Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.

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Mai-Britt Mosbech

Full Text Available Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24, while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22. Here we show that functional loss of HYL-2 decreases lifespan, while loss of HYL-1 or LAGR-1 does not affect lifespan. We show that loss of HYL-1 and LAGR-1 functions extend lifespan in an autophagy-dependent manner, as knock down of the autophagy-associated gene ATG-12 abolishes hyl-1;lagr-1 longevity. The transcription factors PHA-4/FOXA, DAF-16/FOXO, and SKN-1 are also required for the observed lifespan extension, as well as the increased number of autophagosomes in hyl-1;lagr-1 animals. Both autophagic events and the transcription factors PHA-4/FOXA, DAF-16, and SKN-1 have previously been associated with dietary restriction-induced longevity. Accordingly, we find that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR-1 result in dietary restriction-induced autophagy and consequently prolonged longevity.

Lifespan extension by preserving proliferative homeostasis in Drosophila.

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Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension.

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Catterson, James H; Khericha, Mobina; Dyson, Miranda C; Vincent, Alec J; Callard, Rebecca; Haveron, Steven M; Rajasingam, Arjunan; Ahmad, Mumtaz; Partridge, Linda

2018-06-04

Intermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF. Early-life IF also led to higher lipid content in 60-day-old flies, a potential explanation for increased longevity. Guts of flies 40 days post-IF showed a significant reduction in age-related pathologies and improved gut barrier function. Improved gut health was also associated with reduced relative bacterial abundance. Early IF thus induced profound long-term changes. Pharmacological and genetic epistasis analysis showed that IF acted independently of the TOR pathway because rapamycin and IF acted additively to extend lifespan, and global expression of a constitutively active S6K did not attenuate the IF-induced lifespan extension. We conclude that short-term IF during early life can induce long-lasting beneficial effects, with robust increase in lifespan in a TOR-independent manner, probably at least in part by preserving gut health. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

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Li, Yan-Hui; Zhang, Gai-Gai

2016-04-12

DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

Extension of mouse lifespan by overexpression of catalase.

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Schriner, Samuel E; Linford, Nancy J

2006-06-01

The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

Extension of Drosophila lifespan by Rhodiola rosea through a mechanism independent from dietary restriction.

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Samuel E Schriner

Full Text Available Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2 proteins, insulin and insulin-like growth factor signaling (IIS, and the target of rapamycin (TOR. In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.

Nitrogen Ion Form and Spatio-temporal Variation in Root Distribution Mediate Nitrogen Effects on Lifespan of Ectomycorrhizal Roots

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Kou, L.; McCormack, M. L.; Chen, W.; Guo, D.; Wang, H.; Li, S.; Gao, W.; Yang, H.

2017-12-01

Background and Aims Absorptive roots active in soil resource uptake are often intimately associated with mycorrhizal fungi, yet it remains unclear how nitrogen (N) loading affects lifespan of absorptive roots associating with ectomycorrhizal (ECM) fungi. Methods Through a three-year minirhizotron experiment, we investigated the responses of ECM lifespan to different rates of N addition and examined the roles of N ion form, rooting depth, seasonal root cohort, and ECM morphotype in mediating the N effects on ECM lifespan in a slash pine (Pinus elliottii) forest in subtropical China. Results High rates of NH4Cl significantly decreased foliar P concentrations and increased foliar N: P ratios, and mean ECM lifespan was negatively correlated to foliar P concentration. N additions generally increased the lifespan of most ectomycorrhizas, but the specific differences were context dependent. N rates and forms exerted significant positive effects on ECM lifespan with stronger effects occurring at high N rates and under ammonium N addition. N additions extended lifespan of ectomycorrhizas in shallower soil and born in spring and autumn, but shortened lifespan of ectomycorrhizas in deeper soil and born in summer and winter. N additions reduced lifespan of dichotomous ectomycorrhizas, but increased lifespan of coralloid ectomycorrhizas. Conclusions The increased ECM lifespan in response to N additions may primarily be driven by the persistent and aggravated P limitation to plants. Our findings highlight the importance of environmental contexts in controlling ECM lifespan and the need to consider potential differences among mycorrhizal morphotypes when studying N—lifespan relationships of absorptive roots in the context of N deposition.

Intestinal IRE1 Is Required for Increased Triglyceride Metabolism and Longer Lifespan under Dietary Restriction.

