated. Here, TMKP1 was overexpressed in Arabidopsis thaliana and physiological changes were assessed in transgenic plants exposed to stress conditions. Under salt stress and especially LiCl, the TMKP1 overexpressors displayed higher germination rates in comparison to wild type plants. The enhancement of salt stress tolerance was accompanied by increased antioxidant enzyme activities, namely superoxide dismutase, catalase and peroxydases. Such increases in antioxidant activities were concomitant with lower malondialdehyde, superoxide anion O2(-) and hydrogen peroxide levels in the TMKP1 transgenic seedlings. Moreover, we provide evidence that, in contrast to the Arabidopsis ortholog AtMKP1, TMKP1 acts as a positive regulator of salt stress tolerance via its ectopic expression in the Arabidopsis mkp1 mutant. PMID:26927025

  10. Environmental Adversity Increases Genetic Risk for Externalizing Disorders

    PubMed Central

    Hicks, Brian M.; South, Susan C.; DiRago, Ana C.; Iacono, William G.; McGue, Matt

    2008-01-01

    Background Studies of gene-environment (G-E) interplay in the development of psychiatric and substance use disorders are rapidly accumulating. However, few attempts have been made to integrate findings and articulate general mechanisms of G-E influence in the emergence of psychopathology. Objective Identify patterns of G-E interplay between externalizing (EXT; antisocial behavior and substance use) disorders and several environmental risk factors. Design We used quantitative genetic models to examine how genetic and environmental risk for EXT disorders changes as a function of environmental context. Setting Participants were recruited from the community and took part in a day-long assessment at a university laboratory. Participants The sample consisted of 1315 male and female twin pairs participating in the age 17 assessment of the Minnesota Twin Family Study. Main Outcome Measures Multiple measures and informants were employed to construct a composite of EXT disorders and composite measures of 6 environmental risk factors including academic achievement and engagement, antisocial and prosocial peer affiliation, mother-child and father-child relationship problems, and stressful life events. Results A significant G × E interaction was detected between each environmental risk factor and EXT such that greater environmental adversity was associated with increased genetic risk in EXT. Conclusion Our findings demonstrate that in the context of environmental adversity, genetic factors become more important in the etiology of EXT disorders. The consistency of the results further suggests a general mechanism of environmental influence on EXT disorders regardless of the specific form of the environmental risk. PMID:19487629

  11. Regulation of the phenolic profile of berries can increase their antioxidant activity.

    PubMed

    Hudec, Jozef; Kochanová, Radka; Burdová, Mária; Kobida, L'ubomír; Kogan, Grigorij; Turianica, Ivan; Chlebo, Peter; Hanácková, Eva; Slamka, Pavol

    2009-03-11

    The changes of the antioxidant activities (AOA), antiradical activities (ARA), low-density lipoprotein (LDL) oxidation, and total contents of phenolics, anthocyanins, flavonols, hydroxybenzoic acids, and hydroxycinnamic acids in black currant and black chokeberry, after treatment with ornithine decarboxylase inhibitor, a polyamine inhibitor (O-phosphoethanolamine, KF), and a phenol biosynthesis stimulator (carboxymethyl chitin glucan, CCHG), were analyzed spectrophotometrically. Gallic acid, hydroxycinnamic acids, and selected flavonol contents was analyzed by RP-HPLC. Both regulators increased the AOA measured as inhibition of peroxidation (IP) in black chokeberry, 1.71-fold after treatment with KF(1) and 1.74-fold after treatment with CCHG. In black currant IP was elevated after CCHG application only in lower dose (CCHG(1) 63.36% vs control 53.23%). In black chokeberry the total phenolics content was elevated 1.49-fold after KF(1) application and 1.31-fold after CCHG(2) application. The regulators had the lower effect on the phenolic accumulation in black currant. There was a strong relationship between the total phenolics in the both crops and anthocyanins, hydroxybenzoic acids, and hydroxycinnamic acids contents, respectively. Both regulators significantly changed the ratio of conjugated (rutin) to free (quercetin) flavonol mainly in black chokeberry. The antioxidant activities compared using LDL in vitro oxidation assay were increased more expressively after treatment with KF(2) in both crops. PMID:19209908

  12. Continuous light increases growth, daily carbon gain, antioxidants, and alters carbohydrate metabolism in a cultivated and a wild tomato species.

    PubMed

    Haque, Mohammad S; Kjaer, Katrine H; Rosenqvist, Eva; Ottosen, Carl-Otto

    2015-01-01

    Cultivated tomato species develop leaf injury while grown in continuous light (CL). Growth, photosynthesis, carbohydrate metabolism and antioxidative enzyme activities of a cultivated (Solanum lycopersicum L. 'Aromata') and a wild tomato species (Solanum pimpinellifolium L.) were compared in this study aiming to analyze the species-specific differences and thermoperiod effects in responses to CL. The species were subjected to three photoperiodic treatments for 12 days in climate chambers: 16-h photoperiod with a light/dark temperature of 26/16°C (P16D10 or control); CL with a constant temperature of 23°C (P24D0); CL with a variable temperature of 26/16°C (P24D10). The results showed that both species grown in CL had higher dry matter production due to the continuous photosynthesis and a subsequent increase in carbon gain. In S. lycopersicum, the rate of photosynthesis and the maximum photochemical efficiency of photosystem II declined in CL with the development of leaf chlorosis, reduction in the leaf chlorophyll content and a higher activity of antioxidative enzymes. The normal diurnal patterns of starch and sugar were only present under control conditions. The results demonstrated that CL conditions mainly affected the photosynthetic apparatus of a cultivated species (S. lycopersicum), and to a less degree to the wild species (S. pimpinellifolium). The negative effects of the CL could be alleviated by diurnal temperature variations, but the physiological mechanisms behind these are less clear. The results also show that the genetic potential for reducing the negative effects of CL does exist in the tomato germplasm. PMID:26217371

  13. Continuous light increases growth, daily carbon gain, antioxidants, and alters carbohydrate metabolism in a cultivated and a wild tomato species

    PubMed Central

    Haque, Mohammad S.; Kjaer, Katrine H.; Rosenqvist, Eva; Ottosen, Carl-Otto

    2015-01-01

    Cultivated tomato species develop leaf injury while grown in continuous light (CL). Growth, photosynthesis, carbohydrate metabolism and antioxidative enzyme activities of a cultivated (Solanum lycopersicum L. ‘Aromata’) and a wild tomato species (Solanum pimpinellifolium L.) were compared in this study aiming to analyze the species-specific differences and thermoperiod effects in responses to CL. The species were subjected to three photoperiodic treatments for 12 days in climate chambers: 16-h photoperiod with a light/dark temperature of 26/16°C (P16D10 or control); CL with a constant temperature of 23°C (P24D0); CL with a variable temperature of 26/16°C (P24D10). The results showed that both species grown in CL had higher dry matter production due to the continuous photosynthesis and a subsequent increase in carbon gain. In S. lycopersicum, the rate of photosynthesis and the maximum photochemical efficiency of photosystem II declined in CL with the development of leaf chlorosis, reduction in the leaf chlorophyll content and a higher activity of antioxidative enzymes. The normal diurnal patterns of starch and sugar were only present under control conditions. The results demonstrated that CL conditions mainly affected the photosynthetic apparatus of a cultivated species (S. lycopersicum), and to a less degree to the wild species (S. pimpinellifolium). The negative effects of the CL could be alleviated by diurnal temperature variations, but the physiological mechanisms behind these are less clear. The results also show that the genetic potential for reducing the negative effects of CL does exist in the tomato germplasm. PMID:26217371

  14. Spirogyra varians mutant generated by high dose gamma-irradiation shows increased antioxidant properties

    NASA Astrophysics Data System (ADS)

    Lee, Hak-Jyung; Yoon, Minchul; Sung, Nak-Yun; Choi, Jong-il

    2012-08-01

    The aim of this study was to evaluate the antioxidant properties of a Spirogyra varians mutant (Mut) produced by gamma irradiation. Methanol extracts were prepared from Spirogyra varians wild-type and Mut plants, and their antioxidant activities and total phenolic content (TPC) were determined. Antioxidant parameters, including the 2-diphenyl-1-picrylhydrazyl radical-scavenging activity and ferric-reducing/antioxidant power, were higher in the Mut extract. Moreover, the TPC level was higher (P<0.05) in the Mut methanol extract. Therefore, these results suggest that gamma irradiation-induced S. varians Mut has superior antioxidant properties.

  15. Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity.

    PubMed

    Rovcanin, Branislav R; Gopcevic, Kristina R; Kekic, Dusan Lj; Zivaljevic, Vladan R; Diklic, Aleksandar Dj; Paunovic, Ivan R

    2016-01-01

    Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior. PMID:27615359

  16. Oxidative stress is increased in critically ill patients according to antioxidant vitamins intake, independent of severity: a cohort study

    PubMed Central

    Abilés, Jimena; de la Cruz, Antonio Pérez; Castaño, José; Rodríguez-Elvira, Manuel; Aguayo, Eduardo; Moreno-Torres, Rosario; Llopis, Juan; Aranda, Pilar; Argüelles, Sandro; Ayala, Antonio; de la Quintana, Alberto Machado; Planells, Elena Maria

    2006-01-01

    Introduction Critically ill patients suffer from oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although ROS/RNS are constantly produced under normal circumstances, critical illness can drastically increase their production. These patients have reduced plasma and intracellular levels of antioxidants and free electron scavengers or cofactors, and decreased activity of the enzymatic system involved in ROS detoxification. The pro-oxidant/antioxidant balance is of functional relevance during critical illness because it is involved in the pathogenesis of multiple organ failure. In this study the objective was to evaluate the relation between oxidative stress in critically ill patients and antioxidant vitamin intake and severity of illness. Methods Spectrophotometry was used to measure in plasma the total antioxidant capacity and levels of lipid peroxide, carbonyl group, total protein, bilirubin and uric acid at two time points: at intensive care unit (ICU) admission and on day seven. Daily diet records were kept and compliance with recommended dietary allowance (RDA) of antioxidant vitamins (A, C and E) was assessed. Results Between admission and day seven in the ICU, significant increases in lipid peroxide and carbonyl group were associated with decreased antioxidant capacity and greater deterioration in Sequential Organ Failure Assessment score. There was significantly greater worsening in oxidative stress parameters in patients who received antioxidant vitamins at below 66% of RDA than in those who received antioxidant vitamins at above 66% of RDA. An antioxidant vitamin intake from 66% to 100% of RDA reduced the risk for worsening oxidative stress by 94% (ods ratio 0.06, 95% confidence interval 0.010 to 0.39), regardless of change in severity of illness (Sequential Organ Failure Assessment score). Conclusion The critical condition of patients admitted to the ICU is associated with worsening oxidative stress. Intake of

  17. Increasing oxidative stress with molsidomine increases blood pressure in genetically hypertensive rats but not normotensive controls.

    PubMed

    Fortepiani, Lourdes A; Reckelhoff, Jane F

    2005-09-01

    Spontaneously hypertensive rats (SHR) have a higher level of oxidative stress and exhibit a greater depressor response to a superoxide scavenger, tempol, than normotensive Wistar-Kyoto rats (WKY). This study determined whether an increase in oxidative stress with a superoxide/NO donor, molsidomine, would amplify the blood pressure in SHR. Male SHR and WKY were given molsidomine (30 mg.kg(-1).day(-1)) or vehicle (0.01% ethanol) for 1 wk, and blood pressure, renal hemodynamics, nitrate and nitrite excretion (NOx), renal superoxide production, and expression of renal antioxidant enzymes, Mn- and Cu,Zn-SOD, catalase, and glutathione peroxidase (GPx), were measured. Renal superoxide and NOx were higher in control SHR than in WKY. Molsidomine increased superoxide by approximately 35% and NOx by 250% in both SHR and WKY. Mean arterial blood pressure (MAP) was also higher in control SHR than WKY. Molsidomine increased MAP by 14% and caused renal vasoconstriction in SHR but reduced MAP by 16%, with no effect on renal hemodynamics, in WKY. Renal expression of Mn- and Cu,Zn-SOD was not different between SHR and WKY, but expression of catalase and GPx were approximately 30% lower in kidney of SHR than WKY. The levels of Mn- and Cu,Zn-SOD were not increased with molsidomine in either WKY or SHR. Renal catalase and GPx expression was increased by 300-400% with molsidomine in WKY, but there was no effect in SHR. Increasing oxidative stress elevated blood pressure further in SHR but not WKY. WKY are likely protected because of higher bioavailable levels of NO and the ability to upregulate catalase and GPx. PMID:15905221

  18. Short term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior

    PubMed Central

    Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A.; Siegel, Jerome M.

    2009-01-01

    Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. PMID:19850085

  19. Pecans acutely increase plasma postprandial antioxidant capacity and catechins and decrease LDL oxidation in humans.

    PubMed

    Hudthagosol, Chatrapa; Haddad, Ella Hasso; McCarthy, Katie; Wang, Piwen; Oda, Keiji; Sabaté, Joan

    2011-01-01

    Bioactive constituents of pecan nuts such as γ-tocopherol and flavan-3-ol monomers show antioxidant properties in vitro, but bioavailability in humans is not known. We examined postprandial changes in plasma oxygen radical absorbance capacity (ORAC) and in concentrations of tocopherols, catechins, oxidized LDL, and malondialdehyde (MDA) in response to pecan test meals. Sixteen healthy men and women (23-44 y, BMI 22.7 ± 3.4) were randomly assigned to 3 sequences of test meals composed of whole pecans, blended pecans, or an isocaloric meal of equivalent macronutrient composition but formulated of refined ingredients in a crossover design with a 1-wk washout period between treatments. Blood was sampled at baseline and at intervals up to 24 h postingestion. Following the whole and blended pecan test meals, plasma concentrations of γ-tocopherols doubled at 8 h (P < 0.001) and hydrophilic- and lipophilic-ORAC increased 12 and 10% at 2 h, respectively. Post whole pecan consumption, oxidized LDL decreased 30, 33, and 26% at 2, 3, and 8 h, respectively (P < 0.05), and epigallocatechin-3-gallate concentrations at 1 h (mean ± SEM; 95.1 ± 30.6 nmol/L) and 2 h (116.3 ± 80.5 nmol/L) were higher than at baseline (0 h) and after the control test meal at 1 h (P < 0.05). The postprandial molar ratio of MDA:triglycerides decreased by 37, 36, and 40% at 3, 5, and 8 h, respectively (P < 0.05), only when whole and blended pecan data were pooled. These results show that bioactive constituent of pecans are absorbable and contribute to postprandial antioxidant defenses. PMID:21106921

  20. Increased antioxidant response and capability to produce ROS in hemocytes of Pinna nobilis L. exposed to anthropogenic activity.

    PubMed

    Sureda, Antoni; Natalotto, Antonino; Alvarez, Elvira; Deudero, Salud

    2013-10-01

    Environmental pollutants exert immunotoxical effects on aquatic organisms. The aim was to determine the antioxidant response, markers of oxidative damage and reactive oxygen species production in hemocytes of Pinna nobilis, the largest endemic bivalve in the Mediterranean Sea, under anthropogenic pressure. P. nobilis individuals were collected from two locations along Mallorca Island waters attending to different degree of human impact and the hemocytes were obtained. Specimens from the impacted area showed increased activities of the antioxidant enzymes - catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase -, myeloperoxidase activity and reduced glutathione levels. No differences in oxidative damage markers - malondiahdehyde and carbonyl index - were evidenced between the pristine and polluted areas. Hemocytes from the polluted area presented increased capability to generate reactive oxygen species and nitrite/nitrate when activated. In conclusion, the human activities primed hemocytes for oxidative burst and increased the antioxidant mechanism without evidence of oxidative damage. PMID:23871388

  1. Additives increasing antioxidant activity of sesamol in soybean oil at frying temperature

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sesamol has drawn a considerable interest as an alternative to synthetic antioxidants due to its excellent radical scavenging ability at room temperature, low cost and additional health-promoting benefits. However, when it was evaluated for its antioxidant activity in soybean oil at frying temperatu...

  2. Genetic predisposition to schizophrenia associated with increased use of cannabis

    PubMed Central

    Power, Robert A.; Verweij, Karin J.H.; Zuhair, Mohamed; Montgomery, Grant W.; Henders, Anjali K.; Heath, Andrew C.; Madden, Pamela A.F.; Medland, Sarah E.; Wray, Naomi R.; Martin, Nicholas G.

    2015-01-01

    Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric disorder affecting approximately 1% of the population over their lifetime. Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. In a sample of 2,082 healthy individuals, we show an association between an individual’s burden of schizophrenia risk alleles and use of cannabis. This was significant both for comparing those who have ever vs. never used cannabis (p=2.6×10−4), and for quantity of use within users (p=3.0×10−3). While directly predicting only a small amount of the variance in cannabis use, these findings suggest that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology. This form of gene-environment correlation is an important consideration when calculating the impact of environmental risk factors, including cannabis use. PMID:24957864

  3. Multiple trait genomic selection methods increase genetic value prediction accuracy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection predicts genetic values with genome-wide markers. It is rapidly emerging in plant breeding and is widely implemented in animal breeding. Genetic correlations between quantitative traits are pervasive in many breeding programs. These correlations indicate that measurements of one tr...

  4. Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

    PubMed Central

    Balmus, Ioana Miruna; Dobrin, Romeo; Timofte, Daniel

    2016-01-01

    The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID:27563374

  5. Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches.

    PubMed

    Balmus, Ioana Miruna; Ciobica, Alin; Antioch, Iulia; Dobrin, Romeo; Timofte, Daniel

    2016-01-01

    The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context. PMID:27563374

  6. Seasonal foraging patterns of forest-grazing Japanese Black heifers with increased plasma total antioxidant capacity.

    PubMed

    Haga, Satoshi; Nakano, Miwa; Nakao, Seiji; Hirano, Kiyoshi; Yamamoto, Yoshito; Sasaki, Hiroyuki; Ishizaki, Hiroshi

    2016-02-01

    Forest-grazing enables the intake of high total antioxidant capacity (TAC) plants that might be beneficial for the TAC status of cattle. This study evaluated the relation between the seasonal foraging patterns of forest-grazing Japanese Black (JB) heifers or the TAC levels in shrubs and trees and the changes of plasma TAC. We examined 12 JB heifers, four each of which were allocated to forest-grazing (F), pasture-grazing, and pen-housed groups. The plasma TAC level in F heifers on July 26, August 13, 30 and September 17 were significantly higher than those on April 27 and June 4 (P < 0.05). In F group, the mean rates of foraging frequency (FF) of shrubs and trees during July 5-8 and September 13-16 were much higher than that during May 31-June 3 (P < 0.05). The rate of FF of grass significantly decreased later in the season (P < 0.05). The mean TAC levels in these shrubs and trees were higher than those in grasses, concentrates, and timothy hay. Results suggest that an important factor in the increase of plasma TAC in forest-grazing cattle might be the increased foraging of TAC-rich shrubs and trees during summer-fall. PMID:26270936

  7. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    PubMed Central

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

  8. Effect of Dose and Administration Period of Seed Cake of Genetically Modified and Non-Modified Flax on Selected Antioxidative Activities in Rats

    PubMed Central

    Matusiewicz, Magdalena; Kosieradzka, Iwona; Zuk, Magdalena; Szopa, Jan

    2015-01-01

    Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development of rats and selected parameters of their health status. Diets with 15% and 30% addition of genetically modified (GM) flax seed cake with enhanced synthesis of polyphenols, as well as Linola non-GM flax were administered in short-term (33 days) and long-term (90 days) experiments. The 30% addition of flaxseed cake reduced digestibility of dietary nutrients, GM flaxseed cake lowered body weight gains. The relative weight of selected organs, hematological blood markers and serum activities of aspartate and alanine aminotransferases (AST, ALT) were not affected. Flaxseed cake consumption reduced serum concentration of albumins and increased globulins. Administration of 30% flaxseed cake improved plasma total antioxidant status and 30% GM flaxseed cake lowered liver thiobarbituric acid reactive substances. The activities of superoxide dismutase in erythrocytes, glutathione peroxidase in plasma and the liver concentration of 8-oxo-2′-deoxyguanosine were not changed. Most morphometric parameters of the small intestine did not differ between feeding groups. The administration of diets with 30% addition of flaxseed cake for 90 days improved the antioxidant status in rats. PMID:26110393

  9. Effect of Dose and Administration Period of Seed Cake of Genetically Modified and Non-Modified Flax on Selected Antioxidative Activities in Rats.

    PubMed

    Matusiewicz, Magdalena; Kosieradzka, Iwona; Zuk, Magdalena; Szopa, Jan

    2015-01-01

    Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development of rats and selected parameters of their health status. Diets with 15% and 30% addition of genetically modified (GM) flax seed cake with enhanced synthesis of polyphenols, as well as Linola non-GM flax were administered in short-term (33 days) and long-term (90 days) experiments. The 30% addition of flaxseed cake reduced digestibility of dietary nutrients, GM flaxseed cake lowered body weight gains. The relative weight of selected organs, hematological blood markers and serum activities of aspartate and alanine aminotransferases (AST, ALT) were not affected. Flaxseed cake consumption reduced serum concentration of albumins and increased globulins. Administration of 30% flaxseed cake improved plasma total antioxidant status and 30% GM flaxseed cake lowered liver thiobarbituric acid reactive substances. The activities of superoxide dismutase in erythrocytes, glutathione peroxidase in plasma and the liver concentration of 8-oxo-2'-deoxyguanosine were not changed. Most morphometric parameters of the small intestine did not differ between feeding groups. The administration of diets with 30% addition of flaxseed cake for 90 days improved the antioxidant status in rats. PMID:26110393

  10. Proteolytic activity of Oenococcus oeni enables the increase in antioxidant and antihypertensive activities from wine.

    PubMed

    Apud, Gisselle Raquel; Stivala, María Gilda; Fernández, Pedro Aredes; Rodríguez Vaquero, María José

    2013-01-01

    Oenococcus oeni is a lactic acid bacterium involved in winemaking where it generally carries out the malolactic fermentation converting the wine's malic acid into lactic acid. In this work were used the strain m of Oenococcus oeni. The culture was inoculated at 10⁸ Log CFU/mL in a synthetic wine medium (SW) supplemented with a fraction of high molecular weight constituted by proteins and polypeptides (FPP) obtained from Cabernet Sauvignon and Syrah wines from Colalao del Valle, Tucumán, Argentine. In presence of FPP, O. oeni maintains viability after 48 h incubation time and release an extracellular proteolytic activity. Therefore, a release peptides of 1.247 and 1.373 mg N/L at 48 h of incubation time was detected in SW supplemented with FPP from Cabernet Sauvignon and Syrah wines respectively. Concomitantly with the maximum peptide release, the "in vitro" biological activities were increased. The released peptides from Cabernet Sauvignon wine enables the increase in the ferric reducing antioxidant power (FRAP) capacity, the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), and the inhibition of angiotensin I-converting enzyme (ACEI activity) in 392.8 µmol FeSO₄/L, 9.7% and 63.9%, respectively. In presence of FPP of Syrah wine, the released peptides increases in 156.5 µmol FeSO₄/L, 5.5% and 13.8% the FRAP, DPPH and ACEI activities, respectively. The utilization of Oenococcus oeni m to carry out the malolactic fermentation would contribute to enhance the beneficial biological activities of the final product and provide an additional value to regional wines. PMID:24372266

  11. Increased carbon dioxide concentration improves the antioxidative properties of the Malaysian herb kacip fatimah (Labisia pumila Blume).

    PubMed

    Ibrahim, Mohd Hafiz; Jaafar, Hawa Z E

    2011-01-01

    A randomized complete randomized design (RCBD) 3 by 3 experiment was designed to investigate and distinguish the relationships among production of secondary metabolites (total phenolics, TP; total flavonoids, TF), gluthatione (GSH), oxidized gluthatione (GSSG), soluble carbohydrate and antioxidant activities of the Malaysian medicinal herb Labisia pumila Blume under three levels of CO₂ enrichment (400, 800 and 1,200 µmol mol⁻¹) for 15 weeks. It was found that the treatment effects were solely contributed by interaction of CO₂ levels and secondary metabolites distribution in plant parts, GSH, GSHH and antioxidant activities (peroxyl radicals (ROO), superoxide radicals (O₂), hydrogen peroxide (H₂O₂) and hydroxyl radicals (OH). The records of secondary metabolites, glutahione, oxidized gluthathione and antioxidant activities in a descending manner came from the leaf enriched with 1,200 µmol/mol CO₂ > leaf 800 µmol/mol CO₂ > leaf 400 µmol/mol CO₂ > stem 1,200 µmol/mol CO₂ > stem 800 µmol/mol CO₂ > stem 400 µmol/mol CO₂ > root 1,200 µmol/mol CO₂ > root 800 µmol/mol CO₂ > root 400 µmol/mol CO₂. Correlation analyses revealed strong significant positive coefficients of antioxidant activities with total phenolics, flavonoids, GSH and GSHH indicating that an increase in antioxidative activity of L. pumila under elevated CO₂ might be up-regulated by the increase in production of total phenolics, total flavonoids, GSH, GSHH and soluble sugar. This study implied that the medicinal potential of herbal plant such as L. pumila can be enhanced under elevated CO₂, which had simultaneously improved the antioxidative activity that indicated by the high oxygen radical absorbance activity against ROO, O₂, H₂O₂, and OH radicals. PMID:21775936

  12. Rapid range expansion increases genetic differentiation while causing limited reduction in genetic diversity in a damselfly

    PubMed Central

    Swaegers, J; Mergeay, J; Therry, L; Larmuseau, M H D; Bonte, D; Stoks, R

    2013-01-01

    Many ectothermic species are currently expanding their geographic range due to global warming. This can modify the population genetic diversity and structure of these species because of genetic drift during the colonization of new areas. Although the genetic signatures of historical range expansions have been investigated in an array of species, the genetic consequences of natural, contemporary range expansions have received little attention, with the only studies available focusing on range expansions along a narrow front. We investigate the genetic consequences of a natural range expansion in the Mediterranean damselfly Coenagrion scitulum, which is currently rapidly expanding along a broad front in different directions. We assessed genetic diversity and genetic structure using 12 microsatellite markers in five centrally located populations and five recently established populations at the edge of the geographic distribution. Our results suggest that, although a marginal significant decrease in the allelic richness was found in the edge populations, genetic diversity has been preserved during the range expansion of this species. Nevertheless, edge populations were genetically more differentiated compared with core populations, suggesting genetic drift during the range expansion. The smaller effective population sizes of the edge populations compared with central populations also suggest a contribution of genetic drift after colonization. We argue and document that range expansion along multiple axes of a broad expansion front generates little reduction in genetic diversity, yet stronger differentiation of the edge populations. PMID:23820582

  13. Rapid range expansion increases genetic differentiation while causing limited reduction in genetic diversity in a damselfly.

    PubMed

    Swaegers, J; Mergeay, J; Therry, L; Larmuseau, M H D; Bonte, D; Stoks, R

    2013-11-01

    Many ectothermic species are currently expanding their geographic range due to global warming. This can modify the population genetic diversity and structure of these species because of genetic drift during the colonization of new areas. Although the genetic signatures of historical range expansions have been investigated in an array of species, the genetic consequences of natural, contemporary range expansions have received little attention, with the only studies available focusing on range expansions along a narrow front. We investigate the genetic consequences of a natural range expansion in the Mediterranean damselfly Coenagrion scitulum, which is currently rapidly expanding along a broad front in different directions. We assessed genetic diversity and genetic structure using 12 microsatellite markers in five centrally located populations and five recently established populations at the edge of the geographic distribution. Our results suggest that, although a marginal significant decrease in the allelic richness was found in the edge populations, genetic diversity has been preserved during the range expansion of this species. Nevertheless, edge populations were genetically more differentiated compared with core populations, suggesting genetic drift during the range expansion. The smaller effective population sizes of the edge populations compared with central populations also suggest a contribution of genetic drift after colonization. We argue and document that range expansion along multiple axes of a broad expansion front generates little reduction in genetic diversity, yet stronger differentiation of the edge populations. PMID:23820582

  14. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase

    PubMed Central

    2012-01-01

    Background Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7. Methods The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells. Results Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase. Conclusions Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells

  15. Quinclorac-habituation of bean (Phaseolus vulgaris) cultured cells is related to an increase in their antioxidant capacity.

    PubMed

    Largo-Gosens, Asier; de Castro, María; Alonso-Simón, Ana; García-Angulo, Penélope; Acebes, José L; Encina, Antonio; Álvarez, Jesús M

    2016-10-01

    The habituation of bean cells to quinclorac did not rely on cell wall modifications, contrary to what it was previously observed for the well-known cellulose biosynthesis inhibitors dichlobenil or isoxaben. The aim of the present study was to investigate whether or not the bean cells habituation to quinclorac is related to an enhancement of antioxidant activities involved in the scavenging capacity of reactive oxygen species. Treating non-habituated bean calluses with 10 μM quinclorac reduced the relative growth rate and induced a two-fold increase in lipid peroxidation. However, the exposition of quinclorac-habituated cells to a concentration of quinclorac up to 30 μM neither affected their growth rate nor increased their lipid peroxidation levels. Quinclorac-habituated calluses had significantly higher constitutive levels of three antioxidant activities (class-III peroxidase, glutathione reductase, and superoxide dismutase) than those observed in non-habituated calluses, and the treatment of habituated calluses with 30 μM quinclorac significantly increased the level of class III-peroxidase and superoxide dismutase. The results reported here indicate that the process of habituation to quinclorac in bean callus-cultured cells is related, at least partially, to the development of a stable antioxidant capacity that enables them to cope with the oxidative stress caused by quinclorac. Class-III peroxidase and superoxide dismutase activities could play a major role in the quinclorac-habituation. Changes in the antioxidant status of bean cells were stable, since the increase in the antioxidant activities were maintained in quinclorac-dehabituated cells. PMID:27318799

  16. Irrigation of Solanum lycopersicum L. with magnetically treated water increases antioxidant properties of its tomato fruits.

    PubMed

    Dubois, A E Ferrer; Leite, G O; Rocha, J B T

    2013-09-01

    Antioxidant effects of tomatoes (Solanum lycopersicum L.) have been studied and an association between dietary intake of tomatoes and lowered risk of cancer, neurodegenerative, and cardiovascular diseases has been suggested. Here we used magnetically treated water (MTW; 0.03-0.15 T), which promotes better germination and productivity in tomatoes, and we investigated the effects of aqueous and ethanolic (10-400 μg/ml) extracts of S. lycopersicum as potential antioxidant against 10 μM Fe(II)-induced thiobarbituric acid reactive species (TBARS) in liver and brain homogenates from rats. The ethanolic extracts from magnetically treated plants were more effective than aqueous extracts in preventing TBARS formation in brain and liver. The protective effects of ethanolic extract can be associated with antioxidants (polyphenols and flavonoids), lycopene and other lipophilic components found in the extract. In effect, magnetically treated plants had higher content of polyphenolic and flavonoid compounds than nontreated plants and they can be a better source of antioxidants than nontreated plants. Consequently, MTW can be used to produce functional foods with high contents of antioxidant components and may have better beneficial health effects than traditionally produced foods. PMID:23324035

  17. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    PubMed

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes. PMID:18814656

  18. Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury

    PubMed Central

    Conklin, Daniel J.; Guo, Yiru; Jagatheesan, Ganapathy; Kilfoil, Peter; Haberzettl, Petra; Hill, Bradford G.; Baba, Shahid P.; Guo, Luping; Wetzelberger, Karin; Obal, Detlef; Rokosh, D. Gregg; Prough, Russell A.; Prabhu, Sumanth D.; Velayutham, Murugesan; Zweier, Jay L.; Hoetker, David; Riggs, Daniel W.; Srivastava, Sanjay; Bolli, Roberto; Bhatnagar, Aruni

    2016-01-01

    Rationale Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. Objective We tested the hypothesis that removal of aldehydes by glutathione S-transferase P (GSTP) diminishes I/R injury. Methods and Results In adult male C57BL/6 mouse hearts, Gstp1/2 was the most abundant GST transcript followed by Gsta4 and Gstm4.1, and GSTP activity was a significant fraction of the total GST activity. mGstp1/2 deletion reduced total GST activity, but no compensatory increase in GSTA and GSTM or major antioxidant enzymes was observed. Genetic deficiency of GSTP did not alter cardiac function, but in comparison with hearts from wild-type (WT) mice, the hearts isolated from GSTP-null mice were more sensitive to I/R injury. Disruption of the GSTP gene also increased infarct size after coronary occlusion in situ. Ischemia significantly increased acrolein in hearts, and GSTP deficiency induced significant deficits in the metabolism of the unsaturated aldehyde, acrolein, but not in the metabolism 4-hydroxy-trans-2-nonenal (HNE) or trans-2-hexanal; and, upon ischemia, the GSTP-null hearts accumulated more acrolein-modified proteins than WT hearts. GSTP-deficiency did not affect I/R-induced free radical generation, JNK activation or depletion of reduced glutathione. Acrolein-exposure induced a hyperpolarizing shift in INa, and acrolein-induced cell death was delayed by SN-6, a Na+/Ca++ exchange inhibitor. Cardiomyocytes isolated from GSTP-null hearts were more sensitive than WT myocytes to acrolein-induced protein crosslinking and cell death. Conclusions GSTP protects the heart from I/R injury by facilitating the detoxification of cytotoxic aldehydes such as acrolein. PMID:26169370

  19. Soy protein with and without isoflavones fails to substantially increase postprandial antioxidant capacity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five methods for the assessment of antioxidant capacity [whole plasma conjugated diene formation, low-density lipoprotein oxidation susceptibility, ferric-reducing ability of plasma, oxygen radical absorbance capacity and perchloric-acid-treated oxygen radical absorbance capacity (PCA-ORAC)] were us...

  20. Comprehensive assessment of genetic sequence variants in the antioxidant 'master regulator' NRF2 in idiopathic Parkinson's disease.

    PubMed

    Todorovic, Michael; Newman, Jeremy R B; Shan, Jianguo; Bentley, Steven; Wood, Stephen A; Silburn, Peter A; Mellick, George D

    2015-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disorder influenced by a combination of genetic and environmental factors. The molecular mechanisms that underlie PD are unknown; however, oxidative stress and impairment of antioxidant defence mechanisms have been implicated as major contributors to disease pathogenesis. Previously, we have reported a PD patient-derived cellular model generated from biopsies of the olfactory mucosa, termed hONS cells, in which the NRF2-mediated antioxidant response pathway genes were among the most differentially-expressed. To date, few studies have examined the role of the NRF2 encoding gene, NFE2L2, and PD. In this study, we comprehensibly assessed whether rare and common NFE2L2 genetic variations modify susceptibility to PD using a large Australian case-control sample (PD=1338, controls=1379). We employed a haplotype-tagging approach that identified an association with the tagging SNP rs2364725 and PD (OR = 0.849 (0.760-0.948), P = 0.004). Further genetic screening in hONS cell lines produced no obvious pathogenic variants in the coding regions of NFE2L2. Finally, we investigated the relationship between xenobiotic exposures and NRF2 function, through gene-environment interactions, between NFE2L2 SNPs and smoking or pesticide exposure. Our results demonstrated a significant interaction between rs2706110 and pesticide exposure (OR = 0.597 (0.393-0.900), P = 0.014). In addition, we were able to identify some age-at-onset modifying SNPs and replicate an 'early-onset' haplotype that contains a previously identified 'functional promoter' SNP (rs6721961). Our results suggest a role of NFE2L2 genetic variants in modifying PD susceptibility and onset. Our findings also support the utility of testing gene-environment interactions in genetic studies of PD. PMID:26010367

  1. Increased genetic risk for obesity in premature coronary artery disease

    PubMed Central

    Cole, Christopher B; Nikpay, Majid; Stewart, Alexandre FR; McPherson, Ruth

    2016-01-01

    There is ongoing controversy as to whether obesity confers risk for CAD independently of associated risk factors including diabetes mellitus. We have carried out a Mendelian randomization study using a genetic risk score (GRS) for body mass index (BMI) based on 35 risk alleles to investigate this question in a population of 5831 early onset CAD cases without diabetes mellitus and 3832 elderly healthy control subjects, all of strictly European ancestry, with adjustment for traditional risk factors (TRFs). We then estimated the genetic correlation between these BMI and CAD (rg) by relating the pairwise genetic similarity matrix to a phenotypic covariance matrix between these two traits. GRSBMI significantly (P=2.12 × 10−12) associated with CAD status in a multivariate model adjusted for TRFs, with a per allele odds ratio (OR) of 1.06 (95% CI 1.042–1.076). The addition of GRSBMI to TRFs explained 0.75% of CAD variance and yielded a continuous net recombination index of 16.54% (95% CI=11.82–21.26%, P<0.0001). To test whether GRSBMI explained CAD status when adjusted for measured BMI, separate models were constructed in which the score and BMI were either included as covariates or not. The addition of BMI explained ~1.9% of CAD variance and GRSBMI plus BMI explained 2.65% of CAD variance. Finally, using bivariate restricted maximum likelihood analysis, we provide strong evidence of genome-wide pleiotropy between obesity and CAD. This analysis supports the hypothesis that obesity is a causal risk factor for CAD. PMID:26220701

  2. The increasing role of genetics and genomics in women's health.

    PubMed

    Klein, Elisabeth Lisa Z

    2014-01-01

    Genetic and genomic testing are a clinical reality in health care today. Persons at risk for disease or who are simply curious about their genomes can have them analyzed. An individual's genome is a function of ancestry, family history and personal health and environmental exposures. Clinical and pharmacologic information can be obtained through genomic analysis. Genomic testing can be done by health care providers but some results can now be obtained through direct-to-consumer tests. Many ethical questions are being raised regarding genomic testing. Nurses can provide more optimal care by understanding the process of genomic testing as well as the implications of the results. PMID:24750654

  3. Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters.

    PubMed

    McCusker, K; Hoidal, J

    1990-03-01

    Oxidants from cigarette smoke or those produced by phagocytes are implicated in the pathogenesis of emphysema. We reasoned that augmentation of antioxidant enzymes in cigarette smokers may be important in restricting direct and indirect oxidant damage to alveolar structures. Accordingly, we studied the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx), in alveolar macrophages (AM) from cigarette smokers and from smoke-exposed hamsters. The activities of these antioxidant enzymes were compared with the activities found in AM from nonsmoking control subjects. The activities of SOD and CAT from AM of smokers and smoke-exposed hamsters were twice that found in control subjects (p less than 0.01), but there was no change in the activity of GSHPx. Using the hamster model, we found that filtration of smoke attenuated the increase in antioxidant activities, and that after smoking cessation, the increased activities had returned to those found with control subjects. An adaptive response was further suggested by prolonged survival of smoke-exposed hamsters in normobaric hyperoxia (O2 greater than 95%). Chronic smoke exposure in humans or hamsters causes increased SOD and CAT activities in AM. This augmented activity may serve as a mechanism to limit oxidant-mediated damage to alveolar structures. PMID:2310098

  4. Increasing bioavailability of (R)-alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain.

    PubMed

    Maglione, Emilia; Marrese, Cinzia; Migliaro, Elisa; Marcuccio, Fortuna; Panico, Claudia; Salvati, Carmine; Citro, Giuseppe; Quercio, Marco; Roncagliolo, Federico; Torello, Carlo; Brufani, Mario

    2015-01-01

    a-lipoic acid (a-LA) is a potent natural antioxidant because it has a broad spectrum of action towards a great many free radical species and boosts the endogenous antioxidant systems.Although it is a multi-functional molecule, its pharmacokinetic characteristics pose restrictions to its use in the treatment of oxidative stress-dependent illnesses. Formulations that increase the bioavailability of a-LA have a better potential efficacy as adjuvants for the treatment of these conditions.This objective was achieved with a liquid formulation for oral use containing only R-aLA, the natural enantiomeric and most active form of a-lipoic acid.For the first time, the effects of this formulation were evaluated on neuropathic pain, a symptom caused by an increase in oxidative stress, regardless of the underlying cause. Neuropathic patients who have used this dietary supplement noticed an improvement in their quality of life and a significant reduction was observed in a number of certain descriptive pain parameters (intensity, burning, unpleasantness, superficial pain).Undoubtedly further, more in-depth, studies need to be conducted; however, this first investigation confirms the role of R-aLA as an anti-oxidant for the aetiological treatment of peripheral neuropathy. Increasing its plasma bioavailability even after a non-invasive administration through the oral route is a good starting point for proposing a valid adjuvant for the treatment of pain symptoms. PMID:26694149

  5. Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension.

    PubMed

    Horvathova, Martina; Zitnanova, Ingrid; Kralovicova, Zuzana; Balis, Peter; Puzserova, Angelika; Muchova, Jana; Kluknavsky, Michal; Durackova, Zdenka; Bernatova, Iveta

    2016-02-01

    This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension. PMID:26510784

  6. COPD: balancing oxidants and antioxidants

    PubMed Central

    Fischer, Bernard M; Voynow, Judith A; Ghio, Andrew J

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world. The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking. Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease. The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses. In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD. The complexity of COPD will necessitate a multi-target therapeutic approach. It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies. PMID:25673984

  7. Rye and Wheat Bran Extracts Isolated with Pressurized Solvents Increase Oxidative Stability and Antioxidant Potential of Beef Meat Hamburgers.

    PubMed

    Šulniūtė, Vaida; Jaime, Isabel; Rovira, Jordi; Venskutonis, Petras Rimantas

    2016-02-01

    Rye and wheat bran extracts containing phenolic compounds and demonstrating high DPPH• (2,2-diphenyl-1-picrylhydrazyl), ABTS(•+) (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) scavenging and oxygen radical absorbance capacities (ORAC) were tested in beef hamburgers as possible functional ingredients. Bran extracts significantly increased the indicators of antioxidant potential of meat products and their global antioxidant response (GAR) during physiological in vitro digestion. The extracts also inhibited the formation of oxidation products, hexanal and malondialdehyde, of hamburgers during their storage; however, they did not have significant effect on the growth of microorganisms. Hamburgers with 0.8% wheat bran extract demonstrated the highest antioxidant potential. Some effects of bran extracts on other quality characteristics such as pH, color, formation of metmyoglobin were also observed, however, these effects did not have negative influence on the overall sensory evaluation score of hamburgers. Consequently, the use of bran extracts in meat products may be considered as promising means of increasing oxidative product stability and enriching with functional ingredients which might possess health benefits. PMID:26753797

  8. Oxidation Stability of Pig Liver Pâté with Increasing Levels of Natural Antioxidants (Grape and Tea)

    PubMed Central

    Pateiro, Mirian; Lorenzo, José M.; Vázquez, José A.; Franco, Daniel

    2015-01-01

    The present study investigated the effect of the addition of increasing levels of the natural antioxidants tea (TEA) and grape seed extracts (GRA) on the physiochemical and oxidative stability of refrigerated stored pig pâtés. In addition, a synthetic antioxidant and a control batch were used, thus a total of eight batches of liver pâté were prepared: CON, BHT, TEA (TEA50, TEA200 and TEA1000) and GRA (GRA50, GRA200 and GRA1000). Pâté samples were analyzed following 0, 4, 8 and 24 weeks of storage. Color parameters were affected by storage period and level of antioxidant extract. Samples with TEA200 and GRA1000 levels of extracts showed lower total color difference between 0 and 24 weeks. At the end of storage period, the lower TBARs values were obtained in samples with the highest concentration on natural extract. Overall, the evolution of volatile compounds showed an increase in those ones that arise from the lipid oxidation and samples with TEA1000 extract showed the lowest values. PMID:26785340

  9. Oxidation Stability of Pig Liver Pâté with Increasing Levels of Natural Antioxidants (Grape and Tea).

    PubMed

    Pateiro, Mirian; Lorenzo, José M; Vázquez, José A; Franco, Daniel

    2015-01-01

    The present study investigated the effect of the addition of increasing levels of the natural antioxidants tea (TEA) and grape seed extracts (GRA) on the physiochemical and oxidative stability of refrigerated stored pig pâtés. In addition, a synthetic antioxidant and a control batch were used, thus a total of eight batches of liver pâté were prepared: CON, BHT, TEA (TEA50, TEA200 and TEA1000) and GRA (GRA50, GRA200 and GRA1000). Pâté samples were analyzed following 0, 4, 8 and 24 weeks of storage. Color parameters were affected by storage period and level of antioxidant extract. Samples with TEA200 and GRA1000 levels of extracts showed lower total color difference between 0 and 24 weeks. At the end of storage period, the lower TBARs values were obtained in samples with the highest concentration on natural extract. Overall, the evolution of volatile compounds showed an increase in those ones that arise from the lipid oxidation and samples with TEA1000 extract showed the lowest values. PMID:26785340

  10. Grape pomace extract exerts antioxidant effects through an increase in GCS levels and GST activity in muscle and endothelial cells.

    PubMed

    Goutzourelas, Nikolaos; Stagos, Dimitrios; Housmekeridou, Anastasia; Karapouliou, Christina; Kerasioti, Efthalia; Aligiannis, Nektarios; Skaltsounis, Alexios L; Spandidos, Demetrios A; Tsatsakis, Aristidis M; Kouretas, Demetrios

    2015-08-01

    In a previous study, we demonstrated that a grape pomace extract (GPE) exerted antioxidant activity in endothelial (EA.hy926) and muscle (C2C12) cells through an increase in glutathione (GSH) levels. In the present study, in order to elucidate the mechanisms responsible for the antioxidant activity of GPE, its effects on the expression of critical antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD)1, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (GCS) were assessed in EA.hy926 and C2C12 cells. Moreover, the effects of GPE on CAT, SOD and glutathione S-transferase (GST) enzymatic activity were evaluated. For this purpose, the C2C12 and EA.hy926 cells were treated with GPE at low and non-cytotoxic concentrations (2.5 and 10 µg/ml for the C2C12 cells; 0.068 and 0.250 µg/ml for the EA.hy926 cells) for 3, 6, 12, 18 and 24 h. Following incubation, enzymatic expression and activity were assessed. The results revealed that treatment with GPE significantly increased GCS levels and GST activity in both the C2C12 and EA.hy926 cells. However, GPE significantly decreased CAT levels and activity, but only in the muscle cells, while it had no effect on CAT levels and activity in the endothelial cells. Moreover, treatment with GPE had no effect on HO-1 and SOD expression and activity in both cell lines. Therefore, the present results provide further evidence of the crucial role of GSH systems in the antioxidant effects exerted by GPE. Thus, GPE may prove to be effective for use as a food supplement for the treatment of oxidative stress-induced pathological conditions of the cardiovascular and skeletal muscle systems, particularly those associated with low GSH levels. PMID:26082074

  11. Grape pomace extract exerts antioxidant effects through an increase in GCS levels and GST activity in muscle and endothelial cells

    PubMed Central

    GOUTZOURELAS, NIKOLAOS; STAGOS, DIMITRIOS; HOUSMEKERIDOU, ANASTASIA; KARAPOULIOU, CHRISTINA; KERASIOTI, EFTHALIA; ALIGIANNIS, NEKTARIOS; SKALTSOUNIS, ALEXIOS L; SPANDIDOS, DEMETRIOS A; TSATSAKIS, ARISTIDIS M; KOURETAS, DEMETRIOS

    2015-01-01

    In a previous study, we demonstrated that a grape pomace extract (GPE) exerted antioxidant activity in endothelial (EA.hy926) and muscle (C2C12) cells through an increase in glutathione (GSH) levels. In the present study, in order to elucidate the mechanisms responsible for the antioxidant activity of GPE, its effects on the expression of critical antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD)1, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (GCS) were assessed in EA.hy926 and C2C12 cells. Moreover, the effects of GPE on CAT, SOD and glutathione S-transferase (GST) enzymatic activity were evaluated. For this purpose, the C2C12 and EA.hy926 cells were treated with GPE at low and non-cytotoxic concentrations (2.5 and 10 µg/ml for the C2C12 cells; 0.068 and 0.250 µg/ml for the EA.hy926 cells) for 3, 6, 12, 18 and 24 h. Following incubation, enzymatic expression and activity were assessed. The results revealed that treatment with GPE significantly increased GCS levels and GST activity in both the C2C12 and EA.hy926 cells. However, GPE significantly decreased CAT levels and activity, but only in the muscle cells, while it had no effect on CAT levels and activity in the endothelial cells. Moreover, treatment with GPE had no effect on HO-1 and SOD expression and activity in both cell lines. Therefore, the present results provide further evidence of the crucial role of GSH systems in the antioxidant effects exerted by GPE. Thus, GPE may prove to be effective for use as a food supplement for the treatment of oxidative stress-induced pathological conditions of the cardiovascular and skeletal muscle systems, particularly those associated with low GSH levels. PMID:26082074

  12. Dietary selenium increases the antioxidant levels and ATPase activity in the arteries and veins of poultry.

    PubMed

    Cao, Changyu; Zhao, Xia; Fan, Ruifeng; Zhao, Jinxin; Luan, Yilin; Zhang, Ziwei; Xu, Shiwen

    2016-07-01

    Selenium (Se) deficiency is associated with the pathogenesis of vascular diseases. It has been shown that oxidative levels and ATPase activity were involved in Se deficiency diseases in humans and mammals; however, the mechanism by how Se influences the oxidative levels and ATPase activity in the poultry vasculature is unclear. We assessed the effects of dietary Se deficiency on the oxidative stress parameters (superoxide dismutase, catalase, and hydroxyl radical) and ATPase (Na(+)K(+)-ATPase, Ca(++)-ATPase, Mg(++)-ATPase, and Ca(++)Mg(++)-ATPase) activity in broiler poultry. A total of 40 broilers (1-day old) were randomly divided into a Se-deficient group (L group, fed a Se-deficient diet containing 0.08 mg/kg Se) and a control group (C group, fed a diet containing sodium selenite at 0.20 mg/kg Se). Then, arteries and veins were collected following euthanasia when typical symptoms of Se deficiency appeared. Antioxidant indexes and ATPase activity were evaluated using standard assays in arteries and veins. The results indicated that superoxide dismutase activity in the artery according to dietary Se deficiency was significantly lower (p < 0.05) compared with the C group. The catalase activity in the veins and hydroxyl radical inhibition in the arteries and veins by dietary Se deficiency were significantly higher (p < 0.05) compared with the C group. The Se-deficient group showed a significantly lower (p < 0.05) tendency in Na(+)K(+)-ATPase activity, Ca(++)-ATPase activity, and Ca(++)Mg(++)-ATPase activity. There were strong correlations between antioxidant indexes and Ca(++)-ATPase activity. Thus, these results indicate that antioxidant indexes and ATPases may have special roles in broiler artery and vein injuries under Se deficiency. PMID:26637493

  13. Use of different spices as potential natural antioxidant additives on cooked beans (Phaseolus vulgaris). Increase of DPPH radical scavenging activity and total phenolic content.

    PubMed

    Pereira, Marina Pelincer; Tavano, Olga Luisa

    2014-12-01

    Herbs and spices, excellent sources of phenolic compounds, can be considered potential antioxidant additives. The use of spices must strike a balance between their potential antioxidant capabilities during preparation and the flavor acceptance, in order to avoid rejection of the food. The aimed of this study is to evaluate the influence of different spices and their concentrations on cooked common beans, focusing its potential as antioxidant additives. Onion, parsley, spring onion, laurel and coriander increased the antioxidant activity of preparation when used at 7.96 g of onion, 1.06 g parsley, 3.43 g spring onion, 0.25 g laurel (dry leaves), and 0.43 g coriander/100 g of cooked beans. Besides, these spices concentrations enhance total phenolics and alter the mixture protein digestibility minimally. For garlic samples it was not possible to establish a concentration that increases the antioxidant activity of cooked beans. PMID:25179942

  14. Preharvest application of oxalic acid increased fruit size, bioactive compounds, and antioxidant capacity in sweet cherry cultivars (Prunus avium L.).

    PubMed

    Martínez-Esplá, Alejandra; Zapata, Pedro Javier; Valero, Daniel; García-Viguera, Cristina; Castillo, Salvador; Serrano, María

    2014-04-16

    Trees of 'Sweet Heart' and 'Sweet Late' sweet cherry cultivars (Prunus avium L.) were treated with oxalic acid (OA) at 0.5, 1.0, and 2.0 mM at 98, 112, and 126 days after full blossom. Results showed that all treatments increased fruit size at harvest, manifested by higher fruit volume and weight in cherries from treated trees than from controls, the higher effect being found with 2.0 mM OA (18 and 30% higher weight for 'Sweet Heart' and 'Sweet Late', respectively). Other quality parameters, such as color and firmness, were also increased by OA treatments, although no significant differences were found in total soluble solids or total acidity, showing that OA treatments did not affect the on-tree ripening process of sweet cherry. However, the increases in total anthocyanins, total phenolics, and antioxidant activity associated with the ripening process were higher in treated than in control cherries, leading to fruit with high bioactive compounds and antioxidant potential at commercial harvest (≅45% more anthocyanins and ≅20% more total phenolics). In addition, individual anthocyanins, flavonols, and chlorogenic acid derivatives were also increased by OA treatment. Thus, OA preharvest treatments could be an efficient and natural way to increase the quality and functional properties of sweet cherries. PMID:24684635

  15. S-Sulfocysteine simplifies fed-batch processes and increases the CHO specific productivity via anti-oxidant activity.

    PubMed

    Hecklau, Caroline; Pering, Sascha; Seibel, Ronja; Schnellbaecher, Alisa; Wehsling, Maria; Eichhorn, Thomas; Hagen, Joerg von; Zimmer, Aline

    2016-01-20

    Industrial fed-batch cultivation of mammalian cells is used for the production of therapeutic proteins such as monoclonal antibodies. Besides medium ensuring initial growth, feeding is necessary to improve growth, viability and antibody production. Established processes include a slight acidic main feed and a separate alkaline feed containing l-tyrosine and l-cysteine. Since l-cysteine is not stable at neutral pH, a new derivative, S-sulfocysteine, was tested in neutral pH feeds. In small scale fed-batch processes, the S-sulfocysteine process yielded a comparable maximum viable cell density, prolonged viability and increased titer compared to the two feed system. Bioreactor experiments confirmed the increase in specific productivity. In depth characterization of the monoclonal antibody indicated no change in the glycosylation, or charge variant pattern whereas peptide mapping experiments were not able to detect any integration of the modified amino acid in the sequence of the monoclonal antibody. Finally, the mechanism of action of S-sulfocysteine was investigated, and results pointed out the anti-oxidative potential of the molecule, mediated through an increase in superoxide dismutase enzyme levels and in the total intracellular glutathione pool. Finally, we propose that the increase in specific productivity obtained in the S-sulfocysteine process results from the anti-oxidative properties of the molecule. PMID:26654938

  16. Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

    PubMed

    Parihar, P; Shetty, R; Ghafourifar, P; Parihar, M S

    2016-01-01

    Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat. PMID:26828992

  17. The organophosphate insecticide Coumaphos induces oxidative stress and increases antioxidant and detoxification defences in the green macroalgae Ulva pertusa.

    PubMed

    Schweikert, Katja; Burritt, David J

    2012-10-15

    It is well established that many pesticides used in the farming and horticultural industries are harmful to not only the target species they were developed for, but also other organisms. Organophosphates were introduced as a replacement for the organochlorines and are generally considered non-toxic to plants and algae. This study investigated the impact of Coumaphos, a commonly used organophosphate, on the estuarine macrophyte Ulva pertusa. In a seven-day experiment U. pertusa cultures were exposed to four environmentally relevant concentrations of Coumaphos (0.01 mg/L, 0.05 mg/L, 0.1mg/L, 0.5 mg/L), well below the aqueous solubility maximum of the insecticide. The impact of Coumaphos was determined at a cellular level by assessing oxidative damage in the form of protein carbonyl and lipid hydroperoxide levels. Furthermore, non-enzymatic antioxidant levels and changes in the levels of enzymatic antioxidants and the enzyme GST were measured. Concentrations of Coumaphos above 0.01 mg/L caused rapid increases in the levels of protein carbonyls and lipid hydroperoxides peaking after 2-3 days of exposure, followed by a rapid decline in both markers of oxidative stress. Glutathione levels and the activities SOD, CAT, GR, APOX and GST all increased in response to the higher concentrations of Coumaphos tested and remained elevated for the duration of the experiment. These results demonstrate that environmentally relevant levels of the insecticide Coumaphos can cause oxidative damage and increase the antioxidant scavenging capacity, and GST activity in U. pertusa. This could potentially alter resource allocation within this alga, impacting algal growth and development, with possible indirect ecological consequences. PMID:22728208

  18. Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol.

    PubMed

    Kim, Se-Yong; Yang, Eun-Ju; Son, Youn Kyoung; Yeo, Joo-Hong; Song, Kyung-Sik

    2016-05-18

    Viscum album var. coloratum (Korean mistletoe; KM) is an herbal medicine that is used worldwide for the treatment of various immunological disorders and cancers. KM extract showed enhanced anti-oxidative effects in 2,2-diphenyl-1-picrylhydrazyl, Trolox equivalent antioxidant capacity, and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester assays after being fermented with a crude enzyme extract from a soybean paste fungus, Aspergillus kawachii. High-performance liquid chromatography analysis showed four increased peaks in enzyme treated KM. The increased peaks were isolated and identified as caffeic acid (1), hesperetin (2), syringaldehyde (3), and lyoniresinol (4). Among the four compounds, only 1 and 4 showed strong anti-oxidative activity. Therefore, the fermentation increased the contents of 1 and 4, which consequently increased the anti-oxidative activity of KM. PMID:27072079

  19. Antioxidants as potential therapeutics for neuropsychiatric disorders

    PubMed Central

    Pandya, Chirayu D; Howell, Kristy R; Pillai, Anilkumar

    2012-01-01

    Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders. PMID:23123357

  20. Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity

    PubMed Central

    Ahmed, Mahbubl; Dorling, Leila; Kerns, Sarah; Fachal, Laura; Elliott, Rebecca; Partliament, Matt; Rosenstein, Barry S; Vega, Ana; Gómez-Caamaño, Antonio; Barnett, Gill; Dearnaley, David P; Hall, Emma; Sydes, Matt; Burnet, Neil; Pharoah, Paul D P; Eeles, Ros; West, Catharine M L

    2016-01-01

    Background: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. Methods: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods. Results: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity. Conclusion: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens. PMID:27070714

  1. Genetic Factors That Increase Male Facial Masculinity Decrease Facial Attractiveness of Female Relatives

    PubMed Central

    Lee, Anthony J.; Mitchem, Dorian G.; Wright, Margaret J.; Martin, Nicholas G.; Keller, Matthew C.; Zietsch, Brendan P.

    2014-01-01

    For women, choosing a facially masculine man as a mate is thought to confer genetic benefits to offspring. Crucial assumptions of this hypothesis have not been adequately tested. It has been assumed that variation in facial masculinity is due to genetic variation and that genetic factors that increase male facial masculinity do not increase facial masculinity in female relatives. We objectively quantified the facial masculinity in photos of identical (n = 411) and nonidentical (n = 782) twins and their siblings (n = 106). Using biometrical modeling, we found that much of the variation in male and female facial masculinity is genetic. However, we also found that masculinity of male faces is unrelated to their attractiveness and that facially masculine men tend to have facially masculine, less-attractive sisters. These findings challenge the idea that facially masculine men provide net genetic benefits to offspring and call into question this popular theoretical framework. PMID:24379153

  2. Increasing the antioxidant activity, total phenolic and flavonoid contents by optimizing the germination conditions of amaranth seeds.

    PubMed

    Perales-Sánchez, Janitzio X K; Reyes-Moreno, Cuauhtémoc; Gómez-Favela, Mario A; Milán-Carrillo, Jorge; Cuevas-Rodríguez, Edith O; Valdez-Ortiz, Angel; Gutiérrez-Dorado, Roberto

    2014-09-01

    The aim of this study was to optimize the germination conditions of amaranth seeds that would maximize the antioxidant activity (AoxA), total phenolic (TPC), and flavonoid (TFC) contents. To optimize the germination bioprocess, response surface methodology was applied over three response variables (AoxA, TPC, TFC). A central composite rotable experimental design with two factors [germination temperature (GT), 20-45 ºC; germination time (Gt), 14-120 h] in five levels was used; 13 treatments were generated. The amaranth seeds were soaked in distilled water (25 °C/6 h) before germination. The sprouts from each treatment were dried (50 °C/8 h), cooled, and ground to obtain germinated amaranth flours (GAF). The best combination of germination bioprocess variables for producing optimized GAF with the highest AoxA [21.56 mmol trolox equivalent (TE)/100 g sample, dw], TPC [247.63 mg gallic acid equivalent (GAE)/100 g sample, dw], and TFC [81.39 mg catechin equivalent (CAE)/100 g sample, dw] was GT = 30 ºC/Gt = 78 h. The germination bioprocess increased AoxA, TPC, and TFC in 300-470, 829, and 213%, respectively. The germination is an effective strategy to increase the TPC and TFC of amaranth seeds for enhancing functionality with improved antioxidant activity. PMID:24958279

  3. Increase in plasma total antioxidant capacity of grazing Japanese Black heifers and cows in forestland in Japan.

    PubMed

    Haga, Satoshi; Ishizaki, Hiroshi; Nakano, Miwa; Nakao, Seiji; Hirano, Kiyoshi; Yamamoto, Yoshito; Kitagawa, Miya; Sasaki, Hiroyuki; Kariya, Yoshihiro

    2014-02-01

    Blood total antioxidant capacity (TAC) has become a key bio-marker for animal health. Forest-grazing cattle are known to forage various native plants that have high TAC. This study evaluated differences of plasma TAC between forest-grazing (FG) and pasture-grazing cattle (PG). Experiment 1 monitored the plasma TAC levels of 32 Japanese Black cattle. The level in PG did not change throughout the grazing period. However, that in FG, which increased from summer, was significantly higher than that in PG through fall (P < 0.05). In experiment 2, we used nine Japanese Black heifers and investigated their blood antioxidant parameters and the TAC in plants that the cattle consumed in late June and September. The plasma TAC levels in FG were significantly higher than those in PG in both periods (P < 0.05). Plasma levels of lipid peroxidation in FG tended to be lower than that in PG (P = 0.098). Furthermore, the TAC levels in various species of shrubs and trees consumed by FG were higher than those in pasture grasses. Results of this study show that plasma TAC of grazing Japanese Black cattle in forestland increase from summer through fall. PMID:23905879

  4. Antioxidant Protects against Increases in Low Molecular Weight Hyaluronan and Inflammation in Asphyxiated Newborn Pigs Resuscitated with 100% Oxygen

    PubMed Central

    Akgul, Yucel; Ramgopal, Mrithyunjay; Mija, Dan S.; Cheong, Naeun; Longoria, Christopher; Mahendroo, Mala; Nakstad, Britt; Saugstad, Ola D.; Savani, Rashmin C.

    2012-01-01

    Background Newborn resuscitation with 100% oxygen is associated with oxidative-nitrative stresses and inflammation. The mechanisms are unclear. Hyaluronan (HA) is fragmented to low molecular weight (LMW) by oxidative-nitrative stresses and can promote inflammation. We examined the effects of 100% oxygen resuscitation and treatment with the antioxidant, N-acetylcysteine (NAC), on lung 3-nitrotyrosine (3-NT), LMW HA, inflammation, TNFα and IL1ß in a newborn pig model of resuscitation. Methods & Principal Findings Newborn pigs (n = 40) were subjected to severe asphyxia, followed by 30 min ventilation with either 21% or 100% oxygen, and were observed for the subsequent 150 minutes in 21% oxygen. One 100% oxygen group was treated with NAC. Serum, bronchoalveolar lavage (BAL), lung sections, and lung tissue were obtained. Asphyxia resulted in profound hypoxia, hypercarbia and metabolic acidosis. In controls, HA staining was in airway subepithelial matrix and no 3-NT staining was seen. At the end of asphyxia, lavage HA decreased, whereas serum HA increased. At 150 minutes after resuscitation, exposure to 100% oxygen was associated with significantly higher BAL HA, increased 3NT staining, and increased fragmentation of lung HA. Lung neutrophil and macrophage contents, and serum TNFα and IL1ß were higher in animals with LMW than those with HMW HA in the lung. Treatment of 100% oxygen animals with NAC blocked nitrative stress, preserved HMW HA, and decreased inflammation. In vitro, peroxynitrite was able to fragment HA, and macrophages stimulated with LMW HA increased TNFα and IL1ß expression. Conclusions & Significance Compared to 21%, resuscitation with 100% oxygen resulted in increased peroxynitrite, fragmentation of HA, inflammation, as well as TNFα and IL1ß expression. Antioxidant treatment prevented the expression of peroxynitrite, the degradation of HA, and also blocked increases in inflammation and inflammatory cytokines. These findings provide insight

  5. Oxidative Stress Is Associated with an Increased Antioxidant Defense in Elderly Subjects: A Multilevel Approach

    PubMed Central

    Flores-Mateo, Gemma; Elosua, Roberto; Rodriguez-Blanco, Teresa; Basora-Gallisà, Josep; Bulló, Mònica; Salas-Salvadó, Jordi; Martínez-González, Miguel Ángel; Estruch, Ramon; Corella, Dolores; Fitó, Montserrat; Fiol, Miquel; Arós, Fernando; Gómez-Gracia, Enrique; Subirana, Isaac; Lapetra, José; Ruiz-Gutiérrez, Valentina; Sáez, Guillermo T.; Covas, Maria-Isabel

    2014-01-01

    Background Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. Methods We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selected from 8 primary health care centers (PHCCs). We assessed classical CVD risk factors, plasma oxidized low-density lipoproteins (ox-LDL), and glutathione peroxidase (GSH-Px) using multilevel statistical procedures. Results Mean GSH-Px value was 612 U/L (SE: 12 U/L), with variation between PHCCs ranging from 549 to 674 U/L (Variance = 1013.5; P<0.001). Between-participants variability within a PHCC accounted for 89% of the total variation. Both glucose and oxidized LDL were positively associated with GSH-Px activity after adjustment for possible confounder variables (P = 0.03 and P = 0.01, respectively). Conclusion In a population at high cardiovascular risk, a positive linear association was observed between plasma GSH-Px activity and both glucose and ox-LDL levels. The high GSH-Px activity observed when an oxidative stress situation occurred, such as hyperglycemia and lipid oxidative damage, could be interpreted as a healthy defensive response against oxidative injury in our cardiovascular risk population. PMID:25269026

  6. Plant genetic resources: what can they contribute toward increased crop productivity?

    PubMed

    Hoisington, D; Khairallah, M; Reeves, T; Ribaut, J M; Skovmand, B; Taba, S; Warburton, M

    1999-05-25

    To feed a world population growing by up to 160 people per minute, with >90% of them in developing countries, will require an astonishing increase in food production. Forecasts call for wheat to become the most important cereal in the world, with maize close behind; together, these crops will account for approximately 80% of developing countries' cereal import requirements. Access to a range of genetic diversity is critical to the success of breeding programs. The global effort to assemble, document, and utilize these resources is enormous, and the genetic diversity in the collections is critical to the world's fight against hunger. The introgression of genes that reduced plant height and increased disease and viral resistance in wheat provided the foundation for the "Green Revolution" and demonstrated the tremendous impact that genetic resources can have on production. Wheat hybrids and synthetics may provide the yield increases needed in the future. A wild relative of maize, Tripsacum, represents an untapped genetic resource for abiotic and biotic stress resistance and for apomixis, a trait that could provide developing world farmers access to hybrid technology. Ownership of genetic resources and genes must be resolved to ensure global access to these critical resources. The application of molecular and genetic engineering technologies enhances the use of genetic resources. The effective and complementary use of all of our technological tools and resources will be required for meeting the challenge posed by the world's expanding demand for food. PMID:10339521

  7. AZD3582 increases heme oxygenase-1 expression and antioxidant activity in vascular endothelial and gastric mucosal cells.

    PubMed

    Berndt, Georg; Grosser, Nina; Hoogstraate, Janet; Schröder, Henning

    2005-06-01

    AZD3582 [4-(nitrooxy)-butyl-(2S)-2-(6-methoxy-2-naphthyl)-propanoate] is a COX-inhibiting nitric oxide donator (CINOD). Incubation of human endothelial cells (derived from umbilical cord) with AZD3582 (10-100muM) led to increased expression of heme oxygenase (HO)-1 mRNA and protein. Heme oxygenase-1 (HO-1) is a crucial mediator of antioxidant and tissue-protective actions. In contrast, naproxen (a non-selective NSAID) and rofecoxib (a selective inhibitor of COX-2), did not affect HO-1 expression. Pre-treating endothelial cells with AZD3582 at concentrations that were effective at inducing HO-1 also reduced NADPH-dependent production of oxygen radicals. Antioxidant activity in the endothelial cells persisted after AZD3582 had been washed out from the incubation medium. When added exogenously to the cells at low micromolar concentrations, the HO-1 metabolite, bilirubin, virtually abolished NADPH-dependent oxidative stress. AZD3582-induced blockade of free-radical formation was reversed in the presence of the HO-1 inhibitor, tin protoporphyrin-IX (SnPP). Similar results were obtained in human gastric mucosal cells (KATO-III). Our results demonstrate that HO-1 is a novel target of AZD3582. PMID:15911218

  8. Astaxanthin lowers plasma TAG concentrations and increases hepatic antioxidant gene expression in diet-induced obesity mice.

    PubMed

    Yang, Yue; Pham, Tho X; Wegner, Casey J; Kim, Bohkyung; Ku, Chai Siah; Park, Young-Ki; Lee, Ji-Young

    2014-12-14

    Non-alcoholic fatty liver disease (NAFLD) is significantly associated with hyperlipidaemia and oxidative stress. We have previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TAG concentrations in apoE knockout mice. To investigate whether ASTX supplementation can prevent the development of NAFLD in obesity, male C57BL/6J mice (n 8 per group) were fed a high-fat diet (35%, w/w) supplemented with 0, 0.003, 0.01 or 0.03% of ASTX (w/w) for 12 weeks. The 0.03% ASTX-supplemented group, but not the other groups, exhibited a significant decrease in plasma TAG concentrations, suggesting that ASTX at a 0.03% supplementation dosage exerts a hypotriacylglycerolaemic effect. Although there was an increase in the mRNA expression of fatty acid synthase and diglyceride acyltransferase 2, the mRNA levels of acyl-CoA oxidase 1, a critical enzyme in peroxisomal fatty acid β-oxidation, exhibited an increase in the 0.03% ASTX-supplemented group. There was a decrease in plasma alanine transaminase (ALT) and aspartate transaminase (AST) concentrations in the 0.03% ASTX-supplemented group. There was a significant increase in the hepatic mRNA expression of nuclear factor erythroid 2-related factor 2 and its downstream genes, which are critical for endogenous antioxidant mechanism, in the 0.03% ASTX-supplemented group. Furthermore, there was a significant decrease in the mRNA abundance of IL-6 in the primary splenocytes isolated from the 0.03% ASTX-supplemented group upon lipopolysaccharide (LPS) stimulation when compared with that in the splenocytes isolated from the control group. In conclusion, ASTX supplementation lowered the plasma concentrations of TAG, ALT and AST, increased the hepatic expression of endogenous antioxidant genes, and rendered splenocytes less sensitive to LPS stimulation. Therefore, ASTX may prevent obesity-associated metabolic disturbances and inflammation. PMID:25328157

  9. Additive genetic variation and evolvability of a multivariate trait can be increased by epistatic gene action.

    PubMed

    Griswold, Cortland K

    2015-12-21

    Epistatic gene action occurs when mutations or alleles interact to produce a phenotype. Theoretically and empirically it is of interest to know whether gene interactions can facilitate the evolution of diversity. In this paper, we explore how epistatic gene action affects the additive genetic component or heritable component of multivariate trait variation, as well as how epistatic gene action affects the evolvability of multivariate traits. The analysis involves a sexually reproducing and recombining population. Our results indicate that under stabilizing selection conditions a population with a mixed additive and epistatic genetic architecture can have greater multivariate additive genetic variation and evolvability than a population with a purely additive genetic architecture. That greater multivariate additive genetic variation can occur with epistasis is in contrast to previous theory that indicated univariate additive genetic variation is decreased with epistasis under stabilizing selection conditions. In a multivariate setting, epistasis leads to less relative covariance among individuals in their genotypic, as well as their breeding values, which facilitates the maintenance of additive genetic variation and increases a population׳s evolvability. Our analysis involves linking the combinatorial nature of epistatic genetic effects to the ancestral graph structure of a population to provide insight into the consequences of epistasis on multivariate trait variation and evolution. PMID:26431770

  10. The potential use of genetics to increase the effectiveness of treatment programs for criminal offenders.

    PubMed

    Beaver, Kevin M; Jackson, Dylan B; Flesher, Dillon

    2014-01-01

    During the past couple of decades, the amount of research examining the genetic underpinnings to antisocial behaviors, including crime, has exploded. Findings from this body of work have generated a great deal of information linking genetics to criminal involvement. As a partial result, there is now a considerable amount of interest in how these findings should be integrated into the criminal justice system. In the current paper, we outline the potential ways that genetic information can be used to increase the effectiveness of treatment programs designed to reduce recidivism among offenders. We conclude by drawing attention to how genetic information can be used by rehabilitation programs to increase program effectiveness, reduce offender recidivism rates, and enhance public safety. PMID:25860438

  11. Ultraviolet-B light treatment increases antioxidant capacity of carrot products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abiotic stresses such as cutting and ultraviolet (UV) light exposure of plant cells triggers an increased activity response by phenylalanine ammonia-lyase (PAL) and chalcone synthase resulting in increased synthesis of phenolic compounds, mainly anthocyanins and flavonoids. This study investigated ...

  12. Duration of priapism is associated with increased corporal oxidative stress and antioxidant enzymes in a rat model.

    PubMed

    Kucukdurmaz, F; Kucukgergin, C; Akman, T; Salabas, E; Armagan, A; Seckin, S; Kadıoglu, A

    2016-05-01

    Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with resultant corporal fibrosis. Studies reported decreased erectile recovery after treatment of priapism longer than 36 h. However, a recent study revealed that half of patients with 3 days of priapism achieved recovery after T-shunt, although mechanism remains unclear. We aimed to investigate the effect of priapism duration on oxidative stress and antioxidant enzymes. Twenty-four male rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4 represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy and blood withdrawal were performed to investigate levels of malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and 4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but multivariable analysis revealed insignificant differences. Plasma MDA of the experimental groups was significantly higher than that of controls. There were no differences among groups in terms of other parameters. Increased antioxidant enzymes according to duration of priapism suggest that immediate treatment to relieve oxidative stress should be initiated in prolonged cases. However, further studies should be conducted to determine resistance mechanisms of the corpora to prolonged ischaemia. PMID:26223151

  13. Intracolonial genetic diversity in honey bee (Apis mellifera) colonies increases pollen foraging efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple mating by honey bee queens results in colonies of genotypically diverse workers. Recent studies have demonstrated that increased genetic diversity within a honey bee colony increases the variation in the frequency of tasks performed by workers. We show that genotypically diverse colonies, ...

  14. Antioxidant capacity, total phenolic and ascorbate content as a function of the genetic diversity of leek (Allium ampeloprasum var. porrum).

    PubMed

    Bernaert, Nathalie; De Paepe, Domien; Bouten, Charlotte; De Clercq, Hervé; Stewart, Derek; Van Bockstaele, Erik; De Loose, Marc; Van Droogenbroeck, Bart

    2012-09-15

    Extracts of the white shaft and green leaves of 30 leek cultivars were investigated for their antioxidant properties, total phenolic (TP) and l-ascorbic acid (AA) content. The measured antioxidant properties included free radical scavenging activities against peroxyl (ORAC) and 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH) and their Fe(3+) reducing capacity (FRAP). The results from this study suggest that the green leek leaves generally have significantly stronger antioxidant properties than the white shaft. Correlation analysis between the TP and the AA content and the antioxidant activity showed that phenolics and ascorbic acid contribute significantly to the antioxidant activity of leek. The three antioxidant activity assays were all correlated for the extracts of the white shaft of the 30 leek cultivars. Principal component analysis (PCA) elucidated the influence of part and type of cultivar on the antioxidant capacity, TP, and l-ascorbic acid content, whilst the breeding strategy and seed company had no influence. PMID:23107677

  15. Genetic and phytochemical variability of six Teucrium arduini L. populations and their antioxidant/prooxidant behaviour examined by biochemical, macromolecule- and cell-based approaches.

    PubMed

    Šamec, Dunja; Durgo, Ksenija; Grúz, Jiři; Kremer, Dario; Kosalec, Ivan; Piljac-Žegarac, Jasenka; Salopek-Sondi, Branka

    2015-11-01

    Teucrium arduini L., an Ilyric-Balcanic endemic species, has been reported for decades as a valuable plant used in traditional medicine for treating digestive disorders. The present study evaluated genetic and phytochemical variability of six T. arduini populations in order to determine factors that influence an accumulation of polyphenolic compounds. Results strongly suggest that a phytochemical variation was caused by environmental rather than genetic factors. T. arduini leaf extract from the locality Učka, which accumulated significantly more polyphenolic phytochemicals in comparison to others, showed antioxidant activity in DNA and lipid bioassays. Furthermore, the same extract exhibited prooxidant behaviour at protein level and induce formation of reactive oxygen species in human laryngeal carcinoma cells causing cytotoxic activity, in a dose dependent manner. All the results of the present study suggested that T. arduini extract could be responsible for antioxidative/prooxidative mechanisms and would help in determination of optimal conditions for their ethnopharmacological use. PMID:25976825

  16. Reduced Genetic Diversity and Increased Dispersal in Guigna (Leopardus guigna) in Chilean Fragmented Landscapes.

    PubMed

    Napolitano, Constanza; Díaz, Diego; Sanderson, Jim; Johnson, Warren E; Ritland, Kermit; Ritland, Carol E; Poulin, Elie

    2015-01-01

    Landscape fragmentation is often a major cause of species extinction as it can affect a wide variety of ecological processes. The impact of fragmentation varies among species depending on many factors, including their life-history traits and dispersal abilities. Felids are one of the groups most threatened by fragmented landscapes because of their large home ranges, territorial behavior, and low population densities. Here, we model the impacts of habitat fragmentation on patterns of genetic diversity in the guigna (Leopardus guigna), a small felid that is closely associated with the heavily human-impacted temperate rainforests of southern South America. We assessed genetic variation in 1798 base pairs of mitochondrial DNA sequences, 15 microsatellite loci, and 2 sex chromosome genes and estimated genetic diversity, kinship, inbreeding, and dispersal in 38 individuals from landscapes with differing degrees of fragmentation on Chiloé Island in southern Chile. Increased fragmentation was associated with reduced genetic diversity, but not with increased kinship or inbreeding. However, in fragmented landscapes, there was a weaker negative correlation between pairwise kinship and geographic distance, suggesting increased dispersal distances. These results highlight the importance of biological corridors to maximize connectivity in fragmented landscapes and contribute to our understanding of the broader genetic consequences of habitat fragmentation, especially for forest-specialist carnivores. PMID:26245787

  17. Loss of Genetic Diversity and Increased Subdivision in an Endemic Alpine Stonefly Threatened by Climate Change

    PubMed Central

    Jordan, Steve; Giersch, J. Joseph; Muhlfeld, Clint C.; Hotaling, Scott; Fanning, Liz; Tappenbeck, Tyler H.; Luikart, Gordon

    2016-01-01

    Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing “historic” (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms. PMID:27348125

  18. Loss of Genetic Diversity and Increased Subdivision in an Endemic Alpine Stonefly Threatened by Climate Change.

    PubMed

    Jordan, Steve; Giersch, J Joseph; Muhlfeld, Clint C; Hotaling, Scott; Fanning, Liz; Tappenbeck, Tyler H; Luikart, Gordon

    2016-01-01

    Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing "historic" (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms. PMID:27348125

  19. Reed bunting females increase fitness through extra-pair mating with genetically dissimilar males

    PubMed Central

    Suter, Stefan M; Keiser, Martin; Feignoux, Raoul; Meyer, Dietrich R

    2007-01-01

    Females of many socially monogamous species accept or even actively seek copulations outside the social pair bond. As females cannot increase the number of offspring with promiscuous behaviour, the question arises why they engage in extra-pair mating. We used microsatellite data to determine paternity, heterozygosity and genetic relatedness in the reed bunting (Emberiza schoeniclus), a species with high levels of extra-pair paternity (EPP). We found that extra-pair young (EPY) were more heterozygous than within-pair young (WPY). The high heterozygosity of the EPY resulted from a low genetic similarity between females and their extra-pair mates. EPY were heavier and larger when compared with their maternal half-siblings shortly before they left the nest. Recapture data indicated a higher fledgling survival of EPY compared with WPY. Our data suggest that reed bunting females increase the viability of their offspring and thus fitness through extra-pair mating with genetically dissimilar males. PMID:17785270

  20. Increasing Genetic Variance of Body Mass Index during the Swedish Obesity Epidemic

    PubMed Central

    Rokholm, Benjamin; Silventoinen, Karri; Tynelius, Per; Gamborg, Michael; Sørensen, Thorkild I. A.; Rasmussen, Finn

    2011-01-01

    Background and Objectives There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic. Methods The data comprised height and weight measurements of 1,474,065 Swedish conscripts at age 18–19 y born between 1951 and 1983. The data were linked to the Swedish Multi-Generation Register and the Swedish Twin Register from which 264,796 full-brother pairs, 1,736 monozygotic (MZ) and 1,961 dizygotic (DZ) twin pairs were identified. The twin pairs were analysed to identify the most parsimonious model for the genetic and environmental contribution to BMI variance. The full-brother pairs were subsequently divided into subgroups by year of birth to investigate trends in the genetic variance of BMI. Results The twin analysis showed that BMI variation could be explained by additive genetic and environmental factors not shared by co-twins. On the basis of the analyses of the full-siblings, the additive genetic variance of BMI increased from 4.3 [95% CI 4.04–4.53] to 7.9 [95% CI 7.28–8.54] within the study period, as did the unique environmental variance, which increased from 1.4 [95% CI 1.32–1.48] to 2.0 [95% CI 1.89–2.22]. The BMI heritability increased from 75% to 78.8%. Conclusion The results confirm the hypothesis that the additive genetic variance of BMI has increased strongly during the obesity epidemic. This suggests that the obesogenic environment has enhanced the influence of adiposity related genes. PMID:22087252

  1. Treatment of β-Thalassemia/Hemoglobin E with Antioxidant Cocktails Results in Decreased Oxidative Stress, Increased Hemoglobin Concentration, and Improvement of the Hypercoagulable State

    PubMed Central

    Yanpanitch, Orn-uma; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Fucharoen, Suthat; Siritanaratkul, Noppadol; Kalpravidh, Ruchaneekorn W.

    2015-01-01

    Studies on the antioxidant treatment for thalassemia have reported variable outcomes. However, treatment of thalassemia with a combination of hydrophobic and hydrophilic antioxidants and an iron chelator has not been studied. This study investigated the effects of antioxidant cocktails for the treatment of β-thalassemia/hemoglobin E (HbE), which is the most common form of β-thalassemia in Southeast Asia. Sixty patients were divided into two groups receiving N-acetylcysteine, deferiprone, and either curcuminoids (CUR) or vitamin E (Vit-E), and their hematological parameters, iron load, oxidative stress, and blood coagulation potential were evaluated. Patients were classified as responders if they showed the improvements of the markers of iron load and oxidative stress, otherwise as nonresponders. During treatment, the responders in both groups had significantly decreased iron load, oxidative stress, and coagulation potential and significantly increased antioxidant capacity and hemoglobin concentration. The significantly maximum increase (P < 0.01) in hemoglobin concentration was 11% at month 4 in CUR group responders and 10% at month 10 in Vit-E group responders. In conclusion, the two antioxidant cocktails can improve anemia, iron overload, oxidative stress, and hypercoagulable state in β-thalassemia/HbE. PMID:26078808

  2. Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia

    PubMed Central

    Mistry, Hiten D.; Gill, Carolyn A.; Kurlak, Lesia O.; Seed, Paul T.; Hesketh, John E.; Méplan, Catherine; Schomburg, Lutz; Chappell, Lucy C.; Morgan, Linda; Poston, Lucilla

    2015-01-01

    Preeclampsia is a pregnancy-specific condition affecting 2–7% of women and a leading cause of perinatal and maternal morbidity and mortality. Deficiencies of specific micronutrient antioxidant activities associated with copper, selenium, zinc, and manganese have previously been linked to preeclampsia at the time of disease. Our aims were to investigate whether maternal plasma micronutrient concentrations and related antioxidant enzyme activities are altered before preeclampsia onset and to examine the dependence on genetic variations in these antioxidant enzymes. Predisease plasma samples (15±1 weeks׳ gestation) were obtained from women enrolled in the international Screening for Pregnancy Endpoints (SCOPE) study who subsequently developed preeclampsia (n=244) and from age- and BMI-matched normotensive controls (n=472). Micronutrient concentrations were measured by inductively coupled plasma mass spectrometry; associated antioxidant enzyme activities, selenoprotein-P, ceruloplasmin concentration and activity, antioxidant capacity, and markers of oxidative stress were measured by colorimetric assays. Sixty-four tag–single-nucleotide polymorphisms (SNPs) within genes encoding the antioxidant enzymes and selenoprotein-P were genotyped using allele-specific competitive PCR. Plasma copper and ceruloplasmin concentrations were modestly but significantly elevated in women who subsequently developed preeclampsia (both P<0.001) compared to controls (median (IQR), copper, 1957.4 (1787, 2177.5) vs 1850.0 (1663.5, 2051.5) µg/L; ceruloplasmin, 2.5 (1.4, 3.2) vs 2.2 (1.2, 3.0) µg/ml). There were no differences in other micronutrients or enzymes between groups. No relationship was observed between genotype for SNPs and antioxidant enzyme activity. This analysis of a prospective cohort study reports maternal micronutrient concentrations in combination with associated antioxidant enzymes and SNPs in their encoding genes in women at 15 weeks׳ gestation that subsequently

  3. Parenting Moderates a Genetic Vulnerability Factor in Longitudinal Increases in Youths' Substance Use

    ERIC Educational Resources Information Center

    Brody, Gene H.; Beach, Steven R. H.; Philibert, Robert A.; Chen, Yi-fu; Lei, Man-Kit; Murry, Velma McBride; Brown, Anita C.

    2009-01-01

    The authors used a longitudinal, prospective design to investigate a moderation effect in the association between a genetic vulnerability factor, a variable nucleotide repeat polymorphism in the promoter region of "5HTT" (5-HTTLPR), and increases in youths' substance use. The primary study hypothesis predicted that involved-supportive parenting…

  4. Plasmids for Increased Efficiency of Vector Construction and Genetic Engineering in Filamentous Fungi

    PubMed Central

    Schoberle, Taylor J.; Nguyen-Coleman, C. Kim; May, Gregory S.

    2013-01-01

    Fungal species are continuously being studied to not only understand disease in humans and plants but also to identify novel antibiotics and other metabolites of industrial importance. Genetic manipulations, such as gene deletion, gene complementation, and gene over-expression, are common techniques to investigate fungal gene functions. Although advances in transformation efficiency and promoter usage have improved genetic studies, some basic steps in vector construction are still laborious and time-consuming. Gateway cloning technology solves this problem by increasing the efficiency of vector construction through the use of λ phage integrase proteins and att recombination sites. We developed a series of Gateway-compatible vectors for use in genetic studies in a range of fungal species. They contain nutritional and drug-resistance markers and can be utilized to manipulate different filamentous fungal genomes. PMID:23867711

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

    PubMed

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

    2013-01-01

    Antioxidant compounds protect plants against oxidative stress caused by environmental conditions. Different light qualities, such as UV-A radiation and blue light, have shown positive effects on the production of phenols in plants. Kalanchoe pinnata (Lamarck) Persoon (Crassulaceae) is used for treating wounds and inflammations. Some of these beneficial effects are attributed to the antioxidant activity of plant components. We investigated the effects of blue light and UV-A radiation supplementation on the total phenol content, antioxidant activity and chromatographic profile of aqueous extracts from leaves of K. pinnata. Monoclonal plants were grown under white light, white plus blue light and white plus UV-A radiation. Supplemental blue light improved the antioxidant activity and changed the phenolic profile of the extracts. Analysis by HPLC of supplemental blue-light plant extracts revealed a higher proportion of the major flavonoid quercetin 3-O-α-L-arabinopyranosyl (1→2) α-L-rhamnopyranoside, as well as the presence of a wide variety of other phenolic substances. These findings may explain the higher antioxidant activity observed for this extract. Blue light is proposed as a supplemental light source in the cultivation of K. pinnata, to improve its antioxidant activity. PMID:23057576

  6. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    PubMed Central

    Yamamoto, Hirotaka; Morino, Katsutaro; Mengistu, Lemecha; Ishibashi, Taishi; Kiriyama, Kohei; Ikami, Takao; Maegawa, Hiroshi

    2016-01-01

    Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS) levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders. PMID:27340504

  7. Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd.

    PubMed

    Scoccianti, Valeria; Bucchini, Anahi E; Iacobucci, Marta; Ruiz, Karina B; Biondi, Stefania

    2016-11-01

    Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though α- and γ-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time-dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress. PMID:27400061

  8. Anticipating issues related to increasing preimplantation genetic diagnosis use: a research agenda.

    PubMed

    Klitzman, Robert; Appelbaum, Paul S; Chung, Wendy; Sauer, Mark

    2008-01-01

    Increasing use of preimplantation genetic diagnosis (PGD) poses numerous clinical, social, psychological, ethical, legal and policy dilemmas, many of which have received little attention. Patients and providers are now considering and using PGD for a widening array of genetic disorders, and patients may increasingly seek 'designer babies.' In the USA, although governmental oversight policies have been discussed, few specific guidelines exist. Hence, increasingly, patients and providers will face challenging ethical and policy questions of when and for whom to use PGD, and how it should be financed. These issues should be better clarified and addressed through collection of data concerning the current use of PGD in the USA, including factors involved in decision making about PGD use, as well as the education of the various communities that are, and should be, involved in its implementation. Improved understanding of these issues will ultimately enhance the development and implementation of future clinical guidelines and policies. PMID:18644221

  9. Variations in Antioxidant Genes and Male Infertility

    PubMed Central

    Yu, Bolan; Huang, Zhaofeng

    2015-01-01

    Oxidative stress and reactive oxygen species (ROS) are generated from both endogenous and environmental resources, which in turn may cause defective spermatogenesis and male infertility. Antioxidant genes, which include catalase (CAT), glutathione peroxidase (GPX), glutathione S-transferase (GST), nitric oxide synthase (NOS), nuclear factor erythroid 2-related factor 2 (NRF2), and superoxide dismutase (SOD), play important roles in spermatogenesis and normal sperm function. In this review, we discuss the association between variations in major antioxidant genes and male infertility. Numerous studies have suggested that genetic disruption or functional polymorphisms in these antioxidant genes are associated with a higher risk for male infertility, which include low sperm quality, oligoasthenoteratozoospermia, oligozoospermia, and subfertility. The synergistic effects of environmental ROS and functional polymorphisms on antioxidant genes that result in male infertility have also been reported. Therefore, variants in antioxidant genes, which independently or synergistically occur with environmental ROS, affect spermatogenesis and contribute to the occurrence of male infertility. Large cohort and multiple center-based population studies to identify new antioxidant genetic variants that increase susceptibility to male infertility as well as validate its potential as genetic markers for diagnosis and risk assessment for male infertility for precise clinical approaches are warranted. PMID:26618172

  10. Rapid increase in southern elephant seal genetic diversity after a founder event

    PubMed Central

    de Bruyn, Mark; Pinsky, Malin L.; Hall, Brenda; Koch, Paul; Baroni, Carlo; Hoelzel, A. Rus

    2014-01-01

    Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population. PMID:24478305

  11. Rapid increase in southern elephant seal genetic diversity after a founder event.

    PubMed

    de Bruyn, Mark; Pinsky, Malin L; Hall, Brenda; Koch, Paul; Baroni, Carlo; Hoelzel, A Rus

    2014-03-22

    Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population. PMID:24478305

  12. How Swedish breeders can substantially increase the genetic gain for the English Setter's hunting traits.

    PubMed

    Arvelius, P; Klemetsdal, G

    2013-04-01

    In both Sweden (Swe) and Norway (Nor), the English Setter is used for hunting. Similar field trials are arranged to give breeders information on the dogs' hunting abilities. Our main objective was to study if a joint Swe-Nor genetic evaluation can improve accuracy compared with estimation of breeding values on a national level only. Genetic parameters for six hunting traits were estimated in univariate (within country) and bivariate (across country, of equivalent traits between countries and joint pedigree) analyses utilizing 3620 Swe records from 685 dogs and 94,414 Nor records from 7175 dogs. A mixed linear animal model was used, including fixed effects of sex, type of trial, year, month and interaction between age and class of trial, and random effects of animal, permanent environment, judge and residual. Heritabilities ranged from 0.07 to 0.13 for Swe and from 0.08 to 0.18 for Nor. The accuracies were higher in the bivariate analyses, especially for dogs with Swe trial results with an average increase of 19%. If comparing selection based on a joint genetic evaluation over phenotypic results alone (which is today's method), the potential genetic gain in Swe was almost doubled. Our results suggest that a joint genetic evaluation is especially advantageous for a population with limited information, such as the English Setter population in Swe. However, it should also be beneficial for Norwegian breeders because it makes it easier for them to select Swedish dogs, potentially resulting in faster genetic gain and lowered inbreeding rate. PMID:23496015

  13. Increased tolerance to oxidative stress in transgenic tobacco expressing a wheat oxalate oxidase gene via induction of antioxidant enzymes is mediated by H2O2.

    PubMed

    Wan, Xiaoqing; Tan, Jiali; Lu, Shaoyun; Lin, Chuyu; Hu, Yihong; Guo, Zhenfei

    2009-05-01

    Hydrogen peroxide (H(2)O(2)) plays a key role in the regulation of plant responses to various environmental stresses and modulates the expression of related genes including those encoding antioxidant enzymes. A wheat oxalate oxidase (OxO) gene was transformed and expressed in tobacco for production of H(2)O(2). The transgenic plants exhibited enhanced OxO activities and H(2)O(2) concentrations, which was blocked by inhibitors of OxO. The transgenic plants showed increased tolerance to methyl viologen (MV) or high light-induced oxidative stress in both short-time and long-time tests by measuring their maximal photochemical efficiency of PSII (F(v)/F(m)), ion leakage and malondialdehyde. Higher activities and transcripts of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) were observed in the transgenic plants compared to their wild-type controls under normal growth conditions. Pretreatments with inhibitors of OxO and scavenger of H(2)O(2) blocked the increase of tolerance to MV-induced or high light-induced oxidative stress, as well as the induction of antioxidant enzyme activities. Pretreatments with H(2)O(2) increased tolerance to oxidative stresses and antioxidant enzyme activities. It is suggested that H(2)O(2) produced by OxO in the transgenic tobacco plants triggers the signaling pathways to upregulate expressions of antioxidant enzyme genes, which in turn results in the increase of tolerance to MV-induced and high light-induced oxidative stresses. PMID:19508366

  14. Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol.

    PubMed

    Gumral, Nurhan; Kumbul, Duygu Doguc; Aylak, Firdevs; Saygin, Mustafa; Savik, Emin

    2015-01-01

    It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250-300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant-antioxidant effect in the heart tissue of rats. PMID:23293127

  15. Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma.

    PubMed

    Lee, A; Thurnham, D I; Chopra, M

    2000-11-15

    Health benefits of lycopene from tomato products have been suggested to be related to its antioxidant activity. Dietary fat may influence the absorption and hence the plasma levels and antioxidant activity of lycopene. In the present study, we have compared the effect of consumption of tomato products with extra-virgin olive oil vs. tomato products plus sunflower oil on plasma lycopene and antioxidant levels. Results show that the oil composition does not affect the absorption of lycopene from tomato products because similar levels of plasma lycopene (mean +/- SD) were obtained on feeding tomatoes (providing approximately 46 mg lycopene/d) for 7 d with either olive oil (0.66 +/- 0.26 vs 1.20 +/- 0.20 micromol/l, p <.002) or sunflower oil (0.67 +/- 0.27 vs. 1.14 micromol/l, p <.001). However, consumption of tomato products with olive oil significantly raised the plasma antioxidant activity (FRAP) from 930 +/- 150 to 1118 +/- 184 micromol/l, p <.01) but no effect was observed when the sunflower oil was used. The change (supplementation minus start values) in FRAP following the consumption of tomato products with oil was significantly higher for olive oil (190 +/- 101) than for sunflower oil (-9.6 +/- 99, p <. 005). In conclusion, the results of the study show that consumption of tomato products with olive oil but not with sunflower oil improves the antioxidant activity of the plasma. PMID:11084294

  16. Increased apomixis expression concurrent with genetic and epigenetic variation in a newly synthesized Eragrostis curvula polyploid

    NASA Astrophysics Data System (ADS)

    Zappacosta, Diego C.; Ochogavía, Ana C.; Rodrigo, Juan M.; Romero, José R.; Meier, Mauro S.; Garbus, Ingrid; Pessino, Silvina C.; Echenique, Viviana C.

    2014-04-01

    Eragrostis curvula includes biotypes reproducing through obligate and facultative apomixis or, rarely, full sexuality. We previously generated a ``tetraploid-dihaploid-tetraploid'' series of plants consisting of a tetraploid apomictic plant (T), a sexual dihaploid plant (D) and a tetraploid artificial colchiploid (C). Initially, plant C was nearly 100% sexual. However, its capacity to form non-reduced embryo sacs dramatically increased over a four year period (2003-2007) to reach levels of 85-90%. Here, we confirmed high rates of apomixis in plant C, and used AFLPs and MSAPs to characterize the genetic and epigenetic variation observed in this plant in 2007 as compared to 2003. Of the polymorphic sequences, some had no coding potential whereas others were homologous to retrotransposons and/or protein-coding-like sequences. Our results suggest that in this particular plant system increased apomixis expression is concurrent with genetic and epigenetic modifications, possibly involving transposable elements.

  17. Increased apomixis expression concurrent with genetic and epigenetic variation in a newly synthesized Eragrostis curvula polyploid.

    PubMed

    Zappacosta, Diego C; Ochogavía, Ana C; Rodrigo, Juan M; Romero, José R; Meier, Mauro S; Garbus, Ingrid; Pessino, Silvina C; Echenique, Viviana C

    2014-01-01

    Eragrostis curvula includes biotypes reproducing through obligate and facultative apomixis or, rarely, full sexuality. We previously generated a "tetraploid-dihaploid-tetraploid" series of plants consisting of a tetraploid apomictic plant (T), a sexual dihaploid plant (D) and a tetraploid artificial colchiploid (C). Initially, plant C was nearly 100% sexual. However, its capacity to form non-reduced embryo sacs dramatically increased over a four year period (2003-2007) to reach levels of 85-90%. Here, we confirmed high rates of apomixis in plant C, and used AFLPs and MSAPs to characterize the genetic and epigenetic variation observed in this plant in 2007 as compared to 2003. Of the polymorphic sequences, some had no coding potential whereas others were homologous to retrotransposons and/or protein-coding-like sequences. Our results suggest that in this particular plant system increased apomixis expression is concurrent with genetic and epigenetic modifications, possibly involving transposable elements. PMID:24710346

  18. Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

    PubMed Central

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W. B.; de Klerk, Nicholas H.; Hui, Jennie; Beilby, John; James, Alan L.; Creaney, Jenette; Robinson, Bruce W.; Mukherjee, Sutapa; Palmer, Lyle J.; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2–3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52–95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. PMID:23626673

  19. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    PubMed

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W B; de Klerk, Nicholas H; Hui, Jennie; Beilby, John; James, Alan L; Creaney, Jenette; Robinson, Bruce W; Mukherjee, Sutapa; Palmer, Lyle J; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. PMID:23626673

  20. Genomic testing interacts with reproductive surplus in reducing genetic lag and increasing economic net return.

    PubMed

    Hjortø, L; Ettema, J F; Kargo, M; Sørensen, A C

    2015-01-01

    Until now, genomic information has mainly been used to improve the accuracy of genomic breeding values for breeding animals at a population level. However, we hypothesize that the use of information from genotyped females also opens up the possibility of reducing genetic lag in a dairy herd, especially if genomic tests are used in combination with sexed semen or a high management level for reproductive performance, because both factors provide the opportunity for generating a reproductive surplus in the herd. In this study, sexed semen is used in combination with beef semen to produce high-value crossbred beef calves. Thus, on average there is no surplus of and selection among replacement heifers whether to go into the herd or to be sold. In this situation, the selection opportunities arise when deciding which cows to inseminate with sexed semen, conventional semen, or beef semen. We tested the hypothesis by combining the results of 2 stochastic simulation programs, SimHerd and ADAM. SimHerd estimates the economic effect of different strategies for use of sexed semen and beef semen at 3 levels of reproductive performance in a dairy herd. Besides simulating the operational return, SimHerd also simulates the parity distribution of the dams of heifer calves. The ADAM program estimates genetic merit per year in a herd under different strategies for use of sexed semen and genomic tests. The annual net return per slot was calculated as the sum of operational return and value of genetic lag minus costs of genomic tests divided by the total number of slots. Our results showed that the use of genomic tests for decision making decreases genetic lag by as much as 0.14 genetic standard deviation units of the breeding goal and that genetic lag decreases even more (up to 0.30 genetic standard deviation units) when genomic tests are used in combination with strategies for increasing and using a reproductive surplus. Thus, our hypothesis was supported. We also observed that

  1. Lycium chinensis Mill attenuates glutamate induced oxidative toxicity in PC12 cells by increasing antioxidant defense enzymes and down regulating ROS and Ca(2+) generation.

    PubMed

    Olatunji, Opeyemi J; Chen, Hongxia; Zhou, Yifeng

    2016-03-11

    Lycium chinensis Mill is a famous traditional Chinese medicine which displays several medicinal activities including antioxidant and neuroprotective activities. However, the mechanism of action towards the neuroprotective action has not been fully elucidated. This work was aimed at investigating the neuroprotective effects of L. chinensis Mill against glutamate-induced oxidative neurotoxicity in PC12 cells. Oxidative cell death was induced with 5mM glutamate in PC12 cells. Cell viability, LDH release, intracellular Ca(2+) concentration, reactive oxygen species (ROS) accumulation, GSH-Px, CAT and SOD antioxidant enzyme levels were measured. Our results indicated that pretreatment of PC12 cells with L. chinensis Mill extracts markedly attenuated the loss of cell viability, the release of lactate dehydrogenase (LDH), Ca(2+) overload, ROS generation, and cell apoptosis induced by glutamate toxicity. Furthermore, L. chinensis Mill extracts also significantly increased the levels of innate antioxidant enzymes GSH-Px, SOD and CAT in glutamate-induced PC12 cells. Conclusively, our results provided substantial evidence that L. chinensis Mill protected PC12 cells against glutamate-induced cell death by attenuating ROS generation, Ca(2+) influx, and increased the antioxidant defense capacity of PC12 cells against oxidative stress damages, suggesting the possible potential of extracts from the plant as sources of bioactive molecules in the treatment of neurodegenerative disorders. PMID:26536075

  2. Subspecies genetic assignments of worldwide captive tigers increase conservation value of captive populations.

    PubMed

    Luo, Shu-Jin; Johnson, Warren E; Martenson, Janice; Antunes, Agostinho; Martelli, Paolo; Uphyrkina, Olga; Traylor-Holzer, Kathy; Smith, James L D; O'Brien, Stephen J

    2008-04-22

    Tigers (Panthera tigris) are disappearing rapidly from the wild, from over 100,000 in the 1900s to as few as 3000. Javan (P.t. sondaica), Bali (P.t. balica), and Caspian (P.t. virgata) subspecies are extinct, whereas the South China tiger (P.t. amoyensis) persists only in zoos. By contrast, captive tigers are flourishing, with 15,000-20,000 individuals worldwide, outnumbering their wild relatives five to seven times. We assessed subspecies genetic ancestry of 105 captive tigers from 14 countries and regions by using Bayesian analysis and diagnostic genetic markers defined by a prior analysis of 134 voucher tigers of significant genetic distinctiveness. We assigned 49 tigers to one of five subspecies (Bengal P.t. tigris, Sumatran P.t. sumatrae, Indochinese P.t. corbetti, Amur P.t. altaica, and Malayan P.t. jacksoni tigers) and determined 52 had admixed subspecies origins. The tested captive tigers retain appreciable genomic diversity unobserved in their wild counterparts, perhaps a consequence of large population size, century-long introduction of new founders, and managed-breeding strategies to retain genetic variability. Assessment of verified subspecies ancestry offers a powerful tool that, if applied to tigers of uncertain background, may considerably increase the number of purebred tigers suitable for conservation management. PMID:18424146

  3. Genetically Determined Amerindian Ancestry Correlates with Increased Frequency of Risk Alleles for Systemic Lupus Erythematosus

    PubMed Central

    Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.

    2011-01-01

    Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568

  4. THE RELATIONSHIP BETWEEN OZONE-INDUCED LUNG INJURY, ANTIOXIDANT COMPENSATION AND UNDERLYING CARDIOVASCULAR DISEASE (CVD).

    EPA Science Inventory

    Increased levels of oxidants and compromised compensatory response are associated with CVD susceptibility. We hypothesized that rat strains demonstrating genetic CVD will have lower levels of antioxidants and greater ozone-induced pulmonary injury relative to healthy strains. Mal...

  5. Placental genetic variations in circadian clock-related genes increase the risk of placental abruption

    PubMed Central

    Qiu, Chunfang; Gelaye, Bizu; Denis, Marie; Tadesse, Mahlet G; Enquobahrie, Daniel A; Ananth, Cande V; Pacora, Percy N; Salazar, Manuel; Sanchez, Sixto E; Williams, Michelle A

    2016-01-01

    The genetic architecture of placental abruption (PA) remains poorly understood. We examined variations in SNPs of circadian clock-related genes in placenta with PA risk. We also explored placental and maternal genomic contributions to PA risk. Placental genomic DNA samples were isolated from 280 PA cases and 244 controls. Genotyping was performed using the Illumina Cardio-MetaboChip. We examined 116 SNPs in 13 genes known to moderate circadian rhythms. Logistic regression models were fit to estimate odds ratios (ORs). The combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score. We examined independent and joint associations of wGRS derived from placental and maternal genomes with PA. Seven SNPs in five genes (ARNTL2, CRY2, DEC1, PER3 and RORA), in the placental genome, were associated with PA risk. Each copy of the minor allele (G) of a SNP in the RORA gene (rs2899663) was associated with a 30% reduced odds of PA (95% CI 0.52-0.95). The odds of PA increased with increasing placental-wGRS (Ptrend<0.001). The ORs were 1.00, 2.16, 3.24 and 4.48 across quartiles. Associations persisted after the maternal-wGRS was included in the model. There was evidence of an additive contribution of placental and maternal genetic contributions to PA risk. Participants with placental- and maternal-wGRS in the highest quartile, compared with those in the lowest quartile, had a 15.57-fold (95% CI 3.34-72.60) increased odds of PA. Placental variants in circadian clock-related genes are associated with PA risk; and the association persists after control of genetic variants in the maternal genome. PMID:27186326

  6. A Novel Conditional Genetic System Reveals That Increasing Neuronal cAMP Enhances Memory and Retrieval

    PubMed Central

    Isiegas, Carolina; McDonough, Conor; Huang, Ted; Havekes, Robbert; Fabian, Sara; Wu, Long-Jun; Xu, Hui; Zhao, Ming-Gao; Kim, Jae-Ick; Lee, Yong-Seok; Lee, Hye-Ryeon; Ko, Hyoung-Gon; Lee, Nuribalhae; Choi, Sun-Lim; Lee, Jeong-Sik; Son, Hyeon; Zhuo, Min; Kaang, Bong-Kiun; Abel, Ted

    2010-01-01

    Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. However, the potential of the cAMP signaling pathway as a target for memory enhancement remains unclear because of contradictory findings from pharmacological and genetic approaches. To address these issues, we have developed a novel conditional genetic system in mice based on the heterologous expression of an Aplysia octopamine receptor, a G-protein-coupled receptor whose activation by its natural ligand octopamine leads to rapid and transient increases in cAMP. We find that activation of this receptor transgenically expressed in mouse forebrain neurons induces a rapid elevation of hippocampal cAMP levels, facilitates hippocampus synaptic plasticity, and enhances the consolidation and retrieval of fear memory. Our findings clearly demonstrate that acute increases in cAMP levels selectively in neurons facilitate synaptic plasticity and memory, and illustrate the potential of this heterologous system to study cAMP-mediated processes in mammalian systems. PMID:18550764

  7. Raman spectroscopic analysis of the increase of the carotenoid antioxidant concentration in human skin after a 1-week diet with ecological eggs

    NASA Astrophysics Data System (ADS)

    Hesterberg, Karoline; Lademann, Jürgen; Patzelt, Alexa; Sterry, Wolfram; Darvin, Maxim E.

    2009-03-01

    Skin aging is mainly caused by the destructive action of free radicals, produced by the UV light of the sun. The human skin has developed a protection system against these highly reactive molecules in the form of the antioxidative potential. Carotenoids are one of the main components of the antioxidants of the human skin. From former studies, it is known that skin aging is reduced in individuals with high levels of carotenoids. Because most of the antioxidants cannot be produced by the human organism, they must be up taken by nutrition. Using noninvasive Raman spectroscopic measurements it is demonstrated that not only fruits and vegetables but also eggs contain high concentrations of antioxidants including carotenoids, which are even doubled in the case of ecological eggs. After a 1-week diet with ecological eggs performed by six volunteers, it is found that the concentration of the carotenoids in the skin of the volunteers increased by approx. 20%. Our study does not intend to recommend exorbitant egg consumption, as eggs also contain harmful cholesterol. But in the case of egg consumption, ecological eggs from hens kept on pasture should be preferred to also receive a benefit for the skin.

  8. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect).