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Luis, Nuno Miguel; Wang, Lifen; Ortega, Mauricio; Deng, Hansong; Katewa, Subhash D; Li, Patrick Wai-Lun; Karpac, Jason; Jasper, Heinrich; Kapahi, Pankaj

2016-10-25

Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut. Consistently, IRE1/XBP1 function in ECs is required for increased longevity upon DR. We further identify sugarbabe, a Gli-like zinc-finger transcription factor, as a key mediator of the IRE1/XBP1-regulated induction of de novo lipogenesis in ECs. Overexpression of sugarbabe rescues metabolic and lifespan phenotypes of IRE1 loss-of-function conditions. Our study highlights the critical role of metabolic adaptation of the intestinal epithelium for DR-induced lifespan extension and explores the IRE1/XBP1 signaling pathway regulating this adaptation and influencing lifespan. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

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Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G.; Zhang, Nianshu

2016-01-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding ‘signaling’ proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast. PMID:27923067

Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

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Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

2015-12-01

Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

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Doroszuk Agnieszka

2012-05-01

Full Text Available Abstract Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR and compare it with normal-lived control flies (C. We do this at two time points representing middle age (90% survival and old age (10% survival respectively, in three adult diets (malnutrition, optimal food, and overfeeding. Results We found profound differences between Drosophila lines in their age-related expression. Most of the age-associated changes in normal-lived flies were abrogated in long-lived Drosophila. The stress-related genes, including those involved in proteolysis and cytochrome P450, were generally higher expressed in SR flies and showed a smaller increase in expression with age compared to C flies. The genes involved in reproduction showed a lower expression in middle-aged SR than in C flies and, unlike C flies, a lack of their downregulation with age. Further, we found that malnutrition strongly affected age-associated transcript patterns overriding the differences between the lines. However, under less stressful dietary conditions, line and diet affected age-dependent expression similarly. Finally, we present lists of candidate markers of ageing and lifespan extension. Conclusions Our study unveils transcriptional changes associated with lifespan extension in SR Drosophila. The results suggest that natural genetic variation for SR and lifespan can operate through similar transcriptional mechanisms as those of dietary restriction and life-extending mutations.

Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

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Mei, Szu-Chieh; Brenner, Charles

2015-01-01

In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell. PMID:25633578

Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

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Szu-Chieh Mei

2015-01-01

Full Text Available In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA, are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

Malate and fumarate extend lifespan in Caenorhabditis elegans.

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Clare B Edwards

Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

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Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

Calorie restriction extends the chronological lifespan of Saccharomyces cerevisiae independently of the Sirtuins.

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Smith, Daniel L; McClure, Julie M; Matecic, Mirela; Smith, Jeffrey S

2007-10-01

Calorie restriction (CR) extends the mean and maximum lifespan of a wide variety of organisms ranging from yeast to mammals, although the molecular mechanisms of action remain unclear. For the budding yeast Saccharomyces cerevisiae reducing glucose in the growth medium extends both the replicative and chronological lifespans (CLS). The conserved NAD(+)-dependent histone deacetylase, Sir2p, promotes replicative longevity in S. cerevisiae by suppressing recombination within the ribosomal DNA locus and has been proposed to mediate the effects of CR on aging. In this study, we investigated the functional relationships of the yeast Sirtuins (Sir2p, Hst1p, Hst2p, Hst3p and Hst4p) with CLS and CR. SIR2, HST2, and HST4 were not major regulators of CLS and were not required for the lifespan extension caused by shifting the glucose concentration from 2 to 0.5% (CR). Deleting HST1 or HST3 moderately shortened CLS, but did not prevent CR from extending lifespan. CR therefore works through a Sirtuin-independent mechanism in the chronological aging system. We also show that low temperature or high osmolarity additively extends CLS when combined with CR, suggesting that these stresses and CR act through separate pathways. The CR effect on CLS was not specific to glucose. Restricting other simple sugars such as galactose or fructose also extended lifespan. Importantly, growth on nonfermentable carbon sources that force yeast to exclusively utilize respiration extended lifespan at nonrestricted concentrations and provided no additional benefit when restricted, suggesting that elevated respiration capacity is an important determinant of chronological longevity.

The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.

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Mack, Hildegard I D; Zhang, Peichuan; Fonslow, Bryan R; Yates, John R

2017-05-25

In Caenorhabditis elegans , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.