    PubMed

    El Sayed, Salah Mohamed; Mahmoud, Ahmed Alamir; El Sawy, Samer Ahmed; Abdelaal, Esam Abdelrahim; Fouad, Amira Murad; Yousif, Reda Salah; Hashim, Marwa Shaban; Hemdan, Shima Badawy; Kadry, Zainab Mahmoud; Abdelmoaty, Mohamed Ahmed; Gabr, Adel Gomaa; Omran, Faten M; Nabo, Manal Mohamed Helmy; Ahmed, Nagwa Sayed

    2013-11-01

    Cancer cells undergo an increased steady-state ROS condition compared to normal cells. Among the major metabolic differences between cancer cells and normal cells is the dependence of cancer cells on glycolysis as a major source of energy even in the presence of oxygen (Warburg effect). In Warburg effect, glucose is catabolized to lactate that is extruded through monocarboxylate transporters to the microenvironment of cancer cells, while in normal cells, glucose is metabolized into pyruvate that is not extruded. Pyruvate is a potent antioxidant, while lactate has no antioxidant effect. Pyruvate in normal cells may be further metabolized to acetyl CoA and then through Krebs cycle with production of antioxidant intermediates e.g. citrate, malate and oxaloacetate together with the reducing equivalents (NADH.H+). Through activity of mitochondrial transhydrogenase, NADH.H+ replenishes NADPH.H+, coenzyme of glutathione reductase which replenishes reduced form of glutathione (potent antioxidant). This enhances antioxidant capacities of normal cells, while cancer cells exhibiting Warburg effect may be deprived of all that antioxidant capabilities due to loss of extruded lactate (substrate for Krebs cycle). Although intrinsic oxidative stress in cancer cells is high, it may be prevented from reaching progressively increasing levels that are cytotoxic to cancer cells. This may be due to some antioxidant effects exerted by hexokinase II (HK II) and NADPH.H+ produced through HMP shunt. Glycolytic phenotype in cancer cells maintains a high non-toxic oxidative stress in cancer cells and may be responsible for their malignant behavior. Through HK II, glycolysis fuels the energetic arm of malignancy, the mitotic arm of malignancy (DNA synthesis through HMP shunt pathway) and the metastatic arm of malignancy (hyaluronan synthesis through uronic acid pathway) in addition to the role of phosphohexose isomerase (autocrine motility factor). All those critical three arms start with the

  9. Relation of the multilocus genetic composite reflecting high dopamine signaling capacity to future increases in BMI☆

    PubMed Central

    Yokum, Sonja; Marti, C. Nathan; Smolen, Andrew; Stice, Eric

    2014-01-01

    Because food intake exerts its rewarding effect by increasing dopamine (DA) signaling in reward circuitry, it theoretically follows that individuals with a greater number of genotypes putatively associated with high DA signaling capacity are at increased risk for overeating and subsequent weight gain. We tested the association between the multilocus genetic composite risk score, defined by the total number of genotypes putatively associated with greater DA signaling capacity (i.e. TaqIA A2 allele, DRD2-141C Ins/Del and Del/Del genotypes, DRD4-S allele, DAT1-S allele, and COMT Val/Val genotype), and future increases in Body Mass Index (BMI) in three prospective studies. Participants in Study 1 (N = 30; M age = 15.2; M baseline BMI = 26.9), Study 2 (N = 34; M age = 20.9; M baseline BMI = 28.2), and Study 3 (N = 162; M age = 15.3, M baseline BMI = 20.8) provided saliva samples from which epithelial cells were collected, permitting DNA extraction. The multilocus genetic composite risk score was associated with future increases in BMI in all three studies (Study 1, r = 0.37; Study 2, r = 0.22; Study 3, r = 0.14) and the overall sample (r = 0.19). DRD4-S was associated with increases in BMI in Study 1 (r = 0.42), Study 2 (r = 0.27), and in the overall sample (r = 0.17). DAT1-S was associated with increases in BMI in Study 3 (r = 0.17) and in the overall sample (r = 0.12). There were no associations between the other genotypes (TaqIA, COMT, and DRD2-141C) and change in BMI over 2-year follow-up. Data suggest that individuals with a genetic propensity for greater DA signaling capacity are at risk for future weight gain and that combining alleles that theoretically have a similar function may provide a more reliable method of modeling genetic risk associated with future weight gain than individual genotypes. PMID:25523644

  10. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.

    PubMed

    Machiela, Mitchell J; Lan, Qing; Slager, Susan L; Vermeulen, Roel C H; Teras, Lauren R; Camp, Nicola J; Cerhan, James R; Spinelli, John J; Wang, Sophia S; Nieters, Alexandra; Vijai, Joseph; Yeager, Meredith; Wang, Zhaoming; Ghesquières, Hervé; McKay, James; Conde, Lucia; de Bakker, Paul I W; Cox, David G; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R; De Roos, Anneclaire J; Brooks-Wilson, Angela R; Giles, Graham G; Melbye, Mads; Gu, Jian; Jackson, Rebecca D; Kane, Eleanor; Purdue, Mark P; Vajdic, Claire M; Albanes, Demetrius; Kelly, Rachel S; Zucca, Mariagrazia; Bertrand, Kimberly A; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M; Link, Brian K; Novak, Anne J; Dogan, Ahmet; Asmann, Yan W; Liebow, Mark; Thompson, Carrie A; Ansell, Stephen M; Witzig, Thomas E; Tilly, Hervé; Haioun, Corinne; Molina, Thierry J; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans-Olov; Roos, Göran; Bracci, Paige M; Riby, Jacques; Smith, Martyn T; Holly, Elizabeth A; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M; Severson, Richard K; Tinker, Lesley F; North, Kari E; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J; Villano, Danylo J; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R; Turner, Jenny; Southey, Melissa C; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Boeing, Heiner; Tjønneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; De Vivo, Immaculata; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Liang, Liming; Park, Ju-Hyun; Chung, Charles C; Weisenburger, Dennis D; Fraumeni, Joseph F; Salles, Gilles; Glenn, Martha; Cannon-Albright, Lisa; Curtin, Karen; Wu, Xifeng; Smedby, Karin E; de Sanjose, Silvia; Skibola, Christine F; Berndt, Sonja I; Birmann, Brenda M; Chanock, Stephen J; Rothman, Nathaniel

    2016-04-15

    Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk. PMID:27008888

  11. The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.

    PubMed

    Lupton, Michelle K; Strike, Lachlan; Hansell, Narelle K; Wen, Wei; Mather, Karen A; Armstrong, Nicola J; Thalamuthu, Anbupalam; McMahon, Katie L; de Zubicaray, Greig I; Assareh, Amelia A; Simmons, Andrew; Proitsi, Petroula; Powell, John F; Montgomery, Grant W; Hibar, Derrek P; Westman, Eric; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Velas, Bruno; Lovestone, Simon; Brodaty, Henry; Ames, David; Trollor, Julian N; Martin, Nicholas G; Thompson, Paul M; Sachdev, Perminder S; Wright, Margaret J

    2016-04-01

    Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults. PMID:26973105

  12. Genetic selection for increased mean and reduced variance of twinning rate in Belclare ewes.

    PubMed

    Cottle, D J; Gilmour, A R; Pabiou, T; Amer, P R; Fahey, A G

    2016-04-01

    It is sometimes possible to breed for more uniform individuals by selecting animals with a greater tendency to be less variable, that is, those with a smaller environmental variance. This approach has been applied to reproduction traits in various animal species. We have evaluated fecundity in the Irish Belclare sheep breed by analyses of flocks with differing average litter size (number of lambs per ewe per year, NLB) and have estimated the genetic variance in environmental variance of lambing traits using double hierarchical generalized linear models (DHGLM). The data set comprised of 9470 litter size records from 4407 ewes collected in 56 flocks. The percentage of pedigreed lambing ewes with singles, twins and triplets was 30, 54 and 14%, respectively, in 2013 and has been relatively constant for the last 15 years. The variance of NLB increases with the mean in this data; the correlation of mean and standard deviation across sires is 0.50. The breeding goal is to increase the mean NLB without unduly increasing the incidence of triplets and higher litter sizes. The heritability estimates for lambing traits were NLB, 0.09; triplet occurrence (TRI) 0.07; and twin occurrence (TWN), 0.02. The highest and lowest twinning flocks differed by 23% (75% versus 52%) in the proportion of ewes lambing twins. Fitting bivariate sire models to NLB and the residual from the NLB model using a double hierarchical generalized linear model (DHGLM) model found a strong genetic correlation (0.88 ± 0.07) between the sire effect for the magnitude of the residual (VE ) and sire effects for NLB, confirming the general observation that increased average litter size is associated with increased variability in litter size. We propose a threshold model that may help breeders with low litter size increase the percentage of twin bearers without unduly increasing the percentage of ewes bearing triplets in Belclare sheep. PMID:26081782

  13. Why increased nuchal translucency is associated with congenital heart disease: a systematic review on genetic mechanisms.

    PubMed

    Burger, Nicole B; Bekker, Mireille N; de Groot, Christianne J M; Christoffels, Vincent M; Haak, Monique C

    2015-06-01

    This overview provides insight into the underlying genetic mechanism of the high incidence of cardiac defects in fetuses with increased nuchal translucency (NT). Nuchal edema, the morphological equivalent of increased NT, is likely to result from abnormal lymphatic development and is strongly related to cardiac defects. The underlying genetic pathways are, however, unknown. This study aims to present a systematic overview of genes involved in both cardiac and lymphatic development in mouse embryos. A search of PubMed and the Mammalian Phenotype Browser was performed. Fifteen candidate genes involved in both cardiac and lymphatic development were identified: Adrenomedullin; Chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TFII); Cyp51; Ephrin-B2; Forkhead box protein C2 (Foxc2); Nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1); Neurofibromatosis type 1 (Nf1); Phosphoinositide 3-kinase encoding isoform p110α (Pik3ca); Podoplanin; Prospero-related homeobox 1 (Prox1); T-box 1 (Tbx1); Tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains 1 (Tie1); vascular endothelial growth factor (Vegf)-A; Vegf receptor-3 (Vegfr-3); and Vascular endothelial zinc finger 1 (Vezf1). Mutations in all but one gene (Pik3ca) resulted in both a cardiac defect and nuchal edema. Candidate genes - mainly encoding for endothelium - are involved in both cardiac and lymphatic development. Alterations in candidate genes are associated with the strong relation between increased NT and cardiac defects. PMID:25728762

  14. Differences in seminal plasma and spermatozoa antioxidative systems and seminal plasma lipid and protein levels among boar breeds and hybrid genetic traits.

    PubMed

    Žura Žaja, Ivona; Samardžija, Marko; Vince, Silvijo; Vilić, Marinko; Majić-Balić, Ivanka; Đuričić, Dražen; Milinković-Tur, Suzana

    2016-07-01

    The objectives of this study were to determine the influence of breed and hybrid genetic traits of boars on lipid and protein concentrations and antioxidative system variables in seminal plasma (SP) and spermatozoa and their correlations with semen quality variables. Semen samples from 27 boars: Swedish Landraces (SL), German Landraces (GL), Large Whites (LW), Pietrains (P) and Pig Improvement Company hybrids (PIC-hybrid), aged from 1.5 to 3 years old, were collected. SP was spectrophotometrically analyzed to determine total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), total protein (TP), albumin, and zinc concentrations. The antioxidative system in SP and spermatozoa was established spectrophotometrically by determining total antioxidative status (TAS), total superoxide dismutase (TSOD) and glutathione peroxidase (GSH-Px) parameters, as well as copper-zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in spermatozoa. The hybrid boars had higher (P<0.05) SP concentrations of: TC, LDL-C and TAG than P and GL; HDL-C than P, GL and SL; and TP than P and LW. PIC-hybrid had lower values (P<0.05) in spermatozoa of: TAS and CuZnSOD than SL; TSOD and GSH-Px than SL and P; and MnSOD than SL and LW. Differences in SP and spermatozoa antioxidative system variables and the significant differences in SP protein and lipid variables exist among boars of different breeds and hybrid. Novel data and observed differences in semen variables among boar breeds and hybrids and their correlations with semen quality parameters in this study could contribute to better assessment of boar semen quality. PMID:27072624

  15. Dietary quebracho tannins are not absorbed, but increase the antioxidant capacity of liver and plasma in sheep.

    PubMed

    López-Andrés, Patricia; Luciano, Giuseppe; Vasta, Valentina; Gibson, Trevor M; Biondi, Luisa; Priolo, Alessandro; Mueller-Harvey, Irene

    2013-08-01

    A total of sixteen lambs were divided into two groups and fed two different diets. Of these, eight lambs were fed a control diet (C) and eight lambs were fed the C diet supplemented with quebracho tannins (C+T). The objective of the present study was to assess whether dietary quebracho tannins can improve the antioxidant capacity of lamb liver and plasma and if such improvement is due to a direct transfer of phenolic compounds or their metabolites, to the animal tissues. Feed, liver and plasma samples were purified by solid-phase extraction (SPE) and analysed by liquid chromatography-MS for phenolic compounds. Profisitinidin compounds were identified in the C+T diet. However, no phenolic compounds were found in lamb tissues. The liver and the plasma from lambs fed the C+T diet displayed a greater antioxidant capacity than tissues from lambs fed the C diet, but only when samples were not purified with SPE. Profisetinidin tannins from quebracho seem not to be degraded or absorbed in the gastrointestinal tract. However, they induced antioxidant effects in animal tissues. PMID:23312208

  16. Increased Extinction Potential of Insular Fish Populations with Reduced Life History Variation and Low Genetic Diversity

    PubMed Central

    Hellmair, Michael; Kinziger, Andrew P.

    2014-01-01

    Theoretical work has shown that reduced phenotypic heterogeneity leads to population instability and can increase extinction potential, yet few examples exist of natural populations that illustrate how varying levels expressed diversity may influence population persistence, particularly during periods of stochastic environmental fluctuation. In this study, we assess levels of expressed variation and genetic diversity among demographically independent populations of tidewater goby (Eucyclogobius newberryi), show that reductions in both factors typically coincide, and describe how low levels of diversity contribute to the extinction risk of these isolated populations. We illustrate that, for this annual species, continuous reproduction is a safeguard against reproductive failure by any one population segment, as natural, stochastically driven salinity increases frequently result in high mortality among juvenile individuals. Several study populations deviated from the natural pattern of year-round reproduction typical for the species, rendering those with severely truncated reproductive periods vulnerable to extinction in the event of environmental fluctuation. In contrast, demographically diverse populations are more likely to persist through such periods through the continuous presence of adults with broader physiological tolerance to abrupt salinity changes. Notably, we found a significant correlation between genetic diversity and demographic variation in the study populations, which could be the result of population stressors that restrict both of these diversity measures simultaneously, or suggestive of a causative relationship between these population characteristics. These findings demonstrate the importance of biocomplexity at the population level, and assert that the maintenance of diversity contributes to population resilience and conservation of this endangered species. PMID:25409501

  17. Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

    PubMed Central

    Lundbo, Lene F.; Harboe, Zitta Barrella; Clausen, Louise N.; Hollegaard, Mads V.; Sørensen, Henrik T.; Hougaard, David M.; Konradsen, Helle B.; Nørgaard, Mette; Benfield, Thomas

    2015-01-01

    Background Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). Methods Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated. Results 372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20–2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86–1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. Conclusions A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis. PMID:26870821

  18. Increased extinction potential of insular fish populations with reduced life history variation and low genetic diversity.

    PubMed

    Hellmair, Michael; Kinziger, Andrew P

    2014-01-01

    Theoretical work has shown that reduced phenotypic heterogeneity leads to population instability and can increase extinction potential, yet few examples exist of natural populations that illustrate how varying levels expressed diversity may influence population persistence, particularly during periods of stochastic environmental fluctuation. In this study, we assess levels of expressed variation and genetic diversity among demographically independent populations of tidewater goby (Eucyclogobius newberryi), show that reductions in both factors typically coincide, and describe how low levels of diversity contribute to the extinction risk of these isolated populations. We illustrate that, for this annual species, continuous reproduction is a safeguard against reproductive failure by any one population segment, as natural, stochastically driven salinity increases frequently result in high mortality among juvenile individuals. Several study populations deviated from the natural pattern of year-round reproduction typical for the species, rendering those with severely truncated reproductive periods vulnerable to extinction in the event of environmental fluctuation. In contrast, demographically diverse populations are more likely to persist through such periods through the continuous presence of adults with broader physiological tolerance to abrupt salinity changes. Notably, we found a significant correlation between genetic diversity and demographic variation in the study populations, which could be the result of population stressors that restrict both of these diversity measures simultaneously, or suggestive of a causative relationship between these population characteristics. These findings demonstrate the importance of biocomplexity at the population level, and assert that the maintenance of diversity contributes to population resilience and conservation of this endangered species. PMID:25409501

  19. Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease.

    PubMed

    Polidori, M Cristina; Mecocci, Patrizia

    2002-12-01

    Oxidative stress is believed to play a major role in the pathogenesis of Alzheimer disease (AD). Plasma concentrations of vitamins C, A and E, of uric acid, thiols and carotenoids were lower and of malondialdehyde (MDA) higher in 35 AD patients (85.9 +/- 5.5 y) compared to 40 controls 85.5 +/- 4.4 y). Differences were significant for vitamin C, vitamin E, lutein, lycopene, alpha-carotene and MDA (p < 0.001). Plasma exposed to peroxyl radicals showed a rate of antioxidant consumption and of MDA production higher in AD patients than in controls. AD in advanced age is accompanied by a poor plasma antioxidant status and increased plasma lipid peroxidation, as well as by a low resistance to peroxyl radical exposure. PMID:12629261

  20. The Mitochondrial Antioxidants MitoE2 and MitoQ10 Increase Mitochondrial Ca2+ Load upon Cell Stimulation by Inhibiting Ca2+ Efflux from the Organelle

    PubMed Central

    Leo, Sara; Szabadkai, György; Rizzuto, Rosario

    2009-01-01

    Mitochondrial reactive oxygen species (ROS) production is recognized as a major pathogenic event in a number of human diseases, and mitochondrial scavenging of ROS appears a promising therapeutic approach. Recently, two mitochondrial antioxidants have been developed; conjugating α-tocopherol and the ubiquinol moiety of coenzyme Q to the lipophilic triphenylphosphonium cation (TPP+), denominated MitoE2 and MitoQ10, respectively. We have investigated the effect of these compounds on mitochondrial Ca2+ homeostasis, which controls processes as diverse as activation of mitochondrial dehydrogenases and pro-apoptotic morphological changes of the organelle. We demonstrate that treatment of HeLa cells with both MitoE2 and MitoQ10 induces (albeit with different efficacy) a major enhancement of the increase in matrix Ca2+ concentration triggered by cell stimulation with the inositol 1,4,5-trisphosphate-generating agonist histamine. The effect is a result of the inhibition of Ca2+ efflux from the organelle and depends on the TPP+ moiety of these compounds. Overall, the data identify an effect independent of their antioxidant activity, that on the one hand may be useful in addressing disorders in which mitochondrial Ca2+ handling is impaired (e.g., mitochondrial diseases) and on the other may favor mitochondrial Ca2+ overload and thus increase cell sensitivity to apoptosis (thus possibly counteracting the benefits of the antioxidant activity). PMID:19076448

  1. Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense.

    PubMed

    Fetoni, Anna Rita; De Bartolo, Paola; Eramo, Sara Letizia Maria; Rolesi, Rolando; Paciello, Fabiola; Bergamini, Christian; Fato, Romana; Paludetti, Gaetano; Petrosini, Laura; Troiani, Diana

    2013-02-27

    This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10 analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9 and Q10 (CoQ9 and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10 analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9 and CoQ10 content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway. PMID:23447610

  2. Pulmonary function response and effects of antioxidant genetic polymorphisms in healthy young adults exposed to low concentration ozone.

    EPA Science Inventory

    Rational: Ozone is known to induce a variety of pulmonary effects including decrement of spirometric lung function and inflammatory reaction, and antioxidant genes are known to play an important role in modulating the effects. It is unclear, however, if such effects may occur at...

  3. Genome-wide association study dissects the genetic architecture of polyphenols and antioxidant capacity in a sorghum diversified collection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consumption of polyphenol-rich food is associated with decreased risk of several oxidative stress-related chronic diseases. Sorghum, a major cereal crop grown worldwide, has many polyphenol-containing accessions with high antioxidant activity in the grain. However, many of these polyphenol-containin...

  4. Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility

    PubMed Central

    Laddha, Naresh C.; Dwivedi, Mitesh; Gani, Amina R.; Mansuri, Mohmmad Shoab; Begum, Rasheedunnisa

    2013-01-01

    Genetic polymorphisms in TNFB are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of TNFB and ICAM1 affects the disease onset and progression. We have earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms investigated in the TNFB were in strong linkage disequilibrium and significantly associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that TNFB expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher TNFB and ICAM1 expression. Overall, our findings suggest that the increased TNFB transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased ICAM1 expression. For the first time, we show that TNFB +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes influence of TNFB and ICAM1 on the disease progression, onset and gender bias for developing vitiligo. PMID:24312346

  5. Smoking is associated with reduced serum paraoxonase, antioxidants and increased oxidative stress in normolipidaemic acute myocardial infarct patients

    PubMed Central

    Kumar, Arun; Biswas, Utpal Kumar

    2011-01-01

    Background Paraoxonase is a high-density lipoprotein (HDL)-associated enzyme that protects lipoproteins from oxidative modifications and from becoming atherogenic in nature. Smoking is a well-known major cardiovascular risk factor that promotes lipid peroxidation (LP). The present study examined the hypothesis that smoking modulates the activity of paraoxonase and depletes antioxidants. Aim The present study evaluated paraoxonase activity, antioxidant status and LP in smoking and non-smoking normolipidaemic acute myocardial infarct (AMI) patients, and results were compared with controls. Settings and design The serum paraoxonase activities, antioxidants and LP were determined in 86 normolipidaemic patients diagnosed of AMI, and 86 age–sex-matched healthy volunteers served as control. Material and methods Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity was determined by standard methods. Malondialdehyde was measured by the thiobarbituric acid reaction, and conjugated diene levels by the Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin and lipid profiles were analysed by standard methods. Statistics The values were expressed as mean±SD, and data from the patients and control were compared using the Student t test. Results and conclusion The total cholesterol/HDL cholesterol ratio, triglycerides, low-density lipoprotein cholesterol, low-density lipoprotein/HDL cholesterol ratio and triglyceride/HDL cholesterol ratio were significantly higher, and HDL cholesterol significantly lower in smokers compared with non-smoking AMI patients. Superoxide dismutase, glutathione peroxidase and catalase were significantly higher in non-smokers compared with smokers. Serum albumin, uric acid and bilirubin were higher in the control compared with smoking AMI patients. The malondialdehyde and conjugated dienes were significantly higher, and paraoxonase activities were

  6. A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice.

    PubMed

    Kittel, Christian; Wressnigg, Nina; Shurygina, Anna Polina; Wolschek, Markus; Stukova, Marina; Romanovskaya-Romanko, Ekatherina; Romanova, Julia; Kiselev, Oleg; Muster, Thomas; Egorov, Andrej

    2015-10-01

    The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels. PMID:26215439

  7. Genetics

    MedlinePlus

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  8. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  9. Increasing antioxidant activity of procyanidin extracts from the pericarp of Litchi chinensis processing waste by two probiotic bacteria bioconversions.

    PubMed

    Li, Shuyi; Chen, Lu; Yang, Ting; Wu, Qian; Lv, Zhejuan; Xie, Bijun; Sun, Zhida

    2013-03-13

    Litchi chinensis pericarp from litchi processing waste is an important plant source of A-type procyanidins, which were considered a natural dietary supplement because of their high biological activity in vivo. Litchi pericarp oligomeric procyanidins (LPOPCs) did not selectively modify the growth of Streptococcus thermophilus and Lactobacillus casei -01 at concentrations of 0.25 and 0.5 mg/mL, and it was demonstrated that the two strains could transform procyanidins during their log period of growth by two different pathways. S. thermophilus was able to metabolize procyanidin A2 to its isomer, and L. casei could decompose flavan-3-ols into 3,4-hydroxyphenylacetic acid, 4-hydroxyphenylpropionic acid, m-coumaric acid, and p-coumaric acid. The total antioxidant capability (T-AOC) of LPOPCs before and after microbial incubation was estimated, and the results suggested that probiotic bacteria bioconversion is a feasible and efficient method to convert litchi pericarp procyanidins to a more effective antioxidant agent. PMID:23330597

  10. Genetic evidence that culling increases badger movement: implications for the spread of bovine tuberculosis.

    PubMed

    Pope, Lisa C; Butlin, Roger K; Wilson, Gavin J; Woodroffe, Rosie; Erven, Kristien; Conyers, Chris M; Franklin, Tanya; Delahay, Richard J; Cheeseman, Chris L; Burke, Terry

    2007-12-01

    The Eurasian badger (Meles meles) has been implicated in the transmission of bovine tuberculosis (TB, caused by Mycobacterium bovis) to cattle. However, evidence suggests that attempts to reduce the spread of TB among cattle in Britain by culling badgers have mixed effects. A large-scale field experiment (the randomized badger culling trial, RBCT) showed that widespread proactive badger culling reduced the incidence of TB in cattle within culled areas but that TB incidence increased in adjoining areas. Additionally, localized reactive badger culling increased the incidence of TB in cattle. It has been suggested that culling-induced perturbation of badger social structure may increase individual movements and elevate the risk of disease transmission between badgers and cattle. Field studies support this hypothesis, by demonstrating increases in badger group ranges and the prevalence of TB infection in badgers following culling. However, more evidence on the effect of culling on badger movements is needed in order to predict the epidemiological consequences of this control strategy. Here, analysis of the genetic signatures of badger populations in the RBCT revealed increased dispersal following culling. While standard tests provided evidence for greater dispersal after culling, a novel method indicated that this was due to medium- and long-distance dispersal, in addition to previously reported increases in home-range size. Our results also indicated that, on average, badgers infected with M. bovis moved significantly farther than did uninfected badgers. A disease control strategy that included culling would need to take account of the potentially negative epidemiological consequences of increased badger dispersal. PMID:17944854

  11. An uncertain revolution: why the rise of a genetic model of mental illness has not increased tolerance.

    PubMed

    Schnittker, Jason

    2008-11-01

    This study uses the 2006 replication of the 1996 General Social Survey Mental Health Module to explore trends in public beliefs about mental illness in the USA. Drawing on three models related to the framing of genetic arguments in popular media, the study attempts to address why tolerance of the mentally ill has not increased, despite the growing popularity of a biomedical view. The key to resolving this paradox lies in understanding how genetic arguments interact with other beliefs about mental illness, as well as the complex ideational implications of genetic frameworks. Genetic arguments have contingent relationships with tolerance. When applied to schizophrenia, genetic arguments are positively associated with fears regarding violence. Indeed, in this regard, attributing schizophrenia to genes is no different from attributing schizophrenia to bad character. However, when applied to depression, genetic arguments are positively associated with social acceptance. In addition to these contingencies, genetic explanations have discontinuous relationships with beliefs regarding treatment. Although genetic arguments are positively associated with recommending medical treatment, they are not associated with the perceived likelihood of improvement. The net result of these assorted relationships is little change in overall levels of tolerance over time. Because of the blunt nature of the forces propelling a biomedical view--including the growing popularity of psychiatric medications--altering beliefs about the etiology of mental illness is unlikely, on its own, to increase tolerance. PMID:18703264

  12. Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence

    PubMed Central

    Vodusek, Ana Lina; Goricar, Katja; Gazic, Barbara; Dolzan, Vita

    2016-01-01

    Background Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence. Patients and methods In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model. Results Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer. Conclusions We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and

  13. Increasing water-use efficiency directly through genetic manipulation of stomatal density.

    PubMed

    Franks, Peter J; W Doheny-Adams, Timothy; Britton-Harper, Zoe J; Gray, Julie E

    2015-07-01

    Improvement in crop water-use efficiency (WUE) is a critical priority for regions facing increased drought or diminished groundwater resources. Despite new tools for the manipulation of stomatal development, the engineering of plants with high WUE remains a challenge. We used Arabidopsis epidermal patterning factor (EPF) mutants exhibiting altered stomatal density to test whether WUE could be improved directly by manipulation of the genes controlling stomatal density. Specifically, we tested whether constitutive overexpression of EPF2 reduced stomatal density and maximum stomatal conductance (gw(max) ) sufficiently to increase WUE. We found that a reduction in gw(max) via reduced stomatal density in EPF2-overexpressing plants (EPF2OE) increased both instantaneous and long-term WUE without altering significantly the photosynthetic capacity. Conversely, plants lacking both EPF1 and EPF2 expression (epf1epf2) exhibited higher stomatal density, higher gw(max) and lower instantaneous WUE, as well as lower (but not significantly so) long-term WUE. Targeted genetic modification of stomatal conductance, such as in EPF2OE, is a viable approach for the engineering of higher WUE in crops, particularly in future high-carbon-dioxide (CO2 ) atmospheres. PMID:25754246

  14. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

    PubMed Central

    Jearapong, Nattharat; Pimson, Charinya; Chatuphonprasert, Waranya

    2016-01-01

    Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD), associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD) on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD. PMID:27019761

  15. Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

    PubMed

    Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

    2016-01-01

    Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

  16. Increased Genetic Vulnerability to Smoking at CHRNA5 in Early-Onset Smokers

    PubMed Central

    Hartz, Sarah M.; Short, Susan E.; Saccone, Nancy L.; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H.; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Guđbjartsson, Daniel; Hansel, Nadia N.; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Hum, Sc; Rosenberger, Albert; Scheet, Paul; Shaffer, John R.; Teumer, Alexander; Thompson, John R.; Vink, Jacqueline M.; Vogelzangs, Nicole; Wenzlaff, Angela S.; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H.; Balmforth, Anthony J.; Baumeister, Sebastian E.; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W.; Boyd, Heather A.; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M.; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S.; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Lic, Phil; Hewitt, John K.; Hottenga, Jouke Jan; Jensen, Majken K.; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J.; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M.; Mathias, Rasika A.; McNeil, Daniel W.; Medland, Sarah E.; Montgomery, Grant W.; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M.; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I.; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J.; Francks, Clyde; Gejman, Pablo V.; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S.; Lehtimäki, Terho; Levinson, Douglas F.; Marazita, Mary L.; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D.; Murray, Jeffrey C.; Nöthen, Markus M.; Penninx, Brenda W.; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J.; Sanders, Alan R.; Schwartz, Ann G.; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E.; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H.-Erich; Amos, Christopher I.; Breslau, Naomi; Cannon, Dale S.; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O.; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G.; Stevens, Victoria L.; Stitzel, Jerry A.; Weiss, Robert B.; Kraft, Peter; Bierut, Laura J.

    2012-01-01

    Context Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. Objective To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Data Sources Primary data. Study Selection Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Data Extraction Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Data Synthesis Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR]=1.45; 95% CI, 1.36–1.55; n=13 843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21–1.33, n = 19 505) (P = .01). Conclusion These results highlight an increased genetic vulnerability to smoking in early-onset smokers. PMID:22868939

  17. Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

    PubMed Central

    Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.

    2016-01-01

    Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

  18. High altitude genetic adaptation in Tibetans: no role of increased hemoglobin-oxygen affinity.

    PubMed

    Tashi, Tsewang; Feng, Tang; Koul, Parvaiz; Amaru, Ricardo; Hussey, Dottie; Lorenzo, Felipe R; RiLi, Ge; Prchal, Josef T

    2014-01-01

    High altitude exerts selective evolutionary pressure primarily due to its hypoxic environment, resulting in multiple adaptive responses. High hemoglobin-oxygen affinity is postulated to be one such adaptive change, which has been reported in Sherpas of the Himalayas. Tibetans have lived on the Qinghai-Tibetan plateau for thousands of years and have developed unique phenotypes, such as protection from polycythemia which has been linked to PDH2 mutation, resulting in the downregulation of the HIF pathway. In order to see if Tibetans also developed high hemoglobin-oxygen affinity as a part of their genetic adaptation, we conducted this study assessing hemoglobin-oxygen affinity and their fetal hemoglobin levels in Tibetan subjects from 3 different altitudes. We found normal hemoglobin-oxygen affinity in all subjects, fetal hemoglobin levels were normal in all except one and no hemoglobin variants in any of the subjects. We conclude that increased hemoglobin-oxygen affinity or increased fetal hemoglobin are not adaptive phenotypes of the Tibetan highlanders. PMID:24618341

  19. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy

    PubMed Central

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K.

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID:26368933

  20. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy.

    PubMed

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID:26368933

  1. Energy Dense, Protein Restricted Diet Increases Adiposity and Perturbs Metabolism in Young, Genetically Lean Pigs

    PubMed Central

    Fisher, Kimberly D.; Scheffler, Tracy L.; Kasten, Steven C.; Reinholt, Brad M.; van Eyk, Gregory R.; Escobar, Jeffery; Scheffler, Jason M.; Gerrard, David E.

    2013-01-01

    Animal models of obesity and metabolic dysregulation during growth (or childhood) are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12), containing 15% tallow, 35% refined sugars and 9.1–12.9% crude protein, or a control corn-based diet (n = 11) with 12.2–19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001) energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT); blood glucose increased (P<0.05) in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01), even 4 h post-challenge. During OGTT, glucose area under the curve (AUC) was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001). Chronic HED intake increased (P<0.05) subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7) was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs. PMID:23991090

  2. Magnetic separation of algae genetically modified for increased intracellular iron uptake

    NASA Astrophysics Data System (ADS)

    Buck, Amy; Moore, Lee R.; Lane, Christopher D.; Kumar, Anil; Stroff, Clayton; White, Nicolas; Xue, Wei; Chalmers, Jeffrey J.; Zborowski, Maciej

    2015-04-01

    Algae were investigated in the past as a potential source of biofuel and other useful chemical derivatives. Magnetic separation of algae by iron oxide nanoparticle binding to cells has been proposed by others for dewatering of cellular mass prior to lipid extraction. We have investigated feasibility of magnetic separation based on the presence of natural iron stores in the cell, such as the ferritin in Auxenochlorella protothecoides (A. protothecoides) strains. The A. protothecoides cell constructs were tested for inserted genes and for increased intracellular iron concentration by inductively coupled plasma atomic absorption (ICP-AA). They were grown in Sueoka's modified high salt media with added vitamin B1 and increasing concentration of soluble iron compound (FeCl3 EDTA, from 1× to 8× compared to baseline). The cell magnetic separation conditions were tested using a thin rectangular flow channel pressed against interpolar gaps of a permanent magnet forming a separation system of a well-defined fluid flow and magnetic fringing field geometry (up to 2.2 T and 1000 T/m) dubbed "magnetic deposition microscopy", or MDM. The presence of magnetic cells in suspension was detected by formation of characteristic deposition bands at the edges of the magnet interpolar gaps, amenable to optical scanning and microscopic examination. The results demonstrated increasing cellular Fe uptake with increasing Fe concentration in the culture media in wild type strain and in selected genetically-modified constructs, leading to magnetic separation without magnetic particle binding. The throughput in this study is not sufficient for an economical scale harvest.

  3. Genetic Deletion of NOS3 Increases Lethal Cardiac Dysfunction Following Mouse Cardiac Arrest

    PubMed Central

    Beiser, David G.; Orbelyan, Gerasim A.; Inouye, Brendan T.; Costakis, James G.; Hamann, Kimm J.; McNally, Elizabeth M.; Hoek, Terry L. Vanden

    2010-01-01

    Study Aims Cardiac arrest mortality is significantly affected by failure to obtain return of spontaneous circulation (ROSC) despite cardiopulmonary resuscitation (CPR). Severe myocardial dysfunction and cardiovascular collapse further affects mortality within hours of initial ROSC. Recent work suggests that enhancement of nitric oxide (NO) signaling within minutes of CPR can improve myocardial function and survival. We studied the role of NO signaling on cardiovascular outcomes following cardiac arrest and resuscitation using endothelial NO synthase knockout (NOS3-/-) mice. Methods Adult female wild-type (WT) and NOS3-/- mice were anesthetized, intubated, and instrumented with left-ventricular pressure-volume catheters. Cardiac arrest was induced with intravenous potassium chloride. CPR was performed after 8 min of untreated arrest. ROSC rate, cardiac function, whole-blood nitrosylhemoglobin (HbNO) concentrations, heart NOS3 content and phosphorylation (p-NOS3), cyclic guanosine monophosphate (cGMP), and phospho-troponin I (p-TnI) were measured. Results Despite equal quality CPR, NOS3-/- mice displayed lower rates of ROSC compared to WT (47.6% [10/21] vs. 82.4% [14/17], p<0.005). Among ROSC animals, NOS3-/- versus WT mice exhibited increased left-ventricular dysfunction and 120 min mortality. Prior to ROSC, myocardial effectors of NO signaling including cGMP and p-TnI were decreased in NOS3-/- vs. WT mice (p<0.05). Following ROSC in WT mice, significant NOS3-dependent increases in circulating HbNO were seen by 120 min. Significant increases in cardiac p-NOS3 occurred between end-arrest and 15 min post-ROSC, while total NOS3 content was increased by 120 min post-ROSC (p<0.05). Conclusions Genetic deletion of NOS3 decreases ROSC rate and worsens post-ROSC left-ventricular function. Poor cardiovascular outcomes are associated with differences in NOS3-dependent myocardial cGMP signaling and circulating NO metabolites. PMID:20951489

  4. Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney

    PubMed Central

    2013-01-01

    Background Nephrotoxicity is a dose limiting side effect of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection. The mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically toxic to the proximal convoluted tubules and proximal tubular mitochondria are the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of reactive oxygen species and cellular damage is reported to occur after the antioxidants are depleted. The purpose of the study is to investigate the alterations in cellular antioxidant system in tenofovir induced renal damage using a rat model. Results Chronic tenofovir administration to adult Wistar rats resulted in proximal tubular damage (as evidenced by light microscopy), proximal tubular dysfunction (as shown by Fanconi syndrome and tubular proteinuria), and extensive proximal tubular mitochondrial injury (as revealed by electron microscopy). A 50% increase in protein carbonyl content was observed in the kidneys of TDF treated rats as compared with the control. Reduced glutathione was decreased by 50%. The activity of superoxide dismutase was decreased by 57%, glutathione peroxidase by 45%, and glutathione reductase by 150% as compared with control. Carbonic Anhydrase activity was decreased by 45% in the TDF treated rat kidneys as compared with control. Succinate dehydrogenase activity, an indicator of mitochondrial activity was decreased by 29% in the TDF treated rat kidneys as compared with controls, suggesting mitochondrial dysfunction. Conclusion Tenofovir- induced mitochondrial damage and increased oxidative stress in the rat kidneys may be due to depletion of the antioxidant system particularly, the glutathione dependent system and MnSOD. PMID:23957306

  5. Genetic variations in the osteopontin promoters T-443C and G-156GG increase carotid intima–media thickness

    PubMed Central

    Yueniwati, Yuyun; Yurina, Valentina; Sobah, Nurus; Rahayu, Endang

    2016-01-01

    Carotid intima–media thickness (CIMT) is a clear predictor of atherosclerosis. The increase of CIMT is affected by mutations in the osteopontin (OPN) promoters. The purpose of this study was to examine genetic variations in OPN promoters T-443C and G-156GG, identified in Javanese children with ischemic stroke parents, and to investigate their relationship with the increase of CIMT. A case–control analytic study was performed on 20 case and 12 control samples. Case samples were Javanese children aged between 10 to 21 years with ischemic stroke parents. Control samples were children with healthy parents. Mutations of T-443C and G-156GG were determined by employing polymerase chain reaction. Results of sequencing were analyzed using CLC Main Workbench 6.0. CIMT was defined using ultrasound. Genetic variations of T-443C were identified in six samples. Likewise, genetic variations of G-156GG were identified in six samples. Genetic variations in the OPN promoters T-443C and G-156GG were not potential risk factors in an increase of CIMT (P=0.654 and P=0.654). This study proves that genetic variations could be identified at the points of T-443C and G-156GG in children with ischemic stroke parents. Although statistically insignificant, the tendency to increase CIMT occurs in children with genetic variations. Children with ischemic stroke parents have thicker CIMT than children of healthy parents. PMID:27274305

  6. The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

    PubMed

    Babizhayev, Mark A; Strokov, Igor A; Nosikov, Valery V; Savel'yeva, Ekaterina L; Sitnikov, Vladimir F; Yegorov, Yegor E; Lankin, Vadim Z

    2015-04-01

    Diabetic neuropathy (DN) represents the main cause of morbidity and mortality among diabetic patients. Clinical data support the conclusion that the severity of DN is related to the frequency and duration of hyperglycemic periods. The presented experimental and clinical evidences propose that changes in cellular function resulting in oxidative stress act as a leading factor in the development and progression of DN. Hyperglycemia- and dyslipidemia-driven oxidative stress is a major contributor, enhanced by advanced glycation end product (AGE) formation and polyol pathway activation. There are several polymorphous pathways that lead to oxidative stress in the peripheral nervous system in chronic hyperglycemia. This article demonstrates the origin of oxidative stress derived from glycation reactions and genetic variations within the antioxidant genes which could be implicated in the pathogenesis of DN. In the diabetic state, unchecked superoxide accumulation and resultant increases in polyol pathway activity, AGEs accumulation, protein kinase C activity, and hexosamine flux trigger a feed-forward system of progressive cellular dysfunction. In nerve, this confluence of metabolic and vascular disturbances leads to impaired neural function and loss of neurotrophic support, and over the long term, can mediate apoptosis of neurons and Schwann cells, the glial cells of the peripheral nervous system. In this article, we consider AGE-mediated reactive oxygen species (ROS) generation as a pathogenesis factor in the development of DN. It is likely that oxidative modification of proteins and other biomolecules might be the consequence of local generation of superoxide on the interaction of the residues of L-lysine (and probably other amino acids) with α-ketoaldehydes. This phenomenon of non-enzymatic superoxide generation might be an element of autocatalytic intensification of pathophysiological action of carbonyl stress. Glyoxal and methylglyoxal formed during metabolic

  7. Genetic Vulnerability Interacts with Parenting and Early Care and Education to Predict Increasing Externalizing Behavior

    ERIC Educational Resources Information Center

    Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.

    2014-01-01

    The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental…

  8. Effect of chemical stress on germination of cv Dalia bean (Phaseolus vularis L.) as an alternative to increase antioxidant and nutraceutical compounds in sprouts.

    PubMed

    Mendoza-Sánchez, Magdalena; Guevara-González, Ramón G; Castaño-Tostado, Eduardo; Mercado-Silva, Edmundo M; Acosta-Gallegos, Jorge A; Rocha-Guzmán, Nuria E; Reynoso-Camacho, Rosalía

    2016-12-01

    The aim of this study was to determine the effect of chitosan (CH), salicylic acid (SA) and hydrogen peroxide (H2O2) at different concentrations on the antinutritional and nutraceutical content, as well as the antioxidant capacity of bean sprouts (cv Dalia). All elicitors at medium and high concentrations reduced the antinutritional content of lectins (48%), trypsin inhibitor (57%), amylase inhibitor (49%) and phytic acid (56%). Sprouts treated with CH, SA and H2O2 (7μM; 1 and 2mM, and 30mM respectively) increased the content of phenolic compounds (1.8-fold), total flavonoids (3-fold), saponins (1.8-fold) and antioxidant capacity (37%). Furthermore, the UPLC-ESI-MS/MS analysis showed an increase of several nutraceutical compounds in bean sprouts treated with SA such as coumaric (8.5-fold), salicylic (115-fold), gallic (25-fold) and caffeic (1.7-fold) acids, as well as epigallocatechin (63-fold), rutin (41-fold) and quercetin (16.6-fold) flavonoids. The application of elicitors in bean seed during sprouting enhances their nutraceutical properties. PMID:27374516

  9. Effects of Increasing Doses of UV-B on Main Phenolic Acids Content, Antioxidant Activity and Estimated Biomass in Lavandin (Lavandula x intermedia).

    PubMed

    Usano-Alemany, Jaime; Panjai, Lachinee

    2015-07-01

    Lavandin is a well-known aromatic plant cultivated mainly for its valuable essential oil. Nonetheless, little attention has been paid so far to the quantification of other natural products such as polyphenols. Accordingly, we examined the effect of increasing doses of UV-B radiation on the main phenolic content, antioxidant activity and estimated biomass of one year old lavandin pots compared with pots grown outdoors. Significantly higher total phenolic content and concentration of main polyphenols have been found in outdoor plants. Rosmarinic acid has been described as the major phenolic compound in methanolic extracts (max. 25.9 ± 9.7 mg/g(-1) DW). Furthermore, we found that increasing doses of UV-B promote the plant growth of this species as well as the accumulation of phenolic compounds although with less antioxidant capacity in scavenging DPPH radicals. On the other hand, our results showed a remarkable variability among individual plants regarding the content of major phenolic acids. The application of UV-B doses during plant growth could be a method to promote biomass in this species along with the promotion of higher content of valuable secondary metabolites. PMID:26411027

  10. Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer☆

    PubMed Central

    Makowski, Liza; Zhou, Chunxiao; Zhong, Yan; Kuan, Pei Fen; Fan, Cheng; Sampey, Brante P.; Difurio, Megan; Bae-Jump, Victoria L.

    2014-01-01

    Objectives Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer. Methods We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice. Results At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51 g versus 31 g, p = 0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7 cm2 versus 1.2 cm2, p = 0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways. PMID:24680597

  11. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    PubMed

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. PMID:23205714

  12. Brain Tumor Genetic Modification Yields Increased Resistance to Paclitaxel in Physical Confinement

    PubMed Central

    Bui, Loan; Hendricks, Alissa; Wright, Jamie; Chuong, Cheng-Jen; Davé, Digant; Bachoo, Robert; Kim, Young-tae

    2016-01-01

    Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII), and genetically modified mouse astrocytes (wild type, p53−/−, p53−/− PTEN−/−, p53−/− Braf, and p53−/− PTEN−/− Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration. PMID:27184621

  13. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability

    PubMed Central

    Greenbury, Sam F.; Schaper, Steffen; Ahnert, Sebastian E.; Louis, Ard A.

    2016-01-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps—a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure—to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  14. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  15. Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells.

    PubMed

    Vidyashankar, Satyakumar; Sharath Kumar, L M; Barooah, Vandana; Sandeep Varma, R; Nandakumar, Krishna S; Patki, Pralhad Sadashiv

    2012-10-15

    HepG2 cells were rendered steatotic by supplementing 2.0mM oleic acid (OA) in the culture media for 24h. OA induced hepatic steatosis in HepG2 cells was marked by significant accumulation of lipid droplets as determined by Oil-Red-O (ORO) based colorimetric assay, increased triacylglycerol (TAG) and increased lipid peroxidation. It was also marked by increased inflammatory cytokines TNF-α and IL-8 with decreased enzymic and non-enzymic antioxidant molecules and decreased cell proliferation associated with insulin resistance and DNA fragmentation. Addition of Liv.52 hydro-alcoholic extract (LHAE) 50μg/mL to the steatotic cells was effective in increasing the insulin mediated glucose uptake by 3.13 folds and increased cell proliferation by 3.81 folds with decreased TAG content (55%) and cytokines. The intracellular glutathione content was increased by 8.9 folds without substantial increase in GSSG content. LHAE decreased TNF-α and IL-8 by 51% and 6.5% folds respectively, lipid peroxidation by 65% and inhibited DNA fragmentation by 69%. The superoxide dismutase, catalase and glutathione peroxidase activities were increased by 88%, 128% and 64% respectively. Albumin and urea content was increased while the alanine aminotransferase (ALAT) activity was significantly decreased by LHAE. Hence, LHAE effectively attenuate molecular perturbations associated with non-alcoholic fatty liver disease (NAFLD) indications in HepG2 cells. PMID:22940028

  16. Genetic factors associated with population size may increase extinction risks and decrease colonization potential in a keystone tropical pine

    PubMed Central

    del Castillo, Rafael F; Trujillo-Argueta, Sonia; Sánchez-Vargas, Nahúm; Newton, Adrian C

    2011-01-01

    Pioneer species are essential for forest regeneration and ecosystem resilience. Pinus chiapensis is an endangered pioneer key species for tropical montane cloud forest regeneration in Mesoamerica. Human activities have severely reduced some P. chiapensis populations, which exhibited a small or null colonization potential suggesting the involvement of genetic factors associated with small populations. We explored the relationships between (i) population genetic diversity (allozymes) and population size, including sampling size effects, (ii) fitness estimates associated with colonization potential (seed viability and seedling performance) in a common environment and population size, and (iii) fitness estimates and observed heterozygosity in populations with sizes spanning five orders of magnitude. All the estimates of genetic diversity and fitness increased significantly with population size. Low fitness was detected in progenies of small populations of disturbed and undisturbed habitats. Progenies with the lowest observed heterozygosity displayed the lowest fitness estimates, which, in turn, increased with heterozygosity, but seed viability peaked at intermediate heterozygosity values suggesting inbreeding and outbreeding depression. Inbreeding depression appears to be the most immediate genetic factor in population decline. Conservation efforts should try to maintain large and genetically diverse populations, enhance gene flow by restoring connectivity between adjacent populations, and avoid genetically distant individuals. PMID:25568006

  17. Genetic diversity within honeybee colonies increases signal production by waggle-dancing foragers

    PubMed Central

    Mattila, Heather R; Burke, Kelly M; Seeley, Thomas D

    2008-01-01

    Recent work has demonstrated considerable benefits of intracolonial genetic diversity for the productivity of honeybee colonies: single-patriline colonies have depressed foraging rates, smaller food stores and slower weight gain relative to multiple-patriline colonies. We explored whether differences in the use of foraging-related communication behaviour (waggle dances and shaking signals) underlie differences in foraging effort of genetically diverse and genetically uniform colonies. We created three pairs of colonies; each pair had one colony headed by a multiply mated queen (inseminated by 15 drones) and one colony headed by a singly mated queen. For each pair, we monitored the production of foraging-related signals over the course of 3 days. Foragers in genetically diverse colonies had substantially more information available to them about food resources than foragers in uniform colonies. On average, in genetically diverse colonies compared with genetically uniform colonies, 36% more waggle dances were identified daily, dancers performed 62% more waggle runs per dance, foragers reported food discoveries that were farther from the nest and 91% more shaking signals were exchanged among workers each morning prior to foraging. Extreme polyandry by honeybee queens enhances the production of worker–worker communication signals that facilitate the swift discovery and exploitation of food resources. PMID:18198143

  18. Genetic diversity within honeybee colonies increases signal production by waggle-dancing foragers.

    PubMed

    Mattila, Heather R; Burke, Kelly M; Seeley, Thomas D

    2008-04-01

    Recent work has demonstrated considerable benefits of intracolonial genetic diversity for the productivity of honeybee colonies: single-patriline colonies have depressed foraging rates, smaller food stores and slower weight gain relative to multiple-patriline colonies. We explored whether differences in the use of foraging-related communication behaviour (waggle dances and shaking signals) underlie differences in foraging effort of genetically diverse and genetically uniform colonies. We created three pairs of colonies; each pair had one colony headed by a multiply mated queen (inseminated by 15 drones) and one colony headed by a singly mated queen. For each pair, we monitored the production of foraging-related signals over the course of 3 days. Foragers in genetically diverse colonies had substantially more information available to them about food resources than foragers in uniform colonies. On average, in genetically diverse colonies compared with genetically uniform colonies, 36% more waggle dances were identified daily, dancers performed 62% more waggle runs per dance, foragers reported food discoveries that were farther from the nest and 91% more shaking signals were exchanged among workers each morning prior to foraging. Extreme polyandry by honeybee queens enhances the production of worker-worker communication signals that facilitate the swift discovery and exploitation of food resources. PMID:18198143

  19. Riboflavin and vitamin E increase brain calcium and antioxidants, and microsomal calcium-ATP-ase values in rat headache models induced by glyceryl trinitrate.

    PubMed

    Bütün, Ayşe; Nazıroğlu, Mustafa; Demirci, Serpil; Çelik, Ömer; Uğuz, Abdulhadi Cihangir

    2015-04-01

    The essential use of riboflavin is the prevention of migraine headaches, although its effect on migraines is considered to be associated with the increased mitochondrial energy metabolism. Oxidative stress is also important in migraine pathophysiology. Vitamin E is a strong antioxidant in nature and its analgesic effect is not completely clear in migraines. The current study aimed to investigate the effects of glyceryl trinitrate (GTN)-sourced exogen nitric oxide (NO), in particular, and also riboflavin and/or vitamin E on involved in the headache model induced via GTN-sourced exogen NO on oxidative stress, total brain calcium levels, and microsomal membrane Ca(2+)-ATPase levels. GTN infusion is a reliable method to provoke migraine-like headaches in experimental animals and humans. GTN resulted in a significant increase in brain cortex and microsomal lipid peroxidation levels although brain calcium, vitamin A, vitamin C, and vitamin E, and brain microsomal-reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and plasma-membrane Ca(2+)-ATPase values decreased through GTN. The lipid peroxidation, GSH, vitamin A, β-carotene, vitamin C, and vitamin E, and calcium concentrations, GSH-Px, and the Ca(2+)-ATPase activities were increased both by riboflavin and vitamin E treatments. Brain calcium and vitamin A concentrations increased through riboflavin only. In conclusion, riboflavin and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system. However, the effects of vitamin E on the values seem more important than in riboflavin. PMID:25425044

  20. Changes in the fatty acid composition and regulation of antioxidant enzymes and physiology of juvenile genetically improved farmed tilapia Oreochromis niloticus (L.), subjected to short-term low temperature stress.

    PubMed

    He, J; Qiang, J; Yang, H; Xu, P; Zhu, Z X; Yang, R Q

    2015-10-01

    We evaluated the effect of cold shock on the fatty acid composition, antioxidant enzymes, and physiological responses of genetically improved farmed tilapia (GIFT). Experimental GIFT tilapia, a warm-water teleost, were initially acclimated at 28°C and then transferred directly to 13°C. Stress responses were monitored for 120h. There was a significant change in all parameters in response to the cold stressor (P<0.05). Serum cortisol levels increased from 336.93ng/ml to a peak of 1165.31ng/ml 24h after the initial cold shock, and declined rapidly thereafter. Serum glucose and cholesterol levels were significantly lower in the low temperature group than the control group at 120h (P<0.05). Acute low temperature stress enhanced superoxide dismutase, glutathione peroxidase, catalase, and glutathione levels in the liver of GIFT tilapia. The GIFT tilapia were able to selectively metabolize fatty acids for energy needs during the early period of exposure to low-temperature stress. During this time, they primarily used saturated fatty acids for energy. However as the duration of the stressor and loss of muscle fat increased, the fish began to metabolize long-chain polyunsaturated fatty acids. Increased malondialdehyde was produced by oxidation of these fatty acids leading to oxidative damage. Our results provide insight into the changes in fatty acid metabolism physiology that allow GIFT tilapia juveniles to adapt to short-term cold stress. PMID:26590460

  1. Low concentration of 4-hydroxy hexenal increases heme oxygenase-1 expression through activation of Nrf2 and antioxidative activity in vascular endothelial cells

    SciTech Connect

    Ishikado, Atsushi; Nishio, Yoshihiko; Morino, Katsutaro; Ugi, Satoshi; Kondo, Hajime; Makino, Taketoshi; Kashiwagi, Atsunori; Maegawa, Hiroshi

    2010-11-05

    Research highlights: {yields} Low doses of 4-HHE and 4-HNE induce HO-1 expression in vascular endothelial cells. {yields} 4-HHE and 4-HNE increase the intranuclear expression and DNA binding of Nrf2. {yields} 4-HHE and 4-HNE-induced HO-1 expression depends on the activation of Nrf2. {yields} Pretreatment with 4-HHE and 4-HNE prevents oxidative stress-induced cytotoxicity. -- Abstract: Large-scale clinical studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic and docosahexaenoic acids reduce cardiovascular events without improving classical risk factors for atherosclerosis. Recent studies have proposed that direct actions of n-3 PUFAs themselves, or of their enzymatic metabolites, have antioxidative and anti-inflammatory effects on vascular cells. Although a recent study showed that plasma 4-hydroxy hexenal (4-HHE), a peroxidation product of n-3 PUFA, increased after supplementation of docosahexaenoic acid, the antiatherogenic effects of 4-HHE in vascular cells remain unclear. In the present study, we tested the hypothesis that 4-HHE induces the antioxidative enzyme heme oxygenase-1 (HO-1) through activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulatory transcriptional factor, and prevents oxidative stress-induced cytotoxicity in vascular endothelial cells. This mechanism could partly explain the cardioprotective effects of n-3 PUFAs. Human umbilical vein endothelial cells were stimulated with 1-10 {mu}M 4-HHE or 4-hydroxy nonenal (4-HNE), a peroxidation product of n-6 PUFAs. Both 4-HHE and 4-HNE dose-dependently increased HO-1 mRNA and protein expression, and intranuclear expression and DNA binding of Nrf2 at 5 {mu}M. Small interfering RNA for Nrf2 significantly reduced 4-HHE- or 4-HNE-induced HO-1 mRNA and protein expression. Furthermore, pretreatment with 4-HHE or 4-HNE prevented tert-butyl hydroperoxide-induced cytotoxicity. In conclusion, 4-HHE, a peroxidation product of n-3 PUFAs, stimulated

  2. Reduced genetic diversity and increased reproductive isolation follow population-level loss of larval dispersal in a marine gastropod.

    PubMed

    Ellingson, Ryan A; Krug, Patrick J

    2016-01-01

    Population-level consequences of dispersal ability remain poorly understood, especially for marine animals in which dispersal is typically considered a species-level trait governed by oceanographic transport of microscopic larvae. Transitions from dispersive (planktotrophic) to nondispersive, aplanktonic larvae are predicted to reduce connectivity, genetic diversity within populations, and the spatial scale at which reproductive isolation evolves. However, larval dimorphism within a species is rare, precluding population-level tests. We show the sea slug Costasiella ocellifera expresses both larval morphs in Florida and the Caribbean, regions with divergent mitochondrial lineages. Planktotrophy predominated at 11 sites, 10 of which formed a highly connected and genetically diverse Caribbean metapopulation. Four populations expressed mainly aplanktonic development and had markedly reduced connectivity, and lower genetic diversity at one mitochondrial and six nuclear loci. Aplanktonic dams showed partial postzygotic isolation in most interpopulation crosses, regardless of genetic or geographic distance to the sire's source, suggesting that outbreeding depression affects fragmented populations. Dams from genetically isolated and neighboring populations also exhibited premating isolation, consistent with reinforcement contingent on historical interaction. By increasing self-recruitment and genetic drift, the loss of dispersal may thus initiate a feedback loop resulting in the evolution of reproductive isolation over small spatial scales in the sea. PMID:26635309

  3. Reduced Genetic Diversity and Increased Structure in American Mink on the Swedish Coast following Invasive Species Control.

    PubMed

    Zalewski, Andrzej; Zalewska, Hanna; Lunneryd, Sven-Gunnar; André, Carl; Mikusiński, Grzegorz

    2016-01-01

    Eradication and population reductions are often used to mitigate the negative impacts of non-native invasive species on native biodiversity. However, monitoring the effectiveness of non-native species control programmes is necessary to evaluate the efficacy of these measures. Genetic monitoring could provide valuable insights into temporal changes in demographic, ecological, and evolutionary processes in invasive populations being subject to control programmes. Such programmes should cause a decrease in effective population size and/or in genetic diversity of the targeted non-native species and an increase in population genetic structuring over time. We used microsatellite DNA data from American mink (Neovison vison) to determine whether the removal of this predator on the Koster Islands archipelago and the nearby Swedish mainland affected genetic variation over six consecutive years of mink culling by trappers as part of a population control programme. We found that on Koster Islands allelic richness decreased (from on average 4.53 to 3.55), genetic structuring increased, and effective population size did not change. In contrast, the mink population from the Swedish coast showed no changes in genetic diversity or structure, suggesting the stability of this population over 6 years of culling. Effective population size did not change over time but was higher on the coast than on the islands across all years. Migration rates from the islands to the coast were almost two times higher than from the coast to the islands. Most migrants leaving the coast were localised on the southern edge of the archipelago, as expected from the direction of the sea current between the two sites. Genetic monitoring provided valuable information on temporal changes in the population of American mink suggesting that this approach can be used to evaluate and improve control programmes of invasive vertebrates. PMID:27333328

  4. Reduced Genetic Diversity and Increased Structure in American Mink on the Swedish Coast following Invasive Species Control

    PubMed Central

    Zalewska, Hanna; Lunneryd, Sven-Gunnar; André, Carl; Mikusiński, Grzegorz

    2016-01-01

    Eradication and population reductions are often used to mitigate the negative impacts of non-native invasive species on native biodiversity. However, monitoring the effectiveness of non-native species control programmes is necessary to evaluate the efficacy of these measures. Genetic monitoring could provide valuable insights into temporal changes in demographic, ecological, and evolutionary processes in invasive populations being subject to control programmes. Such programmes should cause a decrease in effective population size and/or in genetic diversity of the targeted non-native species and an increase in population genetic structuring over time. We used microsatellite DNA data from American mink (Neovison vison) to determine whether the removal of this predator on the Koster Islands archipelago and the nearby Swedish mainland affected genetic variation over six consecutive years of mink culling by trappers as part of a population control programme. We found that on Koster Islands allelic richness decreased (from on average 4.53 to 3.55), genetic structuring increased, and effective population size did not change. In contrast, the mink population from the Swedish coast showed no changes in genetic diversity or structure, suggesting the stability of this population over 6 years of culling. Effective population size did not change over time but was higher on the coast than on the islands across all years. Migration rates from the islands to the coast were almost two times higher than from the coast to the islands. Most migrants leaving the coast were localised on the southern edge of the archipelago, as expected from the direction of the sea current between the two sites. Genetic monitoring provided valuable information on temporal changes in the population of American mink suggesting that this approach can be used to evaluate and improve control programmes of invasive vertebrates. PMID:27333328

  5. High-Pressure-Assisted Enzymatic Release of Peptides and Phenolics Increases Angiotensin Converting Enzyme I Inhibitory and Antioxidant Activities of Pinto Bean Hydrolysates.

    PubMed

    Garcia-Mora, Patricia; Peñas, Elena; Frias, Juana; Zieliński, Henryk; Wiczkowski, Wiesław; Zielińska, Danuta; Martínez-Villaluenga, Cristina

    2016-03-01

    Pinto bean protein concentrate was hydrolyzed by subtilisins at 0.1, 100, and 200 MPa and 50 °C for 15 min. Alcalase hydrolysis at 100 MPa led to higher ACE inhibition, reducing power, and free radical scavenging activity of hydrolysates. However, hydrolysate obtained by Savinase at 200 MPa showed the best ACE-inhibitory and radical scavenging activities. Proteolysis by Savinase at 200 MPa was considered the most effective treatment to increase small peptides (<3 kDa), flavonoids, total phenolic compounds, and oxygen radical absorbance capacity in hydrolysates. In this hydrolysate, small phaseolin fragments with reported ACE-inhibitory and antioxidant sequences were identified. Catechin, pelargonidin 3-glucoside, and ferulic acid were the main phenolic compounds. Hihg-pressure-assisted hydrolysis of common bean protein concentrates would provide benefits in the production of functional hydrolysates providing higher functionality and added value to the resulting hydrolysate due to synergistic effects of bioactive peptides and soluble phenolics. PMID:26857428

  6. Testing an 'aging gene' in long-lived drosophila strains: increased longevity depends on sex and genetic background.

    PubMed

    Spencer, Christine C; Howell, Christine E; Wright, Amber R; Promislow, Daniel E L

    2003-04-01

    Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived. However, the mutant's high-longevity phenotype may be dependent on interactions with alleles that are common in short-lived laboratory strains. Here we set out to determine whether one particular mutant could extend lifespan in long-lived genetic backgrounds in the fruit fly, Drosophila melanogaster. We measured longevity and resistance to thermal stress in flies that were transgenically altered to overexpress human superoxide dismutase (SOD) in the motorneurones in each of 10 genotypes. Each genotype carried the genetic background from a different naturally long-lived wild-caught Drosophila strain. While SOD increased lifespan on average, the effect was genotype- and sex-specific. Our results indicate that naturally segregating genes interact epistatically with the aging gene superoxide dismutase to modify its ability to extend longevity. This study points to the need to identify mutants that increase longevity not only in the lab strain of origin but also in naturally long-lived genetic backgrounds. PMID:12882325

  7. Genetic Ablation of Nrf2/Antioxidant Response Pathway in Alexander Disease Mice Reduces Hippocampal Gliosis but Does Not Impact Survival

    PubMed Central

    Hagemann, Tracy L.; Jobe, Emily M.; Messing, Albee

    2012-01-01

    In Alexander disease (AxD) the presence of mutant glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes, triggers protein aggregation, with marked induction of a stress response mediated by the transcription factor, Nrf2. To clarify the role of Nrf2 in AxD, we have crossed Gfap mutant and transgenic mouse models into an Nrf2 null background. Deletion of Nrf2 eliminates the phase II stress response normally present in mouse models of AxD, but causes no change in body weight or lifespan, even in a severe lethal model. AxD astrocytes without Nrf2 retain features of reactivity, such as expression of the endothelin-B receptor, but have lower Gfap levels, a decrease in p62 protein and reduced iron accumulation, particularly in hippocampus. Microglial activation, indicated by Iba1 expression, is also diminished. Although the Nrf2 response is generally considered beneficial, these results show that in the context of AxD, loss of the antioxidant pathway has no obvious negative effects, while actually decreasing Gfap accumulation and pathology. Given the attention Nrf2 is receiving as a potential therapeutic target in AxD and other neurodegenerative diseases, it will be interesting to see whether induction of Nrf2, beyond the endogenous response, is beneficial or not in these same models. PMID:22693571

  8. Increased Reliability Of Genetic Evaluations For Dairy Cattle In The United States From Use Of Genomic Information

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of genomic information increased reliability of genetic evaluations compared to parent averages by 28.4% for Holsteins, 20.7% for Jerseys and 12.8% for Brown Swiss when averaged across milk, fat and protein yields and three functional traits. Correlations of genomic predictions based on evaluati...

  9. A GENETIC MUTATION THAT REDUCES CALCIUM OXALATE CONTENT INCREASES CALCIUM AVAILABILITY IN MEDICAGO TRUNCATULA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalate is considered an antinutrient that renders calcium unavailable for nutritional absorption by humans. Efforts have been made to generate and identify edible plants with decreased levels of this antinutrient. The extent to which a food can be nutritionally improved through genetic alterations ...

  10. Catastrophic Floods May Pave the Way for Increased Genetic Diversity in Endemic Artesian Spring Snail Populations

    PubMed Central

    Worthington Wilmer, Jessica; Murray, Lynde; Elkin, Ché; Wilcox, Chris; Niejalke, Darren; Possingham, Hugh

    2011-01-01

    The role of disturbance in the promotion of biological heterogeneity is widely recognised and occurs at a variety of ecological and evolutionary scales. However, within species, the impact of disturbances that decimate populations are neither predicted nor known to result in conditions that promote genetic diversity. Directly examining the population genetic consequences of catastrophic disturbances however, is rarely possible, as it requires both longitudinal genetic data sets and serendipitous timing. Our long-term study of the endemic aquatic invertebrates of the artesian spring ecosystem of arid central Australia has presented such an opportunity. Here we show a catastrophic flood event, which caused a near total population crash in an aquatic snail species (Fonscochlea accepta) endemic to this ecosystem, may have led to enhanced levels of within species genetic diversity. Analyses of individuals sampled and genotyped from the same springs sampled both pre (1988–1990) and post (1995, 2002–2006) a devastating flood event in 1992, revealed significantly higher allelic richness, reduced temporal population structuring and greater effective population sizes in nearly all post flood populations. Our results suggest that the response of individual species to disturbance and severe population bottlenecks is likely to be highly idiosyncratic and may depend on both their ecology (whether they are resilient or resistant to disturbance) and the stability of the environmental conditions (i.e. frequency and intensity of disturbances) in which they have evolved. PMID:22205959

  11. A GENETIC MUTATION THAT REDUCES CALCIUM OXALATE CONTENT INCREASES CALCIUM AVAILABILITY IN MEDICAGO TRUNCATULA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxalate is considered an antinutrient that renders calcium unavailable for nutritional absorption by humans. Efforts have been made to generate and identify edible plants with decreased levels of this antinutrient. The extent to which a food can be nutritionally improved through genetic alteration...

  12. When invasion increases population genetic structure: A study with Centaurea diffusa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biological invasions offer excellent systems to study the evolutionary processes involved in introductions of species to new ranges. Molecular markers can reveal invasion histories and the effects of introductions on amounts and structuring of genetic variation. We used five polymorphic microsatelli...

  13. Antioxidants of Edible Mushrooms.

    PubMed

    Kozarski, Maja; Klaus, Anita; Jakovljevic, Dragica; Todorovic, Nina; Vunduk, Jovana; Petrović, Predrag; Niksic, Miomir; Vrvic, Miroslav M; van Griensven, Leo

    2015-01-01

    Oxidative stress caused by an imbalanced metabolism and an excess of reactive oxygen species (ROS) lead to a range of health disorders in humans. Our endogenous antioxidant defense mechanisms and our dietary intake of antioxidants potentially regulate our oxidative homeostasis. Numerous synthetic antioxidants can effectively improve defense mechanisms, but because of their adverse toxic effects under certain conditions, preference is given to natural compounds. Consequently, the requirements for natural, alternative sources of antioxidant foods identified in edible mushrooms, as well as the mechanistic action involved in their antioxidant properties, have increased rapidly. Chemical composition and antioxidant potential of mushrooms have been intensively studied. Edible mushrooms might be used directly in enhancement of antioxidant defenses through dietary supplementation to reduce the level of oxidative stress. Wild or cultivated, they have been related to significant antioxidant properties due to their bioactive compounds, such as polyphenols, polysaccharides, vitamins, carotenoids and minerals. Antioxidant and health benefits, observed in edible mushrooms, seem an additional reason for their traditional use as a popular delicacy food. This review discusses the consumption of edible mushrooms as a powerful instrument in maintaining health, longevity and life quality. PMID:26516828

  14. Postnatal exposure to chromium through mother’s milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes

    PubMed Central

    Stanley, Jone A.; Sivakumar, Kirthiram K.; Nithy, Thamizh K.; Arosh, Joe A.; Hoyer, Patricia B.; Burghardt, Robert C.; Banu, Sakhila K.

    2013-01-01

    Hexavalent chromium, CrVI, is a heavy metal endocrine disruptor, known as a mutagen, teratogen, and a group A carcinogen. Environmental contamination with CrVI, including drinking water, has been increasing in more than 30 cities in the United States. CrVI is rapidly converted to CrIII intracellularly, and CrIII can cause DNA strand breaks and cancer or apoptosis through different mechanisms. Our previous study demonstrated that lactational exposure to chromium results in a delay or arrest in follicle development and a decrease in steroid hormone levels in F1 female rats, both of which are mitigated (partial inhibition) by vitamin C. The current study tested the hypothesis that lactational exposure to CrIII accelerates follicle atresia in F1 offspring by increasing reactive oxygen species (ROS) and decreasing cellular antioxidants. Results showed that lactational exposure to CrIII dose-dependently increased follicular atresia and decreased steroidogenesis in postnatal day 25, 45, and 65 rats. Vitamin C mitigated or inhibited the effects of CrIII at all doses. CrIII increased hydrogen peroxide and lipid hydroperoxide in plasma and ovary; decreased the antioxidant enzymes (AOXs) GPx1, GR, SOD, and catalase; and increased glutathione S-transferase in plasma and ovary. To understand the effects of CrVI on ROS and AOXs in granulosa (GC) and theca (TC) cell compartments in the ovary, ROS levels and mRNA expression of cytosolic and mitochondrial AOXs, such as SOD1, SOD2, catalase, GLRX1, GSTM1, GSTM2, GSTA4, GR, TXN1, TXN2, TXNRD2, and PRDX3, were studied in GCs and TCs and in a spontaneously immortalized granulosa cell line (SIGC). Overall, CrVI downregulated each of the AOXs; and vitamin C mitigated the effects of CrVI on these enzymes in GCs and SIGCs, but failed to mitigate CrVI effects on GSTM1, GSTM2, TXN1, and TXN2 in TCs. Thus, these data for the first time reveal that lactational exposure to CrIII accelerated follicular atresia and decreased steroidogenesis in F1

  15. A genomewide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?

    PubMed Central

    Chaste, Pauline; Klei, Lambertus; Sanders, Stephan J.; Hus, Vanessa; Murtha, Michael T.; Lowe, Jennifer K.; Willsey, A. Jeremy; Moreno-De-Luca, Daniel; Yu, Timothy W.; Fombonne, Eric; Geschwind, Daniel; Grice, Dorothy E.; Ledbetter, David H.; Mane, Shrikant M.; Martin, Donna M.; Morrow, Eric M.; Walsh, Christopher A.; Sutcliffe, James S.; Martin, Christa Lese; Beaudet, Arthur L.; Lord, Catherine; State, Matthew W.; Cook, Edwin H.; Devlin, Bernie

    2014-01-01

    Background Phenotypic heterogeneity in autism has long been conjectured to be a major hindrance to the discovery of genetic risk factors, leading to numerous attempts to stratify children based on phenotype to increase power of discovery studies. This approach, however, is based on the hypothesis that phenotypic heterogeneity closely maps to genetic variation, which has not been tested. Our study examines the impact of sub-phenotyping of a well-characterized ASD sample on genetic homogeneity and the ability to discover common genetic variants conferring liability to ASD. Methods Genome-wide genotypic data of 2576 families from the Simons Simplex Collection (SSC) were analyzed in the overall sample and phenotypic subgroups defined on the basis of diagnosis, IQ, and symptom profiles. We conducted a family-based association study as well as estimating heritability and evaluating allele scores for each phenotypic subgroup. Results Association analyses revealed no genome-wide significant association signal. Sub-phenotyping did not increase power substantially. Moreover, allele scores built from the most associated SNPs, based on the odds ratio in the full sample, predicted case status in subsets of the sample equally well and heritability estimates were very similar for all subgroups. Conclusions In genome-wide association analysis of the SSC sample, reducing phenotypic heterogeneity had at most a modest impact on genetic homogeneity. Our results are based on a relatively small sample, one with greater homogeneity than the entire population; if they apply more broadly, they imply that analysis of sub-phenotypes is not a productive path forward for discovering genetic risk variants in ASD. PMID:25534755

  16. Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice

    PubMed Central

    Mowry, Annelise V.; Kavazis, Andreas N.; Sirman, Aubrey E.; Potts, Wayne K.; Hood, Wendy R.

    2016-01-01

    Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage. PMID:27537547

  17. Cyclodextrins and antioxidants.

    PubMed

    López-Nicolás, José Manuel; Rodríguez-Bonilla, Pilar; García-Carmona, Francisco

    2014-01-01

    In recent years, the growth of the functional foods industry has increased research into new compounds with high added value for use in the fortification of traditional products. One of the most promising functional food groups is those enriched in antioxidant compounds of a lipophilic nature. In spite of the numerous advantages reported for such antioxidant molecules, they may also have disadvantages that impede their use in functional foods, although these problems may well avoided by the use of encapsulant agents such as cyclodextrins. This explains the recent increase in the number of research papers dealing with the complexation of different guest molecules possesing important antioxidant properties using natural and modified cyclodextrins. This paper presents a review of the most recent studies on the complexes formed between several important types of antioxidant compounds and cyclodextrins, focusing on the contradictory data reported in the literature concerning to the antioxidant activity of the host/guest molecule complexes, the different complexation constants reported for identical complexes, the bioavailability of the antioxidant compound in the presence of cyclodextrins and recommendation concerning the use of natural or modified cyclodextrins. Moreover, the use of cyclodextrins as antibrowning agents to prevent enzymatic browning in different foods is revised. Finally, we look at studies which suggest that cyclodextrins act as ''secondary antioxidants," enhancing the ability of traditional antioxidants to prevent enzymatic browning. PMID:24188271

  18. An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis.

    PubMed

    Sanders, Lisa M; Henderson, Cara E; Hong, Mee Young; Barhoumi, Rola; Burghardt, Robert C; Wang, Naisyin; Spinka, Christine M; Carroll, Raymond J; Turner, Nancy D; Chapkin, Robert S; Lupton, Joanne R

    2004-12-01

    We showed previously that the dietary combination of fish oil, rich in (n-3) fatty acids, and the fermentable fiber pectin enhances colonocyte apoptosis in a rat model of experimentally induced colon cancer. In this study, we propose that the mechanism by which this dietary combination heightens apoptosis is via modulation of the colonocyte redox environment. Male Sprague-Dawley rats (n = 60) were fed 1 of 2 fats (corn oil or fish oil) and 1 of 2 fibers (cellulose or pectin) for 2 wk before determination of reactive oxygen species (ROS), oxidative DNA damage, antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] and apoptosis in isolated colonocytes. Fish oil enhanced ROS, whereas the combination of fish oil and pectin suppressed SOD and CAT and enhanced the SOD/CAT ratio compared with a corn oil and cellulose diet. Despite this modulation to a seemingly prooxidant environment, oxidative DNA damage was inversely related to ROS in the fish oil and pectin diet, and apoptosis was enhanced relative to other diets. Furthermore, apoptosis increased exponentially as ROS increased. These results suggest that the enhancement of apoptosis associated with fish oil and pectin feeding may be due to a modulation of the redox environment that promotes ROS-mediated apoptosis. PMID:15570018

  19. Smoking Cessation Is Followed by Increases in Serum Bilirubin, an Endogenous Antioxidant Associated With Lower Risk of Lung Cancer and Cardiovascular Disease

    PubMed Central

    Wu, Ran; Mayne, Susan T.; Jatlow, Peter I.

    2014-01-01

    Introduction: Lower concentrations of serum bilirubin, an endogenous antioxidant, have been associated with risk of many smoking-related diseases, including lung cancer and cardiovascular disease, and current smokers are reported to have lower bilirubin levels than nonsmokers and past smokers. This study evaluates the effects of smoking cessation on bilirubin levels. Methods: In a secondary analysis of a 6-week placebo-controlled trial of naltrexone for smoking cessation, indirect and total bilirubin concentrations were evaluated at baseline and following smoking cessation. Individuals who were continuously abstinent for 6 weeks (n = 155) were compared to those who were not (n = 193). Participants reported smoking ≥20 cigarettes daily at baseline and received smoking cessation counseling, 21mg nicotine patch daily, and either placebo or 1 of 3 doses of naltrexone (25, 50, or 100mg) for 6 weeks. Change in indirect and total bilirubin following the quit date was measured at Weeks 1, 4, and 6 compared to baseline. Results: Individuals who were continuously abstinent from smoking, independent of naltrexone condition, showed a significantly greater mean increase in indirect (~unconjugated) bilirubin (0.06mg/dl, SD = 0.165) compared to those who did not (mean = 0.02, SD = 0.148, p = .015). Similar results were obtained for total bilirubin (p = .037). Conclusions: Smoking cessation is followed by increases in bilirubin concentration that have been associated with lower risk of lung cancer and cardiovascular disease. PMID:24812024

  20. Isomerization and increase in the antioxidant properties of lycopene from Momordica cochinchinensis (gac) by moderate heat treatment with UV-Vis spectra as a marker.

    PubMed

    Phan-Thi, Hanh; Waché, Yves

    2014-08-01

    Momordica cochinchinensis (gac) is a plant rich in lycopene. This pigment tends to solubilize in oil and get damaged during extraction. The impact of heating on cis-isomerization of oil-free lycopene in hexane was studied at 50 and 80°C during 240min with UV-Vis spectrometry, DAD-HPLC and TEAC test. The initial all-trans-form isomerized to the 13-cis isomer more rapidly at 80°C. After this treatment, 16% of the lycopene compounds were in the 9-cis-form. This isomer triggered an increase in the antioxidant properties which was detectable from concentrations above 9% and resulted in a change from 2.4 to 3.7μmol Trolox equivalent. It is thus possible to increase the bioactivity of lycopene samples by controlling heating. The evolution of ratios calculated from the global UV-Vis spectrum was representative of cis-isomerization and spectrometry can thus be a simple way to evaluate the state of isomerization of lycopene solutions. PMID:24629938

  1. Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

    PubMed

    Usta, Julnar; Hachem, Yassmine; El-Rifai, Omar; Bou-Moughlabey, Yolla; Echtay, Karim; Griffiths, David; Nakkash-Chmaisse, Hania; Makki, Rajaa Fakhoury

    2013-02-01

    We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,β-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death. PMID:22940465

  2. Fibres from flax overproducing β-1,3-glucanase show increased accumulation of pectin and phenolics and thus higher antioxidant capacity

    PubMed Central

    2013-01-01

    Background Recently, in order to improve the resistance of flax plants to pathogen infection, transgenic flax that overproduces β-1,3-glucanase was created. β-1,3-glucanase is a PR protein that hydrolyses the β-glucans, which are a major component of the cell wall in many groups of fungi. For this study, we used fourth-generation field-cultivated plants of the Fusarium -resistant transgenic line B14 to evaluate how overexpression of the β-1,3-glucanase gene influences the quantity, quality and composition of flax fibres, which are the main product obtained from flax straw. Results Overproduction of β-1,3-glucanase did not affect the quantity of the fibre obtained from the flax straw and did not significantly alter the essential mechanical characteristics of the retted fibres. However, changes in the contents of the major components of the cell wall (cellulose, hemicellulose, pectin and lignin) were revealed. Overexpression of the β-1,3-glucanase gene resulted in higher cellulose, hemicellulose and pectin contents and a lower lignin content in the fibres. Increases in the uronic acid content in particular fractions (with the exception of the 1 M KOH-soluble fraction of hemicelluloses) and changes in the sugar composition of the cell wall were detected in the fibres of the transgenic flax when compared to the contents for the control plants. The callose content was lower in the fibres of the transgenic flax. Additionally, the analysis of phenolic compound contents in five fractions of the cell wall revealed important changes, which were reflected in the antioxidant potential of these fractions. Conclusion Overexpression of the β-1,3-glucanase gene has a significant influence on the biochemical composition of flax fibres. The constitutive overproduction of β-1,3-glucanase causes a decrease in the callose content, and the resulting excess glucose serves as a substrate for the production of other polysaccharides. The monosaccharide excess redirects the phenolic

  3. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  4. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  5. Supplementation of Superfine Powder Prepared from Chaenomeles speciosa Fruit Increases Endurance Capacity in Rats via Antioxidant and Nrf2/ARE Signaling Pathway

    PubMed Central

    Chen, Ka; You, Jia; Tang, Yong; Zhou, Yong; Liu, Peng; Zou, Dan; Zhou, Qicheng; Zhang, Ting; Zhu, Jundong; Mi, Mantian

    2014-01-01

    Chaenomeles speciosa fruit is a traditional herb medicine widely used in China. In this study, superfine powder of C. speciosa fruit (SCE), ground by supersonic nitrogen airflow at −140°C, was investigated to assess its in vitro antioxidant activity and in vivo antiphysical fatigue activity. SCE was homogenous (d < 10 μm) and rich in antioxidants like polyphenols, saponins, oleanolic acid, ursolic acid, ascorbic acid, and SOD. According to the in vitro experiments, SCE displayed promising antioxidant activity with powerful FARP, SC-DPPH, and SC-SAR activities. According to the in vivo experiments, rats supplemented with SCE had prolonged exhaustive swimming time (57%) compared to the nonsupplemented rats. Meanwhile, compared to the nonsupplemented rats, the SCE-supplemented rats had higher levels of blood glucose and liver and muscular glycogen and lower levels of LA and BUN. Lower MDA, higher antioxidant enzymes (SOD, CAT, and GSH-Px) activities, and upregulated Nrf2/ARE mediated antioxidant enzymes (HO-1, Trx, GCLM, and GCLC) expression were also detected in the supplemented group. This study indicates that SCE is a potent antioxidant and antifatigue agent, and SCE could be a promising raw material for the food and pharmaceutical industries. PMID:25610489

  6. Coffee intake can promote activity of antioxidant enzymes with increasing MDA level and decreasing HDL-cholesterol in physically trained rats

    PubMed Central

    Choi, Eun-Young; Jang, Jin-Young

    2010-01-01

    This study investigated the effect of coffee intake and exercise on the antioxidative activity and plasma cholesterol profile of physically trained rats while they were exercising. Forty eight rats were under either the control diet with water (C) or control diet with coffee (CF) and at the same time they were given physical training for 4 weeks. In terms of physical training, the rats were exercised on a treadmill for 30 minutes everyday. At the end of 4 weeks, animals in each dietary group were subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). Animals in the DE group were exercised on a treadmill for one hour, immediately before being sacrificed. Animals in the AE group were allowed to take a rest for one hour after exercise. TG levels were significantly high in coffee intake group than in control group. Also TG level of AE group was significantly higher than that of BE group. Exercise and coffee-exercise interaction effects were significant in total cholesterol (P = 0.0004, 0.0170). The AE of coffee intake group showed highest total cholesterol levels. HDL-cholesterol was significantly lower in coffee intake group than in control group. Coffee, exercise, and coffee-exercise interaction effects were significant in SOD (P = 0.0001, 0.0001, and 0.0001). The AE and BE of coffee intake group showed higher SOD levels than the other four groups. Catalase activities were significantly higher in coffee intake group than control group. No significant main effect was found in GSH/GSSG. Coffee, exercise, and coffee-exercise interaction effects were significant in MDA levels (P = 0.0464, 0.0016, and 0.0353). The DE and AE of coffee intake group and the DE of control group showed higher MDA levels than the BE of control group. Therefore, coffee intake can promote activities of antioxidant enzyme but it also increases MDA and decreases HDL-cholesterol in physically trained rats. PMID:20827343

  7. Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

    PubMed Central

    Nunes-Souza, Valéria; César-Gomes, Cheila Juliana; Da Fonseca, Lucas José Sá; Guedes, Glaucevane Da Silva; Smaniotto, Salete; Rabelo, Luíza Antas

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD. PMID:27057272

  8. Increased lead and cadmium tolerance of Typha angustifolia from Huaihe River is associated with enhanced phytochelatin synthesis and improved antioxidative capacity.

    PubMed

    Liu, Yunlei; Chen, Jian; Lu, Shaonan; Yang, Libo; Qian, Jiazhong; Cao, Shuqing

    2016-11-01

    Heavy metal contamination of water is an increasing environmental problem worldwide, and the use of aquatic plants for phytoremediation of heavy metal pollution has become an important subject of research. One key to successful phytoremediation is the identification of plants that are efficient at sequestering heavy metals. In this study, we examined the growth and heavy metal accumulation of Typha angustifolia and compared growth characteristics and tolerance mechanisms in plants from the Huaihe and Chaohu Rivers irrigated with different concentrations of lead (Pb) and cadmium (Cd). T. angustifolia from Huaihe River showed enhanced tolerance and accumulation of Pb and Cd and had greater biomass and more vigorous growth than the ecotype from Chaohu River. In addition, higher phytochelatin (PC) content and significantly higher superoxide dismutase and catalase activities were detected in T. angustifolia from Huaihe River than in T. angustifolia from Chaohu River. These findings suggest that high Pb and Cd accumulation and tolerance in T. angustifolia from Chaohu River is associated with its higher PC synthesis and better antioxidative capacity, and that the Huaihe ecotype of T. angustifolia might also be an efficient species for phytoremediation of Pb and Cd in water contaminated by heavy metals. PMID:26959972

  9. Fragmentation can increase spatial genetic structure without decreasing pollen-mediated gene flow in a wind-pollinated tree.

    PubMed

    Wang, Rong; Compton, Stephen G; Chen, Xiao-Yong

    2011-11-01

    Fragmentation reduces population sizes, increases isolation between habitats and can result in restricted dispersal of pollen and seeds. Given that diploid seed dispersal contributes more to shaping fine-scale spatial genetic structure (SGS) than haploid pollen flow, we tested whether fine-scale SGS can be sensitive to fragmentation even if extensive pollen dispersal is maintained. Castanopsis sclerophylla (Lindley & Paxton) Schottky (Fagaceae), a wind-pollinated and gravity seed-dispersed tree, was studied in an area of southeast China where its populations have been fragmented to varying extents by human activity. Using different age classes of trees in areas subject to varying extents of fragmentation, we found no significant difference in genetic diversity between prefragmentation vs. postfragmentation C. sclerophylla subpopulations. Genetic differentiation among postfragmentation subpopulations was also only slightly lower than among prefragmentation subpopulations. In the most fragmented habitat, selfing rates were significantly higher than zero in prefragmentation, but not postfragmentation, cohorts. These results suggest that fragmentation had not decreased gene flow among these populations and that pollen flow remains extensive. However, significantly greater fine-scale SGS was found in postfragmentation subpopulations in the most fragmented habitat, but not in less fragmented habitats. This alteration in SGS reflected more restricted seed dispersal, induced by changes in the physical environments and the prevention of secondary seed dispersal by rodents. An increase in SGS can therefore result from more restricted seed dispersal, even in the face of extensive pollen flow, making it a sensitive indicator of the negative consequences of population fragmentation. PMID:21981067

  10. A Genetic Mouse Model of Parkinson's Disease Shows Involuntary Movements and Increased Postsynaptic Sensitivity to Apomorphine.

    PubMed

    Brehm, N; Bez, F; Carlsson, T; Kern, B; Gispert, S; Auburger, G; Cenci, M A

    2015-12-01

    Alpha-synuclein (SNCA) protein aggregation plays a causal role in Parkinson's disease (PD). The SNCA protein modulates neurotransmission via the SNAP receptor (SNARE) complex assembly and presynaptic vesicle trafficking. The striatal presynaptic dopamine deficit is alleviated by treatment with levodopa (L-DOPA), but postsynaptic plastic changes induced by this treatment lead to a development of involuntary movements (dyskinesia). While this process is currently modeled in rodents harboring neurotoxin-induced lesions of the nigrostriatal pathway, we have here explored the postsynaptic supersensitivity of dopamine receptor-mediated signaling in a genetic mouse model of early PD. To this end, we used mice with prion promoter-driven overexpression of A53T-SNCA in the nigrostriatal and corticostriatal projections. At a symptomatic age (18 months), mice were challenged with apomorphine (5 mg/kg s.c.) and examined using both behavioral and molecular assays. After the administration of apomorphine, A53T-transgenic mice showed more severe stereotypic and dystonic movements in comparison with wild-type controls. Molecular markers of extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and dephosphorylation, and Fos messenger RNA (mRNA), were examined in striatal tissue at 30 and 100 min after apomorphine injection. At 30 min, wild-type and transgenic mice showed a similar induction of phosphorylated ERK1/2, Dusp1, and Dusp6 mRNA (two MAPK phosphatases). At the same time point, Fos mRNA was induced more strongly in mutant mice than in wild-type controls. At 100 min after apomorphine treatment, the induction of both Fos, Dusp1, and Dusp6 mRNA was significantly larger in mutant mice than wild-type controls. At this time point, apomorphine caused a reduction in phospho-ERK1/2 levels specifically in the transgenic mice. Our results document for the first time a disturbance of ERK1/2 signaling regulation associated with apomorphine-induced involuntary movements

  11. Antioxidant-induced modification of INrf2 cysteine 151 and PKC-δ-mediated phosphorylation of Nrf2 serine 40 are both required for stabilization and nuclear translocation of Nrf2 and increased drug resistance

    PubMed Central

    Niture, Suryakant K.; Jain, Abhinav K.; Jaiswal, Anil K.

    2009-01-01

    Summary Antioxidants cause dissociation of nuclear factor erythroid 2-related factor 2 (Nrf2) from inhibitor of Nrf2 (INrf2) and so Nrf2:INrf2 can serve as a sensor of oxidative stress. Nrf2 translocates to the nucleus, binds to antioxidant response element (ARE) and activates defensive gene expression, which protects cells. Controversies exist regarding the role of antioxidant-induced modification of INrf2 cysteine 151 or protein kinase C (PKC)-mediated phosphorylation of Nrf2 serine 40 in the release of Nrf2 from INrf2. In addition, the PKC isoform that phosphorylates Nrf2S40 remains unknown. Here, we demonstrate that antioxidant-induced PKC-δ-mediated phosphorylation of Nrf2S40 leads to release of Nrf2 from INrf2. This was evident from specific chemical inhibitors of PKC isoenzymes in reporter assays, in vitro kinase assays with purified Nrf2 and PKC isoenzymes, in vivo analysis with dominant-negative mutants and siRNA against PKC isoforms, use of PKC-δ+/+ and PKC-δ–/– cells, and use of Nrf2S40 phospho-specific antibody. The studies also showed that antioxidant-induced INrf2C151 modification was insufficient for the dissociation of Nrf2 from INrf2. PKC-δ-mediated Nrf2S40 phosphorylation was also required. Nrf2 and mutant Nrf2S40A both bind to INrf2. However, antioxidant treatment led to release of Nrf2 but not Nrf2S40A from INrf2. In addition, Nrf2 and mutant Nrf2S40A both failed to dissociate from mutant INrf2C151A. Furthermore, antioxidant-induced ubiquitylation of INrf2 in PKC-δ+/+ and PKC-δ–/– cells occurred, but Nrf2 failed to be released in PKC-δ–/– cells. The antioxidant activation of Nrf2 reduced etoposide-mediated DNA fragmentation and promoted cell survival in PKC-δ+/+ but not in PKC-δ–/– cells. These data together demonstrate that both modification of INrf2C151 and PKC-δ-mediated phosphorylation of Nrf2S40 play crucial roles in Nrf2 release from INrf2, antioxidant induction of defensive gene expression, promoting cell

  12. Increased Virulence in Sunflower Broomrape (Orobanche cumana Wallr.) Populations from Southern Spain Is Associated with Greater Genetic Diversity

    PubMed Central

    Martín-Sanz, Alberto; Malek, Jebri; Fernández-Martínez, José M.; Pérez-Vich, Begoña; Velasco, Leonardo

    2016-01-01

    Orobanche cumana Wallr. (sunflower broomrape) is a holoparasitic weed that infects roots of sunflower in large areas of Europe and Asia. Two distant O. cumana gene pools have been identified in Spain, one in Cuenca province in the Center and another one in the Guadalquivir Valley in the South. Race F has been hypothesized to have arisen by separate mutational events in both gene pools. In the Guadalquivir Valley, race F spread in the middle 1990’s to become predominant and contained so far with race F hybrids. Recently, enhanced virulent populations of O. cumana have been observed in commercial fields parasitizing race F resistant hybrids. From them, we collected four independent populations and conducted virulence and SSR marker-based genetic diversity analysis. Virulence essays confirmed that the four populations studied can parasitize most of the race F resistant hybrids tested, but they cannot parasitize the differential inbred lines DEB-2, carrying resistance to race F and G, and P-96, resistant to F but susceptible to races G from other countries. Accordingly, the new populations have been classified as race GGV to distinguish them from other races G. Cluster analysis with a set of populations from the two Spanish gene pools and from other areas, mainly Eastern Europe, confirmed that race GGV populations maintain close genetic relatedness with the Guadalquivir Valley gene pool. This suggested that increased virulence was not caused by new introductions from other countries. Genetic diversity parameters revealed that the four populations had much greater genetic diversity than conventional populations of the same area, containing only alleles present in the Guadalquivir Valley and Cuenca gene pools. The results suggested that increased virulence may have resulted from admixture of populations from the Guadalquivir Valley and Cuenca followed by recombination of avirulence genes. PMID:27200060

  13. Increased Virulence in Sunflower Broomrape (Orobanche cumana Wallr.) Populations from Southern Spain Is Associated with Greater Genetic Diversity.

    PubMed

    Martín-Sanz, Alberto; Malek, Jebri; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

    2016-01-01

    Orobanche cumana Wallr. (sunflower broomrape) is a holoparasitic weed that infects roots of sunflower in large areas of Europe and Asia. Two distant O. cumana gene pools have been identified in Spain, one in Cuenca province in the Center and another one in the Guadalquivir Valley in the South. Race F has been hypothesized to have arisen by separate mutational events in both gene pools. In the Guadalquivir Valley, race F spread in the middle 1990's to become predominant and contained so far with race F hybrids. Recently, enhanced virulent populations of O. cumana have been observed in commercial fields parasitizing race F resistant hybrids. From them, we collected four independent populations and conducted virulence and SSR marker-based genetic diversity analysis. Virulence essays confirmed that the four populations studied can parasitize most of the race F resistant hybrids tested, but they cannot parasitize the differential inbred lines DEB-2, carrying resistance to race F and G, and P-96, resistant to F but susceptible to races G from other countries. Accordingly, the new populations have been classified as race GGV to distinguish them from other races G. Cluster analysis with a set of populations from the two Spanish gene pools and from other areas, mainly Eastern Europe, confirmed that race GGV populations maintain close genetic relatedness with the Guadalquivir Valley gene pool. This suggested that increased virulence was not caused by new introductions from other countries. Genetic diversity parameters revealed that the four populations had much greater genetic diversity than conventional populations of the same area, containing only alleles present in the Guadalquivir Valley and Cuenca gene pools. The results suggested that increased virulence may have resulted from admixture of populations from the Guadalquivir Valley and Cuenca followed by recombination of avirulence genes. PMID:27200060

  14. DNA looping increases the range of bistability in a stochastic model of the lac genetic switch.

    PubMed

    Earnest, Tyler M; Roberts, Elijah; Assaf, Michael; Dahmen, Karin; Luthey-Schulten, Zaida

    2013-04-01

    Conditions and parameters affecting the range of bistability of the lac genetic switch in Escherichia coli are examined for a model which includes DNA looping interactions with the lac repressor and a lactose analogue. This stochastic gene-mRNA-protein model of the lac switch describes DNA looping using a third transcriptional state. We exploit the fast bursting dynamics of mRNA by combining a novel geometric burst extension with the finite state projection method. This limits the number of protein/mRNA states, allowing for an accelerated search of the model's parameter space. We evaluate how the addition of the third state changes the bistability properties of the model and find a critical region of parameter space where the phenotypic switching occurs in a range seen in single molecule fluorescence studies. Stochastic simulations show induction in the looping model is preceded by a rare complete dissociation of the loop followed by an immediate burst of mRNA rather than a slower build up of mRNA as in the two-state model. The overall effect of the looped state is to allow for faster switching times while at the same time further differentiating the uninduced and induced phenotypes. Furthermore, the kinetic parameters are consistent with free energies derived from thermodynamic studies suggesting that this minimal model of DNA looping could have a broader range of application. PMID:23406725

  15. DNA looping increases the range of bistability in a stochastic model of the lac genetic switch

    NASA Astrophysics Data System (ADS)

    Earnest, Tyler M.; Roberts, Elijah; Assaf, Michael; Dahmen, Karin; Luthey-Schulten, Zaida

    2013-04-01

    Conditions and parameters affecting the range of bistability of the lac genetic switch in Escherichia coli are examined for a model which includes DNA looping interactions with the lac repressor and a lactose analogue. This stochastic gene-mRNA-protein model of the lac switch describes DNA looping using a third transcriptional state. We exploit the fast bursting dynamics of mRNA by combining a novel geometric burst extension with the finite state projection method. This limits the number of protein/mRNA states, allowing for an accelerated search of the model's parameter space. We evaluate how the addition of the third state changes the bistability properties of the model and find a critical region of parameter space where the phenotypic switching occurs in a range seen in single molecule fluorescence studies. Stochastic simulations show induction in the looping model is preceded by a rare complete dissociation of the loop followed by an immediate burst of mRNA rather than a slower build up of mRNA as in the two-state model. The overall effect of the looped state is to allow for faster switching times while at the same time further differentiating the uninduced and induced phenotypes. Furthermore, the kinetic parameters are consistent with free energies derived from thermodynamic studies suggesting that this minimal model of DNA looping could have a broader range of application.

  16. Saikosaponin-D attenuates heat stress-induced oxidative damage in LLC-PK1 cells by increasing the expression of anti-oxidant enzymes and HSP72.

    PubMed

    Zhang, Bao-Zhen; Guo, Xiao-Tong; Chen, Jian-Wei; Zhao, Yuan; Cong, Xia; Jiang, Zhong-Ling; Cao, Rong-Feng; Cui, Kai; Gao, Shan-Song; Tian, Wen-Ru

    2014-01-01

    Heat stress stimulates the production of reactive oxygen species (ROS), which cause oxidative damage in the kidney. This study clarifies the mechanism by which saikosaponin-d (SSd), which is extracted from the roots of Bupleurum falcatum L, protects heat-stressed pig kidney proximal tubular (LLC-PK1) cells against oxidative damage. SSd alone is not cytotoxic at concentrations of 1 or 3 μg/mL as demonstrated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To assess the effects of SSd on heat stress-induced cellular damage, LLC-PK1 cells were pretreated with various concentrations of SSd, heat stressed at 42°C for 1 h, and then returned to 37°C for 9 h. DNA ladder and MTT assays demonstrated that SSd helped to prevent heat stress-induced cellular damage when compared to untreated cells. Additionally, pretreatment with SSd increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) but decreased the concentration of malondialdehyde (MDA) in a dose-dependent manner when compared to controls. Furthermore, real-time PCR and Western blot analysis demonstrated that SSd significantly increased the expression of copper and zinc superoxide dismutase (SOD-1), CAT, GPx-1 and heat shock protein 72 (HSP72) at both the mRNA and protein levels. In conclusion, these results are the first to demonstrate that SSd ameliorates heat stress-induced oxidative damage by modulating the activity of anti-oxidant enzymes and HSP72 in LLC-PK1 cells. PMID:25169909

  17. Supplementation with Japanese bunching onion (Allium fistulosum L.) expressing a single alien chromosome from shallot increases the antioxidant activity of Kamaboko fish jelly paste in vitro.

    PubMed

    Harada, Kazuki; Wada, Ritsuko; Yaguchi, Shigenori; Maeda, Toshimichi; Date, Rie; Tokunaga, Takushi; Kazumura, Kimiko; Shimada, Kazuko; Matsumoto, Misato; Wako, Tadayuki; Yamauchi, Naoki; Shigyo, Masayoshi

    2013-05-01

    Kamaboko is a traditional type of processed seafood made from fish jelly paste that is unique to Japan. We supplemented Kamaboko with Japanese bunching onion (Allium fistulosum L.) with an alien monosome from shallot (Allium cepa L. Aggregatum group) and we measured in vitro the oxygen radical absorbance capacity (ORAC) value, an index of antioxidant activity. We also evaluated the results of sensory testing. The ORAC value of plain Kamaboko was 166±14 μmol trolox equivalent (TE)/100 g fresh weight (FW). The values of the edible Alliaceae powder, i.e., Japanese bunching onion (JBO, genome FF, 2n=2x=16) and the alien addition line of JBO carrying the 6A chromosome from shallot (FF+6A, 2n=2x+1=17), were 6,659±238 and 14,096±635 μmol TE/100 g dry weight (DW). We hypothesized that the 6A chromosome encoded the enhancement of polyphenol production. Subsequently, we created Kamaboko containing 4.8% JBO powder or 4.8% FF+6A powder. The ORAC value of each modified Kamaboko product was increased to 376±24 μmol TE/100 g FW for the JBO powder and to 460±16 μmol TE/100 g FW for the FF+6A powder, respectively. We next created Kamaboko containing 9.0% JBO powder or 9.0% FF+6A powder and the ORAC values of the respective modified Kamaboko products was increased to 671±16 and 740±21 μmol TE/100 g FW, i.e., 4.1- and 4.5-times the value of plain Kamaboko. Consequently, taking into consideration the sensory evaluation regarding taste and appearance as well, the use of Kamaboko supplemented with 4.8% FF+6A powder is recommended. PMID:24648948

  18. Antioxidant measurements.

    PubMed

    Somogyi, Anikó; Rosta, Klára; Pusztai, Péter; Tulassay, Zsolt; Nagy, Géza

    2007-04-01

    Chemical reactions, including oxidation and reduction of molecules, occur in every cell. These reactions can lead to the production of free radicals. Free radicals react with organic substrates such as lipids, proteins, and DNA. Through oxidation free radicals cause damage to these molecules, disturbing their normal function, and may therefore contribute to a variety of diseases. The anti-oxidation system, which consists of enzymatic antioxidants and non-enzymatic antioxidants, defends against oxidative stress. The aim of this review is to summarize general aspects of methods to measure the antioxidant defence system all in one (total antioxidant capacity) and discuss a number of methods which are currently used for detection of antioxidant properties. PMID:17395989

  19. Natural antioxidants.

    PubMed

    Berson, Diane S

    2008-07-01

    The constant exposure of the skin to oxidative stress results in damage to cellular DNA and cell membrane lipids and proteins. To combat this problem, the skin contains a number of antioxidants that protect against oxidative injury. However, these cutaneous antioxidants can be depleted by sun exposure and environmental insults, resulting in an overload of oxidation products. Thus, topical antioxidants that replenish the antioxidant capacity of the skin have the potential to prevent oxidative damage. A number of natural antioxidant ingredients also have anti-inflammatory properties, and can be used in the treatment of oxidative damage such as photoaging and perhaps even skin cancer. This article summarizes the active components, pharmacologic properties, and clinical effectiveness of a number of natural antioxidant ingredients including soy, feverfew, mushroom extracts, teas, Coffea arabica (CoffeeBerry), Pinus pinaster (Pycnogenol), and Polypodium leucotomos. Recent clinical trials suggest that these compounds have promising efficacy in the topical treatment of oxidative stress-induced dermatoses. PMID:18681153

  20. Genetic deletion of trkB.T1 increases neuromuscular function

    PubMed Central

    Dorsey, Susan G.; Lovering, Richard M.; Renn, Cynthia L.; Leitch, Carmen C.; Liu, Xinyue; Tallon, Luke J.; Sadzewicz, Lisa DeShong; Pratap, Abhishek; Ott, Sandra; Sengamalay, Naomi; Jones, Kristie M.; Barrick, Colleen; Fulgenzi, Gianluca; Becker, Jodi; Voelker, Kevin; Talmadge, Robert; Harvey, Brandon K.; Wyatt, Ryan M.; Vernon-Pitts, Elizabeth; Zhang, Chao; Shokat, Kevan; Fraser-Liggett, Claire; Balice-Gordon, Rita J.; Tessarollo, Lino

    2012-01-01

    Neurotrophin-dependent activation of the tyrosine kinase receptor trkB.FL modulates neuromuscular synapse maintenance and function; however, it is unclear what role the alternative splice variant, truncated trkB (trkB.T1), may have in the peripheral neuromuscular axis. We examined this question in trkB.T1 null mice and demonstrate that in vivo neuromuscular performance and nerve-evoked muscle tension are significantly increased. In vitro assays indicated that the gain-in-function in trkB.T1−/− animals resulted specifically from an increased muscle contractility, and increased electrically evoked calcium release. In the trkB.T1 null muscle, we identified an increase in Akt activation in resting muscle as well as a significant increase in trkB.FL and Akt activation in response to contractile activity. On the basis of these findings, we conclude that the trkB signaling pathway might represent a novel target for intervention across diseases characterized by deficits in neuromuscular function. PMID:21865582

  1. Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

    PubMed

    Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

    2016-03-01

    A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. PMID:26964713

  2. Developmentally dynamic genome: Evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence

    PubMed Central

    Pingault, Jean-Baptiste; Rijsdijk, Frühling; Zheng, Yao; Plomin, Robert; Viding, Essi

    2015-01-01

    The development of conduct problems in childhood and adolescence is associated with adverse long-term outcomes, including psychiatric morbidity. Although genes constitute a proven factor of stability in conduct problems, less is known regarding their role in conduct problems’ developmental course (i.e. systematic age changes, for instance linear increases or decreases).Mothers rated conduct problems from age 4 to 16 years in 10,038 twin pairs from the Twins Early Development Study. Individual differences in the baseline level (.78; 95% CI: .68-.88) and the developmental course of conduct problems (.73; 95% CI: .60-.86) were under high and largely independent additive genetic influences. Shared environment made a small contribution to the baseline level but not to the developmental course of conduct problems. These results show that genetic influences not only contribute to behavioural stability but also explain systematic change in conduct problems. Different sets of genes may be associated with the developmental course versus the baseline level of conduct problems. The structure of genetic and environmental influences on the development of conduct problems suggests that repeated preventive interventions at different developmental stages might be necessary to achieve a long-term impact. PMID:25944445

  3. Genetic ablation and short-duration inhibition of lipoxygenase results in increased macroautophagy

    SciTech Connect

    Jang, Insook; Park, Sujin; Cho, Jin Won; Yigitkanli, Kazim; Leyen, Klaus van; Roth, Jürgen

    2014-02-15

    12/15-lipoxygenase (12/15-LOX) is involved in organelle homeostasis by degrading mitochondria in maturing red blood cells and by eliminating excess peroxisomes in liver. Furthermore, 12/15-LOX contributes to diseases by exacerbating oxidative stress-related injury, notably in stroke. Nonetheless, it is unclear what the consequences are of abolishing 12/15-LOX activity. Mice in which the alox15 gene has been ablated do not show an obvious phenotype, and LOX enzyme inhibition is not overtly detrimental. We show here that liver histology is also unremarkable. However, electron microscopy demonstrated that 12/15-LOX knockout surprisingly leads to increased macroautophagy in the liver. Not only macroautophagy but also mitophagy and pexophagy were increased in hepatocytes, which otherwise showed unaltered fine structure and organelle morphology. These findings were substantiated by immunofluorescence showing significantly increased number of LC3 puncta and by Western blotting demonstrating a significant increase for LC3-II protein in both liver and brain homogenates of 12/15-LOX knockout mice. Inhibition of 12/15-LOX activity by treatment with four structurally different inhibitors had similar effects in cultured HepG2 hepatoma cells and SH-SY5Y neuroblastoma cells with significantly increased autophagy discernable already after 2 hours. Hence, our study reveals a link between ablation or inhibition of 12/15-LOX and stimulation of macroautophagy. The enhanced macroautophagy may be related to the known tissue-protective effects of LOX ablation or inhibition under various diseased conditions caused by oxidative stress and ischemia. This could provide an important cleaning mechanism of cells and tissues to prevent accumulation of damaged mitochondria and other cellular components. - Highlights: • A relationship between lipoxygenases and autophagy is disclosed. • 12/15-lipoxygenase knockout increases autophagy in mice liver and brain. • Lipoxygenase inhibition boosts

  4. The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome

    PubMed Central

    Sailani, M. Reza; Makrythanasis, Periklis; Valsesia, Armand; Santoni, Federico A.; Deutsch, Samuel; Popadin, Konstantin; Borel, Christelle; Migliavacca, Eugenia; Sharp, Andrew J.; Duriaux Sail, Genevieve; Falconnet, Emilie; Rabionet, Kelly; Serra-Juhé, Clara; Vicari, Stefano; Laux, Daniela; Grattau, Yann; Dembour, Guy; Megarbane, Andre; Touraine, Renaud; Stora, Samantha; Kitsiou, Sofia; Fryssira, Helena; Chatzisevastou-Loukidou, Chariklia; Kanavakis, Emmanouel; Merla, Giuseppe; Bonnet, Damien; Pérez-Jurado, Luis A.; Estivill, Xavier; Delabar, Jean M.; Antonarakis, Stylianos E.

    2013-01-01

    Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk. Here we report genomic variations that in concert with trisomy 21, determine the risk for CHD in DS. This case-control GWAS includes 187 DS with CHD (AVSD = 69, ASD = 53, VSD = 65) as cases, and 151 DS without CHD as controls. Chromosome 21–specific association studies revealed rs2832616 and rs1943950 as CHD risk alleles (adjusted genotypic P-values <0.05). These signals were confirmed in a replication cohort of 92 DS-CHD cases and 80 DS-without CHD (nominal P-value 0.0022). Furthermore, CNV analyses using a customized chromosome 21 aCGH of 135K probes in 55 DS-AVSD and 53 DS-without CHD revealed three CNV regions associated with AVSD risk (FDR ≤ 0.05). Two of these regions that are located within the previously identified CHD region on chromosome 21 were further confirmed in a replication study of 49 DS-AVSD and 45 DS- without CHD (FDR ≤ 0.05). One of these CNVs maps near the RIPK4 gene, and the second includes the ZBTB21 (previously ZNF295) gene, highlighting the potential role of these genes in the pathogenesis of CHD in DS. We propose that the genetic architecture of the CHD risk of DS is complex and includes trisomy 21, and SNP and CNV variations in chromosome 21. In addition, a yet-unidentified genetic variation in the rest of the genome may contribute to this complex genetic architecture. PMID:23783273

  5. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation?

    PubMed Central

    Buhner, S; Buning, C; Genschel, J; Kling, K; Herrmann, D; Dignass, A; Kuechler, I; Krueger, S; Schmidt, H H‐J; Lochs, H

    2006-01-01

    Background and aim A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. Methods We studied 128 patients with quiescent CD, 129 first degree relatives (CD‐R), 66 non‐related household members (CD‐NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. Results Intestinal permeability was significantly increased in CD and CD‐R groups compared with CD‐NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD‐R but only in 6% of CD‐NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD‐R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild‐types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. Conclusions In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD. PMID:16000642

  6. Mixed Compound of DCPTA and CCC Increases Maize Yield by Improving Plant Morphology and Up-Regulating Photosynthetic Capacity and Antioxidants

    PubMed Central

    Wang, Yongchao; Gu, Wanrong; Xie, Tenglong; Li, Lijie; Sun, Yang; Zhang, He; Li, Jing; Wei, Shi

    2016-01-01

    DCPTA (2-diethylaminoethyl-3, 4-dichlorophenylether) and CCC (2-chloroethyltrimethyl- ammonium chloride) have a great effect on maize growth, but applying DCPTA individually can promote the increase of plant height, resulting in the rise of lodging percent. Plant height and lodging percent decrease in CCC-treated plants, but the accumulation of biomass reduce, resulting in yield decrease. Based on the former experiments, the performance of a mixture which contained 40 mg DCPTA and 20 mg CCC as active ingredients per liter of solution, called PCH was tested with applying 40mg/L DCPTA and 20mg/L CCC individually. Grain yield, yield components, internode characters, leaf area per plant, plant height and lodging percent as well as chlorophyll content, chlorophyll fluorescence, enzymatic antioxidants, membranous peroxide and organic osmolyte were analyzed in two years (2011 and 2012), using maize hybrid, Zhengdan 958 (ZD 958) at density of 6.75 plants m-2. CCC, DCPTA and PCH were sprayed on the whole plant leaves at 7 expanded leaves stage and water was used as control. Compared to control, PCH significantly increased grain yield (by 9.53% and 6.68%) from 2011 to 2012. CCC significantly decreased kernel number per ear (by 6.78% and 5.69%) and thousand kernel weight (TKW) (by 8.57% and 6.55%) from 2011 to 2012. Kernel number per ear and TKW increased in DCPTA-treated and PCH-treated plants, but showed no significant difference between them. In CCC-treated and PCH-treated plants, internode length and plant height decreased, internode diameter increased, resulting in the significant decline of lodging percent. With DCPTA application, internode diameter increased, but internode length and plant height increased at the same time, resulting in the augment of lodging percent. Bending strength and puncture strength were increased by applying different plant growth regulators (PGRs). In PCH-treated plants, bending strength and puncture strength were greater than other treatments

  7. Mixed Compound of DCPTA and CCC Increases Maize Yield by Improving Plant Morphology and Up-Regulating Photosynthetic Capacity and Antioxidants.

    PubMed

    Wang, Yongchao; Gu, Wanrong; Xie, Tenglong; Li, Lijie; Sun, Yang; Zhang, He; Li, Jing; Wei, Shi

    2016-01-01

    DCPTA (2-diethylaminoethyl-3, 4-dichlorophenylether) and CCC (2-chloroethyltrimethyl- ammonium chloride) have a great effect on maize growth, but applying DCPTA individually can promote the increase of plant height, resulting in the rise of lodging percent. Plant height and lodging percent decrease in CCC-treated plants, but the accumulation of biomass reduce, resulting in yield decrease. Based on the former experiments, the performance of a mixture which contained 40 mg DCPTA and 20 mg CCC as active ingredients per liter of solution, called PCH was tested with applying 40mg/L DCPTA and 20mg/L CCC individually. Grain yield, yield components, internode characters, leaf area per plant, plant height and lodging percent as well as chlorophyll content, chlorophyll fluorescence, enzymatic antioxidants, membranous peroxide and organic osmolyte were analyzed in two years (2011 and 2012), using maize hybrid, Zhengdan 958 (ZD 958) at density of 6.75 plants m-2. CCC, DCPTA and PCH were sprayed on the whole plant leaves at 7 expanded leaves stage and water was used as control. Compared to control, PCH significantly increased grain yield (by 9.53% and 6.68%) from 2011 to 2012. CCC significantly decreased kernel number per ear (by 6.78% and 5.69%) and thousand kernel weight (TKW) (by 8.57% and 6.55%) from 2011 to 2012. Kernel number per ear and TKW increased in DCPTA-treated and PCH-treated plants, but showed no significant difference between them. In CCC-treated and PCH-treated plants, internode length and plant height decreased, internode diameter increased, resulting in the significant decline of lodging percent. With DCPTA application, internode diameter increased, but internode length and plant height increased at the same time, resulting in the augment of lodging percent. Bending strength and puncture strength were increased by applying different plant growth regulators (PGRs). In PCH-treated plants, bending strength and puncture strength were greater than other treatments

  8. Antioxidants in Translational Medicine

    PubMed Central

    Schmidt, Harald H.H.W.; Stocker, Roland; Vollbracht, Claudia; Paulsen, Gøran; Riley, Dennis

    2015-01-01

    Abstract Significance: It is generally accepted that reactive oxygen species (ROS) scavenging molecules or antioxidants exert health-promoting effects and thus their consumption as food additives and nutraceuticals has been greatly encouraged. Antioxidants may be beneficial in situations of subclinical deficiency and increased demand or acutely upon high-dose infusion. However, to date, there is little clinical evidence for the long-term benefit of most antioxidants. Alarmingly, recent evidence points even to health risks, in particular for supplements of lipophilic antioxidants. Recent Advances: The biological impact of ROS depends not only on their quantities but also on their chemical nature, (sub)cellular and tissue location, and the rates of their formation and degradation. Moreover, ROS serve important physiological functions; thus, inappropriate removal of ROS may cause paradoxical reductive stress and thereby induce or promote disease. Critical Issues: Any recommendation on antioxidants must be based on solid clinical evidence and patient-relevant outcomes rather than surrogate parameters. Future Directions: Such evidence-based use may include site-directed application, time-limited high dosing, (functional) pharmacological repair of oxidized biomolecules, and triggers of endogenous antioxidant response systems. Ideally, these approaches need guidance by patient stratification through predictive biomarkers and possibly imaging modalities. Antioxid. Redox Signal. 23, 1130–1143. PMID:26154592

  9. Selection for increased desiccation resistance in Drosophila melanogaster: Additive genetic control and correlated responses for other stresses

    SciTech Connect

    Hoffmann, A.A.; Parsons, P.A. )

    1989-08-01

    Previously we found that Drosophila melanogaster lines selected for increased desiccation resistance have lowered metabolic rate and behavioral activity levels, and show correlated responses for resistance to starvation and a toxic ethanol level. These results were consistent with a prediction that increased resistance to many environmental stresses may be genetically correlated because of a reduction in metabolic energy expenditure. Here we present experiments on the genetic basis of the selection response and extend the study of correlated responses to other stresses. The response to selection was not sex-specific and involved X-linked and autosomal genes acting additively. Activity differences contributed little to differences in desiccation resistance between selected and control lines. Selected lines had lower metabolic rates than controls in darkness when activity was inhibited. Adults from selected lines showed increased resistance to a heat shock, {sup 60}Co-gamma-radiation, and acute ethanol and acetic acid stress. The desiccation, ethanol and starvation resistance of isofemale lines set up from the F2s of a cross between one of the selected and one of the control lines were correlated. Selected and control lines did not differ in ether-extractable lipid content or in resistance to acetone, ether or a cold shock.

  10. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

    PubMed

    Parlanti, Eleonora; Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara; Zijno, Andrea; D'Errico, Mariarosaria; Simonelli, Valeria; Sanchez, Massimo; Fattibene, Paola; Falchi, Mario; Dogliotti, Eugenia

    2015-12-01

    Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O₂₋• and H₂O₂ being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine. PMID:26546826

  11. Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.

    PubMed

    Choudhary, Dharmendra; Pandey, Ashutosh; Adhikary, Sulekha; Ahmad, Naseer; Bhatia, Chitra; Bhambhani, Sweta; Trivedi, Prabodh Kumar; Trivedi, Ritu

    2016-01-01

    Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence. PMID:26917158

  12. Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals

    PubMed Central

    Choudhary, Dharmendra; Pandey, Ashutosh; Adhikary, Sulekha; Ahmad, Naseer; Bhatia, Chitra; Bhambhani, Sweta; Trivedi, Prabodh Kumar; Trivedi, Ritu

    2016-01-01

    Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence. PMID:26917158

  13. MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity.

    PubMed

    Chen, Yi-Fen; Yang, Cheng-Chieh; Kao, Shou-Yen; Liu, Chung-Ji; Lin, Shu-Chun; Chang, Kuo-Wei

    2016-08-15

    miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872-86. ©2016 AACR. PMID:27221705

  14. Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

    PubMed Central

    Zaruma-Torres, Fausto; Lares-Asseff, Ismael; Lima, Aurea; Reyes-Espinoza, Aarón; Loera-Castañeda, Verónica; Sosa-Macías, Martha; Galaviz-Hernández, Carlos; Arias-Peláez, María C.; Reyes-López, Miguel A.; Quiñones, Luis A.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11–5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62–78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42–191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94–31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05–6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19–31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children. PMID:27547186

  15. Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children.

    PubMed

    Zaruma-Torres, Fausto; Lares-Asseff, Ismael; Lima, Aurea; Reyes-Espinoza, Aarón; Loera-Castañeda, Verónica; Sosa-Macías, Martha; Galaviz-Hernández, Carlos; Arias-Peláez, María C; Reyes-López, Miguel A; Quiñones, Luis A

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11-5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62-78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42-191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94-31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05-6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19-31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children. PMID:27547186

  16. A yeast-based genetic screening to identify human proteins that increase homologous recombination.

    PubMed

    Collavoli, Anita; Comelli, Laura; Rainaldi, Giuseppe; Galli, Alvaro

    2008-05-01

    To identify new human proteins implicated in homologous recombination (HR), we set up 'a papillae assay' to screen a human cDNA library using the RS112 strain of Saccharomyces cerevisiae containing an intrachromosomal recombination substrate. We isolated 23 cDNAs, 11 coding for complete proteins and 12 for partially deleted proteins that increased HR when overexpressed in yeast. We characterized the effect induced by the overexpression of the complete human proteasome subunit beta 2, the partially deleted proteasome subunits alpha 3 and beta 8, the ribosomal protein L12, the brain abundant membrane signal protein (BASP1) and the human homologue to v-Ha-RAS (HRAS), which elevated HR by 2-6.5-fold over the control. We found that deletion of the RAD52 gene, which has a key role in most HR events, abolished the increase of HR induced by the proteasome subunits and HRAS; by contrast, the RAD52 deletion did not affect the high level of HR due to BASP1 and RPL12. This suggests that the proteins stimulated yeast HR via different mechanisms. Overexpression of the complete beta 2 human proteasome subunit or the partially deleted alpha 3 and beta 8 subunits increased methyl methanesulphonate (MMS) resistance much more in the rad52 Delta mutant than in the wild-type. Overexpression of RPL12 and BASP1 did not affect MMS resistance in both the wild-type and the rad52 Delta mutant, whereas HRAS decreased MMS resistance in the rad52 Delta mutant. The results indicate that these proteins may interfere with the pathway(s) involved in the repair of MMS-induced DNA damage. Finally, we provide further evidence that yeast is a helpful tool to identify human proteins that may have a regulatory role in HR. PMID:18248415

  17. Genetic Changes Accompanying Increased Fitness in Evolving Populations of Escherichia Coli

    PubMed Central

    Modi, R. I.; Castilla, L. H.; Puskas-Rozsa, S.; Helling, R. B.; Adams, J.

    1992-01-01

    Two populations of Escherichia coli, each initiated with a single clone containing a derivative of the plasmid pBR322, were maintained for long periods in glucose-limited continuous culture. In both populations, after an extensive number of generations had elapsed, clones were isolated in which the transposon Tn3 from the plasmid had integrated into the bacterial chromosome. In both cases examined, the transpositions were shown to increase relative fitness approximately 6-7%, in the environment in which the populations were maintained. The loci of integration were mapped to ~13.2 min (population 1) and ~32.8 min (population 2). PMID:1311694

  18. New evidence of genetic factors influencing sexual orientation in men: female fecundity increase in the maternal line.

    PubMed

    Iemmola, Francesca; Camperio Ciani, Andrea

    2009-06-01

    There is a long-standing debate on the role of genetic factors influencing homosexuality because the presence of these factors contradicts the Darwinian prediction according to which natural selection should progressively eliminate the factors that reduce individual fecundity and fitness. Recently, however, Camperio Ciani, Corna, and Capiluppi (Proceedings of the Royal Society of London, Series B: Biological Sciences, 271, 2217-2221, 2004), comparing the family trees of homosexuals with heterosexuals, reported a significant increase in fecundity in the females related to the homosexual probands from the maternal line but not in those related from the paternal one. This suggested that genetic factors that are partly linked to the X-chromosome and that influence homosexual orientation in males are not selected against because they increase fecundity in female carriers, thus offering a solution to the Darwinian paradox and an explanation of why natural selection does not progressively eliminate homosexuals. Since then, new data have emerged suggesting not only an increase in maternal fecundity but also larger paternal family sizes for homosexuals. These results are partly conflicting and indicate the need for a replication on a wider sample with a larger geographic distribution. This study examined the family trees of 250 male probands, of which 152 were homosexuals. The results confirmed the study of Camperio Ciani et al. (2004). We observed a significant fecundity increase even in primiparous mothers, which was not evident in the previous study. No evidence of increased paternal fecundity was found; thus, our data confirmed a sexually antagonistic inheritance partly linked to the X-chromosome that promotes fecundity in females and a homosexual sexual orientation in males. PMID:18561014

  19. Topical Substance P Increases Inflammatory Cell Density in Genetically Diabetic Murine Wounds

    PubMed Central

    Scott, Jeffrey R; Tamura, Richard N.; Muangman, Pornprom; Isik, F. Frank; Xie, Chengyu; Gibran, Nicole S.

    2008-01-01

    The neuropeptide substance P (SP) is a known inflammatory mediator released from cutaneous peripheral nerve terminals. SP effects on cellular composition in the cutaneous response to injury remain unclear. Based on our previous observations about SP effects on wound repair, we hypothesized that topical SP increases inflammatory cell density infiltration early after injury. A full thickness 1.5×1.5 cm-square wound was created on the dorsum of 8–9 wk old C57BL/6J-m+Leprdb mice (db/db). Wounds were treated daily with 300μl of either normal saline (0.9% NaCl) or 10−9M SP for seven days. Three wounds from each group were harvested at 2,3,7,14, and 28 days. Samples underwent enzymatic digestion and were incubated with fluorescent-labeled antibodies. Using flow cytometry, cellular content and density for each sample was derived. Masson Trichrome stained histology specimens were prepared to confirm results. Cell density in the SP-treated wounds (11.3×107 cells/gram tissue, SD +/−1.5×107) was greater than in NaCl-treated wounds (7×107 cells/gram tissue, SD +/−2.3×107, p<.05) at day 7 post-wounding. Substance P significantly increased the density of leukocytes (2.1×107, SD +/−3.6×106 vs. 1.8×107, SD+/−4.9×105, p<.02) 3 days after wounding and the density of macrophages (2.9 ×107, SD+/−7.5×106 vs. 1.3×107, SD+/−1.4×106, p<.05) 7 days after wounding. There were no significant differences in endothelial cell, leukocyte or macrophage density at later time points. Topical SP treatment increases early inflammatory density in the healing wounds of db/db mice. These data support a role for nerve-mediated inflammation in cutaneous wound repair. PMID:18638272

  20. Adrenalectomy in genetically obese ob/ob and db/db mice increases the proton conductance pathway.

    PubMed

    Shargill, N S; Lupien, J R; Bray, G A

    1989-09-01

    Adrenalectomy (ADX) prevents the excessive weight gain in the genetically obese ob/ob and db/db mice. To test the possibility that this results from increased energy expenditure due to increased thermogenesis in brown adipose tissue (BAT), we measured GDP binding to mitochondria from interscapular brown adipose tissue (BAT) in db/db and ob/ob mice and their lean controls after adrenalectomy, with and without corticosterone replacement. Both the vehicle treated and corticosterone treated db/db and ob/ob mice had lower body weights than the sham-operated mice GDP binding to mitochondria from IBAT was significantly lower in both the db/db and ob/ob mice than in their lean controls. Adrenalectomy significantly increased GDP binding in all mice compared to the respective sham-operated mice, but, the percentage increase was always greater in the db/db and ob/ob mice. Corticosterone treatment of adrenalectomized db/db, ob/ob or lean mice lowered GDP binding to sham levels. Our data confirm previous findings that adrenalectomy results in increased GDP binding to mitochondria from IBAT. Injections of corticosterone into adrenalectomized mice results in a decrease in GDP binding to values which are similar to values in sham-operated mice. Thus adrenalectomy may inhibit the development of obesity by increasing the thermic activity in IBAT. PMID:2583669

  1. Past evolutionary tradeoffs represent opportunities for crop genetic improvement and increased human lifespan

    PubMed Central

    Denison, R Ford

    2011-01-01

    The repeated evolution of complex adaptations – crop mimicry by weeds, for example, or CO2-concentrating C4 photosynthesis – shows the power of natural selection to solve difficult problems that limited fitness in past environments. The sophistication of natural selection's innovations contrasts with the relatively simple changes (e.g., increasing the expression of existing genes) readily achievable by today's biotechnology. Mutants with greater expression of these genes arose repeatedly over the course of evolution, so their present rarity indicates rejection by natural selection. Similarly, medical interventions that simply up- or down-regulate existing physiological mechanisms presumably recreate phenotypes also rejected by past natural selection. Some tradeoffs that constrained past natural selection still apply, such as those resulting from conservation of matter. But tradeoffs between present human goals and individual fitness in past environments may represent fairly easy opportunities to achieve our goals by reversing some effects of past selection. This point is illustrated with three examples, based on tradeoffs between (i) individual-plant fitness versus whole-crop performance, (ii) the fitness of symbionts (rhizobia) versus that of their legume hosts, and (iii) human fertility versus longevity in the context of environmental cues, such as consumption of ‘famine foods’, that predict trends in population size. PMID:25567969

  2. Use of pantothenate as a metabolic switch increases the genetic stability of farnesene producing Saccharomyces cerevisiae.

    PubMed

    Sandoval, Celeste M; Ayson, Marites; Moss, Nathan; Lieu, Bonny; Jackson, Peter; Gaucher, Sara P; Horning, Tizita; Dahl, Robert H; Denery, Judith R; Abbott, Derek A; Meadows, Adam L

    2014-09-01

    We observed that removing pantothenate (vitamin B5), a precursor to co-enzyme A, from the growth medium of Saccharomyces cerevisiae engineered to produce β-farnesene reduced the strain׳s farnesene flux by 70%, but increased its viability, growth rate and biomass yield. Conversely, the growth rate and biomass yield of wild-type yeast were reduced. Cultivation in media lacking pantothenate eliminates the growth advantage of low-producing mutants, leading to improved production upon scale-up to lab-scale bioreactor testing. An omics investigation revealed that when exogenous pantothenate levels are limited, acyl-CoA metabolites decrease, β-oxidation decreases from unexpectedly high levels in the farnesene producer, and sterol and fatty acid synthesis likely limits the growth rate of the wild-type strain. Thus pantothenate supplementation can be utilized as a "metabolic switch" for tuning the synthesis rates of molecules relying on CoA intermediates and aid the economic scale-up of strains producing acyl-CoA derived molecules to manufacturing facilities. PMID:25076380

  3. CHRONIC CIGARETTE SMOKING IS ASSOCIATED WITH DIMINISHED FOLATE STATUS, ALTERED FOLATE FORM DISTRIBUTION, AND INCREASED GENETIC DAMAGE IN THE BUCCAL MUCOSA OF HEALTHY ADULTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Smoking causes genetic damage in buccal cells and increases the risk of oral cancer. Since folate is instrumental in DNA synthesis and repair, it is a determinant of genetic stability and therefore might attenuate the genotoxic effects of smoking. Objective: To compare folate metabolites...

  4. A Twelve-SNP Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke

    PubMed Central

    Smith, J. Gustav; Sjögren, Marketa; Lubitz, Steven A.; Ellinor, Patrick T.; Louie, Judy Z.; Catanese, Joseph J.; Engström, Gunnar; Devlin, James J.

    2015-01-01

    Background and Purpose Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms (SNPs) together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF. Methods In 27,471 participants of the Malmö Diet and Cancer Study, a prospective, community-based cohort, we used Cox models that adjusted for established AF risk factors to assess the association of AF-GRS with incident AF and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5 years for ischemic stroke. The AF-GRS comprised 12 SNPs that had been previously shown to be associated with AF at genome-wide significance. Results During follow-up, 2,160 participants experienced a first AF event and 1,495 had a first ischemic stroke event. Participants in the top AF-GRS quintile were at increased risk for incident AF (HR = 2.00; 95%CI = 1.73 to 2.31; P=2.7×10−21) and ischemic stroke (HR = 1.23; 95%CI = 1.04 to 1.46; P=0.02) when compared with the bottom quintile. Addition of the AF-GRS to established AF risk factors modestly improved both discrimination and reclassification (P<0.0001 for both). Conclusions An AF-GRS can identify 20% of individuals who are at approximately two-fold increased risk for incident AF and at 23% increased risk for ischemic stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful. PMID:25123217

  5. Oxidant/antioxidant effects of chronic exposure to predator odor in prefrontal cortex, amygdala, and hypothalamus.

    PubMed

    Mejia-Carmona, G E; Gosselink, K L; Pérez-Ishiwara, G; Martínez-Martínez, A

    2015-08-01

    The incidence of anxiety-related diseases is increasing these days, hence there is a need to understand the mechanisms that underlie its nature and consequences. It is known that limbic structures, mainly the prefrontal cortex and amygdala, are involved in the processing of anxiety, and that projections from prefrontal cortex and amygdala can induce activity of the hypothalamic-pituitary-adrenal axis with consequent cardiovascular changes, increase in oxygen consumption, and ROS production. The compensatory reaction can include increased antioxidant enzymes activities, overexpression of antioxidant enzymes, and genetic shifts that could include the activation of antioxidant genes. The main objective of this study was to evaluate the oxidant/antioxidant effect that chronic anxiogenic stress exposure can have in prefrontal cortex, amygdala, and hypothalamus by exposition to predator odor. Results showed (a) sensitization of the HPA axis response, (b) an enzymatic phase 1 and 2 antioxidant response to oxidative stress in amygdala, (c) an antioxidant stability without elevation of oxidative markers in prefrontal cortex, (d) an elevation in phase 1 antioxidant response in hypothalamus. Chronic exposure to predator odor has an impact in the metabolic REDOX state in amygdala, prefrontal cortex, and hypothalamus, with oxidative stress being prevalent in amygdala as this is the principal structure responsible for the management of anxiety. PMID:25981530

  6. Pulmonary antioxidants

    SciTech Connect

    Massaro, E.J.; Grose, E.C.; Hatch, G.E.; Slade, R.

    1987-05-01

    One of the most vital of the cellular defenses against pollution is an antioxidant armanentarium which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate reductase, catalase, GSH synthetase, GSH peroxidase, GSH reductase, and GSH transferase) and appears to function in keeping oxidant forces under control. Pollutants can upset the oxidant/antioxidant balance of cells by inhibiting vital enzymes, by reacting with oxidant scavengers, or by forming free radical intermediates which initiate uncontrolled tissue reactions with molecular oxygen. The book chapter reviews possible interactions between pollutants and the oxidant/antioxidant balance.

  7. Increased virulence of Rabbit Haemorrhagic Disease Virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus)

    PubMed Central

    Elsworth, Peter; Cooke, Brian D.; Kovaliski, John; Sinclair, Ronald; Holmes, Edward C.; Strive, Tanja

    2015-01-01

    The release of myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV) in Australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. In contrast to MYXV, which attenuated shortly after its introduction, rapid attenuation of RHDV has not been observed. By studying the change in virulence of recent field isolates at a single field site we show, for the first time, that RHDV virulence has increased through time, likely because of selection to overcome developing genetic resistance in Australian wild rabbits. High virulence also appears to be favoured as rabbit carcasses, rather than diseased animals, are the likely source of mechanical insect transmission. These findings not only help elucidate the co-evolutionary interaction between rabbits and RHDV, but reveal some of the key factors shaping virulence evolution. PMID:25146599

  8. Genetic predisposition increases the tic severity, rate of comorbidities, and psychosocial and educational difficulties in children with Tourette syndrome.

    PubMed

    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-03-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition. PMID:25156665

  9. Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

    PubMed Central

    Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.

    2014-01-01

    Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller

  10. Peer Network Drinking Predicts Increased Alcohol Use From Adolescence to Early Adulthood After Controlling for Genetic and Shared Environmental Selection

    PubMed Central

    Cruz, Jennifer E.; Emery, Robert E.; Turkheimer, Eric

    2013-01-01

    Research consistently links adolescents' and young adults' drinking with their peers' alcohol intake. In interpreting this correlation, 2 essential questions are often overlooked. First, which peers are more important, best friends or broader social networks? Second, do peers cause increased drinking, or do young people select friends whose drinking habits match their own? The present study combines social network analyses with family (twin and sibling) designs to answer these questions via data from the National Longitudinal Study of Adolescent Health. Analysis of peer nomination data from 134 schools (n = 82,629) and 1,846 twin and sibling pairs shows that peer network substance use predicts changes in drinking from adolescence into young adult life even after controlling for genetic and shared environmental selection, as well as best friend substance use. This effect was particularly strong for high-intensity friendships. Although the peer-adolescent drinking correlation is partially explained by selection, the present finding offers powerful evidence that peers also cause increased drinking. PMID:22390657

  11. Dietary alpha-ketoglutarate increases cold tolerance in Drosophila melanogaster and enhances protein pool and antioxidant defense in sex-specific manner.

    PubMed

    Bayliak, Maria M; Lylyk, Maria P; Shmihel, Halyna V; Sorochynska, Oksana M; Manyukh, Oksana V; Pierzynowski, Stefan G; Lushchak, Volodymyr I

    2016-08-01

    Alpha-ketoglutarate (AKG) is an important intermediate in Krebs cycle which bridges the metabolism of amino acids and carbohydrates. Its effects as a dietary supplement on cold tolerance were studied in Drosophila melanogaster Canton S. Two-day-old adult flies fed at larval and adult stages with AKG at moderate concentrations (5-10mM) recovered faster from chill coma (0°C for 15min or 3h) than control ones. The beneficial effect of AKG on chill coma recovery was not found at its higher concentrations, which suggests hormetic like action of this keto acid. Time of 50% observed mortality after 2h recovery from continuous cold exposure (-1°C for 3-31h) (LTi50) was higher for flies reared on 10mM AKG compared with control ones, showing that the diet with AKG enhanced insect cold tolerance. In parallel with enhancement of cold tolerance, dietary AKG improved fly locomotor activity. Metabolic effects of AKG differed partly in males and females. In males fed on AKG, there were no differences in total protein and free amino acid levels, but the total antioxidant capacity, catalase activity and low molecular mass thiol content were higher than in control animals. In females, dietary AKG promoted higher total antioxidant capacity and higher levels of proteins, total amino acids, proline and low molecular mass thiols. The levels of lipid peroxides were lower in both fly sexes reared on AKG as compared with control ones. We conclude that both enhancement of antioxidant system capacity and synthesis of amino acids can be important for AKG-promoted cold tolerance in D. melanogaster. The involvement of AKG in metabolic pathways of Drosophila males and females is discussed. PMID:27503710

  12. Genotypic variation in tomatoes affecting processing and antioxidant attributes.

    PubMed

    Siddiqui, Mohammed Wasim; Ayala-Zavala, J F; Dhua, R S

    2015-01-01

    Tomatoes are widely consumed either raw or after processing and can provide a significant proportion of the total antioxidants in the diet associated with beneficial health properties. Over the last two or three decades an increasing interest for processing and antioxidant attributes in tomatoes has arisen. The screening of processing attributes of tomatoes is subject of a large number of articles; however, special interest has been addressed to the biochemical composition. The postharvest and industrial processing of tomato in tomato-based products includes several steps. Processing and antioxidant characteristics of the raw fruit are important considering the processing steps and final product. To respond to consumer and industrial complaints, breeders should know the range of genetic variability available in tomato resources, including local genotypes, for improving the mentioned attributes. Characterization and conservation of traditional and modern varieties is a major goal for their preservation and utilization. The bioactive contents have an impact on the processed destines so their stability must be contemplated while selecting the tomato fruits for processing. The endeavor of this review was to examine comprehensively the variation in processing and antioxidant attributes among tomatoes. Role of tomato peel in terms of bioactive contents and information on high pigment (hp) tomato mutants are also touched to some extent. Probably, patterns of variation identified/discussed in this paper would give impetus for planning breeding strategies to develop and improve the new processing cultivars with good antioxidant status. PMID:24279355

  13. Exposure and genetics increase risk of beryllium sensitisation and chronic beryllium disease in the nuclear weapons industry

    SciTech Connect

    Van Dyke, M. V.; Martyny, John W.; Mroz, M. M.; Silveira, L. J.; Strand, M.; Cragle, D. L.; Tankersley, W. G.; Wells, S. M.; Newman, L. S.; Maier, L. A.

    2011-04-02

    Beryllium sensitisation (BeS) and chronic beryllium disease (CBD) are caused by exposure to beryllium with susceptibility affected by at least one well-studied genetic host factor, a glutamic acid residue at position 69 (E69) of the HLA-DPb chain (DPbE69). However, the nature of the relationship between exposure and carriage of the DPbE69 genotype has not been well studied. The goal of this study was to determine the relationship between DP{beta}E69 and exposure in BeS and CBD. Current and former workers (n=181) from a US nuclear weapons production facility, the Y-12 National Security Complex (Oak Ridge, Tennessee, USA), were enrolled in a case-control study including 35 individuals with BeS and 19 with CBD. HLA-DPB1 genotypes were determined by PCR-SSP. Beryllium exposures were assessed through worker interviews and industrial hygiene assessment of work tasks. After removing the confounding effect of potential beryllium exposure at another facility, multivariate models showed a sixfold (OR 6.06, 95% CI 1.96 to 18.7) increased odds for BeS and CBD combined among DP{beta}E69 carriers and a fourfold (OR 3.98, 95% CI 1.43 to 11.0) increased odds for those exposed over an assigned lifetime-weighted average exposure of 0.1 {micro}g/m{sup 3}. Those with both risk factors had higher increased odds (OR 24.1, 95% CI 4.77 to 122). DP{beta}E69 carriage and high exposure to beryllium appear to contribute individually to the development of BeS and CBD. Among workers at a beryllium-using facility, the magnitude of risk associated with either elevated beryllium exposure or carriage of DP{beta}E69 alone appears to be similar.

  14. Using Public Control Genotype Data to Increase Power and Decrease Cost of Case-Control Genetic Association Studies

    PubMed Central

    Ho, Lindsey A.; Lange, Ethan M.

    2011-01-01

    Genome-wide association (GWA) studies are a powerful approach for identifying novel genetic risk factors associated with human disease. A GWA study typically requires the inclusion of thousands of samples to have sufficient statistical power to detect single nucleotide polymorphisms (SNPs) that are associated with only modest increases in risk of disease given the heavy burden of a multiple test correction that is necessary to maintain valid statistical tests. Low statistical power and the high financial cost of performing a GWA study remains prohibitive for many scientific investigators anxious to perform such a study using their own samples. A number of remedies have been suggested to increase statistical power and decrease cost, including the utilization of free publicly available genotype data and multi-stage genotyping designs. Herein, we compare the statistical power and relative costs of alternative association study designs that use cases and screened controls to study designs that are based only on, or additionally include, free public control genotype data. We describe a novel replication-based two-stage study design, which uses free public control genotype data in the first stage and follow-up genotype data on case-matched controls in the second stage, that preserves many of the advantages inherent when using only an epidemiologically matched set of controls. Specifically, we show that our proposed two-stage design can substantially increase statistical power and decrease cost of performing a GWA study while controlling the type I error rate that can be inflated when using public controls due to differences in ancestry and batch genotype effects. PMID:20821337

  15. Will Genetic Testing for Complex Diseases Increase Motivation to Quit Smoking? Anticipated Reactions in a Survey of Smokers

    ERIC Educational Resources Information Center

    Sanderson, Saskia C.; Wardle, Jane

    2005-01-01

    The aim of this study was to improve understanding of smokers' potential reactions to genetic testing for smoking-related diseases. One thousand twenty-four respondents completed a postal survey; 186 were smokers. Questions addressed anticipated psychological and behavioral reactions to genetic test results using hypothetical scenarios. Of…

  16. Antioxidant status, lipid and color stability of aged beef from grazing steers supplemented with corn grain and increasing levels of flaxseed.

    PubMed

    Pouzo, L B; Descalzo, A M; Zaritzky, N E; Rossetti, L; Pavan, E

    2016-01-01

    Angus steers were grazed on unsupplemented pasture (CNTRL), pasture supplemented with 0.7% BW cracked corn (FLAX-0), FLAX-0 with 0.125% and 0.250% BW of whole flaxseed (FLAX-1 and FLAX-2). Six steers were grazed per treatment for 70 days, with start and finish weights of 458 and 508 kg. At 24 h post slaughter, longissimus thoracis were harvested, and steaks assigned to treatments of postmortem aging time under vacuum (PM; 3, 14 and 56 days) with or without five days of aerobic exposure (AE). Meat antioxidant status was higher (P<0.05) when feeding CNTRL and FLAX-1 than FLAX-0 and FLAX-2. Under AE, lipid oxidation was highest for FLAX-2 (P<0.05), and lowest for FLAX-1. Greatest TBARs and lowest antioxidant capacity and redness values were obtained with AE and the longer PM (P<0.05). Beef oxidative stability through AE improved by adding a low flaxseed level to supplemented corn grain, but deteriorated by adding a high flaxseed level or by extending PM. PMID:26318758

  17. Antioxidants and vascular health.

    PubMed

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies. PMID:26585821

  18. Genetic engineering to enhance the Ehrlich pathway and alter carbon flux for increased isobutanol production from glucose by Saccharomyces cerevisiae.

    PubMed

    Kondo, Takashi; Tezuka, Hironori; Ishii, Jun; Matsuda, Fumio; Ogino, Chiaki; Kondo, Akihiko

    2012-05-31

    The production of higher alcohols by engineered bacteria has received significant attention. The budding yeast, Saccharomyces cerevisiae, has considerable potential as a producer of higher alcohols because of its capacity to naturally fabricate fusel alcohols, in addition to its robustness and tolerance to low pH. However, because its natural productivity is not significant, we considered a strategy of genetic engineering to increase production of the branched-chain higher alcohol isobutanol, which is involved in valine biosynthesis. Initially, we overexpressed 2-keto acid decarboxylase (KDC) and alcohol dehydrogenase (ADH) in S. cerevisiae to enhance the endogenous activity of the Ehrlich pathway. We then overexpressed Ilv2, which catalyzes the first step in the valine synthetic pathway, and deleted the PDC1 gene encoding a major pyruvate decarboxylase with the intent of altering the abundant ethanol flux via pyruvate. Through these engineering steps, along with modification of culture conditions, the isobutanol titer of S. cerevisiae was elevated 13-fold, from 11 mg/l to 143 mg/l, and the yield was 6.6 mg/g glucose, which is higher than any previously reported value for S. cerevisiae. PMID:22342368

  19. Genetic p53 deficiency partially rescues the adrenocortical dysplasia (acd) phenotype at the expense of increased tumorigenesis

    PubMed Central

    Else, Tobias; Trovato, Alessia; Kim, Alex C.; Wu, Yipin; Ferguson, David O.; Kuick, Rork D.; Lucas, Peter C.; Hammer, Gary D.

    2009-01-01

    Summary Telomere dysfunction and shortening induce chromosomal instability and tumorigenesis. In this study, we analyze the adrenocortical dysplasia (acd) mouse, harboring a mutation in Tpp1/Acd. Additional loss of p53 dramatically rescues the acd phenotype in an organ-specific manner, including skin hyperpigmentation and adrenal morphology, but not germ cell atrophy. Survival to weaning age is significantly increased in Acdacd/acd p53−/− mice. On the contrary p53−/− and p53+/− mice with the Acdacd/acd genotype show a decreased tumor free survival compared to Acd+/+ mice. Tumors from Acdacd/acd p53+/− mice show a striking switch from the classical spectrum of p53−/− mice towards carcinomas. The acd mouse model provides further support for an in vivo role of telomere deprotection in tumorigenesis. Significance Critically shortened dysfunctional telomeres of the Terc−/− mice have been shown to impact tissue development and maintenance and lead to the occurrence of a pro-cancer genome. The present study examines the contribution of telomere shortening vs. telomere deprotection to the development of genetic instability and cancer. By studying the acd mouse, we show that telomere deprotection without significant telomere shortening is sufficient to induce tumor formation in the context of p53 absence. It also raises the possibility that telomere deprotection contributes to the high prevalence of carcinomas in humans. PMID:19477426

  20. Metabolic Biosynthesis of Potato (Solanum tuberosum l.) Antioxidants and Implications for Human Health.

    PubMed

    Lovat, Christie; Nassar, Atef M K; Kubow, Stan; Li, Xiu-Qing; Donnelly, Danielle J

    2016-10-25

    Potato (Solanum tuberosum L.) is common, affordable, readily stored, easily prepared for consumption, and nutritious. For these reasons, potato has become one of the top five crops consumed worldwide. Consequently, it is important to understand its contribution to both our daily and long-term health. Potato is one of the most important sources of antioxidants in the human diet. As such, it supports the antioxidant defense network in our bodies that reduces cellular and tissue toxicities that result from free radical-induced protein, lipid, carbohydrate, and DNA damage. In this way, potato antioxidants may reduce the risk for cancers, cardiovascular diseases, diabetes, and even radiation damage. A better understanding of these components of potato is needed by the food industry, health professionals, and consumers. This review provides referenced summaries of all of the antioxidant groups present in potato tubers and updated schematics including genetic regulation for the major antioxidant biosynthesis pathways. This review complements current knowledge on the role of potato in human health. We hope it will provide impetus toward breeding efforts to develop cultivars with increased antioxidant capacity as 'functional foods' and encourage potato consumers and processors to work toward preservation of antioxidant capacity in cooked potato and potato products. PMID:25674927

  1. Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

    PubMed

    Chakraborti, Barnali; Verma, Deepak; Karmakar, Arijit; Jaiswal, Preeti; Sanyal, Aritrika; Paul, Debarshi; Sinha, Swagata; Singh, Asem Surindro; Guhathakurta, Subhrangshu; Roychowdhury, Anirban; Panda, Chinmoy Kumar; Ghosh, Saurabh; Mohanakumar, Kochupurackal P; Mukhophadhyay, Kanchan; Rajamma, Usha

    2016-11-01

    Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5-HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over-distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior. PMID:27381555

  2. Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells

    PubMed Central

    Noh, Jung-Ran; Gang, Gil-Tae; Kim, Yong-Hoon; Yang, Keum-Jin; Lee, Chul-Ho; Na, O-Su; Kim, Gi-Ju; Oh, Won-Keun

    2010-01-01

    This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, free radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress. PMID:20198202

  3. Germination and extrusion as combined processes for reducing phytates and increasing phenolics content and antioxidant capacity of Oryza sativa L. whole grain flours.

    PubMed

    Albarracín, M; De Greef, D M; González, R J; Drago, S R

    2015-01-01

    Whole rice (WR) products with low phytic acid (PA) content and enhanced bio-functional components were obtained by the combination of germination and extrusion processes. Germination conditions (24 h - 35 °C), with a previous soaking process (24 h - 20 °C), were chosen according to the remnant PA content and germination rate. Specific mechanical energy consumption, expansion, sensorial and mechanical hardness, specific volume, solubility, water absorption, free phenolic content (FPC) and antioxidant capacity were evaluated. Results indicated that 175 °C and 14 g 100 g(-1) of moisture were the most appropriate conditions to obtain expanded products and precooked flours based on germinated WR. Selected extruded product presented less PA content (821.6 9 ± 10.3 versus 695.2 0 ± 1.6 mg 100 g(-1)) and higher Fe bio-accessibility, FPC (45.2 9 ± 1.61 versus 66.3 5 ± 3.35 mg GAE g(-1)) and antioxidant capacity compared with WR (34.9 5 ± 0.8 versus 54.6 3 ± 1.6 µmol trolox g(-1)). Combining germination-extrusion processes could be a strategy to obtain expanded products or precooked flours based on WR with enhanced health benefits. PMID:26560879

  4. PULMONARY ANTIOXIDANTS

    EPA Science Inventory

    One of the most vital of the cellular defenses against pollution is an 'antioxidant armanentarium' which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate re...

  5. Synergistic exposure of rice seeds to different doses of γ-ray and salinity stress resulted in increased antioxidant enzyme activities and gene-specific modulation of TC-NER pathway.

    PubMed

    Macovei, Anca; Garg, Bharti; Raikwar, Shailendra; Balestrazzi, Alma; Carbonera, Daniela; Buttafava, Armando; Bremont, Juan Francisco Jiménez; Gill, Sarvajeet Singh; Tuteja, Narendra

    2014-01-01

    Recent reports have underlined the potential of gamma (γ)-rays as tools for seed priming, a process used in seed industry to increase seed vigor and to enhance plant tolerance to biotic/abiotic stresses. However, the impact of γ -rays on key aspects of plant metabolism still needs to be carefully evaluated. In the present study, rice seeds were challenged with different doses of γ -rays and grown in absence/presence of NaCl to assess the impact of these treatments on the early stages of plant life. Enhanced germination efficiency associated with increase in radicle and hypocotyl length was observed, while at later stages no increase in plant tolerance to salinity stress was evident. APX, CAT, and GR were enhanced at transcriptional level and in terms of enzyme activity, indicating the activation of antioxidant defence. The profiles of DNA damage accumulation were obtained using SCGE and the implication of TC-NER pathway in DNA damage sensing and repair mechanisms is discussed. OsXPB2, OsXPD, OsTFIIS, and OsTFIIS-like genes showed differential modulation in seedlings and plantlets in response to γ -irradiation and salinity stress. Altogether, the synergistic exposure to γ -rays and NaCl resulted in enhanced oxidative stress and proper activation of antioxidant mechanisms, thus being compatible with plant survival. PMID:24551849

  6. Synergistic Exposure of Rice Seeds to Different Doses of γ-Ray and Salinity Stress Resulted in Increased Antioxidant Enzyme Activities and Gene-Specific Modulation of TC-NER Pathway

    PubMed Central

    Macovei, Anca; Garg, Bharti; Raikwar, Shailendra; Carbonera, Daniela; Bremont, Juan Francisco Jiménez; Gill, Sarvajeet Singh; Tuteja, Narendra

    2014-01-01

    Recent reports have underlined the potential of gamma (γ)-rays as tools for seed priming, a process used in seed industry to increase seed vigor and to enhance plant tolerance to biotic/abiotic stresses. However, the impact of γ-rays on key aspects of plant metabolism still needs to be carefully evaluated. In the present study, rice seeds were challenged with different doses of γ-rays and grown in absence/presence of NaCl to assess the impact of these treatments on the early stages of plant life. Enhanced germination efficiency associated with increase in radicle and hypocotyl length was observed, while at later stages no increase in plant tolerance to salinity stress was evident. APX, CAT, and GR were enhanced at transcriptional level and in terms of enzyme activity, indicating the activation of antioxidant defence. The profiles of DNA damage accumulation were obtained using SCGE and the implication of TC-NER pathway in DNA damage sensing and repair mechanisms is discussed. OsXPB2, OsXPD, OsTFIIS, and OsTFIIS-like genes showed differential modulation in seedlings and plantlets in response to γ-irradiation and salinity stress. Altogether, the synergistic exposure to γ-rays and NaCl resulted in enhanced oxidative stress and proper activation of antioxidant mechanisms, thus being compatible with plant survival. PMID:24551849

  7. Antioxidant relevance to human health.

    PubMed

    Wahlqvist, Mark L

    2013-01-01

    Human ecology requires both oxygen and water with the generation from food of an immediate energy source, ATP, by oxidative phosphorylation. A continuing balance between oxidation and antioxidation is necessary for longer less-disabled lives, taking account of oxidative stresses and the critical roles of oxidants in defence against infection, tissue repair and signalling. Antioxidant capacity is derived both exogenously (from food, beverage and sunlight) and endogenously (from enzymatic and non-enzymatic pathways). A number of oxidant food factors service antioxidant metallo-enzymes. The capacity operates extra- or intracellularly. Uric acid is the major antioxidant in primate blood. Uric acid synthesis is increased by dietary fructose from fruit, sugary foods and drinks. This indirect antioxidant effect of fruit is separate from that attributable to its flavonoids. Alcohol also increases serum uric acid. Urate excess and retention is associated with disease. The high prevalence of hyperuricaemia in NE Asia presents a major public health dilemma in regard to putative benefits and risks. Foods with high antioxidant activity include berries, nuts and legumes, tomatoes and sweet potato leaves. Each of the antioxidants in these foods is pleiotropic being inter-alia anti-inflammatory, anti-angiogenic or anti-neoplastic. Moreover, food matrices and patterns contribute to the safety of antioxidant consumption. There is no evidence to date that isolated antioxidants as food supplements improve health outcomes or survival; and some that indicate unacceptable risk. Their use as biomarkers of food cannot justify their isolated use. Nevertheless, a spectrum of dietary pluripotential antioxidants for tissues, metabolic and immune systems is advantageous. PMID:23635359

  8. Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer

    PubMed Central

    Latifa, Khlifi; Sondess, Sahli; Hajer, Graiet; Manel, Ben-Hadj-Mohamed; Souhir, Khelil; Nadia, Bouzidi; Abir, Jaballah; Salima, Ferchichi; Abdelhedi, Miled

    2016-01-01

    Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant–antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease. PMID:27405842

  9. Evaluation of physiological risk factors, oxidant-antioxidant imbalance, proteolytic and genetic variations of matrix metalloproteinase-9 in patients with pressure ulcer.

    PubMed

    Latifa, Khlifi; Sondess, Sahli; Hajer, Graiet; Manel, Ben-Hadj-Mohamed; Souhir, Khelil; Nadia, Bouzidi; Abir, Jaballah; Salima, Ferchichi; Abdelhedi, Miled

    2016-01-01

    Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant-antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers. In this study, we aimed to evaluate the major clinical elements and biological scars in Tunisian patients suffering from PU. Consistently, non-healing wound remains a challenging clinical problem. The complex challenges of the wound environment, involving nutrient deficiencies, bacterial infection, as well as the critical role played by inflammatory cells, should be considered because of their negative impact on wound healing. In addition, an imbalance between pro-oxidants and antioxidant systems seems to be more aggravated in patients with PU compared to healthy subjects. Of interest, this study provides further evidence to support a core role of the biological activity of MMP-9 in the pathogenesis of PU and indicates that the MMP9-1562 C/T (rs 3918242) functional polymorphism is associated with protection against this disease. PMID:27405842

  10. Isolation-hypoxia and re-oxygenation of the pallial cavity of female Crepipatella dilatata during estuarine salinity changes requires increased glyoxylase activity and antioxidant metabolism to avoid oxidative damage to female tissues and developing embryos.

    PubMed

    Cubillos, Víctor; Chaparro, Oscar; Segura, Cristian; Montory, Jaime; Cruces, Edgardo; Burritt, David

    2016-08-01

    The estuarine slipper limpet Crepipatella dilatata is a gastropod that can survive prolonged periods of low salinities (< 24 PSU) caused by tidal changes and/or prolonged periods of rain. During low salinity events, C. dilatata can isolate its body from the outside environment, by sealing its shell against the substrate on which it grows. Prolonged isolation periods from the surrounding environment can greatly lower available oxygen levels inside of the pallial cavity, impacting on the physiology of both females and their incubated encapsulated embryos. When salinity levels return to normal, isolation is terminated and the inflow of seawater results in re-oxygenation. In this study we show that when re-oxygenation of the pallial cavity takes place, oxidative damage, in the form of increased levels of lipid peroxides and protein carbonyls, occurs in both maternal tissues and in incubated embryos. To avoid terminal oxidative damage both females and their embryos increase their levels of the glyoxalase pathway enzymes (GLX-I and GLX-II) and general antioxidant metabolism (SOD, CAT, GR, GPOX and GST). As a result the levels of oxidative damage decline to basal levels within 24 h of reoxygenation. Thus the combination of isolation, a behavioural strategy, combined with encapsulation of embryos and a capacity to up regulate relatively rapidly the glyoxylase pathway and general antioxidant metabolism, play major roles in facilitating the survival of C. dilatata in the small estuaries of Southern Chile. PMID:27232979

  11. ANTIOXIDANT THERAPEUTIC ADVANCES IN COPD

    PubMed Central

    Rahman, Irfan

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. PMID:19124382

  12. Interactions between demography, genetics, and landscape connectivity increase extinction probability for a small population of large carnivores in a major metropolitan area.

    PubMed

    Benson, John F; Mahoney, Peter J; Sikich, Jeff A; Serieys, Laurel E K; Pollinger, John P; Ernest, Holly B; Riley, Seth P D

    2016-08-31

    The extinction vortex is a theoretical model describing the process by which extinction risk is elevated in small, isolated populations owing to interactions between environmental, demographic, and genetic factors. However, empirical demonstrations of these interactions have been elusive. We modelled the dynamics of a small mountain lion population isolated by anthropogenic barriers in greater Los Angeles, California, to evaluate the influence of demographic, genetic, and landscape factors on extinction probability. The population exhibited strong survival and reproduction, and the model predicted stable median population growth and a 15% probability of extinction over 50 years in the absence of inbreeding depression. However, our model also predicted the population will lose 40-57% of its heterozygosity in 50 years. When we reduced demographic parameters proportional to reductions documented in another wild population of mountain lions that experienced inbreeding depression, extinction probability rose to 99.7%. Simulating greater landscape connectivity by increasing immigration to greater than or equal to one migrant per generation appears sufficient to largely maintain genetic diversity and reduce extinction probability. We provide empirical support for the central tenet of the extinction vortex as interactions between genetics and demography greatly increased extinction probability relative to the risk from demographic and environmental stochasticity alone. Our modelling approach realistically integrates demographic and genetic data to provide a comprehensive assessment of factors threatening small populations. PMID:27581877

  13. Estimation of genetic marker effects for CAPN1, CAST, and GHR on carcass quality traits in Angus cattle selected to increase minor marker frequencies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and interactions cannot be accurately estimated when minor marker allele frequencies (MAF) are low. To increase the accuracy of estimation for three marker systems in commercial use, an Angus population at USMARC was subjected to marker assisted-selection for multiple years t...

  14. "Chromoseratops Meiosus": A Simple, Two-Phase Exercise to Represent the Connection between Meiosis & Increased Genetic Diversity

    ERIC Educational Resources Information Center

    Eliyahu, Dorit

    2014-01-01

    I present an activity to help students make the connection between meiosis and genetic variation. The students model meiosis in the first phase of the activity, and by that process they produce gametes of a fictitious reptilobird species, "Chromoseratops meiosus." Later on, they will "mate" their gametes and produce a zygote…

  15. Patterns of genetic diversity and migration in increasingly fragmented and declining orang-utan (Pongo pygmaeus) populations from Sabah, Malaysia.

    PubMed

    Goossens, B; Chikhi, L; Jalil, M F; Ancrenaz, M; Lackman-Ancrenaz, I; Mohamed, M; Andau, P; Bruford, M W

    2005-02-01

    We investigated the genetic structure within and among Bornean orang-utans (Pongo pygmaeus) in forest fragments of the Lower Kinabatangan flood plain in Sabah, Malaysia. DNA was extracted from hair and faecal samples for 200 wild individuals collected during boat surveys on the Kinabatangan River. Fourteen microsatellite loci were used to characterize patterns of genetic diversity. We found that genetic diversity was high in the set of samples (mean H(E) = 0.74) and that genetic differentiation was significant between the samples (average F(ST) = 0.04, P < 0.001) with F(ST) values ranging from low (0.01) to moderately large (0.12) values. Pairwise F(ST) values were significantly higher across the Kinabatangan River than between samples from the same river side, thereby confirming the role of the river as a natural barrier to gene flow. The correlation between genetic and geographical distance was tested by means of a series of Mantel tests based on different measures of geographical distance. We used a Bayesian method to estimate immigration rates. The results indicate that migration is unlikely across the river but cannot be completely ruled out because of the limited F(ST) values. Assignment tests confirm the overall picture that gene flow is limited across the river. We found that migration between samples from the same side of the river had a high probability indicating that orang-utans used to move relatively freely between neighbouring areas. This strongly suggests that there is a need to maintain migration between isolated forest fragments. This could be done by restoring forest corridors alongside the river banks and between patches. PMID:15660936

  16. Why (--)deprenyl prolongs survivals of experimental animals: increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects.

    PubMed

    Kitani, Kenichi; Minami, Chiyoko; Isobe, Ken-ichi; Maehara, Kayoko; Kanai, Setsuko; Ivy, Gwen O; Carrillo, Maria-Christina

    2002-04-30

    (--)Deprenyl, a monoamine oxidase B (MAO B) inhibitor is known to upregulate activities of anti-oxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions. The drug is also the sole chemical which has been repeatedly shown to increase life spans of several animal species including rats, mice, hamsters and dogs. Further, the drug was recently found to enhance anti-oxidant enzyme activities not only in brain dopaminergic regions but also in extra-brain tissues such as the heart, kidneys, adrenal glands and the spleen. We and others have also observed mobilization of many humoral factors (interferone (INF)-gamma, tumor necrosis factor (TNF)-alpha, interleukine (IL)-1beta,2,6, trophic factors, etc.) and enhancement of natural killer (NK) cell functions by (-)deprenyl administration. An apparent extension of life spans of experimental animals reported in the past may be better explained by these new observations that (-)deprenyl upregulate SOD and CAT activities not only in the brain but also in extra-brain vital organs and involve anti-tumorigenic as well as immunomodulatory effect as well. These combined drug effects may lead to the protection of the homeostatic regulations of the neuro-immuno-endocrine axis of an organism against aging. PMID:12044958

  17. Genetic variation in rates of nondisjunction: association of two naturally occurring polymorphisms in the chromokinesin nod with increased rates of nondisjunction in Drosophila melanogaster.

    PubMed Central

    Zwick, M E; Salstrom, J L; Langley, C H

    1999-01-01

    Genetic variation in nondisjunction frequency among X chromosomes from two Drosophila melanogaster natural populations is examined in a sensitized assay. A high level of genetic variation is observed (a range of 0.006-0.241). Two naturally occurring variants at the nod locus, a chromokinesin required for proper achiasmate chromosome segregation, are significantly associated with an increased frequency of nondisjunction. Both of these polymorphisms are found at intermediate frequency in widely distributed natural populations. To account for these observations, we propose a general model incorporating unique opportunities for meiotic drive during female meiosis. The oötid competition model can account for both high mean rates of female-specific nondisjunction in Drosophila and humans as well as the standing genetic variation in this critical fitness character in natural populations. PMID:10430586

  18. Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

    PubMed

    Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

    2016-05-01

    The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. PMID:26944960

  19. Increased Risk of Genetic and Epigenetic Instability in Human Embryonic Stem Cells Associated with Specific Culture Conditions

    PubMed Central

    Garitaonandia, Ibon; Amir, Hadar; Boscolo, Francesca Sesillo; Wambua, Gerald K.; Schultheisz, Heather L.; Sabatini, Karen; Morey, Robert; Waltz, Shannon; Wang, Yu-Chieh; Tran, Ha; Leonardo, Trevor R.; Nazor, Kristopher; Slavin, Ileana; Lynch, Candace; Li, Yingchun; Coleman, Ronald; Gallego Romero, Irene; Altun, Gulsah; Reynolds, David; Dalton, Stephen; Parast, Mana; Loring, Jeanne F.; Laurent, Louise C.

    2015-01-01

    The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them a promising source of material for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a combinatorial study on both hESCs and hiPSCs to compare the effects of enzymatic vs. mechanical passaging, and feeder-free vs. mouse embryonic fibroblast feeder substrate, on the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. In extensive experiments involving over 100 continuous passages, we observed that both enzymatic passaging and feeder-free culture were associated with genetic instability, higher rates of cell proliferation, and persistence of OCT4/POU5F1-positive cells in teratomas, with enzymatic passaging having the stronger effect. In all combinations of culture conditions except for mechanical passaging on feeder layers, we noted recurrent deletions in the genomic region containing the tumor suppressor gene TP53, which was associated with decreased mRNA expression of TP53, as well as alterations in the expression of several downstream genes consistent with a decrease in the activity of the TP53 pathway. Among the hESC cultures, we also observed culture-associated variations in global gene expression and DNA methylation. The effects of enzymatic passaging and feeder-free conditions were also observed in hiPSC cultures. Our results highlight the need for careful assessment of the effects of culture conditions on cells intended for clinical therapies. PMID:25714340

  20. Recent and Projected Increases in Atmospheric CO2 Concentration Can Enhance Gene Flow between Wild and Genetically Altered Rice (Oryza sativa)

    PubMed Central

    Ziska, Lewis H.; Gealy, David R.; Tomecek, Martha B.; Jackson, Aaron K.; Black, Howard L.

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO2 from an early 20th century concentration (300 µmol mol−1) to current (400 µmol mol−1) and projected, mid-21st century (600 µmol mol−1) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol−1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems. PMID:22649533

  1. Natural antioxidants in meat and poultry products.

    PubMed

    Karre, Liz; Lopez, Keyla; Getty, Kelly J K

    2013-06-01

    In response to recent claims that synthetic antioxidants have the potential to cause toxicological effects and consumers' increased interest in purchasing natural products, the meat and poultry industry has been seeking sources of natural antioxidants. Due to their high phenolic compound content, fruits and other plant materials provide a good alternative to conventional antioxidants. Plum, grape seed extract, cranberry, pomegranate, bearberry, pine bark extract, rosemary, oregano, and other spices functions as antioxidants in meat and poultry products. Pomegranate, pine bark extract, cinnamon, and cloves have exhibited stronger antioxidant properties than some synthetic options. Plum products, grape seed extract, pine bark extract, rosemary, and some spices all have been shown to affect the color of finished meat or poultry products; however, in some products such as pork sausage or uncured meats, an increase in red color may be desired. When selecting a natural antioxidant, sensory and quality impact on the product should be considered to achieve desired traits. PMID:23501254

  2. Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma

    PubMed Central

    Cabaña-Muñoz, María Eugenia; Parmigiani-Izquierdo, José María; Bravo-González, Luis Alberto; Kyung, Hee-Moon; Merino, José Joaquín

    2015-01-01

    Background The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems. Objectives To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings. Materials and Methods 55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (μg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42). Findings Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury. Conclusions Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity. PMID:26076368

  3. Increased sampling reveals novel lineages of Entamoeba: consequences of genetic diversity and host specificity for taxonomy and molecular detection.

    PubMed

    Stensvold, C Rune; Lebbad, Marianne; Victory, Emma L; Verweij, Jaco J; Tannich, Egbert; Alfellani, Mohammed; Legarraga, Paulette; Clark, C Graham

    2011-07-01

    To expand the representation for phylogenetic analysis, ten additional complete Entamoeba small-subunit rRNA gene sequences were obtained from humans, non-human primates, cattle and a tortoise. For some novel sequences no corresponding morphological data were available, and we suggest that these organisms should be referred to as ribosomal lineages (RL) rather than being assigned species names at present. To investigate genetic diversity and host specificity of selected Entamoeba species, a total of 91 new partial small subunit rRNA gene sequences were obtained, including 49 from Entamoeba coli, 18 from Entamoeba polecki, and 17 from Entamoeba hartmanni. We propose a new nomenclature for significant variants within established Entamoeba species. Based on current data we propose that the uninucleated-cyst-producing Entamoeba infecting humans is called Entamoeba polecki and divided into four subtypes (ST1-ST4) and that Entamoeba coli is divided into two subtypes (ST1-ST2). New hosts for several species were detected and, while host specificity and genetic diversity of several species remain to be clarified, it is clear that previous reliance on cultivated material has given us a misleading and incomplete picture of variation within the genus Entamoeba. PMID:21295520

  4. Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health

    PubMed Central

    Ruth, Katherine S.; Beaumont, Robin N.; Tyrrell, Jessica; Jones, Samuel E.; Tuke, Marcus A.; Yaghootkar, Hanieh; Wood, Andrew R.; Freathy, Rachel M.; Weedon, Michael N.; Frayling, Timothy M.; Murray, Anna

    2016-01-01

    STUDY QUESTION How does a genetic variant in the FSHB promoter, known to alter FSH levels, impact female reproductive health? SUMMARY ANSWER The T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) results in longer menstrual cycles and later menopause and, while having detrimental effects on fertility, is protective against endometriosis. WHAT IS KNOWN ALREADY The FSHB promoter polymorphism (rs10835638; c.-211G>T) affects levels of FSHB transcription and, as a result, circulating levels of FSH. FSH is required for normal fertility and genetic variants at the FSHB locus are associated with age at menopause and polycystic ovary syndrome (PCOS). STUDY DESIGN, SIZE, DURATION We used cross-sectional data from the UK Biobank to look at associations between the FSHB promoter polymorphism and reproductive traits, and performed a genome-wide association study (GWAS) for length of menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS We included white British individuals aged 40–69 years in 2006–2010, in the May 2015 release of genetic data from UK Biobank. We tested the FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) for associations with 29, mainly female, reproductive phenotypes in up to 63 350 women and 56 608 men. We conducted a GWAS in 9534 individuals to identify genetic variants associated with length of menstrual cycle. MAIN RESULTS AND THE ROLE OF CHANCE The FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; MAF 0.16) was associated with longer menstrual cycles [0.16 SD (c. 1 day) per minor allele; 95% confidence interval (CI) 0.12–0.20; P = 6 × 10−16], later age at menopause (0.13 years per minor allele; 95% CI 0.04–0.22; P = 5.7 × 10−3), greater female nulliparity [odds ratio (OR) = 1.06; 95% CI 1.02–1.11; P = 4.8 × 10−3] and lower risk of endometriosis (OR = 0.79; 95% CI 0.69–0.90; P = 4.1 × 10−4). The FSH-lowering T allele was not associated with other female

  5. Genetic perturbations that impair functional trait interactions lead to reduced bone strength and increased fragility in mice

    PubMed Central

    Smith, Lauren M.; Bigelow, Erin M.R.; Nolan, Bonnie T.; Faillace, Meghan E.; Nadeau, Joseph H.; Jepsen, Karl J.

    2014-01-01

    Functional adaptation may complicate the choice of phenotype used in genetic studies that seek to identify genes contributing to fracture susceptibility. Often, genetic variants affecting one trait are compensated by coordinated changes in other traits. Bone fracture is a prototypic example because mechanical function of long bones (stiffness and strength) depends on how the system coordinately adjusts the amount (cortical area) and quality (tissue-mineral density, TMD) of bone tissue to mechanically offset the natural variation in bone robustness (total area/length). We propose that efforts aimed at identifying genes regulating fracture resistance will benefit from better understanding how functional adaptation contributes to the genotype-phenotype relationship. We analyzed the femurs of C57BL/6J – ChrA/J/NaJ Chromosome Substitution Strains (CSSs) to systemically interrogate the mouse genome for chromosomes harboring genes that regulate mechanical function. These CSSs (CSS-i, i = the substituted chromosome) showed changes in mechanical function on the order of -26.6 to 11.5% relative to the B6 reference strain after adjusting for body size. Seven substitutions showed altered robustness, cortical area, or TMD, but no effect on mechanical function (CSS-4, 5, 8, 9, 17, 18, 19); six substitutions showed altered robustness, cortical area, or TMD, and reduced mechanical function (CSS-1, 2, 6, 10, 12, 15); and one substitution also showed reduced mechanical function but exhibited no significant changes in the three physical traits analyzed in this study (CSS-3). A key feature that distinguished CSSs that maintained function from those with reduced function was whether the system adjusted cortical area and TMD to the levels needed to compensate for the natural variation in bone robustness. These results provide a novel biomechanical mechanism linking genotype with phenotype, indicating that genes control function not only by regulating individual traits, but also by

  6. Antioxidant Impregnated Ultra-High Molecular Weight Polyethylene Wear Debris Particles Display Increased Bone Remodeling and a Superior Osteogenic:Osteolytic Profile vs. Conventional UHMWPE Particles in a Murine Calvaria Model

    PubMed Central

    Chen, Yu; Hallab, Nadim J.; Liao, Yen-Shuo; Narayan, Venkat; Schwarz, Edward M.; Xie, Chao

    2015-01-01

    Periprosthetic osteolysis remains a major limitation of long-term successful total hip replacements with ultra-high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris-induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX™), versus similar wear particles made from COVERNOX™ containing UHMWPE (AOX™), in an established murine calvaria model. Eight-week-old female C57B/6 mice (n=10/Group) received a pre-op micro-CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro-CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72-fold) and osteoclast numbers (1.99-fold) vs. AltrX (p<0.001). However, AOX also significantly induced 1.64-fold more new bone formation vs. AltrX (p<0.01). Moreover, while the osteolytic:osteogenic ratio of both particles was very close to 1.0, which is indicative of coupled remodeling, AOX was more osteogenic (Slope=1.13±0.10 vs. 0.97±0.10). Histomorphometry of the metabolically labeled undecalcified calvaria revealed a consistent trend of greater MAR in AOX vs. AltrX. Collectively, these results demonstrate that anti-oxidant impregnated UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. PMID:26495749

  7. Simultaneous analysis of multiple enzymes increases accuracy of pulsed-field gel electrophoresis in assigning genetic relationships among homogeneous Salmonella strains.

    PubMed

    Zheng, Jie; Keys, Christine E; Zhao, Shaohua; Ahmed, Rafiq; Meng, Jianghong; Brown, Eric W

    2011-01-01

    Due to a highly homogeneous genetic composition, the subtyping of Salmonella enterica serovar Enteritidis strains to an epidemiologically relevant level remains intangible for pulsed-field gel electrophoresis (PFGE). We reported previously on a highly discriminatory PFGE-based subtyping scheme for S. enterica serovar Enteritidis that relies on a single combined cluster analysis of multiple restriction enzymes. However, the ability of a subtyping method to correctly infer genetic relatedness among outbreak strains is also essential for effective molecular epidemiological traceback. In this study, genetic and phylogenetic analyses were performed to assess whether concatenated enzyme methods can cluster closely related salmonellae into epidemiologically relevant hierarchies. PFGE profiles were generated by use of six restriction enzymes (XbaI, BlnI, SpeI, SfiI, PacI, and NotI) for 74 strains each of S. enterica serovar Enteritidis and S. enterica serovar Typhimurium. Correlation analysis of Dice similarity coefficients for all pairwise strain comparisons underscored the importance of combining multiple enzymes for the accurate assignment of genetic relatedness among Salmonella strains. The mean correlation increased from 81% and 41% for single-enzyme PFGE up to 99% and 96% for five-enzyme combined PFGE for S. enterica serovar Enteritidis and S. enterica serovar Typhimurium strains, respectively. Data regressions approached 100% correlation among Dice similarities for S. enterica serovar Enteritidis and S. enterica serovar Typhimurium strains when a minimum of six enzymes were concatenated. Phylogenetic congruence measures singled out XbaI, BlnI, SfiI, and PacI as most concordant for S. enterica serovar Enteritidis, while XbaI, BlnI, and SpeI were most concordant among S. enterica serovar Typhimurium strains. Together, these data indicate that PFGE coupled with sufficient enzyme numbers and combinations is capable of discerning accurate genetic relationships among

  8. Functional analysis of genetic polymorphism in Wuchereria bancrofti glutathione S-transferase antioxidant gene: impact on protein structure and enzyme catalysis.

    PubMed

    Sakthidevi, Moorthy; Prabhu, Prince Rajaiah; Chowdhary, Swati; Hoti, Sugeerappa Laxmanappa; Kaliraj, Perumal

    2013-01-01

    Wuchereria bancrofti glutathione S-transferase (Wb-GST) is referred as a promising chemotherapeutic target for lymphatic filariasis. GST represents the major class of detoxifying enzymes of the tissue dwelling parasitic helminths. Though many inhibition studies were carried out for Wb-GST, understanding its genetic distribution in parasite population is necessary to develop ideal inhibitor. Our genetic polymorphic studies exposed the existence of three variant Wb-GST alleles in the four endemic regions of India. Moreover, it also revealed the variability in the distribution of Wb-GST alleles in the studied population. Therefore we cloned, expressed and purified the recombinant variant Wb-GST proteins to study the mutation impact on its structure and hence on its catalysis. Among the studied mutations, the I60F/G78S substitutions in the N-terminal domain and loop region connecting the two domains of Wb-GST lowered the affinity for glutathione and its analog, S-hexyl glutathione. Moreover, molecular modeling and docking studies revealed that the I60F/G78S mutations affected the proximity of Trp38 and Arg95 in glutathione binding site resulting in weaker interaction with S-hexyl glutathione. Besides, the variants also had lower affinity (Ki) and higher IC50 values for well-known GST inhibitors. Interestingly, the Wb-GST variant proteins showed enhanced catalytic efficiency for lipid peroxidation products which are produced due to oxidative stress. Thus, our study provides evidence for the functional impact of mutations on Wb-GST protein and also spotlights the mechanisms of parasite survival against the host oxidative stress environment. PMID:24188745

  9. Oxidative stress and antioxidant strategies in dermatology.

    PubMed

    Baek, Jinok; Lee, Min-Geol

    2016-07-01

    Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology. PMID:26020527

  10. Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes

    PubMed Central

    Zhang, Luoping; Hayes, Richard B.; Guo, Weihong; McHale, Cliona M.; Yin, Songnian; Wiencke, John K.; O’Neill, J. Patrick; Rothman, Nathaniel; Li, Gui-Lan; Smith, Martyn T.

    2005-01-01

    1,3-Butadiene (BD) is an important industrial chemical and pollutant. Its ability to induce genetic damage and cause hematological malignancies in humans is controversial. We have examined chromosome damage by fluorescence in situ hybridization (FISH) and mutations in the HPRT gene in the blood of Chinese workers exposed to BD. Peripheral blood samples were collected and cultured from 39 workers exposed to BD (median level 2 ppm, 6 h time-weighted average) and 38 matched controls in Yanshan, China. No difference in the level of aneuploidy or structural changes in chromosomes 1, 7, 8, and 12 was detected in metaphase cells from exposed subjects in comparison with matched controls, nor was there an increase in the frequency of HPRT mutations in the BD-exposed workers. Because genetic polymorphisms in glutathione S-transferase (GST) enzymes and microsomal epoxide hydrolase (EPHX1) may affect the genotoxic effects of BD and its metabolites, we also related chromosome alterations and gene mutations to GSTT1, GSTM1 and EPHX1 genotypes. Overall, there was no effect of variants in these genotypes on numerical or structural changes in chromosomes 1, 7, 8 and 12 or on HPRT mutant frequency in relation to BD exposure, but the GST genotypes did influence background levels of both hyperdiploidy and HPRT mutant frequency. In conclusion, our data show no increase in chromosomal aberrations or HPRT mutations among workers exposed to BD, even in potentially susceptible genetic subgroups. The study is, however, quite small and the levels of BD exposure are not extremely high, but our findings in China do support those from a similar study conducted in the Czech Republic. Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage. PMID:15036120

  11. Inositol deficiency increases the susceptibility to neural tube defects of genetically predisposed (curly tail) mouse embryos in vitro.

    PubMed

    Cockroft, D L; Brook, F A; Copp, A J

    1992-02-01

    Curly tail (ct/ct) mouse embryos, which have a genetic predisposition for neural tube defects (NTD), were grown in culture from the 2-5 somite stage, before the initiation of neurulation, up to the 22-24 somite stage, when closure of the anterior neural tube is normally complete. The embryos were cultured in whole rat serum or in extensively dialysed serum supplemented with glucose, amino acids, and vitamins, with inositol omitted or added at concentrations of 2, 10, 20, and 50 mg/l. Two strains were used as controls; CBA mice, which are related to curly tails, and an unrelated PO stock. It was found that ct/ct embryos were particularly sensitive to inositol deficiency; both they and the CBA embryos showed a similar high incidence of cranial NTD after culture in inositol deficient medium (12/17 and 11/18, respectively). Furthermore, the lowest dose of inositol had no effect on the frequency of head defects in ct/ct mice, though it halved the incidence in CBA embryos. With higher inositol concentrations, the majority of ct/ct embryos completed head closure normally, and their development was generally similar to that obtained in whole serum. PO embryos showed a lower proportion (5/19) of cranial NTD in the inositol deficient medium than the other two strains, and this was further reduced by even the lowest inositol dose. PMID:1615432

  12. Testing directed evolution strategies for space exploration: genetic modification of photosystem II to increase stress tolerance under space conditions

    NASA Astrophysics Data System (ADS)

    Bertalan, I.; Giardi, M. T.; Johanningmeier, U.

    Plants and many microorganisms are able to convert and store solar energy in chemical bonds by a process called photosynthesis They remove CO 2 from the atmosphere fix it as carbohydrate and simultaneously evolve oxygen Oxygen evolution is of supreme relevance for all higher life forms and results from the splitting of water molecules This process is catalyzed by the so called photosystem II PSII complex and represents the very beginning of biomass production PS II is also a central point of regulation being responsive to various physical and physiological parameters Complex space radiation is damaging PS II and reduces photosynthetic efficiency Thus bioregenerative life-support systems are severely disturbed at this point Genetic manipulation of photosynthesis checkpoints offer the possibility to adjust biomass and oxygen production to changing environmental conditions As the photosynthetic apparatus has adapted to terrestrial and not to space conditions we are trying to adapt a central and particularly stress-susceptible element of the photosynthesis apparatus - the D1 subunit of PS II - to space radiation by a strategy of directed evolution The D1 subunit together with its sister subunit D2 form the reaction centre of PS II D1 presents a central weak point for radiation energy that hits the chloroplast We have constructed a mutant of the green alga Chlamydomonas reinhardtii with a defect D1 protein This mutant is easily transformable with D1-encoding PCR fragments without purification and cloning steps 1 When

  13. Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity

    PubMed Central

    Rahmani, Arshad H; Albutti, Aqel S; Aly, Salah M

    2014-01-01

    The current mode of treatment for various diseases is based on synthetic drugs are effective but they show adverse effect and also alter the genetic and metabolic activity. Moreover, some drugs prepared from plants and their constituents show potentiality with more efficacy than synthetic agents used in clinical therapy. Earlier report has shown that regular consumption of fruits and vegetables is strongly related with reduced risk of developing various diseases. Several epidemiological studies has shown that, the incidence heart disease and cancers is lowest in the Mediterranean basin as compared to the part of the world because of their diet rich in olives and olive products. Olives are commonly consumed in Mediterranean and Arabian Peninsula and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that, the constituents from olive such as oleuropein, squalene and hydroxytyrosol modulate the genes functions and other activities. In this review, the medicinal value of olives and their constituents are summarized in terms of therapeutic approach in the diseases management through regulation of various activities. PMID:24955148

  14. Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity.

    PubMed

    Rahmani, Arshad H; Albutti, Aqel S; Aly, Salah M

    2014-01-01

    The current mode of treatment for various diseases is based on synthetic drugs are effective but they show adverse effect and also alter the genetic and metabolic activity. Moreover, some drugs prepared from plants and their constituents show potentiality with more efficacy than synthetic agents used in clinical therapy. Earlier report has shown that regular consumption of fruits and vegetables is strongly related with reduced risk of developing various diseases. Several epidemiological studies has shown that, the incidence heart disease and cancers is lowest in the Mediterranean basin as compared to the part of the world because of their diet rich in olives and olive products. Olives are commonly consumed in Mediterranean and Arabian Peninsula and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that, the constituents from olive such as oleuropein, squalene and hydroxytyrosol modulate the genes functions and other activities. In this review, the medicinal value of olives and their constituents are summarized in terms of therapeutic approach in the diseases management through regulation of various activities. PMID:24955148

  15. The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump.

    PubMed

    Gooijert, K E R; Havinga, R; Wolters, H; Wang, R; Ling, V; Tazuma, S; Verkade, H J

    2015-03-01

    Human bile salt export pump (BSEP) mutations underlie progressive familial intrahepatic cholestasis type 2 (PFIC2). In the PFIC2 animal model, Bsep(-/-) mice, biliary secretion of bile salts (BS) is decreased, but that of phospholipids (PL) and cholesterol (CH) is increased. Under physiological conditions, the biliary secretion of PL and CH is positively related ("coupled") to that of BS. We aimed to elucidate the mechanism of increased biliary lipid secretion in Bsep(-/-) mice. The secretion of the BS tauro-β-muricholic acid (TβMCA) is relatively preserved in Bsep(-/-) mice. We infused Bsep(-/-) and Bsep(+/+) (control) mice with TβMCA in stepwise increasing dosages (150-600 nmol/min) and determined biliary bile flow, BS, PL, and CH secretion. mRNA and protein expression of relevant canalicular transporters was analyzed in livers from noninfused Bsep(-/-) and control mice. TβMCA infusion increased BS secretion in both Bsep(-/-) and control mice. The secreted PL or CH amount per BS, i.e., the "coupling," was continuously two- to threefold higher in Bsep(-/-) mice (P < 0.05). Hepatic mRNA expression of canalicular lipid transporters Mdr2, Abcg5, and Abcg8 was 45-55% higher in Bsep(-/-) mice (Abcg5; P < 0.05), as was canalicular Mdr2 and Abcg5 protein expression. Potential other explanations for the increased coupling of the biliary secretion of PL and CH to that of BS in Bsep(-/-) mice could be excluded. We conclude that the mechanism of increased biliary lipid secretion in Bsep(-/-) mice is based on increased expression of the responsible canalicular transporter proteins. PMID:25552583

  16. Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients: Increased Genetic Load of Islet-Expressed and Cytokine-Regulated Candidate Genes Predicts Poorer Glycemic Control.

    PubMed

    Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie Louise; Kaur, Simranjeet; Bergholdt, Regine; Hansen, Lars; Mortensen, Henrik B; Pociot, Flemming; Størling, Joachim

    2016-01-01

    Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease progression. Two-thirds of 46 GWAS candidate genes examined were expressed in human islets, and 11 of these significantly changed expression levels following exposure to proinflammatory cytokines (IL-1β + IFNγ + TNFα) for 48 h. Using the GWAS single nucleotide polymorphisms (SNPs) from each locus, we constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several of the 11 candidate genes have overlapping biological functions and interact in a common network. Our results may help predict disease progression in newly diagnosed children with T1D which can be exploited for optimizing treatment. PMID:26904692

  17. Antioxidant activities from different rosemary clonal lines.

    PubMed

    Ban, Lan; Narasimhamoorthy, Brindha; Zhao, Liuqing; Greaves, John A; Schroeder, William D

    2016-06-15

    Rosemary extract is widely used in food industry and carnosic acid is reported to be the major component that is responsible for its antioxidant activities. However, it is unclear how the numerous plant metabolites interact and contribute to the overall antioxidant activity. In this study, with poultry fat as the model food system, rosemary extract from six clonal lines were evaluated that each represented a different genetic variant. As expected, rosemary extract with higher carnosic acid content had higher antioxidant activity. However, rosemary extract which had carnosic acid removed retained a significant amount of activity. Furthermore, when the individual contributions of carnosic acid and the portion without carnosic acid were evaluated separately, neither was shown to be responsible for the overall level of its stabilization effect from rosemary extract as a whole entity. The interactions among different plant metabolites have a major impact on the overall antioxidant capabilities of rosemary extract. PMID:26868574

  18. Increased total number of genetic aberrations and changes affecting specific chromosomal regions may underlie prostate cancer recurrence and development of hormone-independent growth

    SciTech Connect

    Hyytinen, E.; Visakorpi, T.; Kallioniemi, A.

    1994-09-01

    At the time of diagnosis, prostate carcinomas are often rather slowly proliferating and shows a favorable response to anti-androgen treatment. However, often the tumors metastasize or recur locally and thereafter show an aggressive behavior and rapid growth despite of the endocrine therapy. In order to understand the genetic basis of this change in phenotype and clinical behavior, we used comparative genomic hybridization to analyze for losses and gains of DNA sequences along all human chromosomes in primary prostate carcinomas as well as in local recurrencies during hormonal therapy. The total number of genetic changes in 9 recurrences was almost three times higher than that observed in 31 primary prostate carcinomas. Whereas gains and amplifications were only seen in 6/31 primary tumors, all recurrences showed gains of at least one chromosomal site. Gain of 8q was seen at 89% of recurrences as compared to 6% in the primary tumors. Other prominent increases of prevalence were +X (56% vs. 0%), +7 (50% vs. 6%), and 8p- (78% vs. 32%). In one case where DNA was available from both the primary tumor and recurrence of the same patient, appearance of some of these gains during tumor progression was validated. Analysis of archival formalin-fixed paraffin-embedded tissues by CGH is in progress and will make it possible to extensively compare genetic changes between the primary tumor and its local recurrence or metastasis.

  19. From observation to intervention: development of a psychoeducational intervention to increase uptake of BRCA genetic counseling among high-risk breast cancer survivors.

    PubMed

    Vadaparampil, Susan T; Malo, Teri L; Nam, Kelli M; Nelson, Alison; de la Cruz, Cara Z; Quinn, Gwendolyn P

    2014-12-01

    We describe the development of a psychoeducational intervention (PEI) to increase uptake of genetic counseling targeted to high-risk breast cancer survivors. Based on previous research, scientific literature, and a review of cancer education websites, we identified potential PEI content. We then assessed the initial acceptability and preference of two booklets of identical content but different layouts, by presenting the booklets to individuals with a personal or family history of breast cancer (n = 57). The preferred booklet was evaluated by two focus groups of ten breast cancer patients who had not attended genetic counseling. The booklet was refined based on participants' feedback at each stage. Focus group participants generally found the booklet visually appealing, informative, and helpful, but some thought that it was too long. Final changes were made based on learner verification principles of attraction, comprehension, cultural acceptability, and persuasion. This project produced an interventional tool to present key constructs that may facilitate decision making about risk-appropriate genetic counseling uptake among high-risk breast cancer survivors. The process described for creating, testing, and adapting materials from a patient perspective can be used for developing other PEIs. This newly developed, unique PEI can be used in many clinical settings. PMID:24706196

  20. Antioxidant activity potential of gamma irradiated carrageenan.

    PubMed

    Abad, Lucille V; Relleve, Lorna S; Racadio, Charles Darwin T; Aranilla, Charito T; De la Rosa, Alumanda M

    2013-09-01

    The antioxidant capacity of irradiated κ-, ι-, λ-carrageenans were investigated using the hydroxyl radical scavenging assay, reducing power assay and DPPH radical scavenging capacity assay. The degree of oxidative inhibition increased with increasing concentration and dose. The type of carrageenan had also an influence on its antioxidant activity which followed the order of lambdaIncrease in oxidative property with radiation dose can be attributed mainly to the depolymerization of the carrageenans with corresponding increase in reducing sugar. The antioxidant properties of these carrageenan oligomers were lower than that of ascorbic acid and galactose sugar. PMID:23733032

  1. Calcium addition at the Hubbard Brook Experimental Forest increases sugar storage, antioxidant activity and cold tolerance in native red spruce (Picea rubens).

    PubMed

    Halman, Joshua M; Schaberg, Paul G; Hawley, Gary J; Eagar, Christopher

    2008-06-01

    In fall (November 2005) and winter (February 2006), we collected current-year foliage of native red spruce (Picea rubens Sarg.) growing in a reference watershed and in a watershed treated in 1999 with wollastonite (CaSiO(3), a slow-release calcium source) to simulate preindustrial soil calcium concentrations (Ca-addition watershed) at the Hubbard Brook Experimental Forest (Thornton, NH). We analyzed nutrition, soluble sugar concentrations, ascorbate peroxidase (APX) activity and cold tolerance, to evaluate the basis of recent (2003) differences between watersheds in red spruce foliar winter injury. Foliar Ca and total sugar concentrations were significantly higher in trees in the Ca-addition watershed than in trees in the reference watershed during both fall (P=0.037 and 0.035, respectively) and winter (P=0.055 and 0.036, respectively). The Ca-addition treatment significantly increased foliar fructose and glucose concentrations in November (P=0.013 and 0.007, respectively) and foliar sucrose concentrations in winter (P=0.040). Foliar APX activity was similar in trees in both watersheds during fall (P=0.28), but higher in trees in the Ca-addition watershed during winter (P=0.063). Cold tolerance of foliage was significantly greater in trees in the Ca-addition watershed than in trees in the reference watershed (P<0.001). Our results suggest that low foliar sugar concentrations and APX activity, and reduced cold tolerance in trees in the reference watershed contributed to their high vulnerability to winter injury in 2003. Because the reference watershed reflects forest conditions in the region, the consequences of impaired physiological function caused by soil Ca depletion may have widespread implications for forest health. PMID:18381266

  2. Carotenoids, Birdsong and Oxidative Status: Administration of Dietary Lutein Is Associated with an Increase in Song Rate and Circulating Antioxidants (Albumin and Cholesterol) and a Decrease in Oxidative Damage

    PubMed Central

    Casagrande, Stefania; Pinxten, Rianne; Zaid, Erika; Eens, Marcel

    2014-01-01

    Despite the appealing hypothesis that carotenoid-based colouration signals oxidative status, evidence supporting the antioxidant function of these pigments is scarce. Recent studies have shown that lutein, the most common carotenoid used by birds, can enhance the expression of non-visual traits, such as birdsong. Nevertheless, the underlying physiological mechanisms remain unclear. In this study we hypothesized that male European starlings (Sturnus vulgaris) fed extra lutein increase their song rate as a consequence of an improved oxidative status. Although birdsong may be especially sensitive to the redox status, this has, to the best of our knowledge, never been tested. Together with the determination of circulating oxidative damage (ROMs, reactive oxygen metabolites), we quantified uric acid, albumin, total proteins, cholesterol, and testosterone, which are physiological parameters potentially sensitive to oxidation and/or related to both carotenoid functions and birdsong expression. We found that the birds fed extra lutein sang more frequently than control birds and showed an increase of albumin and cholesterol together with a decrease of oxidative damage. Moreover, we could show that song rate was associated with high levels of albumin and cholesterol and low levels of oxidative damage, independently from testosterone levels. Our study shows for the first time that song rate honestly signals the oxidative status of males and that dietary lutein is associated with the circulation of albumin and cholesterol in birds, providing a novel insight to the theoretical framework related to the honest signalling of carotenoid-based traits. PMID:25549336

  3. Increased risk of stroke in oral contraceptive users carried replicated genetic variants: a population-based case-control study in China.

    PubMed

    Wang, Chun; Li, Ying; Li, Huiqiao; Sun, Tao; Jin, Guangfu; Sun, Zhiming; Zhou, Jian; Ba, Lei; Huang, Zhizheng; Bai, Jianling

    2012-08-01

    Combined oral contraceptives (COC) use is a unique risk factor for stroke in women, and may modify the associations between genetic polymorphisms and stroke. To investigate whether the genetic variants identified in a recent genome-wide association study (GWAS) could be replicated in Chinese women, as well as, whether related risk was different in COC users, 451 stroke cases and 831 age- and region-matched controls were recruited from our cohort. Genotyping of 3 SNPs (rs700651, rs10958409, and rs1333040) was performed by the polymerase chain reaction assay with TaqMan probes. The history of contraceptive use and relevant information were obtained from a face-to-face interview. Odds ratios (OR) with 95 % confidence interval (CI) were estimated under conditional logistic regression model after adjustment for cardiovascular covariates. Our study replicated the associations of rs10958409 and rs1333040, with the risk of stroke, especially hemorrhagic subtype, but failed to confirm association of rs700651. COC use was associated with a 1.56-fold (OR 1.56, 95 % CI 1.21-2.01) increased risk of stroke. COC users with rs10958409 GA/AA or rs1333040 CT/TT genotypes had an increased risk of overall stroke by 1.59-fold (OR 2.59, 95 % CI 1.59-4.19) and 3.24-fold (OR 4.24, 95 % CI 1.71-10.49), respectively, compared with the non-users with wild-type genotypes. Moreover, the risk of hemorrhagic stroke increased by 4.81- and 15.06-fold when risk allele carriers of rs10958409 or rs1333040 who took COC. Our results confirmed the associations of two GWAS SNPs, also suggested combination effects of these genetic variants and COC use on stroke risk. PMID:22476622

  4. Rare Genetic Variation at Zea mays crtRB1 Increases B-Carotene in Maize Grain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breeding to increase b-carotene levels in cereal grains, termed Provitamin A biofortification, is an economical approach to address the challenge of dietary vitamin A deficiency in the developing world. We draw upon experimental evidence from DNA sequence, transcriptional expression, and recombinant...

  5. Antioxidants: basic principles, emerging concepts, and problems.

    PubMed

    Niki, Etsuo

    2014-01-01

    The radical scavenging antioxidants play an essential role in the maintenance of health and prevention of diseases, and a thorough understanding of the action and capacity of antioxidants is critically important. Despite the assumption that antioxidants must exert beneficial effects against oxidative stress, many large-scale randomized controlled trials gave inconsistent and disappointing results on the prevention of chronic diseases. It is now generally accepted that there is no evidence to support the use of non-discriminative antioxidant supplements for prevention of diseases. On the other hand, recent data show that antioxidants may be effective in the prevention and/or treatment of diseases when the right antioxidant is given to the right subject at the right time for the right duration. Now it is accepted that reactive oxygen species (ROS) act as physiologically important signaling messengers as well as deleterious agents. The signaling ROS are produced in a subtly regulated manner, while many deleterious ROS are produced and react randomly. Free radical-mediated lipid peroxidation products which, in contrast to enzymatic oxidation products, are produced by non-specific mechanisms cause oxidative damage, but may also induce adaptive response to enhance the expression of antioxidant enzymes and compounds. This has raised a question if removal of too many ROS by supplementation of antioxidants may upset the cell signaling pathways and actually increase the risk of chronic diseases. However, it is unlikely that antioxidants impair physiologically essential signaling pathways. PMID:24923567

  6. Antioxidant-Induced Stress

    PubMed Central

    Villanueva, Cleva; Kross, Robert D.

    2012-01-01

    Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals. PMID:22408440

  7. Antioxidants accelerate lung cancer progression in mice.

    PubMed

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production. PMID:24477002

  8. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  9. Antioxidants and antioxidant activity of several pigmented rice brans.

    PubMed

    Laokuldilok, Thunnop; Shoemaker, Charles F; Jongkaewwattana, Sakda; Tulyathan, Vanna

    2011-01-12

    This study investigated the antioxidant content and activity of phenolic acids, anthocyanins, α-tocopherol and γ-oryzanol in pigmented rice (black and red rice) brans. After methanolic extraction, the DPPH free radical scavenging activity and antioxidant activity were measured. The pigmented rice bran extract had a greater reducing power than a normal rice bran extract from a long grain white rice. All bran extracts were highly effective in inhibiting linoleic acid peroxidation (60-85%). High-performance liquid chromatography (HPLC) analysis of antioxidants in rice bran found that γ-oryzanol (39-63%) and phenolic acids (33-43%) were the major antioxidants in all bran samples, and black rice bran also contained anthocyanins 18-26%. HPLC analysis of anthocyanins showed that pigmented bran was rich in cyanidin-3-glucoside (58-95%). Ferulic acid was the dominant phenolic acid in the rice bran samples. Black rice bran contained gallic, hydroxybenzoic, and protocatechuic acids in higher contents than red rice bran and normal rice bran. Furthermore, the addition of 5% black rice bran to wheat flour used for making bread produced a marked increase in the free radical scavenging and antioxidant activity compared to a control bread. PMID:21141962

  10. Association between sperm DNA integrity and seminal plasma antioxidant levels in health workers occupationally exposed to ionizing radiation

    SciTech Connect

    Kumar, Dayanidhi; Salian, Sujith Raj; Kalthur, Guruprasad; Uppangala, Shubhashree; Kumari, Sandhya; Challapalli, Srinivas; Chandraguthi, Shrinidhi Gururajarao; Jain, Navya; Krishnamurthy, Hanumanthappa; Kumar, Pratap; Adiga, Satish Kumar

    2014-07-15

    There is a paucity of data regarding the association between occupational radiation exposure and risk to human fertility. Recently, we provided the first evidence on altered sperm functional characteristics, DNA damage and hypermethylation in radiation health workers. However, there is no report elucidating the association between seminal plasma antioxidants and sperm chromatin integrity in occupationally exposed subjects. Here, we assessed the seminal plasma antioxidants and lipid peroxidation level in 83 men who were occupationally exposed to ionizing radiation and then correlated with the sperm chromatin integrity. Flow cytometry based sperm chromatin integrity assay revealed a significant decline in αt value in the exposed group in comparison to the non-exposed group (P<0.0001). Similarly, both total and reduced glutathione levels and total antioxidant capacity in the seminal plasma were significantly higher in exposed group than the non-exposed group (P<0.01, 0.001 and 0.0001, respectively). However, superoxide dismutase level and malondialdehyde level, which is an indicator of lipid peroxidation in the seminal plasma, did not differ significantly between two groups. The total antioxidant capacity (TAC) and GSH level exhibited a positive correlation with sperm DNA integrity in exposed subjects. To conclude, this study distinctly shows that altered sperm chromatin integrity in radiation health workers is associated with increase in seminal plasma antioxidant level. Further, the increased seminal plasma GSH and TAC could be an adaptive measure to tackle the oxidative stress to protect genetic and functional sperm deformities in radiation health workers. - Highlights: • Seminal plasma antioxidants were measured in men occupationally exposed to radiation. • Sperm chromatin integrity was significantly affected in the exposed group. • Glutathione and total antioxidant capacity was significantly higher in exposed group. • Sperm DNA damage in exposed subjects

  11. Genetically Enhanced Sorghum and Sugarcane: Engineering Hydrocarbon Biosynthesis and Storage together with Increased Photosynthetic Efficiency into the Saccharinae

    SciTech Connect

    2012-02-15

    PETRO Project: UIUC is working to convert sugarcane and sorghum—already 2 of the most productive crops in the world—into dedicated bio-oil crop systems. Three components will be engineered to produce new crops that have a 50% higher yield, produce easily extractable oils, and have a wider growing range across the U.S. This will be achieved by modifying the crop canopy to better distribute sunlight and increase its cold tolerance. By directly producing oil in the shoots of these plants, these biofuels could be easily extracted with the conventional crushing techniques used today to extract sugar.

  12. Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels

    PubMed Central

    Chang, Ming-Kang; Kramer, Ina; Huber, Thomas; Kinzel, Bernd; Guth-Gundel, Sabine; Leupin, Olivier; Kneissel, Michaela

    2014-01-01

    We identified previously in vitro LRP4 (low-density lipoprotein receptor-related protein 4) as a facilitator of the WNT (Wingless-type) antagonist sclerostin and found mutations disrupting this function to be associated with high bone mass in humans similar to patients lacking sclerostin. To further delineate the role of LRP4 in bone in vivo, we generated mice lacking Lrp4 in osteoblasts/osteocytes or osteocytes only. Lrp4 deficiency promoted progressive cancellous and cortical bone gain in both mutants, although more pronouncedly in mice deficient in osteoblast/osteocyte Lrp4, consistent with our observation in human bone that LRP4 is most strongly expressed by osteoblasts and early osteocytes. Bone gain was related primarily to increased bone formation. Interestingly, Lrp4 deficiency in bone dramatically elevated serum sclerostin levels whereas bone expression of Sost encoding for sclerostin was unaltered, indicating that osteoblastic Lrp4 retains sclerostin within bone. Moreover, we generated anti-LRP4 antibodies selectively blocking sclerostin facilitator function while leaving unperturbed LRP4–agrin interaction, which is essential for neuromuscular junction function. These antibodies increased bone formation and thus cancellous and cortical bone mass in skeletally mature rodents. Together, we demonstrate a pivotal role of LRP4 in bone homeostasis by retaining and facilitating sclerostin action locally and provide a novel avenue to bone anabolic therapy by antagonizing LRP4 sclerostin facilitator function. PMID:25404300

  13. Antioxidant impregnated ultra-high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model.

    PubMed

    Chen, Yu; Hallab, Nadim J; Liao, Yen-Shuo; Narayan, Venkat; Schwarz, Edward M; Xie, Chao

    2016-05-01

    Periprosthetic osteolysis remains a major limitation of long-term successful total hip replacements with ultra-high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris-induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX(™) ), versus similar wear particles made from COVERNOX(™) containing UHMWPE (AOX(™) ), in an established murine calvaria model. Eight-week-old female C57B/6 mice (n = 10/Group) received a pre-op micro-CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro-CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72-fold) and osteoclast numbers (1.99-fold) vs. AltrX (p < 0.001). However, AOX also significantly induced 1.64-fold more new bone formation vs. AltrX (p < 0.01). Moreover, while the osteolytic:osteogenic ratio of both particles was very close to 1.0, which is indicative of coupled remodeling, AOX was more osteogenic (Slope = 1.13 ± 0.10 vs. 0.97 ± 0.10). Histomorphometry of the metabolically labeled undecalcified calvaria revealed a consistent trend of greater MAR in AOX vs. AltrX. Collectively, these results demonstrate that anti-oxidant impregnated UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:845-851, 2016. PMID:26495749

  14. Oxidative stress, circulating antioxidants, and dietary preferences in songbirds.

    PubMed

    Alan, Rebecca R; McWilliams, Scott R

    2013-03-01

    Oxidative stress is an unavoidable consequence of metabolism and increases during intensive exercise. This is especially problematic for migratory birds that metabolize fat to fuel long-distance flight. Birds can mitigate damage by increasing endogenous antioxidants (e.g. uric acid) or by consuming dietary antioxidants (e.g. tocopherol). During flight, birds may increase protein catabolism of lean tissue which may increase circulating uric acid and many birds also consume an antioxidant-rich frugivorous diet during autumn migration. We evaluated three related hypotheses in a migratory passerine: (1) protein consumption is positively related to circulating antioxidants, (2) a dietary oxidative stressor [i.e. polyunsaturated fatty acid (PUFA)] influences antioxidant capacity and oxidative damage, and (3) oxidative stress influences dietary antioxidant preferences. White-throated Sparrows (Zonotrichia albicollis) consuming a high protein diet increased circulating uric acid; however, uric acid, antioxidant capacity, and oxidative stress did not differ between birds consuming a high PUFA versus a low PUFA diet, despite increased oxidative damage in high PUFA birds. Birds did not prefer antioxidant-rich diets even when fed high PUFA, low protein. We conclude that White-throated Sparrows successfully mitigated oxidative damage associated with a high PUFA diet and mounted an endogenous antioxidant response independent of uric acid, other circulating antioxidants, and dietary antioxidants. PMID:23270695

  15. Maximizing Antioxidants in Fruits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fruits contain high levels of antioxidant compounds, such as carotenoids, flavonoids, vitamins, and phenols. These antioxidants are capable of performing a number of functions including free radical scavengers, peroxide decomposers, singlet and triplet oxygen quenchers, enzyme inhibitors, and synerg...

  16. Maximizing Antioxidants in Fruits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fruits contain high levels of antioxidant compounds, such as carotenoids, flavonoids, vitamins, and phenols. These antioxidants are capable of performing a number of functions including free radical scavengers, peroxide decomposers, singlet and triplet oxygen quenchers, enzyme inhibitors, and syner...

  17. Soy isoflavones increase quinone reductase in hepa-1c1c7 cells via estrogen receptor beta and nuclear factor erythroid 2-related factor 2 binding to the antioxidant response element.

    PubMed

    Froyen, Erik B; Steinberg, Francene M

    2011-09-01

    Soy protein and isoflavones (genistein and daidzein) have been demonstrated to increase quinone reductase (QR) activity, protein, and mRNA in animal and cell culture models. However, their mechanism of action has not been completely characterized. Additionally, it has not been determined if equol, a daidzein metabolite, can modulate QR activity and expression. Estrogen receptor beta (ERβ) is thought to be involved in stimulating QR gene transcription by anti-estrogens and phytoestrogens, along with nuclear factor erythroid 2-related factor 2 (Nrf2). This study tested the hypothesis that genistein, daidzein and equol increase quinone reductase activity, protein and mRNA via ERβ and Nrf2 binding to the QR antioxidant response element (ARE). QR expression and activity were determined using TaqMan polymerase chain reaction, protein immunoblots and activity assays. Molecular events were investigated using luciferase reporter gene assays and chromatin immunoprecipitation (ChIP). Hepa-1c1c7 cells were treated with control [0.1% (v:v) dimethyl sulfoxide (DMSO)]; 1 μmol/L β-naphthoflavone (positive control); 5 μmol/L resveratrol (ChIP positive control for ERβ binding) and 1, 5 and 25 μmol/L genistein, daidzein or equol. Treatment durations were 1 h (ChIP), 24 h (mRNA and luciferase assays) and 24 and 48 h (protein and activity). Genistein, daidzein and equol increased QR activity, protein and mRNA, with daidzein and equol having more of an impact at physiologic concentrations (1 and 5 μmol/L) compared to genistein. Furthermore, the study results demonstrate that genistein, daidzein and equol interact with the QR ARE and that daidzein and equol act via both ERβ and Nrf2 binding strongly to the QR ARE. PMID:21167702

  18. Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population.

    PubMed

    Kimpimäki, T; Kulmala, P; Savola, K; Kupila, A; Korhonen, S; Simell, T; Ilonen, J; Simell, O; Knip, M

    2002-10-01

    The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants, 1,005 with increased genetic risk of type 1 diabetes (high risk, human leukocyte antigen DQB1*02/*0302; moderate risk, DQB1*0302/x, where x = other than *02, *0301, or *0602) were monitored for ICA, IAA, GADA, and IA-2A at 3- to 6-month intervals from birth up to a minimum age of 2 yr. In addition, all 15 genetically susceptible children from the general population who had participated in regular immunological follow-up and developed clinical type 1 diabetes by the end of April 2000 were analyzed for the development of autoantibodies. Among 1,005 children, 63 (6.3%) tested positive for at least one autoantibody, 31 for ICA (3.1%), 48 for IAA (4.8%), 23 for GADA (2.3%), and 13 for IA-2A (1.3%) at least once by the age of 2 yr. Both ICA and IAA identified 95% [95% confidence interval (CI), 77.2-99.9%] of those who tested persistently positive for multiple (> or = 2) antibodies at the age of 2 yr, GADA identified 86% (CI, 65.1-97.1%), and IA-2A identified 55% (CI, 32.2-75.6%). Close to half of the antibody-positive children (29 of 63) reverted back to antibody negativity. Autoantibodies disappeared more often among those who tested positive for IAA than among those who tested positive for other autoantibodies (P < or = 0.021). Among the 15 children who developed type 1 diabetes, the disease sensitivity of ICA was 80% (CI, 51.9-95.7%), that of IAA was 93% (CI, 68.0-99.8%), that of GADA was 60% (CI, 32.3-83.7%), and that of IA-2A was 40% (CI, 16.3-67.7%). These results suggest that IAA are characterized by high sensitivity, early appearance, and high frequency of transient antibody positivity, whereas ICA detected with a

  19. Cytochrome 4A11 Genetic Polymorphisms Increase Susceptibility to Ischemic Stroke and Associate with Atherothrombotic Events After Stroke in Chinese

    PubMed Central

    Zhang, Biao; Wang, Chun; Liao, Duanxiu; Lin, Jing; Chi, Lifen

    2015-01-01

    To evaluate the associations between four single-nucleotide polymorphisms (SNPs) in CYP4A11 and CYP4F2 and ischemic stroke (IS), and between these variants and atherothrombotic events after stroke. IS patients (n=396) and controls (n=378) were genotyped for two CYP4A11 SNPs (rs2269231 and rs9333025) and two CYP4F2 SNPs (rs2108622 and rs3093135). Patients were followed up for 12 months after the stroke for the atherothrombotic events. The frequency of the rs9333025 GG genotype was significantly higher in IS patients than in controls. Logistic regression analysis showed that the presence of rs9333025 GG in patients was associated with significantly higher risk of IS. Cox regression analysis revealed that the rs9333025 GG genotype was an independent risk factor for atherothrombotic events after stroke. The rs9333025 GG genotype increases patients' susceptibility to IS and is associated with high frequencies of atherothrombotic events in stroke patients. PMID:25734770

  20. Increase of genetic diversity and clonal replacement of epidemic methicillin-resistant Staphylococcus aureus strains in South-East Austria

    PubMed Central

    Zarfel, Gernot; Luxner, Josefa; Folli, Bettina; Leitner, Eva; Feierl, Gebhard; Kittinger, Clemens; Grisold, Andrea

    2016-01-01

    Spa-typing and microarray techniques were used to study epidemiological changes in methicillin-resistant Staphylococcus aureus (MRSA) in South-East Austria. The population structure of 327 MRSA isolated between 2002 and 2012 was investigated. MRSA was assigned to 58 different spa types and 14 different MLST CC (multilocus sequence type clonal complexes); in particular, between 2007 and 2012, an increasing diversity in MRSA clones could be observed. The most abundant clonal complex was CC5. On the respective SCCmec cassettes, the CC5 isolates differed clearly within this decade and CC5/SCCmecI, the South German MRSA, predominant in 2002, was replaced by CC5/SCCmecII, the Rhine-Hesse MRSA in 2012. Whereas in many European countries MLST CC22-MRSA (EMRSA 15, the Barnim epidemic MRSA) is predominant, this clone occurred in Austria nearly 10 years later than in neighbouring countries. CC45, the Berlin EMRSA, epidemic in Germany, was only sporadically found in South-East Austria. The Irish ST8-MRSA-II represented by spa-type t190 was frequently found in 2002 and 2007, but disappeared in 2012. Our results demonstrate clonal replacement of MRSA clones within the last years in Austria. Ongoing surveillance is warranted for detection of changes within the MRSA population. PMID:27231237

  1. Increase of genetic diversity and clonal replacement of epidemic methicillin-resistant Staphylococcus aureus strains in South-East Austria.

    PubMed

    Zarfel, Gernot; Luxner, Josefa; Folli, Bettina; Leitner, Eva; Feierl, Gebhard; Kittinger, Clemens; Grisold, Andrea

    2016-07-01

    Spa-typing and microarray techniques were used to study epidemiological changes in methicillin-resistant Staphylococcus aureus (MRSA) in South-East Austria. The population structure of 327 MRSA isolated between 2002 and 2012 was investigated. MRSA was assigned to 58 different spa types and 14 different MLST CC (multilocus sequence type clonal complexes); in particular, between 2007 and 2012, an increasing diversity in MRSA clones could be observed. The most abundant clonal complex was CC5. On the respective SCCmec cassettes, the CC5 isolates differed clearly within this decade and CC5/SCCmecI, the South German MRSA, predominant in 2002, was replaced by CC5/SCCmecII, the Rhine-Hesse MRSA in 2012. Whereas in many European countries MLST CC22-MRSA (EMRSA 15, the Barnim epidemic MRSA) is predominant, this clone occurred in Austria nearly 10 years later than in neighbouring countries. CC45, the Berlin EMRSA, epidemic in Germany, was only sporadically found in South-East Austria. The Irish ST8-MRSA-II represented by spa-type t190 was frequently found in 2002 and 2007, but disappeared in 2012. Our results demonstrate clonal replacement of MRSA clones within the last years in Austria. Ongoing surveillance is warranted for detection of changes within the MRSA population. PMID:27231237

  2. Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylationa

    PubMed Central

    Chow, Jenny D.Y.; Lawrence, Robert T.; Healy, Marin E.; Dominy, John E.; Liao, Jason A.; Breen, David S.; Byrne, Frances L.; Kenwood, Brandon M.; Lackner, Carolin; Okutsu, Saeko; Mas, Valeria R.; Caldwell, Stephen H.; Tomsig, Jose L.; Cooney, Gregory J.; Puigserver, Pere B.; Turner, Nigel; James, David E.; Villén, Judit; Hoehn, Kyle L.

    2014-01-01

    Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology. Characterization of LDKO mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation of proteins in the extra-mitochondrial space. In sum, these data reveal the existence of a compensatory pathway that protects hepatic fat stores when ACC enzymes are inhibited. Furthermore, we identified an important role for ACC enzymes in the regulation of protein acetylation in the extra-mitochondrial space. PMID:24944901

  3. Cutaneous delivery of natural antioxidants: the enhancement approaches.

    PubMed

    Aljuffali, Ibrahim A; Hsu, Ching-Yun; Lin, Yin-Ku; Fang, Jia-You

    2015-01-01

    Topically applied natural antioxidants can be an effective treatment for inhibiting oxidative damage and photoaging of the skin. Due to the barrier function of the stratum corneum (SC), it is necessary to use an enhancement approach to promote the cutaneous absorption of natural antioxidants. Some factors that should be considered when developing delivery systems for natural antioxidants include increased solubility, enhanced storage stability, improved permeability and bioavailability, skin targeting, and minimal side effects. This review describes the skin delivery systems for natural antioxidant permeation that have been developed during the last decade. The antioxidants introduced include vitamins, polyphenols, and carotenoids. Various types of formulations are employed to improve the skin penetration of the antioxidants, such as hydrogels, cyclodextrin, microemulsions, nanoparticles, liposomes and niosomes. This review focuses on the introduction of natural antioxidants used in skin protection, the mechanisms of antioxidant activity on the skin, and formulation designs for enhancing absorption and efficacy. PMID:25925121

  4. COLD-PCR enriches low-level variant DNA sequences and increases the sensitivity of genetic testing.

    PubMed

    Castellanos-Rizaldos, Elena; Milbury, Coren A; Guha, Minakshi; Makrigiorgos, G Mike

    2014-01-01

    Detection of low-level mutations is important for cancer biomarker and therapy targets discovery, but reliable detection remains a technical challenge. The newly developed method of CO-amplification at Lower Denaturation temperature PCR (COLD-PCR) helps to circumvent this issue. This PCR-based technology preferentially enriches minor known or unknown variants present in samples with a high background of wild type DNA which often hampers the accurate identification of these minority alleles. This is a simple process that consists of lowering the temperature at the denaturation step during the PCR-cycling protocol (critical denaturation temperature, T c) and inducing DNA heteroduplexing during an intermediate step. COLD-PCR in its simplest forms does not need additional reagents or specific instrumentation and thus, can easily replace conventional PCR and at the same time improve the mutation detection sensitivity limit of downstream technologies. COLD-PCR can be applied in two basic formats: fast-COLD-PCR that can enrich T m-reducing mutations and full-COLD-PCR that can enrich all mutations, though it requires an intermediate cross-hybridization step that lengthens the thermocycling program. An improved version of full-COLD-PCR (improved and complete enrichment, ice-COLD-PCR) has also been described. Finally, most recently, we developed yet another form of COLD-PCR, temperature-tolerant-COLD-PCR, which gradually increases the denaturation temperature during the COLD-PCR reaction, enriching diverse targets using a single cycling program. This report describes practical considerations for application of fast-, full-, ice-, and temperature-tolerant-COLD-PCR for enrichment of mutations prior to downstream screening. PMID:24259002

  5. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs.

    PubMed

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS-LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  6. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs

    PubMed Central

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS–LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  7. Genetic damage in patients moving from hemodialysis to online hemodiafiltration.

    PubMed

    Rodríguez-Ribera, Lara; Pastor, Susana; Corredor, Zuray; Silva, Irene; Diaz, Juan Manuel; Ballarin, José; Marcos, Ricardo; Coll, Elisabeth

    2016-03-01

    End-stage renal failure patients exhibit a high incidence of genetic damage and genomic instability. Part of this genetic damage is assumed to be caused by the hemodialysis (HD) procedure. To reduce these effects, different alternative HD procedures have been proposed, such as the use of high efficiency convective therapies to improve the reactive oxygen species/antioxidant ratio. To determine the efficiency of online hemodiafiltration (HDF) technique on the levels of DNA damage, we have measured the frequency of micronucleus in peripheral blood lymphocytes of 33 individuals moving from low-flux HD to post-dilution online HDF. In addition to basal levels of genetic damage, potential changes in radiosensitivity were measured as indicators of genomic instability. Plasma antioxidant capacity was also determined. Second samples were obtained after 6 months on the HDF protocol. Results indicate that moving to online HDF therapy produce a significant reduction of the basal levels of genetic damage, but does not affect the genomic instability status. In addition, a greater increase in plasma antioxidant capacity was observed. In spite of the lack of correlation between these parameters, our results confirm the usefulness of the online HDF technique as a way to reduce DNA damage in HD patients. PMID:26285921

  8. Antioxidant compounds and antioxidant activity in "early potatoes".

    PubMed

    Leo, Lucia; Leone, Antonella; Longo, Cristiano; Lombardi, Domenico Antonio; Raimo, Francesco; Zacheo, Giuseppe

    2008-06-11

    The antioxidant content and the antioxidant capacity of both hydrophilic and lipophilic antioxidant extracts from four "early potato" cultivars, grown in two different locations (Racale and Monteroni), were examined. There was a considerable variation in carotenoid content and weak differences in the ascorbic acid concentration of the examined cultivars of "early potato" and between the harvested locations. An increase in both methanol/water (8:2 v/v) and phosphate buffer soluble (PBS) free phenols (70%) and bound phenols (28%) in the extracts from the cultivars grown at Racale site was found and discussed. Examination of individual phenols revealed that chlorogenic acid and catechin were the major phenols present in potato tuber extracts; a moderate amount of caffeic acid and ferulic acid was also detected. The total equivalent antioxidant capacity (TEAC) was higher in the Racale extracts and a highly positive linear relationship ( R (2) = 0.8193) between TEAC values and total phenolic content was observed. The oxyradical scavenging capacity (TOSC) of methanol/water and PBS extracts of peel and whole potatoes against the reactive oxygen species (ROS) peroxyl radicals, peroxynitrite, and hydroxyl radicals was also analyzed. A highly significant linear correlation ( R (2) = 0.9613) between total antioxidant capacity (as a sum of peroxyl radicals + peroxynitrite) and total phenol content of methanol/water extracts was established. Moreover, proliferation of human mammalian cancer (MCF-7) cells was significantly inhibited in a dose-dependent manner after exposure to potato extracts. These data can be useful for "early potato" tuber characterization and suggest that the "early potato" has a potential as a dietary source of antioxidants. PMID:18476702

  9. Increased support for linkage of a novel locus on chromosome 5q13 for essential hypertension in the British Genetics of Hypertension Study.

    PubMed

    Munroe, Patricia B; Wallace, Chris; Xue, Ming-Zhan; Marçano, Ana Carolina B; Dobson, Richard J; Onipinla, Abiodun K; Burke, Beverley; Gungadoo, Johannie; Newhouse, Stephen J; Pembroke, Janine; Brown, Morris; Dominiczak, Anna F; Samani, Nilesh J; Lathrop, Mark; Connell, John; Webster, John; Clayton, David; Farrall, Martin; Mein, Charles A; Caulfield, Mark

    2006-07-01

    Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of odds=2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22, 2.84, and 2.51. The placement of additional markers on 2q, 6q, and 9q diminished support for linkage in these regions. However, the addition of new data and families identified novel regions of interest on chromosomes 1q and 11q. The 3 positive markers in the chromosome 5 region were also genotyped in 712 distinct parent-offspring trios with the same severe phenotype to replicate linkage and association. Borderline support for replication was found (P=0.07). We found increased evidence for linkage and borderline-significant evidence for association for a hypertension susceptibility locus on chromosome 5q13 that is worthy of detailed fine mapping and assessment of candidate genes. PMID:16754790

  10. Replication of a Gene-Environment Interaction via Multimodel Inference: Additive-Genetic Variance in Adolescents’ General Cognitive Ability Increases with Family-of-Origin Socioeconomic Status

    PubMed Central

    Kirkpatrick, Robert M.; McGue, Matt; Iacono, William G.

    2015-01-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES—an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  11. Impact of NGS in the medical sciences: Genetic syndromes with an increased risk of developing cancer as an example of the use of new technologies.

    PubMed

    Lapunzina, Pablo; López, Rocío Ortiz; Rodríguez-Laguna, Lara; García-Miguel, Purificación; Martínez, Augusto Rojas; Martínez-Glez, Víctor

    2014-03-01

    The increased speed and decreasing cost of sequencing, along with an understanding of the clinical relevance of emerging information for patient management, has led to an explosion of potential applications in healthcare. Currently, SNP arrays and Next-Generation Sequencing (NGS) technologies are relatively new techniques used to scan genomes for gains and losses, losses of heterozygosity (LOH), SNPs, and indel variants as well as to perform complete sequencing of a panel of candidate genes, the entire exome (whole exome sequencing) or even the whole genome. As a result, these new high-throughput technologies have facilitated progress in the understanding and diagnosis of genetic syndromes and cancers, two disorders traditionally considered to be separate diseases but that can share causal genetic alterations in a group of developmental disorders associated with congenital malformations and cancer risk. The purpose of this work is to review these syndromes as an example of a group of disorders that has been included in a panel of genes for NGS analysis. We also highlight the relationship between development and cancer and underline the connections between these syndromes. PMID:24764758

  12. Impact of NGS in the medical sciences: Genetic syndromes with an increased risk of developing cancer as an example of the use of new technologies

    PubMed Central

    Lapunzina, Pablo; López, Rocío Ortiz; Rodríguez-Laguna, Lara; García-Miguel, Purificación; Martínez, Augusto Rojas; Martínez-Glez, Víctor

    2014-01-01

    The increased speed and decreasing cost of sequencing, along with an understanding of the clinical relevance of emerging information for patient management, has led to an explosion of potential applications in healthcare. Currently, SNP arrays and Next-Generation Sequencing (NGS) technologies are relatively new techniques used to scan genomes for gains and losses, losses of heterozygosity (LOH), SNPs, and indel variants as well as to perform complete sequencing of a panel of candidate genes, the entire exome (whole exome sequencing) or even the whole genome. As a result, these new high-throughput technologies have facilitated progress in the understanding and diagnosis of genetic syndromes and cancers, two disorders traditionally considered to be separate diseases but that can share causal genetic alterations in a group of developmental disorders associated with congenital malformations and cancer risk. The purpose of this work is to review these syndromes as an example of a group of disorders that has been included in a panel of genes for NGS analysis. We also highlight the relationship between development and cancer and underline the connections between these syndromes. PMID:24764758

  13. Replication of a gene-environment interaction Via Multimodel inference: additive-genetic variance in adolescents' general cognitive ability increases with family-of-origin socioeconomic status.

    PubMed

    Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

    2015-03-01

    The present study of general cognitive ability attempts to replicate and extend previous investigations of a biometric moderator, family-of-origin socioeconomic status (SES), in a sample of 2,494 pairs of adolescent twins, non-twin biological siblings, and adoptive siblings assessed with individually administered IQ tests. We hypothesized that SES would covary positively with additive-genetic variance and negatively with shared-environmental variance. Important potential confounds unaddressed in some past studies, such as twin-specific effects, assortative mating, and differential heritability by trait level, were found to be negligible. In our main analysis, we compared models by their sample-size corrected AIC, and base our statistical inference on model-averaged point estimates and standard errors. Additive-genetic variance increased with SES-an effect that was statistically significant and robust to model specification. We found no evidence that SES moderated shared-environmental influence. We attempt to explain the inconsistent replication record of these effects, and provide suggestions for future research. PMID:25539975

  14. An Analysis of Factors Affecting Genotyping Success from Museum Specimens Reveals an Increase of Genetic and Morphological Variation during a Historical Range Expansion of a European Spider

    PubMed Central

    Krehenwinkel, Henrik; Pekar, Stano

    2015-01-01

    Natural history collections house an enormous amount of plant and animal specimens, which constitute a promising source for molecular analyses. Storage conditions differ among taxa and can have a dramatic effect on the success of DNA work. Here, we analyze the feasibility of DNA extraction from ethanol preserved spiders (Araneae). We tested genotyping success using several hundred specimens of the wasp spider, Argiope bruennichi, deposited in two large German natural history collections. We tested the influence of different factors on the utility of specimens for genotyping. Our results show that not the specimen’s age, but the museum collection is a major predictor of genotyping success. These results indicate that long term storage conditions should be optimized in natural history museums to assure the utility of collections for DNA work. Using historical material, we also traced historical genetic and morphological variation in the course of a poleward range expansion of A. bruennichi by comparing contemporary and historical specimens from a native and an invasive population in Germany. We show that the invasion of A. bruennichi is tightly correlated with an historical increase of genetic and phenotypic variation in the invasive population. PMID:26309219

  15. An Analysis of Factors Affecting Genotyping Success from Museum Specimens Reveals an Increase of Genetic and Morphological Variation during a Historical Range Expansion of a European Spider.

    PubMed

    Krehenwinkel, Henrik; Pekar, Stano

    2015-01-01

    Natural history collections house an enormous amount of plant and animal specimens, which constitute a promising source for molecular analyses. Storage conditions differ among taxa and can have a dramatic effect on the success of DNA work. Here, we analyze the feasibility of DNA extraction from ethanol preserved spiders (Araneae). We tested genotyping success using several hundred specimens of the wasp spider, Argiope bruennichi, deposited in two large German natural history collections. We tested the influence of different factors on the utility of specimens for genotyping. Our results show that not the specimen's age, but the museum collection is a major predictor of genotyping success. These results indicate that long term storage conditions should be optimized in natural history museums to assure the utility of collections for DNA work. Using historical material, we also traced historical genetic and morphological variation in the course of a poleward range expansion of A. bruennichi by comparing contemporary and historical specimens from a native and an invasive population in Germany. We show that the invasion of A. bruennichi is tightly correlated with an historical increase of genetic and phenotypic variation in the invasive population. PMID:26309219

  16. Healthy Chilean Adolescents with HOMA-IR ≥ 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors

    PubMed Central

    Burrows, R.; Correa-Burrows, P.; Reyes, M.; Blanco, E.; Albala, C.; Gahagan, S.

    2015-01-01

    Objective. To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. Methods. In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. Results. Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. Conclusions. In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk. PMID:26273675

  17. CRP genetic variation and CRP levels are associated with increased PTSD symptoms and physiological responses in a highly traumatized civilian population

    PubMed Central

    Michopoulos, Vasiliki; Rothbaum, Alex O.; Jovanovic, Tanja; Almli, Lynn M.; Bradley, Bekh; Rothbaum, Barbara O.; Gillespie, Charles F.; Ressler, Kerry J.

    2015-01-01

    Objective Increased systemic inflammation is associated with stress-related psychopathology. Specifically, levels of the pro-inflammatory marker C-reactive protein (CRP) are increased in individuals with posttraumatic stress disorder (PTSD). Furthermore, single nucleotide polymorphisms (SNPs) in the CRP gene are associated with CRP levels, risk for cardiovascular disease and obesity. We examined whether polymorphisms within the CRP gene and increased CRP levels are associated with PTSD symptoms and fear physiology in a highly traumatized civilian population. Method Cross-sectional data were collected from subjects recruited from an inner-city public hospital that serves a primarily African American, low socioeconomic population. Participants were interviewed to determine PTSD symptom severity, and a fear-potentiated startle (FPS) paradigm was administered to assess fear-related phenotypes of PTSD. Results One SNP within the CRP gene, rs1130864, was significantly associated with increased PTSD symptoms (N=2692; p=0.004), including ‘being overly alert’ as the most significant individual symptom (N=2698; p =1.5×10−5). Additionally CRP genotype was also associated with the odds of PTSD diagnosis (N=2692; p=0.004). This SNP was also associated with increased CRP levels (N=137; p=0.007), and high CRP levels (>3mg/L) were positively associated with PTSD symptoms (N=187; p=0.032) and FPS to a safety signal (N=135; p<0.005). Conclusions Together, these data indicate that genetic variability in the CRP gene is associated with increased CRP levels and PTSD symptoms, including hyperarousal symptoms. Increased CRP levels were also associated with exacerbated fear-related psychophysiology and PTSD symptoms and diagnosis. These findings offer a potential mechanism by which an increased pro-inflammatory state may lead to heightened PTSD symptoms. PMID:25827033

  18. Simultaneous Activation of Nrf2 and Elevation of Dietary and Endogenous Antioxidant Chemicals for Cancer Prevention in Humans.

    PubMed

    Prasad, Kedar N

    2016-01-01

    Despite extensive studies in cancer prevention, the incidence of cancer is increasing. We review studies that have identified several biochemical and genetic defects as well as potential carcinogens in the diet, environmental factors, and lifestyle-related habits. Two of the biochemical abnormalities increased oxidative stress and chronic inflammation, and chronic exposure to carcinogens and mutagens play a significant role in the initiation of multistage carcinogenesis. Therefore, attenuation of these biochemical defects may be useful in reducing the incidence of cancer. Activation of the transcriptional factor called nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which enhances the levels of antioxidant enzymes and phase-2-detoxifying enzymes by complex mechanisms, may be one of the ways to reduce oxidative stress and chronic inflammation. Antioxidant enzymes destroy free radicals by catalysis, whereas phase-2-detoxifying enzymes remove potential carcinogens by converting them to harmless compounds for elimination from the body. However, increasing the levels of antioxidant enzymes by activating Nrf2 may not be sufficient to decrease oxidative stress and chronic inflammation optimally, because antioxidant chemicals, which are decreased in a high oxidative environment, must also be elevated. This review discusses the regulation of activation of Nrf2 and proposes a hypothesis that an elevation of the levels of antioxidant enzymes and dietary and endogenous antioxidant chemicals simultaneously may reduce the incidence of cancer by decreasing oxidative stress and chronic inflammation. The levels of antioxidant chemicals can be increased by supplementation, but increasing the levels of antioxidant enzymes requires activation of Nrf2 by reactive oxygen species (ROS)-dependent and-independent mechanisms. Several phytochemicals and antioxidant chemicals that activate Nrf2 have been identified. This review also describes clinical studies on antioxidants in cancer

  19. Antioxidant activity of capsaicinoid in canola oil.

    PubMed

    Si, Wenhui; Liang, Yintong; Ma, Ka Ying; Chung, Hau Yin; Chen, Zhen-Yu

    2012-06-20

    Interest in replacing synthetic antioxidants, namely, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), with natural antioxidants is increasing. The present study examined the antioxidant activity of capsaicinoid from chili pepper in heated canola oil. The oxidation was conducted at 60, 90, 120, and 180 °C by monitoring oxygen consumption and the decrease in linoleic acid and α-linolenic acid in canola oil. At 60 °C, capsaicinoid was more effective against oxidation of canola oil compared with BHT. At higher temperatures of 90, 120, and 180 °C, capsaicinoid possessed an antioxidant activity similar to or slightly weaker that that of BHT. It was found that capsaicinoid prevented canola oil from oxidation in a dose-dependent manner. To study the structure-antioxidant relationship, it was found that the trimethylsiloxy (TMS) derivatives of capsaicinoid did not exhibit any antioxidant activity, suggesting the hydroxyl moiety was the functional group responsible for the antioxidant activity of capsaicinoid. It was concluded that capsaicinoid had the potential to be further explored as a natural antioxidant in foods, particularly spicy foods. PMID:22642555

  20. Antioxidants from tropical herbs.

    PubMed

    Razab, Rasyidah; Abdul-Aziz, Azlina

    2010-03-01

    Plants that contain high amounts of polyphenolic compounds are potential candidates for natural antioxidant sources. Studies are on going in the search for new sources of antioxidants. Not much data are available on the antioxidant capacity of tropical herbs. With this in mind, 19 commonly consumed Malaysian herbs were analyzed for their polyphenolic content and antioxidant activities. A majority of these plants have never been studied before with regards to their polyphenolic content and antioxidant activities. The shoots of Anacardium occidentale, the shoots and fruits of Barringtonia racemosa, Pithecellobium jiringa and Parkia speciosa had high polyphenolic contents (> 150 microg gallic acid equivalents/mg dried plant) and antioxidant activities when measured using the ferric reducing antioxidant power (FRAP) (>1.2 mM) and Trolox equivalent antioxidant capacity (TEAC) assays (>2.4 mM). A strong correlation was observed between the two antioxidant assays (FRAP vs TEAC) implying that the plants could both scavenge free radicals and reduce oxidants. There was also a strong correlation between the antioxidant activities and polyphenolic content suggesting the observed antioxidant activities were contributed mainly by the polyphenolics in the plants. PMID:20420325

  1. In Vivo Antioxidant Assays.

    PubMed

    2016-01-01

    Oxidative stress and antioxidant deficiency have been implicated in the pathophysiology of a wide range of diseases and conditions. Consequently, over recent years many different supplementation trials have been implemented, aimed at improving clinical outcomes by boosting antioxidant levels. These trials included supplementation with individual antioxidants, antioxidant combinations, and antioxidant-rich foods such as fruit and vegetable juices and other plant extracts. To ensure that data from these trials are interpreted correctly, it is essential that suitable biomarkers are used to assess changes in in vivo antioxidant activity resulting from supplementation. Therefore, the measurement of antioxidant systems, such as superoxide dismutase, catalase, glutathione reductase, and status of other molecules in biological fluids with their quantification methods are simplified in this chapter. PMID:26939271

  2. Peppermint antioxidants revisited.

    PubMed

    Riachi, Liza G; De Maria, Carlos A B

    2015-06-01

    This review discusses the relationship between the chemical composition and antioxidant property of peppermint tisane and essential oil. Phenolic acids (e.g. rosmarinic and caffeic acids), flavones (e.g. luteolin derivatives) and flavanones (e.g. eriocitrin derivatives) are possibly the major infusion antioxidants. Vitamin antioxidants (e.g. ascorbic acid and carotenoids) are minor contributors to the overall antioxidant potential. Unsaturated terpenes having a cyclohexadiene structure (e.g. terpinene) and minor cyclic oxygenated terpenes (e.g. thymol), may contribute to antioxidant potential whilst acyclic unsaturated oxygenated monoterpenes (e.g. linalool) may act as pro-oxidants in essential oil. Findings on the antioxidant potential of major cyclic oxygenated terpenes (menthol and menthone) are conflicting. Antioxidant behaviour of aqueous/organic solvent extracts and essential oil as well as the effect of environmental stresses on essential oil and phenolic composition are briefly discussed. PMID:25624208

  3. Antioxidants in liver health

    PubMed Central

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  4. Genetic Improvements in Rice Yield and Concomitant Increases in Radiation- and Nitrogen-Use Efficiency in Middle Reaches of Yangtze River.

    PubMed

    Zhu, Guanglong; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao; Wang, Fei

    2016-01-01

    The yield potential of rice (Oryza sativa L.) has experienced two significant growth periods that coincide with the introduction of semi-dwarfism and the utilization of heterosis. In present study, we determined the annual increase in the grain yield of rice varieties grown from 1936 to 2005 in Middle Reaches of Yangtze River and examined the contributions of RUE (radiation-use efficiency, the conversion efficiency of pre-anthesis intercepted global radiation to biomass) and NUE (nitrogen-use efficiency, the ratio of grain yield to aboveground N accumulation) to these improvements. An examination of the 70-year period showed that the annual gains of 61.9 and 75.3 kg ha(-1) in 2013 and 2014, respectively, corresponded to an annual increase of 1.18 and 1.16% in grain yields, respectively. The improvements in grain yield resulted from increases in the harvest index and biomass, and the sink size (spikelets per panicle) was significantly enlarged because of breeding for larger panicles. Improvements were observed in RUE and NUE through advancements in breeding. Moreover, both RUE and NUE were significantly correlated with the grain yield. Thus, our study suggests that genetic improvements in rice grain yield are associated with increased RUE and NUE. PMID:26876641

  5. Genetic Improvements in Rice Yield and Concomitant Increases in Radiation- and Nitrogen-Use Efficiency in Middle Reaches of Yangtze River

    PubMed Central

    Zhu, Guanglong; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao; Wang, Fei

    2016-01-01

    The yield potential of rice (Oryza sativa L.) has experienced two significant growth periods that coincide with the introduction of semi-dwarfism and the utilization of heterosis. In present study, we determined the annual increase in the grain yield of rice varieties grown from 1936 to 2005 in Middle Reaches of Yangtze River and examined the contributions of RUE (radiation-use efficiency, the conversion efficiency of pre-anthesis intercepted global radiation to biomass) and NUE (nitrogen-use efficiency, the ratio of grain yield to aboveground N accumulation) to these improvements. An examination of the 70-year period showed that the annual gains of 61.9 and 75.3 kg ha−1 in 2013 and 2014, respectively, corresponded to an annual increase of 1.18 and 1.16% in grain yields, respectively. The improvements in grain yield resulted from increases in the harvest index and biomass, and the sink size (spikelets per panicle) was significantly enlarged because of breeding for larger panicles. Improvements were observed in RUE and NUE through advancements in breeding. Moreover, both RUE and NUE were significantly correlated with the grain yield. Thus, our study suggests that genetic improvements in rice grain yield are associated with increased RUE and NUE. PMID:26876641

  6. In vitro antioxidant properties of dantrolene sodium.

    PubMed

    Büyükokuroğlu, M E; GülçIn, I; Oktay, M; Küfrevioğlu, O I

    2001-12-01

    Dantrolene sodium is a skeletal muscle relaxant, which inhibits intracellular Ca2+ release from the sarcoplasmic reticulum. The aim of this study is to examine possible in vitro antioxidant effects of dantrolene sodium. For this reason, the in vitro antioxidant effects of dantrolene sodium were studied using thiocyanate methods. Additionally, the reducing power and free radical scavenging activity were determined. Dantrolene sodium showed strong antioxidant activity in the linoleic acid emulsion system. The antioxidant activity increased with an increasing amount of dantrolene sodium (50, 100, 250 microg). The 50, 100 and 250 microg samples of dantrolene sodium showed 55%, 70% and 82% inhibition on peroxidation of linoleic acid, respectively. On the other hand, the 250 microg sample of alpha-tocopherol showed 62% inhibition of peroxidation of linoleic acid. Like antioxidant activity, the reducing power of dantrolene sodium increased in a dose-dependent manner. The reducing power of dantrolene was statistically significant vs control, but lower than butylated hydroxytoluene (BHT) and quercetin. Although dantrolene sodium had free radical scavenging activity this was not statistically significant. In contrast to dantrolene sodium, quercetin and butylated hydroxyanisole (BHA) had highly potent free radical scavenging activities and those were statistically significant. According to the these results, it may be said that antioxidant effect of dantrolene sodium is more related to its antioxidant activity in linoleic acid emulsion and reducing power, than to its free radical scavenging activity. These properties may be major reasons for the inhibition of lipid peroxidation. PMID:11735355

  7. Increased population sampling confirms low genetic divergence among Pteropus (Chiroptera: Pteropodidae) fruit bats of Madagascar and other western Indian Ocean islands

    PubMed Central

    Chan, Lauren M.; Goodman, Steven M.; Nowak, Michael D.; Weisrock, David W.; Yoder, Anne D.

    2011-01-01

    Fruit bats of the genus Pteropus occur throughout the Austral-Asian region west to islands off the eastern coast of Africa. Recent phylogenetic analyses of Pteropus from the western Indian Ocean found low sequence divergence and poor phylogenetic resolution among several morphologically defined species. We reexamine the phylogenetic relationships of these taxa by using multiple individuals per species. In addition, we estimate population genetic structure in two well-sampled taxa occurring on Madagascar and the Comoro Islands (P. rufus and P. seychellensis comorensis). Despite finding a similar pattern of low sequence divergence among species, increased sampling provides insight into the phylogeographic history of western Indian Ocean Pteropus, uncovering high levels of gene flow within species. PMID:21479256

  8. Genetic heterogeneity of primary open angle glaucoma and ocular hypertension: linkage to GLC1A associated with an increased risk of severe glaucomatous optic neuropathy.

    PubMed Central

    Brézin, A P; Béchetoille, A; Hamard, P; Valtot, F; Berkani, M; Belmouden, A; Adam, M F; Dupont de Dinechin, S; Bach, J F; Garchon, H J

    1997-01-01

    The GLC1A locus for autosomal dominant juvenile and middle age onset primary open angle glaucoma (OAG) has been mapped to chromosome 1q21-q31. OAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT), a major risk factor for OAG, to GLC1A in eight French families with multiple cases of juvenile and middle age onset OAG. There was strong evidence of genetic heterogeneity, four families being linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT. Peak intraocular pressure (IOP) did not differ significantly between the two groups of families, while linkage to GLC1A conferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy. Testing linkage of familial OAG to GLC1A may therefore have prognostic value too. PMID:9222961

  9. DIFFERENTIATION-INDUCING POTENCY OF THE SECO-STEROID JK-1624F2-2 CAN BE INCREASED BY COMBINATION WITH AN ANTIOXIDANT AND A p38 MAPK INHIBITOR WHICH UPREGULATES THE JNK PATHWAY

    PubMed Central

    Zhang, Jing; Posner, Gary H.; Danilenko, Michael; Studzinski, George P.

    2007-01-01

    Low calcemic analogs of vitamin D are candidates for differentiation therapy of human myeloid leukemias. We report here that the seco-steroid synthesized to have resistance to intracellular degradation and low calcemia-inducing activity, 1alpha-hydroxymethyl-3beta-16-ene-24,24-difluoro-25-hydroxy-vitamin D3 (JKF), induces monocytic differentiation in four established human myeloid leukemia cell lines, HL60, U937, THP-1, NB4, and murine myeloid leukemia cells WEHI-3B D-. JKF has differentiation-inducing potency which is slightly lower than the physiologically active form of vitamin D, 1,25(OH)2vitamin D3 (1,25D). However, simultaneous addition of carnosic acid (CA), an antioxidant, and SB20190 (SB), an inhibitor of p38 MAP kinase, increases the differentiation efficiency of JKF to a level similar to the level observed when 1,25D is used in such combinations. We also show for the first time that SB inhibits the phosphorylation of MAPKAPK-2, a downstream target of p38MAPK, but upregulates the phosphorylation of at least one of the isoforms of JNK (p46 JNK1) and of c-jun in all four human myeloid cell lines studied here. These studies indicate that the JNK1 pathway is positively associated with monocytic differentiation of several subtypes of myeloid leukemia cells arrested at different developmental stages. Further, since JKF is less calcemic than 1,25D, the data suggest that JKF combined with CA and SB is likely to have a therapeutic advantage over 1,25D-based experimental regimens for myeloid leukemias. PMID:17583492

  10. Cumulative role of bioinoculants on growth, antioxidant potential and artemisinin content in Artemisia annua L. under organic field conditions.

    PubMed

    Gupta, Rupali; Singh, Akanksha; Gupta, M M; Pandey, Rakesh

    2016-10-01

    Artemisia annua L. is mostly known for a bioactive metabolite, artemisinin, an effective sesquiterpene lactone used against malaria without any reputed cases of resistance. In this experiment, bioinoculants viz., Streptomyces sp. MTN14, Bacillus megaterium MTN2RP and Trichoderma harzianum Thu were applied as growth promoting substances to exploit full genetic potential of crops in terms of growth, yield, nutrient uptake and particularly artemisinin content. Further, multi-use of the bioinoculants singly and in combinations for the enhancement of antioxidant potential and therapeutic value was also undertaken which to our knowledge has never been investigated in context with microbial application. The results demonstrated that a significant (P < 0.05) increase in growth, nutrient uptake, total phenolic, flavonoid, free radical scavenging activity, ferric reducing antioxidant power, reducing power and total antioxidant capacity were observed in the A. annua treated with a combination of bioinoculants in comparison to control. Most importantly, an increase in artemisinin content and yield by 34 and 72 % respectively in the treatment having all the three microbes was observed. These results were further authenticated by the PCA analysis which showed positive correlation between plant macronutrients and antioxidant content with plant growth and artemisinin yield of A. annua. The present study thus highlights a possible new application of compatible bioinoculants for enhancing the growth along with antioxidant and therapeutic value of A. annua. PMID:27565777

  11. Macrophage adaptation leads to parallel evolution of genetically diverse Escherichia coli small-colony variants with increased fitness in vivo and antibiotic collateral sensitivity.

    PubMed

    Ramiro, Ricardo S; Costa, Henrique; Gordo, Isabel

    2016-09-01

    Small-colony variants (SCVs) are commonly observed in evolution experiments and clinical isolates, being associated with antibiotic resistance and persistent infections. We recently observed the repeated emergence of Escherichia coli SCVs during adaptation to the interaction with macrophages. To identify the genetic targets underlying the emergence of this clinically relevant morphotype, we performed whole-genome sequencing of independently evolved SCV clones. We uncovered novel mutational targets, not previously associated with SCVs (e.g. cydA, pepP) and observed widespread functional parallelism. All SCV clones had mutations in genes related to the electron-transport chain. As SCVs emerged during adaptation to macrophages, and often show increased antibiotic resistance, we measured SCV fitness inside macrophages and measured their antibiotic resistance profiles. SCVs had a fitness advantage inside macrophages and showed increased aminoglycoside resistance in vitro, but had collateral sensitivity to other antibiotics (e.g. tetracycline). Importantly, we observed similar results in vivo. SCVs had a fitness advantage upon colonization of the mouse gut, which could be tuned by antibiotic treatment: kanamycin (aminoglycoside) increased SCV fitness, but tetracycline strongly reduced it. Our results highlight the power of using experimental evolution as the basis for identifying the causes and consequences of adaptation during host-microbe interactions. PMID:27606007

  12. Stress, metabolism, and antioxidants in two wild passerine bird species.

    PubMed

    Cohen, Alan A; Hau, Michaela; Wikelski, Martin

    2008-01-01

    Antioxidants protect against free-radical damage, and free radicals, in turn, are thought to underlie aging. Thus, measuring antioxidants may aid field ecologists in understanding the physiological mechanisms that underlie life-history trade-offs. Antioxidant levels are known to vary markedly in response to the stress of capture in many birds. These changes in antioxidants could result from regulation (e.g., by stress-related hormones) or consumption (e.g., by an increase in free radicals due to increased metabolic rate). Here we experimentally test the effect of increased metabolic rate on circulating antioxidant and corticosterone concentrations in two wild passerine bird species, house sparrows (Passer domesticus) and gray catbirds (Dumetella carolinensis). We increased metabolic rate via exposure to low ambient temperatures overnight in captivity and measured circulating antioxidant capacity, uric acid, corticosterone, and oxygen consumption in cold-exposed and control individuals. Both species showed increases rather than decreases in all antioxidant parameters overnight, contradicting a consumption-by-energy-expenditure hypothesis. Both positive and negative correlations between antioxidant response and corticosterone response were occasionally but not consistently present, refuting a generalized regulation-by-corticosterone hypothesis. High baseline uric acid predicted diminished response of corticosterone and all antioxidants. Thus, high uric acid may reflect recent stress, poor condition, or a compensatory response. Relationships among metabolic rate, antioxidants, and corticosterone differed qualitatively between the species. PMID:18518772

  13. Determination of antioxidant activity of lichen Cetraria islandica (L) Ach.

    PubMed

    Gülçin, Ilhami; Oktay, Münir; Küfrevioğlu, O Irfan; Aslan, Ali

    2002-03-01

    The study was aimed at evaluating the antioxidant activity of aqueous extract of C. islandica. The antioxidant activity, reducing power, superoxide anion radical scavenging and free radical scavenging activities were studied. The antioxidant activity increased with the increasing amount of extracts (from 50 to 500 microg) added to linoleic acid emulsion. About 50, 100, 250, and 500 microg of aqueous extract of C. islandica showed higher antioxidant activity than 500 microg of alpha-tocopherol. The samples showed 96, 99, 100, and 100% inhibition on peroxidation of linoleic acid, respectively. On the other hand, the 500 microg of alpha-tocopherol showed 77% inhibition on peroxidation on linoleic acid emulsion. Like antioxidant activity, the reducing power, superoxide anion radical scavenging and free radical scavenging activities of C. islandica depends on concentration and increasing with increased amount of sample. The results obtained in the present study indicate that C. islandica is a potential source of natural antioxidant. PMID:11849836

  14. Acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw

    PubMed Central

    Dera, Paulina; Religioni, Urszula; Duda-Zalewska, Aneta; Deptała, Andrzej

    2016-01-01

    Aim of the study To check the degree of acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw Material and methods This study involved 562 women between 20 and 77 years of age, all of whom were patients visiting gynaecologists practising in clinics in the City of Warsaw. The studied population was divided into six age categories. The study method was a diagnostic poll conducted with the use of an original questionnaire containing 10 multiple-choice questions. Results Nearly 70% of the women showed an interest in taking a test to detect predispositions to develop breast and ovarian cancer. More than 10% did not want to take such a test, while every fifth women was undecided. No statistically significant differences between the respondents’ willingness to pay and education were found (p = 0.05). The most frequent answer given by women in all groups was that the amount to pay was too high. Such an answer was given by 52.17% of women with primary education, 65.22% of women with vocational education, 58.61% of women with secondary education, and 41.62% of women with higher education. Conclusions Women with a confirmed increased risk of developing breast and/or ovarian cancer due to inter alia the presence of BRCA1 and BRCA2 gene mutations should pay particular attention to 1st and 2nd level prophylaxis. PMID:27095945

  15. Genetic and pharmacological inactivation of the purinergic P2RX7 receptor dampens inflammation but increases tumor incidence in a mouse model of colitis-associated cancer.

    PubMed

    Hofman, Paul; Cherfils-Vicini, Julien; Bazin, Marie; Ilie, Marius; Juhel, Thierry; Hébuterne, Xavier; Gilson, Eric; Schmid-Alliana, Annie; Boyer, Olivier; Adriouch, Sahil; Vouret-Craviari, Valérie

    2015-03-01

    Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD). Binding of extracellular ATP to the purinergic receptor P2RX7 has emerged as a critical event in controlling intestinal inflammation, acting to limit elevation of proinflammatory mast cells and cytokines and promote survival of regulatory T cells (Treg) and enteric neurons. In this study, we investigated the effect of P2RX7 blockade in an established mouse model of CAC. Using genetic and pharmacologic tools, we found unexpectedly that while P2RX7 mediated inflammatory responses, it also acted at an early time to suppress CAC development. P2RX7 blockade enhanced proliferation of intestinal epithelial cells and protected them from apoptosis. The proliferative effects of P2RX7 blockade were associated with an increased production of TGFβ1 that was sufficient to stimulate the proliferation of intestinal epithelial cells. Finally, P2RX7 blockade also altered immune cell infiltration and promoted Treg accumulation within lesions of the digestive system. Taken together, our findings reveal an unexpected role for P2RX7 in preventing CAC, suggesting cautions in the use of P2RX7 inhibitors to treat IBD given the possibility of increasing risks CAC as a result. PMID:25564520

  16. Antioxidants and diabetic retinopathy.

    PubMed

    Williams, Michael; Hogg, Ruth E; Chakravarthy, Usha

    2013-08-01

    The biochemical perturbations in diabetes mellitus (DM) create the conditions for the production of free radicals, the consequence of which is increased oxidative stress. Evidence has accrued over the past 2 decades that suggests that oxidative stress is an important pathogenetic factor in the development of diabetic retinopathy (DR). Experimental data show that the use of strategies that ameliorate oxidative stress can prevent and retard the development of DR in the animal model. Clinical observations also suggest that reducing oxidative stress may help to reverse pathological manifestations of DR. The present article constitutes an examination of the role of antioxidants in the management of DR and the current state of clinically relevant knowledge. PMID:23649947

  17. Customized cooking method improves total antioxidant activity in selected vegetables.

    PubMed

    Ng, Zhi-Xiang; Chai, Jen-Wai; Kuppusamy, Umah Rani

    2011-03-01

    The present study compares water-soluble phenolic content (WPC) and antioxidant activities in Chinese long bean (Vigna unguiculata), bitter gourd (Momordica charantia), water convolvulus (Ipomoea aquatica) and broccoli (Brassica olearacea) prior to and after subjecting to boiling, microwaving and pressure cooking. The total antioxidant activity was increased in cooked water convolvulus, broccoli and bitter gourd, estimated based on the ferric reducing antioxidant power, the Trolox equivalent antioxidant capacity and 2,2-diphenyl-1-picryl-hydrazyl radical scavenging activity. Pressure cooking did not cause any significant decline in the antioxidant property. Boiling generally improved the overall antioxidant activity in all the vegetables. Correlation analysis suggests that WPC contributed to significant antioxidant activities in these vegetables. Thus, prudence in selecting an appropriate cooking method for different vegetables may improve or preserve their nutritional value. PMID:21250903

  18. Identification and characterization of antioxidant peptides from chickpea protein hydrolysates.

    PubMed

    Torres-Fuentes, Cristina; Contreras, María del Mar; Recio, Isidra; Alaiz, Manuel; Vioque, Javier

    2015-08-01

    Oxidative stress due to the excess of radical oxygen species (ROS) contribute to the development of different diseases. The use of antioxidants may prevent the development of these diseases by counteracting ROS levels. There is an increasing interest in natural antioxidants as they are safer for consumers than synthetic antioxidants. In this work, reducing power, free radical scavenging and cellular antioxidant activities of chickpea peptides fractions have been investigated. Peptide sequences included in fractions with antioxidant activity were identified. Main sequences, ALEPDHR, TETWNPNHPEL, FVPH and SAEHGSLH, corresponded to legumin, the main seed protein. Most peptides contained histidine, which has shown antioxidant activity. Two peptides also included tryptophan and phenylalanine, in which the phenolic group could also serve as hydrogen donor. These results show that legumin is a source of antioxidant peptides of high interest for food and pharmaceutical industries to develop new nutraceuticals and functional foods. PMID:25766818

  19. Plant extracts as natural antioxidants in meat and meat products.

    PubMed

    Shah, Manzoor Ahmad; Bosco, Sowriappan John Don; Mir, Shabir Ahmad

    2014-09-01

    Antioxidants are used to minimize the oxidative changes in meat and meat products. Oxidative changes may have negative effects on the quality of meat and meat products, causing changes in their sensory and nutritional properties. Although synthetic antioxidants have already been used but in recent years, the demand for natural antioxidants has been increased mainly because of adverse effects of synthetic antioxidants. Thus most of the recent investigations have been directed towards the identification of natural antioxidants from various plant sources. Plant extracts have been prepared using different solvents and extraction methods. Grape seed, green tea, pine bark, rosemary, pomegranate, nettle and cinnamon have exhibited similar or better antioxidant properties compared to some synthetic ones. This review provides the recent information on plant extracts used as natural antioxidants in meat and meat products, specifically red meat. PMID:24824531

  20. Identification and evaluation of antioxidants in Japanese parsley.

    PubMed

    Ogita, Tasuku; Manaois, Rosaly Vallejo; Wakagi, Manabu; Oki, Tomoyuki; Takano Ishikawa, Yuko; Watanabe, Jun

    2016-06-01

    Two cultivars of Japanese parsley were harvested in different seasons; their antioxidant capacities were evaluated by oxygen radical absorbance capacity (ORAC) methods, and the contents of hydrophilic and lipophilic antioxidants were compared. Japanese parsley possessed potent antioxidant capacities both in hydrophilic and lipophilic extracts when evaluated by ORAC methods. LC/MS/MS analyses revealed that chlorogenic acid and four kinds of quercetin glycosides were major antioxidants in the hydrophilic extract. Lutein was the main contributor to the antioxidant capacity of the lipophilic extract. Antioxidant capacities of the hydrophilic extracts of both cultivars tended to be higher in winter because of the increase in the contents of chlorogenic acid and quercetin glycosides. An obvious trend in the lipophilic antioxidant capacities or lutein contents was not observed irrespective of the cultivar. PMID:27075296

  1. Enteromorpha compressa Exhibits Potent Antioxidant Activity

    PubMed Central

    Shanab, Sanaa M. M.; Shalaby, Emad A.; El-Fayoumy, Eman A.

    2011-01-01

    The green macroalgae, Enteromorpha compressa (Linnaeus) Nees, Ulva lactuca, and E. linza, were seasonally collected from Abu Qir bay at Alexandria (Mediterranean Sea) This work aimed to investigate the seasonal environmental conditions, controlling the green algal growth, predominance, or disappearance and determining antioxidant activity. The freshly collected selected alga (E. compressa) was subjected to pigment analysis (chlorophyll and carotenoids) essential oil and antioxidant enzyme determination (ascorbate oxidase and catalase). The air-dried ground alga was extracted with ethanol (crude extract) then sequentially fractionated by organic solvents of increasing polarity (petroleum ether, chloroform, ethyl acetate, and water). Antioxidant activity of all extracts was assayed using different methods (total antioxidant, DPPH [2, 2 diphenyl-1-picrylhydrazyl], ABTS [2, 2 azino-bis ethylbenzthiazoline-6-sulfonic acid], and reducing power, and β-carotene linoleic acid bleaching methods). The results indicated that the antioxidant activity was concentration and time dependent. Ethyl acetate fraction demonstrated higher antioxidant activity against DPPH method (82.80%) compared to the synthetic standard butylated hydroxyl toluene (BHT, 88.5%). However, the crude ethanolic extract, pet ether, chloroform fractions recorded lower to moderate antioxidant activities (49.0, 66.0, and 78.0%, resp.). Using chromatographic and spectroscopic analyses, an active compound was separated and identified from the promising ethyl acetate fraction. PMID:21869863

  2. Gamma Radiation Effects on Peanut Skin Antioxidants

    PubMed Central

    de Camargo, Adriano Costa; de Souza Vieira, Thais Maria Ferreira; Regitano-D’Arce, Marisa Aparecida Bismara; Calori-Domingues, Maria Antonia; Canniatti-Brazaca, Solange Guidolin

    2012-01-01

    Peanut skin, which is removed in the peanut blanching process, is rich in bioactive compounds with antioxidant properties. The aims of this study were to measure bioactive compounds in peanut skins and evaluate the effect of gamma radiation on their antioxidant activity. Peanut skin samples were treated with 0.0, 5.0, 7.5, or 10.0 kGy gamma rays. Total phenolics, condensed tannins, total flavonoids, and antioxidant activity were evaluated. Extracts obtained from the peanut skins were added to refined-bleached-deodorized (RBD) soybean oil. The oxidative stability of the oil samples was determined using the Oil Stability Index method and compared to a control and synthetic antioxidants (100 mg/kg BHT and 200 mg/kg TBHQ). Gamma radiation changed total phenolic content, total condensed tannins, total flavonoid content, and the antioxidant activity. All extracts, gamma irradiated or not, presented increasing induction period (h), measured by the Oil Stability Index method, when compared with the control. Antioxidant activity of the peanut skins was higher than BHT. The present study confirmed that gamma radiation did not affect the peanut skin extracts’ antioxidative properties when added to soybean oil. PMID:22489142

  3. Gamma radiation effects on peanut skin antioxidants.

    PubMed

    de Camargo, Adriano Costa; de Souza Vieira, Thais Maria Ferreira; Regitano-D'Arce, Marisa Aparecida Bismara; Calori-Domingues, Maria Antonia; Canniatti-Brazaca, Solange Guidolin

    2012-01-01

    Peanut skin, which is removed in the peanut blanching process, is rich in bioactive compounds with antioxidant properties. The aims of this study were to measure bioactive compounds in peanut skins and evaluate the effect of gamma radiation on their antioxidant activity. Peanut skin samples were treated with 0.0, 5.0, 7.5, or 10.0 kGy gamma rays. Total phenolics, condensed tannins, total flavonoids, and antioxidant activity were evaluated. Extracts obtained from the peanut skins were added to refined-bleached-deodorized (RBD) soybean oil. The oxidative stability of the oil samples was determined using the Oil Stability Index method and compared to a control and synthetic antioxidants (100 mg/kg BHT and 200 mg/kg TBHQ). Gamma radiation changed total phenolic content, total condensed tannins, total flavonoid content, and the antioxidant activity. All extracts, gamma irradiated or not, presented increasing induction period (h), measured by the Oil Stability Index method, when compared with the control. Antioxidant activity of the peanut skins was higher than BHT. The present study confirmed that gamma radiation did not affect the peanut skin extracts' antioxidative properties when added to soybean oil. PMID:22489142

  4. Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

    PubMed Central

    Ngo, Ha Thi; Hetland, Ragna Bogen; Nygaard, Unni Cecilie; Steffensen, Inger-Lise

    2015-01-01

    We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-ApcMin/+ X C57BL/6J-Lepob/+ mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in ApcMin/+ mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice. PMID:26347815

  5. Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids.

    PubMed

    Ameur, Adam; Enroth, Stefan; Johansson, Asa; Zaboli, Ghazal; Igl, Wilmar; Johansson, Anna C V; Rivas, Manuel A; Daly, Mark J; Schmitz, Gerd; Hicks, Andrew A; Meitinger, Thomas; Feuk, Lars; van Duijn, Cornelia; Oostra, Ben; Pramstaller, Peter P; Rudan, Igor; Wright, Alan F; Wilson, James F; Campbell, Harry; Gyllensten, Ulf

    2012-05-01

    Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease. PMID:22503634

  6. Evaluation of oxidant, antioxidant, and S100B levels in patients with conversion disorder

    PubMed Central

    Büyükaslan, Hasan; Kandemir, Sultan Basmacı; Asoğlu, Mehmet; Kaya, Halil; Gökdemir, Mehmet Tahir; Karababa, İbrahim Fatih; Güngörmez, Fatih; Kılıçaslan, Fethiye; Şavik, Emin

    2016-01-01

    Introduction Various psychodynamic, neurobiological, genetic, and sociocultural factors are believed to be involved in the etiology of conversion disorder (CD). Oxidative metabolism has been shown to deteriorate in association with many health problems and psychiatric disorders. We evaluated oxidative metabolism and S100B levels in the context of this multifactorial disease. Methods Thirty-seven patients with CD (25 females and 12 males) and 42 healthy volunteers (21 females and 21 males), all matched for age and sex, were included in this study. The total oxidant status, total antioxidant status, oxidative stress index, and S100B levels were compared between the two groups. Results The total oxidant status, oxidative stress index, and S100B levels were significantly higher in patients with CD than in the control group, whereas the total antioxidant status was significantly lower. Conclusion CD is associated with deterioration of oxidative metabolism and increased neuronal damage. PMID:27471386

  7. Genetic Modification of Mesenchymal Stem Cells Overexpressing CCR1 Increases Cell Viability, Migration, Engraftment and Capillary Density in the Injured Myocardium

    PubMed Central

    Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

    2010-01-01

    Rationale Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly due to poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (e.g. CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. Objective To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Methods and Results Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs three days post-myocardial infarction (MI). CCR1-MSC injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium three days post-MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks post-MI. Conclusions Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium. PMID:20378860

  8. Antioxidants, metabolic rate and aging in Drosophila

    NASA Technical Reports Server (NTRS)

    Miquel, J.; Fleming, J.; Economos, A. C.

    1982-01-01

    The metabolic rate-of-living theory of aging was investigated by determining the effect of several life-prolonging antioxidants on the metabolic rate and life span of Drosophila. The respiration rate of groups of continuously agitated flies was determined in a Gilson respirometer. Vitamin E, 2,4-dinitrophenol, nordihydroguaiaretic acid, and thiazolidine carboxylic acid were employed as antioxidants. Results show that all of these antioxidants reduced the oxygen consumption rate and increased the mean life span, and a significant negative linear correlation was found between the mean life span and the metabolic rate. It is concluded that these findings indicate that some antioxidants may inhibit respiration rate in addition to their protective effect against free radical-induced cellular damage.

  9. Antioxidant enzymes activities in obese Tunisian children

    PubMed Central

    2013-01-01

    Background The oxidant stress, expected to increase in obese adults, has an important role in the pathogenesis of many diseases. It results when free radical formation is greatly increased or protective antioxidant mechanisms are compromised. The main objective of this study is to evaluate the antioxidant response to obesity-related stress in healthy children. Methods A hundred and six healthy children (54 obese and 52 controls), aged 6–12 years old, participated in this study. The collected data included anthropometric measures, blood pressure, fasting glucose, total cholesterol, triglycerides and enzymatic antioxidants (Superoxide dismutase: SOD, Catalase: CAT and Glutathione peroxidase: GPx). Results The first step antioxidant response, estimated by the SOD activity, was significantly higher in obese children compared with normal-weight controls (p < 0.05). Mean activities of anti-radical GPx and CAT enzymes were not affected by the BMI increase. Although, total cholesterol levels were statistically higher in the obese group, there was no significant association with the SOD activity. Conclusions The obesity-related increase of the oxidant stress can be observed even in the childhood period. In addition to the complications of an increased BMI, obesity itself can be considered as an independent risk factor of free radical production resulting in an increased antioxidant response. PMID:23360568

  10. Genetic counseling.

    PubMed

    Fraser, F C

    1974-09-01

    A workshop was sponsored by the National Genetics Foundation to evaluate and make recommendations about the status of genetic counseling, its goals, nature, achievements, and needs. The process of genetic workup and counseling is divided into 5 stages: validation of the diagnosis; obtaining family history; estimation of the risk of recurrence; helping the family make a decision and take appropriate action; and extending counseling to other members of the family. Counseling can be directed at individuals or at special groups with the potential of carrying such diseases as sickle cell amenia or Tay-Sachs. No consensus exists on an optimal counseling approach. Genetic counseling is regarded as a team effort, requiring, in addition to the counselor, laboratory facilities and a variety of specialists. The source of payment for genetic counseling services is regarded as a problem of increasing concern. Generally, the fee paid rarely covers the cost of the many procedures and it is suggested that the cost, like that of other public health services, should be subsidized by the state. Considerable argument exists over whether a genetic counselor must have a M.D. degree or whether a Ph. D. in medical genetics is suitable enough. The quality of much genetic counseling, which is often done in the office of doctors unskilled in the field, would be increased if better training in genetics were offered to medical students and if physicians were informed of the existence of counseling centers. Further, there is a growing feeling that some sort of accreditation of genetic counselors is desirable. PMID:4609197

  11. Antioxidants and its Properties as Affected by Extrusion Process: A Review.

    PubMed

    Wani, Sajad A; Kumar, Pradyuman

    2015-01-01

    Antioxidants are important for plant and animal's life or health. These are the substances that protect them from the damage produced by unstable molecules called as free radicals. There are various types of antioxidants to be reported both natural as well as synthetic such as melatonin, Vitamin C, glutathione, tocopherols and tocotrienols, BHA and BHT, etc. A new antioxidant 5-O-[6˝-(3- hydroxy-3methyl glutarate) β-D-glucodise was found while studying bioactive antioxidants from plant foods for nutraceutical product development. Antioxidants have been used for increasing shelf life of various food products including extruded product. Antioxidants, their beneficial advantages and the effect of extrusion on antioxidants were reviewed and found to be effective in increasing the shelf life. This review article discusses recent patents, presents importance of antioxidant, phytochemicals and effect of process of extrusion on antioxidants. PMID:26152136

  12. The nature of antioxidant defense mechanisms: a lesson from transgenic studies.

    PubMed Central

    Ho, Y S; Magnenat, J L; Gargano, M; Cao, J

    1998-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury. Images Figure 1 Figure 3 Figure 4 PMID:9788901

  13. Role of the Immune System in Hypertension: Modulation by Dietary Antioxidants

    PubMed Central

    Vasdev, Sudesh; Stuckless, Jennifer; Richardson, Vernon

    2011-01-01

    Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans and animal models affecting glucose and lipid metabolism producing excess aldehydes including methylglyoxal. These aldehydes react with proteins to form conjugates called advanced glycation end products (AGEs). This alters protein structure and function and can affect vascular and immune cells leading to their activation and secretion of inflammatory cytokines. AGEs also act via receptors for advanced glycation end products on these cells altering the function of antioxidant and metabolic enzymes, and ion channels. This results in an increase in cytosolic free calcium, decrease in nitric oxide, endothelial dysfunction, oxidative stress, peripheral vascular resistance, and infiltration of vascular and kidney tissue with inflammatory cells leading to hypertension. Supplementation with dietary antioxidants including vitamins C, E, or B6, thiols such as cysteine and lipoic acid, have been shown to lower blood pressure and plasma inflammatory cytokines in animal models and humans with essential hypertension. A well-balanced diet rich in antioxidants that includes vegetables, fruits, low fat dairy products, low salt, and includes whole grains, poultry, fish and nuts, lowers blood pressure and vascular inflammation. These antioxidants may achieve their antihypertensive and anti-inflammatory/immunomodulatory effects by reducing AGEs and improving insulin resistance and associated alterations. Dietary supplementation with antioxidants may be a beneficial, inexpensive, front-line alterative treatment modality for hypertension. PMID:23204821

  14. H-Ras Increases Urokinase Expression and Cell Invasion in Genetically Modified Human Astrocytes Through Ras/Raf/MEK Signaling Pathway

    PubMed Central

    ZHAO, YUNGE; XIAO, AIZHEN; DIPIERRO, CHARLES G.; ABDEL-FATTAH, RANA; AMOS, SAMSON; REDPATH, GERARD T.; CARPENTER, JOAN E.; PIEPER, RUSSELL O.; HUSSAINI, ISA M.

    2008-01-01

    Previous study reported that the activation of Ras pathway cooperated with E6/E7-mediated inactivation of p53/pRb to transform immortalized normal human astrocytes (NHA/hTERT) into intracranial tumors strongly resembling human astrocytomas. The mechanism of how H-Ras contributes to astrocytoma formation is unclear. Using genetically modified NHA cells (E6/E7/hTERT and E6/E7/hTERT/Ras cells) as models, we investigated the mechanism of Ras-induced tumorigenesis. The overexpression of constitutively active H-RasV12 in E6/E7/hTERT cells robustly increased the levels of urokinase plasminogen activator (uPA) mRNA, protein, activity and invasive capacity of the E6/E7/hTERT/Ras cells. However, the expressions of MMP-9 and MMP-2 did not significantly change in the E6/E7/hTERT and E6/E7/hTERT/Ras cells. Furthermore, E6/E7/hTERT/Ras cells also displayed higher level of uPA activity and were more invasive than E6/E7/hTERT cells in 3D culture, and formed an intracranial tumor mass in a NOD-SCID mouse model. uPA specific inhibitor (B428) and uPA neutralizing antibody decreased uPA activity and invasion in E6/E7/hTERT/Ras cells. uPA-deficient U-1242 glioblastoma cells were less invasive in vitro and exhibited reduced tumor growth and infiltration into normal brain in xenograft mouse model. Inhibitors of Ras (FTA), Raf (Bay 54−9085) and MEK (UO126), but not of phosphatidylinositol 3-kinase (PI3K) (LY294002) and of protein kinase C (BIM) pathways, inhibited uPA activity and cell invasion. Our results suggest that H-Ras increased uPA expression and activity via the Ras/Raf/MEK signaling pathway leading to enhanced cell invasion and this may contribute to increased invasive growth properties of astrocytomas. PMID:18383343

  15. Increased rodenticide exposure rate and risk of toxicosis in barn owls (Tyto alba) from southwestern Canada and linkage with demographic but not genetic factors.

    PubMed

    Huang, Andrew C; Elliott, John E; Hindmarch, Sofi; Lee, Sandi L; Maisonneuve, France; Bowes, Victoria; Cheng, Kimberly M; Martin, Kathy

    2016-08-01

    Among many anthropogenic drivers of population decline, continual rapid urbanization and industrialization pose major challenges for the survival of wildlife species. Barn owls (Tyto alba) in southwestern British Columbia (BC) face a multitude of threats ranging from habitat fragmentation to vehicle strikes. They are also at risk from secondary poisoning of second-generation anticoagulant rodenticides (SGARs), a suite of toxic compounds which at high doses results in a depletion of blood clotting factors leading to internal bleeding and death. Here, using long-term data (N = 119) for the hepatic residue levels of SGAR, we assessed the risk of toxicosis from SGAR for the BC barn owl population over the past two decades. We also investigated whether sensitivity to SGAR is associated with genetic factors, namely Single Nucleotide Polymorphisms (SNPs) found in the CYP2C45 gene of barn owls. We found that residue concentration for total SGAR was significantly higher in 2006-2013 (141 ng/g) relative to 1992-2003 (57 ng/g). The proportion of owls exposed to multiple SGAR types was also significantly higher in 2006-2013. Those measures accordingly translate directly into an increase in toxicosis risk level. We also detected demographic differences, where adult females showed on average lower concentration of total SGAR (64 ng/g) when compared to adult males (106 ng/g). Juveniles were overall more likely to show signs of toxicosis than adults (33.3 and 6.9 %, respectively), and those symptoms were positively predicted by SGAR concentrations. We found no evidence that SNPs in the CYP2C45 gene of barn owls were associated with intraspecific variation in SGAR sensitivity. We recommend several preventative measures be taken to minimize wildlife exposure to SGAR. PMID:27151403

  16. Rapid evolution of antioxidant defence in a natural population of Daphnia magna.

    PubMed

    Oexle, S; Jansen, M; Pauwels, K; Sommaruga, R; De Meester, L; Stoks, R

    2016-07-01

    Natural populations can cope with rapid changes in stressors by relying on sets of physiological defence mechanisms. Little is known onto what extent these physiological responses reflect plasticity and/or genetic adaptation, evolve in the same direction and result in an increased defence ability. Using resurrection ecology, we studied how a natural Daphnia magna population adjusted its antioxidant defence to ultraviolet radiation (UVR) during a period with increasing incident UVR reaching the water surface. We demonstrate a rapid evolution of the induction patterns of key antioxidant enzymes under UVR exposure in the laboratory. Notably, evolutionary changes strongly differed among enzymes and mainly involved the evolution of UV-induced plasticity. Whereas D. magna evolved a strong plastic up-regulation of glutathione peroxidase under UVR, it evolved a lower plastic up-regulation of glutathione S-transferase and superoxide dismutase and a plastic down-regulation of catalase. The differentially evolved antioxidant strategies were collectively equally effective in dealing with oxidative stress because they resulted in the same high levels of oxidative damage (to lipids, proteins and DNA) and lowered fitness (intrinsic growth rate) under UVR exposure. The lack of better protection against UVR may suggest that the UVR exposure did not increase between both periods. Predator-induced evolution to migrate to lower depths that occurred during the same period may have contributed to the evolved defence strategy. Our results highlight the need for a multiple trait approach when focusing on the evolution of defence mechanisms. PMID:27018861

  17. Antioxidant Stabilisation of Polymers

    NASA Astrophysics Data System (ADS)

    Shlyapnikov, Yurii A.

    1981-06-01

    Physicochemical aspects of the stabilisation of polymers are discussed. Attention is paid mainly to the aging and stabilisation of polymers under processing conditions. Topics considered are the kinetics and mechanism of the high-temperature oxidation of polymers, critical phenomena in the inhibited oxidation of polymers, the theory of synergism and antagonism among antioxidants, the reasons for differences in efficiency of antioxidants, and certain aspects of the relation between the efficiency of antioxidants and their molecular structure. A list of 132 references is included.

  18. A combined strategy involving Sanger and 454 pyrosequencing increases genomic resources to aid in the management of reproduction, disease control and genetic selection in the turbot (Scophthalmus maximus)

    PubMed Central

    2013-01-01

    Background Genomic resources for plant and animal species that are under exploitation primarily for human consumption are increasingly important, among other things, for understanding physiological processes and for establishing adequate genetic selection programs. Current available techniques for high-throughput sequencing have been implemented in a number of species, including fish, to obtain a proper description of the transcriptome. The objective of this study was to generate a comprehensive transcriptomic database in turbot, a highly priced farmed fish species in Europe, with potential expansion to other areas of the world, for which there are unsolved production bottlenecks, to understand better reproductive- and immune-related functions. This information is essential to implement marker assisted selection programs useful for the turbot industry. Results Expressed sequence tags were generated by Sanger sequencing of cDNA libraries from different immune-related tissues after several parasitic challenges. The resulting database (“Turbot 2 database”) was enlarged with sequences generated from a 454 sequencing run of brain-hypophysis-gonadal axis-derived RNA obtained from turbot at different development stages. The assembly of Sanger and 454 sequences generated 52,427 consensus sequences (“Turbot 3 database”), of which 23,661 were successfully annotated. A total of 1,410 sequences were confirmed to be related to reproduction and key genes involved in sex differentiation and maturation were identified for the first time in turbot (AR, AMH, SRY-related genes, CYP19A, ZPGs, STAR FSHR, etc.). Similarly, 2,241 sequences were related to the immune system and several novel key immune genes were identified (BCL, TRAF, NCK, CD28 and TOLLIP, among others). The number of genes of many relevant reproduction- and immune-related pathways present in the database was 50–90% of the total gene count of each pathway. In addition, 1,237 microsatellites and 7,362 single

  19. Antioxidants as novel therapy in a murine model of colitis.

    PubMed

    Oz, Helieh S; Chen, Theresa S; McClain, Craig J; de Villiers, Willem J S

    2005-05-01

    Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD) and have been implicated as mediators of intestinal inflammation. We investigated the hypothesis that antioxidants with diverse properties attenuate disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model. These antioxidants were (A) S-adenosylmethionine, a glutathione (GSH) precursor; (B) green tea polyphenols, a well-known antioxidant; and (C) 2(R,S)-n-propylthiazolidine-4(R)-carboxylic acid (PTCA), a cysteine prodrug, involved in GSH biosynthesis. BALB/c mice were divided into four groups and provided with the above mentioned antioxidants or the vehicle incorporated into chow. The animals were further divided into two subgroups and given normal drinking water (control) or water supplemented with DSS (to induce colitis), and the progression of the disease was studied. DSS-treated mice developed severe colitis as shown by bloody diarrhea, weight loss and pathological involvement (P<.001). However, all the antioxidants significantly improved diarrhea and colon lesions (P<.01), and increased body weights (P<.05). Hematocrits were significantly less affected in DSS-treated animals receiving antioxidants (P<.01). Colon lengths were significantly decreased due to mucosal inflammation in DSS-treated animals, but antioxidant therapy normalized this pathological finding (P<.001). The blood level of reduced GSH was decreased in DSS-treated mice (P<.05) and returned to normal when treated with antioxidants. Serum amyloid A (acute phase protein; P=.0015) and tumor necrosis factor-alpha (TNF-alpha; pro-inflammatory cytokine; P<.01) were significantly increased in DSS-treated animals (161+/-40 pg/ml) and improved with antioxidant treatment (P<.01). Finally, actin cytoskeleton was distorted and fragmented in the mucosa of DSS-treated mice and improved with antioxidant therapy. In conclusion, three structurally dissimilar antioxidants provided protection against DSS

  20. Antioxidant capacity of lycopene-containing foods.

    PubMed

    Djuric, Z; Powell, L C

    2001-03-01

    Increased consumption of tomatoes and tomato products has been associated with decreased cancer risks. One fat-soluble compound identified in tomatoes which may be responsible for this association is lycopene. There may, however, be other antioxidants present in tomato-based foods, and total antioxidant capacity may be another way to rate the health benefits of these foods. In this work, we examined the Trolox-equivalent antioxidant capacity (TEAC) of aqueous and organic extracts of lycopene-containing foods: ketchup, fresh tomatoes, tomato paste, tomato sauce, tomato soup, tomato juice, vegetable juice, canned tomatoes and watermelon. Antioxidant activity in these food extracts was greater in the aqueous versus organic fractions, except for watermelon and tomato sauce where the levels were similar in the two fractions. Lycopene levels in the food samples tested, however, were relatively greater in the organic fractions, with the exception of the two juices, which had similar levels in the two fractions, and two highly concentrated tomato products, tomato paste and ketchup, which had relatively higher lycopene levels in the aqueous fractions. The foods with the highest antioxidant capacity per serving overall (tomato soup was highest) did not have the highest lycopene levels. This indicates that it may be important to consume a variety of tomato-containing products in order to obtain the largest variety of dietary antioxidants possible. PMID:11303462

  1. Antioxidant capacity and antioxidant content in roots of 4 sweetpotato varieties.

    PubMed

    Rautenbach, Fanie; Faber, Mieke; Laurie, Sunette; Laurie, Robert

    2010-06-01

    The antioxidant contents (beta-carotene, chlorogenic acid, and vitamin C) as well as the antioxidant capacity (ORAC, FRAP, and ABTS) of 4 sweetpotato varieties were measured in this study. The sweetpotato varieties were cultivated under different water regimes and also subjected to thermal processing. The results show that the 2 orange-fleshed varieties (Resisto and W-119) contain significant more beta-carotene, chlorogenic acid, and vitamin C than the 2 cream-fleshed varieties (Bosbok and Ndou). Thermal processing decreased the carotenoid and vitamin C content of all the varieties but increased the chlorogenic acid content and antioxidant capacity. Drought stress appears to increase the beta-carotene, vitamin C, and chlorogenic acid contents as well as the antioxidant capacity of some of the sweetpotato varieties, especially W-119. PMID:20629859

  2. Definite, probable or dubious: antioxidants trilogy in clinical dentistry.

    PubMed

    Carnelio, S; Khan, S A; Rodrigues, G

    2008-01-12

    Recent years have shown the presence of free radicals in causation and progression of various dental diseases and antioxidant usage in dental therapeutics. Antioxidant micronutrients are important not only for limiting oxidative and tissue damage, but also in preventing increased cytokine production, which is a result of prolonged activation of the immune response. There has been a widespread availability and clinical claims on the safety and efficacy of antioxidants. However, lack of randomised controlled trials in dental research limits their usage. There is a substantial gap between these clinical claims and efficacy/safety of antioxidants in dental therapeutics which needs to be addressed. This article highlights the clinical significance of antioxidant therapy in dental practice and touches upon controversial areas and research lacunae. An evidence based approach for making recommendations about antioxidant usage and efficacy in routine dental practice seems to be the need of the hour. PMID:18192996

  3. The Antioxidants Changes in Ornamental Flowers during Development and Senescence

    PubMed Central

    Cavaiuolo, Marina; Cocetta, Giacomo; Ferrante, Antonio

    2013-01-01

    The concentration of antioxidant compounds is constitutive and variable from species to species and is also variable considering the development of the plant tissue. In this review, we take into consideration the antioxidant changes and the physiological, biochemical and molecular factors that are able to modulate the accumulation of antioxidant compounds in ornamental flowers during the whole development process until the senescence. Many ornamental flowers are natural sources of very important bioactive compounds with benefit to the human health and their possible role as dietary components has been reported. The most part of antioxidants are flower pigments such as carotenoids and polyphenols, often present in higher concentration compared with the most common fruits and vegetables. The antioxidants content changes during development and during senescence many biochemical systems and molecular mechanisms are activated to counteract the increase of reactive oxygen species and free radicals. There is a tight correlation between antioxidants and senescence processes and this aspect is detailed and appropriately discussed. PMID:26784342

  4. Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses

    PubMed Central

    Chaiprasongsuk, Anyamanee; Onkoksoong, Tasanee; Pluemsamran, Thanyawan; Limsaengurai, Saowalak; Panich, Uraiwan

    2015-01-01

    Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8 J/cm2) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway. PMID:26765101

  5. Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses.

    PubMed

    Chaiprasongsuk, Anyamanee; Onkoksoong, Tasanee; Pluemsamran, Thanyawan; Limsaengurai, Saowalak; Panich, Uraiwan

    2016-08-01

    Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8J/cm(2)) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway. PMID:26765101

  6. Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet

    PubMed Central

    Mier-Cabrera, Jennifer; Aburto-Soto, Tania; Burrola-Méndez, Soraya; Jiménez-Zamudio, Luis; Tolentino, Mari C; Casanueva, Esther; Hernández-Guerrero, César

    2009-01-01

    Background Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis. Methods Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 μg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month. Results Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p < 0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group. Conclusion WEN had a lower

  7. Catalytic Antioxidants and Neurodegeneration

    PubMed Central

    Golden, Tamara R.

    2009-01-01

    Abstract Oxidative stress, resulting from mitochondrial dysfunction, excitotoxicity, or neuroinflammation, is implicated in numerous neurodegenerative conditions. Damage due to superoxide, hydroxyl radical, and peroxynitrite has been observed in diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as in acute conditions that lead to neuronal death, such as stroke and epilepsy. Antioxidant therapies to remove these toxic compounds have been of great interest in treating these disorders. Catalytic antioxidants mimic the activities of superoxide dismutase or catalase or both, detoxifying superoxide and hydrogen peroxide, and in some cases, peroxynitrite and other toxic species as well. Several compounds have demonstrated efficacy in in vitro and in animal models of neurodegeneration, leading to optimism that catalytic antioxidants may prove to be useful therapies in human disease. Antioxid. Redox Signal. 11, 555–569. PMID:18754709

  8. Antioxidant content of foods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant-based foods, especially fruits, vegetables, and nuts, contain bioactive components which have various biological functions, including free radical scavenging and metal chelating (antioxidant), inhibition of lipid peroxidation, anti-inflammatory properties, etc. Oxidative stress may contribute...

  9. Improving Asthma during Pregnancy with Dietary Antioxidants: The Current Evidence

    PubMed Central

    Grieger, Jessica A.; Wood, Lisa G.; Clifton, Vicki L.

    2013-01-01

    The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health. PMID:23948757

  10. Critical Evaluation of Ayurvedic Plants for Stimulating Intrinsic Antioxidant Response

    PubMed Central

    Shukla, Sunil Dutt; Bhatnagar, Maheep; Khurana, Sukant

    2012-01-01

    Oxidative damage caused by free radicals plays an important role in the causation and progression of many diseases, including aging. Free-radical damage is countered by many mechanisms, including both active antioxidant enzymatic activity in our body and passive antioxidants. Antioxidant response of our body can accommodate increased oxidative damage in diseased states to a level but beyond that level, additional antioxidants are required to combat the increased stress. Apart from the regular dietary sources of antioxidants, many traditional herbal medicines demonstrate a potential to boost antioxidant activity. Rasayana chikitsa that deals with rejuvenation and revitalization is a branch of the Indian traditional medical system of ayurveda. We review some select herbs described in rasayana chikitsa that have been assessed by modern means for stimulating intrinsic antioxidant responses in humans. A critical evaluation of rasayana chikitsa will likely provide urgently needed, actual stimulants of our physiological antioxidant responses and not just more passive antioxidants to add to an already large catalog. PMID:22855669

  11. Processed sweet corn has higher antioxidant activity.

    PubMed

    Dewanto, Veronica; Wu, Xianzhong; Liu, Rui Hai

    2002-08-14

    Processed fruits and vegetables have been long considered to have lower nutritional value than the fresh produce due to the loss of vitamin C during processing. Vitamin C in apples has been found to contribute <0.4% of total antioxidant activity, indicating most of the activity comes from the natural combination of phytochemicals. This suggests that processed fruits and vegetables may retain their antioxidant activity despite the loss of vitamin C. Here it is shown that thermal processing at 115 degrees C for 25 min significantly elevated the total antioxidant activity of sweet corn by 44% and increased phytochemical content such as ferulic acid by 550% and total phenolics by 54%, although 25% vitamin C loss was observed. Processed sweet corn has increased antioxidant activity equivalent to 210 mg of vitamin C/100 g of corn compared to the remaining 3.2 mg of vitamin C in the sample that contributed only 1.5% of its total antioxidant activity. These findings do not support the notion that processed fruits and vegetables have lower nutritional value than fresh produce. This information may have a significant impact on consumers' food selection by increasing their consumption of fruits and vegetables to reduce the risk of chronic diseases. PMID:12166989

  12. µ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype ... frequencies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size an...

  13. Genetic Screening

    PubMed Central

    Burke, Wylie; Tarini, Beth; Press, Nancy A.; Evans, James P.

    2011-01-01

    Current approaches to genetic screening include newborn screening to identify infants who would benefit from early treatment, reproductive genetic screening to assist reproductive decision making, and family history assessment to identify individuals who would benefit from additional prevention measures. Although the traditional goal of screening is to identify early disease or risk in order to implement preventive therapy, genetic screening has always included an atypical element—information relevant to reproductive decisions. New technologies offer increasingly comprehensive identification of genetic conditions and susceptibilities. Tests based on these technologies are generating a different approach to screening that seeks to inform individuals about all of their genetic traits and susceptibilities for purposes that incorporate rapid diagnosis, family planning, and expediting of research, as well as the traditional screening goal of improving prevention. Use of these tests in population screening will increase the challenges already encountered in genetic screening programs, including false-positive and ambiguous test results, overdiagnosis, and incidental findings. Whether this approach is desirable requires further empiric research, but it also requires careful deliberation on the part of all concerned, including genomic researchers, clinicians, public health officials, health care payers, and especially those who will be the recipients of this novel screening approach. PMID:21709145

  14. Increased non-eosinophilic nasal polyps in chronic rhinosinusitis in U.S. second-generation Asians suggests genetic regulation of eosinophilia

    PubMed Central

    Mahdavinia, Mahboobeh; Suh, Lydia A.; Carter, Roderick G.; Stevens, Whitney W.; Norton, James E; Kato, Atsushi; Tan, Bruce K.; Kern, Robert C.; Conley, David B.; Chandra, Rakesh; Lavin, Jennifer; Peters, Anju T.; Grammer, Leslie C.; Schleimer, Robert P.

    2014-01-01

    Capsule Summary In this study we found a significantly lower eosinophilia in nasal polyps surgically removed from second-generation Asian patients, similar to studies of native-born patients in Asian countries, suggesting the hypothesis that there may be genetic regulation of eosinophilia. PMID:25312761

  15. Paradoxical effects of antioxidants on cancer.

    PubMed

    Mendelsohn, Andrew R; Larrick, James W

    2014-06-01

    Antioxidants have had a checkered history concerning their reported ability to prevent or treat cancer. Early studies that showed ascorbate had benefit in cancer were followed by more definitive studies that demonstrated no benefit. Recent work suggests that biological context may be key to predicting whether antioxidants impede or even promote tumorigenesis. In a recent report, the antioxidants N-acetylcysteine and vitamin E accelerated tumorigenesis of lung cancer in mice. antioxidants decrease reactive oxygen species (ROS) levels, which paradoxically increase the proliferation rate of lung cancer cells, resulting in greater tumor burdens and reduced survival. Increased proliferation rates result from decreased expression of the genomic watchdog protein p53. In mice lacking p53, neither anti-oxidant affects tumor growth. But antioxidants can be used to kill cancer, at least in rodents. High concentrations of the "antioxidant" ascorbate, achievable only by injection in vivo, result in the production of ascorbate radicals and hydrogen peroxide in the extracellular fluid that kills cancer cells, but not normal cells. In preliminary human trials, ascorbate reduced the toxicity of chemotherapy, but showed no statistical benefit on disease progression. Vitamin C is beneficial when it acts as an oxidant. These studies are consistent with others that suggest that even tumor suppressor genes, such as Nrf2, which stimulate innate cellular stress protection pathways that reduce ROS, can promote cancer progression. Nrf2 is required for the cancer preventive effects of compounds such as sulforaphane, but Nrf2 can help maintain an aggressive tumor phenotype by stimulating proliferation and offering protection from chemotherapy. Context determines whether a specific gene is a tumor enhancer or a suppressor. Such paradoxical behavior creates difficult problems for the development of conventional therapeutics to fight cancer. Personal genomic analysis may provide the means to

  16. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England.

    PubMed

    Salway, Sarah; Ali, Parveen; Ratcliffe, Giles; Such, Elizabeth; Khan, Nasaim; Kingston, Helen; Quarrell, Oliver

    2016-07-01

    Populations practising customary consanguineous marriage have a higher incidence of autosomal recessive genetic disorders than those in which reproductive partners are usually unrelated. In the absence of any national-level response, English service developments to address the additional needs of families living with or at risk of such disorders have been locally led. These interventions remain in their infancy here, as elsewhere in Europe, and important questions remain regarding how appropriate, effective and sustainable responses can be operationalised in practice. This formative service review employed four local case studies together with wider consultation exercises over a 4-year period (2011-2015) to document recent responses to this area of need, issues arising and lessons to inform future work. Service components included the following: enhancements to genetic services to provide family-centred, culturally competent approaches to counselling and testing; community genetic literacy approaches; and capacity development among health professionals. Local approaches were, however, very varied in their detail, scope, level of investment and longevity. The provisions of culturally competent genetic counselling services and community-level genetic literacy interventions were generally well received by those who accessed them. Coordinated action across all service components appeared important for an effective service, but healthcare professionals, particularly general practitioners, were often difficult to engage in this agenda. An evaluative culture and engagement in a wider community of practice had supported service development across sites. However, sustaining investment was challenging, particularly where new services were not well integrated into core provision and where commissioning was driven by expectations of short-term reductions in infant mortality and disability. PMID:27311843

  17. Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review

    PubMed Central

    BLOKHINA, OLGA; VIROLAINEN, EIJA; FAGERSTEDT, KURT V.

    2003-01-01

    antioxidant status have been obtained. Experiments on overexpression of antioxidant production do not always result in the enhancement of the antioxidative defence, and hence increased antioxidative capacity does not always correlate positively with the degree of protection. Here we present a consideration of factors which possibly affect the effectiveness of antioxidant protection under oxygen deprivation as well as under other environmental stresses. Such aspects as compartmentalization of ROS formation and antioxidant localization, synthesis and transport of antioxidants, the ability to induce the antioxidant defense and cooperation (and/or compensation) between different antioxidant systems are the determinants of the competence of the antioxidant system. PMID:12509339

  18. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases.

    PubMed

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  19. Antioxidant Supplementation in the Treatment of Aging-Associated Diseases

    PubMed Central

    Conti, Valeria; Izzo, Viviana; Corbi, Graziamaria; Russomanno, Giusy; Manzo, Valentina; De Lise, Federica; Di Donato, Alberto; Filippelli, Amelia

    2016-01-01

    Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented. PMID:26903869

  20. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans

    PubMed Central

    Wilson, Mark A; Shukitt-Hale, Barbara; Kalt, Wilhelmina; Ingram, Donald K; Joseph, James A; Wolkow, Catherine A

    2006-01-01

    Summary The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blue-berry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects. PMID:16441844

  1. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans.

    PubMed

    Wilson, Mark A; Shukitt-Hale, Barbara; Kalt, Wilhelmina; Ingram, Donald K; Joseph, James A; Wolkow, Catherine A

    2006-02-01

    The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects. PMID:16441844

  2. Antioxidant responses of wheat plants under stress

    PubMed Central

    Caverzan, Andréia; Casassola, Alice; Brammer, Sandra Patussi

    2016-01-01

    Abstract Currently, food security depends on the increased production of cereals such as wheat (Triticum aestivum L.), which is an important source of calories and protein for humans. However, cells of the crop have suffered from the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to the plants, due to environmental stresses. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. In the present review, we offer a brief summary of antioxidant defense and hydrogen peroxide (H2O2) signaling in wheat plants. Wheat plants increase antioxidant defense mechanisms under abiotic stresses, such as drought, cold, heat, salinity and UV-B radiation, to alleviate oxidative damage. Moreover, H2O2 signaling is an important factor contributing to stress tolerance in cereals. PMID:27007891

  3. Antioxidant responses of wheat plants under stress.

    PubMed

    Caverzan, Andréia; Casassola, Alice; Brammer, Sandra Patussi

    2016-03-01

    Currently, food security depends on the increased production of cereals such as wheat (Triticum aestivum L.), which is an important source of calories and protein for humans. However, cells of the crop have suffered from the accumulation of reactive oxygen species (ROS), which can cause severe oxidative damage to the plants, due to environmental stresses. ROS are toxic molecules found in various subcellular compartments. The equilibrium between the production and detoxification of ROS is sustained by enzymatic and nonenzymatic antioxidants. In the present review, we offer a brief summary of antioxidant defense and hydrogen peroxide (H2O2) signaling in wheat plants. Wheat plants increase antioxidant defense mechanisms under abiotic stresses, such as drought, cold, heat, salinity and UV-B radiation, to alleviate oxidative damage. Moreover, H2O2 signaling is an important factor contributing to stress tolerance in cereals. PMID:27007891

  4. Application of Lignin as Antioxidant in Styrene Butadiene Rubber Composite

    NASA Astrophysics Data System (ADS)

    Liu, Shusheng; Cheng, Xiansu

    2010-11-01

    Lignin isolated from enzymatic hydrolyzed cornstalks (EHL) is a renewable natural polymer, and rubber is one of the most important polymer materials. The application of EHL in rubber industry is of great significance. The influence of EHL and antioxidant RD on the vulcanizing characteristics, thermal oxidative aging stability under free condition, and water extraction resistance of styrene-butadiene rubber (SBR) were investigated. The effect of EHL/antioxidant D composite antioxidant on the thermal oxidative ageing of SBR was also evaluated. Results showed that the protection of SBR from thermal oxidative aging by EHL/antioxidant D composite antioxidant was superior to that of antioxidant D. This is because EHL molecules have hindered phenol group and have excellent auxiliary antioxidant role with antioxidant D. Moreover, the influence of EHL on the vulcanizing characteristics of SBR compounds was better than that of antioxidant RD, and EHL can reduce the cure rate and increase the optimum cure time. It is because that the EHL molecules have hindered phenol group and methoxy group, which can form a special structure to capture free radical and terminate the chain reaction. The retained tensile strength of SBR compounds with EHL was similar to that of the samples with antioxidant RD, while the retained elongation at break of SBR compounds with EHL was higher than that of the samples with antioxidant RD. In addition, the SBR compounds with EHL have a good water extraction resistance property, which was similar to the samples with antioxidant RD. This is because EHL have large molecular weight, good stability and low solubility in water. In conclusion, due to the low price, abundant resources, non-toxic and pollution-free, etc., EHL will have broad application prospect.

  5. Antioxidant activity of whey protein hydrolysates in milk beverage system.

    PubMed

    Mann, Bimlesh; Kumari, Anuradha; Kumar, Rajesh; Sharma, Rajan; Prajapati, Kishore; Mahboob, Shaik; Athira, S

    2015-06-01

    The aim of the present study was to evaluate the antioxidant activity of flavoured milk enriched with antioxidative whey protein hydrolysates (WPHs) by radical scavenging method. Whey protein concentrate (WPC) was hydrolyzed by using three commercial proteases; flavouzyme, alcalase and corolase PP and these WPHs were analyzed for degree of hydrolysis and antioxidant activity. The antioxidant activities of these WPHs were evaluated using ABTS method. Trolox equivalent antioxidant activity of all the hydrolysates i.e. flavourzyme (0.81 ± 0.04), alcalase (1.16 ± 0.05) and corolase (1.42 ± 0.12) was higher than the WPC (0.19 ± 0.01). Among these, whey protein hydrolysates prepared using corolase showed maximum antioxidant activity. Total 15 β-lactoglobulin, 1 α-lactoalbumin, and 6 β-casein derived peptide fragments were identified in the WPHs by LC-MS/MS. Due to their size and characteristic amino acid composition, all the identified peptides may contribute for the antioxidant activity. The strawberry and chocolate flavoured milk was supplemented with WPC and WPHs and 2 % addition has shown increase in antioxidant activity upto 42 %. The result suggests that WPH could be used as natural biofunctional ingredients in enhancing antioxidant properties of food products. PMID:26028704

  6. In vitro antioxidant activity of Holarrhena antidysenterica Wall. methanolic leaf extract

    PubMed Central

    Ganapathy, P. S. Sujan; Ramachandra, Y. L.; Rai, S. Padmalatha

    2011-01-01

    Antioxidative potential of methanolic leaf extract of Holarrhena antidysenterica was evaluated using hydroxyl radical, superoxide anion scavenging and reducing power assays. The antioxidant activity of the methanol extract increased in a concentration-dependent manner. The extract showed significant reactive oxygen species (ROS) scavenging activity in all in vitro antioxidant assays and contained high level of total phenolic content PMID:24826020

  7. Cardiovascular diseases: oxidative damage and antioxidant protection.

    PubMed

    Zhang, P-Y; Xu, X; Li, X-C

    2014-10-01

    Atherosclerosis, the hardening of arteries under oxidative stress is related to oxidative changes of low density lipoproteins (LDL). The antioxidants prevent the formation of oxidized LDL during atherogenesis. Perhaps more than one mechanism is involved in the atherosclerosis disease where LDL is oxidized in all the cells of arterial wall during the development of this disease. The oxidation of LDL produces lipid peroxidation products such as isoprostans from arachidonic, eicosapentaenoic and docosahexaenoic acids, oxysterols from cholesterol, hydroxyl fatty acids, lipid peroxides and aldehydes. The lipid peroxidation bioassay can serve as a marker for the risk of cardiovascular. An in vivo test of levels of oxidative lipid damage is an early prediction of development of cardiovascular disease (CVD). Serum paraoxonase (PON) activity is correlated to severity of the coronary artery disease. The antioxidants level in the serum and serum paraoxonase activity provides information for the risk of CVD. The antioxidant enzyme superoxide dismutase is responsible for dismutation of superoxide, a free radical chain initiator. The subcellular changes in the equilibrium in favor of free radicals can cause increase in the oxidative stress which leads to cardiomyopathy, heart attack or cardiac dysfunction. The oxidative damage and defense of heart disease has been reported where dietary antioxidants protect the free radical damage to DNA, proteins and lipids. The ascorbic acid, vitamin C is an effective antioxidant and high vitamin E intake can reduce the risk of coronary heart disease (CHD) by inhibition of atherogenic forms of oxidized LDL. The vitamin A and beta-carotene protect lipid peroxidation and provitamin-A activity. It has been recently suggested that the protection of oxidative damage and related CVD is best served by antioxidants found in the fruits and vegetables. The oxidative damage and antioxidant protection of CVD have been described here. PMID:25392110

  8. The antioxidant network of the stratum corneum.

    PubMed

    Thiele, J J; Schroeter, C; Hsieh, S N; Podda, M; Packer, L

    2001-01-01

    Many studies have demonstrated beneficial health effects of topical antioxidant application; however, the underlying mechanisms are not well understood. To better understand the protective mechanism of oxogenous anti-oxidants, it is important to clarify the physiological distribution, activity and regulation of antioxidants. Also, the generation of ROS by the resident and transient microbial flora and their interaction with cutaneous antioxidants appears to be of relevance for the redox properties of skin. Our studies have demonstrated that alpha-tocopherol is, relative to the respective levels in the epidermis, the major antioxidant in the human SC, that alpha-tocopherol depletion is a very early and sensitive biomarker of environmentally induced oxidation and that a physiological mechanism exists to transport alpha-tocopherol to the skin surface via sebaceous gland secretion. Furthermore, there is conclusive evidence that the introduction of carbonyl groups into human SC keratins is inducible by oxidants and that the levels of protein oxidation increase towards outer SC layers. The demonstration of specific redox gradients within the human SC may contribute to a better understanding of the complex biochemical processes of keratinization and desquamation. Taken together, the presented data suggest that, under conditions of environmentally challenged skin or during prooxidative dermatological treatment, topical and/or systemic application of antioxidants could support physiological mechanisms to maintain or restore a healthy skin barrier. Growing experimental evidence should lead to the development of more powerful pharmaceutical and cosmetic strategies involving antioxidant formulations to prevent UV-induced carcinogenesis and photoaging as well as to modulate desquamatory skin disorders. PMID:11225199

  9. Dairy Cattle: Breeding and Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five primary factors affect breeding genetically improved dairy cattle: 1) identification, 2) pedigree, 3) performance recording, 4) artificial insemination, and 5) genetic evaluation systems (traditional and genomic). Genetic progress can be measured as increased efficiency (higher performance with...

  10. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    PubMed Central

    Reddy, P. Hemachandra

    2011-01-01

    Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma. PMID:21461182

  11. Medical genetics and genetic counseling in Chile.

    PubMed

    Margarit, Sonia B; Alvarado, Mónica; Alvarez, Karin; Lay-Son, Guillermo

    2013-12-01

    In the South American Republic of Chile genetic counseling is not currently recognized as an independent clinical discipline, and in general is provided by physicians with training in clinical genetics. At present only one genetic counselor and 28 clinical geneticists practice in this country of over 16 million inhabitants. Pediatric dysmorphology constitutes the primary area of practice in clinical genetics. Although the country has a universal health care system and an adequate level of health care, genetic conditions are not considered a health care priority and there is a lack of clinical and laboratory resources designated for clinical genetics services. Multiple educational, cultural and financial barriers exist to the growth and development of genetic counseling services in Chile. However, during the last 10 years increased awareness of the importance of identifying individuals at risk for inherited cancer syndromes led to growing interest in the practice of cancer genetics. PMID:23744184

  12. Dietary antioxidants and environmental stress.

    PubMed

    Kelly, Frank J

    2004-11-01

    Air is one of our most important natural resources; however, it is also in the front line for receiving environmental pollution. Air quality decreased markedly following the industrial revolution, but it was not until the great London Smog in 1952 that air quality made it onto the political agenda. The introduction of the Clean Air Act in 1956 led to dramatic decreases in black smoke and SO2 concentrations over the next two decades, as domestic and industrial coal-burning activities ceased. However, as these improvements progressed, a new threat to public health was being released into the air in ever-increasing quantities. Rapid motorisation of society from the 1960s onwards has led to the increased release of atmospheric pollutants such as tiny particles (particulate matter of <10 microm in aerodynamic diameter) and oxides of N, and the generation of the secondary pollutant O3. These primary and secondary traffic-related pollutants have all proved to be major risks factors to public health. Recently, oxidative stress has been identified as a unifying feature underlying the toxic actions of these pollutants. Fortunately, the surface of the lung is covered with a thin layer of fluid containing a range of antioxidants that appear to provide the first line of defence against oxidant pollutants. As diet is the only source of antioxidant micronutrients, a plausible link now exists between the sensitivity to air pollution and the quality of the food eaten. However, many questions remain unanswered in relation to inter-individual sensitivity to ambient air pollution, and extent to which this sensitivity is modified by airway antioxidant defences. PMID:15831130

  13. Studies on antioxidant activity of teasaponins after hydrolyzed by enzyme

    NASA Astrophysics Data System (ADS)

    Tian, Jing; Zhao, Sen; Xu, Longquan; Fei, Xu; Wang, Xiuying; Wang, Yi

    The biological activity of teasaponins and their molecular structure are closely related, and the activity of saponins may be increased with the change of their molecular structure. In this report, teasaponins were hydrolyzed by Aspergillus niger for increasing the antioxidant activity. The antioxidant activity of teasaponins before and after hydrolyzed was tested by DPPH, and the result showed four new teasaponins were produced after hydrolysis, and their antioxidant activity was increased significantly than the original teasaponins before hydrolysis, the radical scavenging capacity (RSC) was partly up to 95 %.

  14. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  15. Nutraceutical Antioxidants as Novel Neuroprotective Agents

    PubMed Central

    Kelsey, Natalie A.; Wilkins, Heather M.; Linseman, Daniel A.

    2015-01-01

    A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases. PMID:21060289

  16. Nutraceutical antioxidants as novel neuroprotective agents.

    PubMed

    Kelsey, Natalie A; Wilkins, Heather M; Linseman, Daniel A

    2010-11-01

    A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic. All of these compounds are generally considered to be antioxidants. They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases. PMID:21060289

  17. Antioxidant properties of kilned and roasted malts.

    PubMed

    Samaras, Thomas S; Camburn, Philip A; Chandra, Sachin X; Gordon, Michael H; Ames, Jennifer M

    2005-10-01

    Compounds possessing antioxidant activity play a crucial role in delaying or preventing lipid oxidation in foods and beverages during processing and storage. Such reactions lead to loss of product quality, especially as a consequence of off-flavor formation. The aim of this study was to determine the antioxidant activity of kilned (standard) and roasted (speciality) malts in relation to phenolic compounds, sugars, amino acids, and color [assessed as European Brewing Convention units (degrees EBC) and absorbance at 420 nm]. The concentrations of sugars and amino acids decreased with the intensity of the applied heat treatment, and this was attributed to the extent of the Maillard reaction, as well as sugar caramelization, in the highly roasted malts. Proline, followed by glutamine, was the most abundant free amino/imino acid in the malt samples, except those that were highly roasted, and maltose was the most abundant sugar in all malts. Levels of total phenolic compounds decreased with heat treatment. Catechin and ferulic acid were the most abundant phenolic compounds in the majority of the malts, and amounts were highest in the kilned samples. In highly roasted malts, degradation products of ferulic acid were identified. Antioxidant activity increased with the intensity of heating, in parallel with color formation, and was significantly higher for roasted malts compared to kilned malts. In kilned malts, phenolic compounds were the main identified contributors to antioxidant activity, with Maillard reaction products also playing a role. In roasted malts, Maillard reaction products were responsible for the majority of the antioxidant activity. PMID:16190672

  18. Genome-wide Association Mapping of Polyphenol Contents and Antioxidant Capacity in Whole-Grain Rice.

    PubMed

    Xu, Feifei; Bao, Jinsong; Kim, Tae-Sung; Park, Yong-Jin

    2016-06-01

    Whole grains contain various bioactive phytochemicals including phenolic acids, and consumption of whole grains may provide desirable health benefits and reduce the risks of chronic diseases due to their antioxidant activities. In this study, we qualified and quantified 9 bound phenolic compounds in 32 red and 88 white pericarp accessions of rice. A genome-wide association study (GWAS) was conducted for free (FP) and bound (BP) phenolic compounds and their antioxidant capacities with high-quality single-nucleotide polymorphisms (SNPs) in two colored grain panels and the whole panel. Rc was detected for all FP and antioxidant capacities in the whole panel. Three loci (chr.1:30970095, chr.6:24392269, and chr.9:6670223) for more than five phenolic-related traits, two loci (chr.4:34120529 and chr.11:28947480) for more than two FP-related traits, and one locus (chr.11:23220681) for ferulic acid detected in two panels were potentially new genes that are valuable for further gene cloning. Overall, this study increases our understanding on the genetics of phenolic acid biosynthesis in the phenylpropanoid pathway. PMID:27163766

  19. Portable nanoparticle based sensors for antioxidant analysis.

    PubMed

    Sharpe, Erica; Andreescu, Silvana

    2015-01-01

    Interest in portable sensing devices has increased throughout the past decade. Portable sensors are convenient for use in remote locations and in places with limited resources for advanced instrumentation. Often such devices utilize advanced technology that allows the final user to simply deposit the sample onto the sensing platform without preparation of multiple reagents. Herein, we describe preparation and characterization of a colorimetric paper-based metal oxide sensing array designed for the field detection of polyphenolic antioxidants. This sensor is a good candidate for use in analysis of the antioxidant character of food, drink, botanical medicines, physiological fluids, and more. PMID:25323510

  20. Enzymes of the antioxidant network as novel determiners of Trypanosoma cruzi virulence

    PubMed Central

    Piacenza, L.; Zago, M.P.; Peluffo, G.; Alvarez, M.N.; Basombrio, M.A.; Radi, R.

    2013-01-01

    Virulence of Trypanosoma cruzi depends on a variety of genetic and biochemical factors. It has been proposed that components of the parasites' antioxidant system may play a key part in this process by pre-adapting the pathogen to the oxidative environment encountered during host cell invasion. Using several isolates (10 strains) belonging to the two major phylogenetic lineages (T. cruzi-I and T. cruzi-II), we investigated whether there was an association between virulence (ranging from highly aggressive to attenuated isolates at the parasitemia and histopathological level) and the antioxidant enzyme content. Antibodies raised against trypanothione synthetase (TcTS), ascorbate peroxidase (TcAPX), mitochondrial and cytosolic tryparedoxin peroxidases (TcMPX and TcCPX) and trypanothione reductase (TcTR) were used to evaluate the antioxidant enzyme levels in epimastigote and metacyclic trypomastigote forms in the T. cruzi strains. Levels of TcCPX, TcMPX and TcTS were shown to increase during differentiation from the non-infective epimastigote to the infective metacyclic trypomastigote stage in all parasite strains examined. Peroxiredoxins were found to be present at higher levels in the metacyclic infective forms of the virulent isolates compared with the attenuated strains. Additionally, an increased resistance of epimastigotes from virulent T. cruzi populations to hydrogen peroxide and peroxynitrite challenge was observed. In mouse infection models, a direct correlation was found between protein levels of TcCPX, TcMPX and TcTS, and the parasitemia elicited by the different isolates studied (Pearson's coefficient: 0.617, 0.771, 0.499; respectively, P < 0.01). No correlation with parasitemia was found for TcAPX and TcTR proteins in any of the strains analyzed. Our data support that enzymes of the parasite antioxidant armamentarium at the onset of infection represent new virulence factors involved in the establishment of disease. PMID:19505468

  1. Antioxidant properties of HDL

    PubMed Central

    Soran, Handrean; Schofield, Jonathan D.; Durrington, Paul N.

    2015-01-01

    High-density lipoprotein (HDL) provides a pathway for the passage of lipid peroxides and lysophospholipids to the liver via hepatic scavenger receptors. Perhaps more importantly, HDL actually metabolizes lipid hydroperoxides preventing their accumulation on low-density lipoprotein (LDL), thus impeding its atherogenic structural modification. A number of candidates have been suggested to be responsible for HDL's antioxidant function, with paraoxonase-1 (PON1) perhaps the most prominent. Here we review the evidence for HDL anti-oxidative function and the potential contributions of apolipoproteins, lipid transfer proteins, paraoxonases and other enzymes associated with HDL. PMID:26528181

  2. Antioxidant properties of diverse cereal grains: A review on in vitro and in vivo studies.

    PubMed

    Masisi, Kabo; Beta, Trust; Moghadasian, Mohammed H

    2016-04-01

    Cereal grains and products have gained popularity in contributing to healthy eating behavior because of their antioxidant properties associated with protection against chronic diseases. In this review, notable studies on the in vitro and in vivo antioxidant activity of commonly consumed cereal grains are summarized. Cereals contain phytochemicals or certain minor components with antioxidant properties. The antioxidant potential of cereals depends on their bioaccessibility, absorption in the gastrointestinal and their bioavailability utilization in vivo. The in vitro gastrointestinal digestion and fermentation of cereals increased their antioxidant potentials which are significantly correlated with their total phenolic contents. Most studies performed in vivo have been concerned with the antioxidant properties of colored rice, wheat bran and rye products. There are inadequate in vitro and in vivo studies on antioxidative potentials of fermented versus unfermented cereals. Therefore, further studies are necessary to maximize possible health benefits of cereal antioxidative phytochemicals. PMID:26593469

  3. GENETIC MAPPING OF VOCALIZATION TO A SERIES OF INCREASING ACUTE FOOTSHOCKS USING B6.A CONSOMIC AND B6.D2 CONGENIC MOUSE STRAINS

    SciTech Connect

    Matthews, Douglas B; Chesler, Elissa J; Cook, Melloni N.; Cockroft, Judy; Philip, Vivek M; Goldowitz, Daniel

    2008-01-01

    Footshock response is used to study biological functions in mammals. However, the genetics underlying variability in footshock sensitivity are not well understood. In the current studies, a panel of B6.A consomic mouse strains, two B6.D2 congenic mouse strains and the progenitor strains were screened for footshock sensitivity as measured by audible vocalization. It was found that A/J (A) mice and C57BL/6J (B6) mice with an A Chromosome 1 (Chr 1) were less sensitive to footshock compared to B6 animals. Furthermore, the offspring of Chr 1 consomic mice crossed with B6 mice had vocalization levels that were intermediate to A/J and B6 animals. A F2 mapping panel revealed two significant QTLs for footshock vocalization centered around D1Mit490 and D1Mit206 on Chr 1. The role of these Chr 1 loci in footshock sensitivity was confirmed in B6.D2 congenic mice. These data identify genetic regions involved in footshock sensitivity and establish additional mouse resources for use in investigating complex behaviors.

  4. Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome

    PubMed Central

    Broedl, Uli C; Lehrke, Michael; Fleischer-Brielmaier, Elisabeth; Tietz, Anne B; Nagel, Jutta M; Göke, Burkhard; Lohse, Peter; Parhofer, Klaus G

    2006-01-01

    Background Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. Aim The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. Methods We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. Results We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. Conclusion To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism. PMID:16700915

  5. Targeting antioxidants for cancer therapy.

    PubMed

    Glasauer, Andrea; Chandel, Navdeep S

    2014-11-01

    Cancer cells are characterized by an increase in the rate of reactive oxygen species (ROS) production and an altered redox environment compared to normal cells. Furthermore, redox regulation and redox signaling play a key role in tumorigenesis and in the response to cancer therapeutics. ROS have contradictory roles in tumorigenesis, which has important implications for the development of potential anticancer therapies that aim to modulate cellular redox levels. ROS play a causal role in tumor development and progression by inducing DNA mutations, genomic instability, and aberrant pro-tumorigenic signaling. On the other hand, high levels of ROS can also be toxic to cancer cells and can potentially induce cell death. To balance the state of oxidative stress, cancer cells increase their antioxidant capacity, which strongly suggests that high ROS levels have the potential to actually block tumorigenesis. This fact makes pro-oxidant cancer therapy an interesting area of study. In this review, we discuss the controversial role of ROS in tumorigenesis and especially elaborate on the advantages of targeting ROS scavengers, hence the antioxidant capacity of cancer cells, and how this can be utilized for cancer therapeutics. PMID:25078786

  6. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

  7. Lentinus squarrosulus (Mont.) mycelium enhanced antioxidant status in rat model

    PubMed Central

    Mhd Omar, Nor Adila; Abdullah, Sumaiyah; Abdullah, Noorlidah; Kuppusamy, Umah Rani; Abdulla, Mahmood Ameen; Sabaratnam, Vikineswary

    2015-01-01

    Aim Lentinus squarrosulus is an edible wild mushroom commonly found in Asia. This species has several interesting features such as rapid mycelial growth, and hence has the potential to be used as food, functional food, and nutraceuticals. Our previous study shows that L. squarrosulus contains potent antioxidant compounds in vitro. This study aims to investigate the in vivo bioavailability of L. squarrosulus mycelium extract and its antioxidant effect on biomarkers of antioxidant defense and oxidative stress. Methods Water extract of mycelial biomass of L. squarrosulus was analyzed for in vivo antioxidant effects, including cupric-reducing antioxidant capacity (CUPRAC), glutathione peroxidase (GPx), xanthine oxidase (XO), advanced oxidation protein products (AOPPs), and lipid hydroperoxides (LHPs) at 0 and 28 days. GPx and XO were also analyzed in liver homogenates. Normal Sprague Dawley rats were treated with 250 and 500 mg/kg of extract for 28 days. Results The serum CUPRAC level increased after treatment with both concentrations, indicating that there was sufficient bioavailability of the extract which contributed to the total antioxidant capacity. GPx activity in both serum and liver was increased and this correlated with LHP level after treatment with 250 mg/kg of extract, but XO activity was significantly decreased after treatment with 500 mg/kg of the extract. Lack of difference between AOPP levels implied that there were no significant changes in oxidative damage of protein after treatment. Conclusion This study clearly showed that L. squarrosulus mycelium antioxidant extract contains absorbable antioxidants that enter the circulating plasma and cause a significant acute increase in plasma antioxidant capacity. Thus, the water extract of L. squarrosulus mycelium, which can be obtained abundantly by liquid fermentation, may serve as an antioxidant ingredient in functional foods and nutraceuticals. PMID:26604694

  8. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist. PMID:27067213

  9. Antioxidant effect of green tea on polymer gel dosimeter

    NASA Astrophysics Data System (ADS)

    Samuel, E. J. J.; Sathiyaraj, P.; Deena, T.; Kumar, D. S.

    2015-01-01

    Extract from Green Tea (GTE) acts as an antioxidant in acrylamide based polymer gel dosimeter. In this work, PAGAT gel was used for investigation of antioxidant effect of GTE.PAGAT was called PAGTEG (Polyacrylamide green tea extract gel dosimeter) after adding GTE. Free radicals in water cause pre polymerization of polymer gel before irradiation. Polyphenols from GTE are highly effective to absorb the free radicals in water. THPC is used as an antioxidant in polymer gel dosimeter but here we were replaced it by GTE and investigated its effect by spectrophotometer. GTE added PAGAT samples response was lower compared to THPC added sample. To increase the sensitivity of the PAGTEG, sugar was added. This study confirmed that THPC was a good antioxidant for polymer gel dosimeter. However, GTE also can be used as an antioxidant in polymer gel if use less quantity (GTE) and add sugar as sensitivity enhancer.

  10. Global genetic analysis.

    PubMed

    Elahi, Elahe; Kumm, Jochen; Ronaghi, Mostafa

    2004-01-31

    The introduction of molecular markers in genetic analysis has revolutionized medicine. These molecular markers are genetic variations associated with a predisposition to common diseases and individual variations in drug responses. Identification and genotyping a vast number of genetic polymorphisms in large populations are increasingly important for disease gene identification, pharmacogenetics and population-based studies. Among variations being analyzed, single nucleotide polymorphisms seem to be most useful in large-scale genetic analysis. This review discusses approaches for genetic analysis, use of different markers, and emerging technologies for large-scale genetic analysis where millions of genotyping need to be performed. PMID:14761299

  11. LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

    PubMed Central

    Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

    2009-01-01

    LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies. PMID:19165201

  12. Genetic modifications to temperate Enterococcus faecalis phage Ef11 that abolish the establishment of lysogeny and sensitivity to repressor, and increase host range and productivity of lytic infection.

    PubMed

    Zhang, H; Fouts, D E; DePew, J; Stevens, R H

    2013-06-01

    Ef11 is a temperate bacteriophage originally isolated by induction from a lysogenic Enterococcus faecalis strain recovered from an infected root canal, and the Ef11 prophage is widely disseminated among strains of E. faecalis. Because E. faecalis has emerged as a significant opportunistic human pathogen, we were interested in examining the genes and regulatory sequences predicted to be critical in the establishment/maintenance of lysogeny by Ef11 as a first step in the construction of the genome of a virulent, highly lytic phage that could be used in treating serious E. faecalis infections. Passage of Ef11 in E. faecalis JH2-2 yielded a variant that produced large, extensively spreading plaques in lawns of indicator cells, and elevated phage titres in broth cultures. Genetic analysis of the cloned virus producing the large plaques revealed that the variant was a recombinant between Ef11 and a defective FL1C-like prophage located in the E. faecalis JH2-2 chromosome. The recombinant possessed five ORFs of the defective FL1C-like prophage in place of six ORFs of the Ef11 genome. Deletion of the putative lysogeny gene module (ORFs 31-36) and replacement of the putative cro promoter from the recombinant phage genome with a nisin-inducible promoter resulted in no loss of virus infectivity. The genetic construct incorporating all the aforementioned Ef11 genomic modifications resulted in the generation of a variant that was incapable of lysogeny and insensitive to repressor, rendering it virulent and highly lytic, with a notably extended host range. PMID:23579685

  13. Development of a Markerless Genetic Exchange System in Desulfovibrio vulgaris Hildenborough and Its Use in Generating a Strain with Increased Transformation Efficiency

    SciTech Connect

    Keller, Kimberly L.; Bender, Kelly S.; Wall, Judy D.

    2009-07-21

    In recent years, the genetic manipulation of the sulfate-reducing bacterium Desulfovibrio vulgaris Hi