Gender differences in depression and anxiety across the adult lifespan: the role of psychosocial mediators.

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Leach, Liana S; Christensen, Helen; Mackinnon, Andrew J; Windsor, Timothy D; Butterworth, Peter

2008-12-01

There is robust epidemiological and clinical evidence that a greater number of women than men experience depression and anxiety. This study investigated a number of socio-demographic, health and lifestyle, psychological and social factors as possible mediators for the gender difference in depression and anxiety in three cohorts (20-24, 40-44, 60-64). Responses were from a representative, community based survey (n = 7,485) conducted in Canberra and Queanbeyan (NSW), in Australia. Depression and anxiety were measured using the self-report Goldberg Anxiety and Depression Scales. The analyses initially identified gender differences in the potential mediators, followed by univariate and multivariate mediation models. The results indicated several shared mediators for depression and anxiety across the three age groups including: childhood adversity, mastery, behavioural inhibition, ruminative style, neuroticism, physical health, physical activity, and perceived interpersonal and employment problems. There was a decrease in the number of social mediators as age increased. The multivariate models accounted for gender differences in both conditions for all age groups, except for anxiety in the 20-24 years old. This suggests further important unmeasured mediators for this age group. These findings add to the literature surrounding gender differences in depression and anxiety, and provide a basis for future research exploring variation in these gender disparities over the adult lifespan.

An engineering approach to extending lifespan in C. elegans.

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Dror Sagi

Full Text Available We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome.

Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

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Hyun Won Seo

2015-01-01

Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

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Romey-Glüsing, Renja; Li, Yang; Hoffmann, Julia; von Frieling, Jakob; Knop, Mirjam; Pfefferkorn, Roxana; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

2018-04-01

Nutritional interventions such as caloric and dietary restriction increase lifespan in various animal models. To identify alternative and less demanding nutritional interventions that extend lifespan, we subjected fruit flies ( Drosophila melanogaster) to weekly nutritional regimens that involved alternating a conventional diet with dietary restriction. Short periods of dietary restriction (up to 2 d) followed by longer periods of a conventional diet yielded minimal increases in lifespan. We found that 3 or more days of contiguous dietary restriction (DR) was necessary to yield a lifespan extension similar to that observed with persistent DR. Female flies were more responsive to these interventions than males. Physiologic changes known to be associated with prolonged DR, such as reduced metabolic rates, showed the same time course as lifespan extension. Moreover, concurrent transcriptional changes indicative of reduced insulin signaling were identified with DR. These physiologic and transcriptional changes were sustained, as they were detectable several days after switching to conventional diets. Taken together, diets with longer periods of DR extended lifespan concurrently with physiologic and transcriptional changes that may underlie this increase in lifespan.-Romey-Glüsing, R., Li, Y., Hoffmann, J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder, T. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan.

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Brian H Lee

2008-10-01

Full Text Available For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1 stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

Metabolome analysis of effect of aspirin on Drosophila lifespan extension.

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Song, Chaochun; Zhu, Chenxing; Wu, Qi; Qi, Jiancheng; Gao, Yue; Zhang, Zhichao; Gaur, Uma; Yang, Deying; Fan, Xiaolan; Yang, Mingyao

2017-09-01

Effective approaches for drug development involve the repurposing of existing drugs which are already approved by the FDA. Aspirin has been shown to have many health benefits since its discovery as a nonsteroidal anti-inflammatory drug (NSAID) to treat pain and inflammation. Recent experiments demonstrated the longevity effects of aspirin in Drosophila, but its mechanism remains to be explored. In order to elucidate the effects of drug on metabolism, we carried out the metabolic analysis of aspirin-treated flies. The results identified 404 active metabolites in addition to the extended lifespan and improved healthspan in fly. There were 28 metabolites having significant changes between aspirin-treated group and the control group, out of which 22 compounds were found to have detailed information. These compounds are reported to have important functions in energy metabolism, amino sugar metabolism, and urea metabolism, indicating that aspirin might be playing positive roles in the fly's lifespan and healthspan improvement. Because of the conservation of major longevity pathways and mechanisms in different species, the health benefits of aspirin administration could be extended to other animals and humans as well. Copyright © 2017 Elsevier Inc. All rights reserved.

Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans

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Devon eChandler-Brown

2015-10-01

Full Text Available The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370 and independently of daf-16(mu86, sir-2.1(ok434, aak-2(ok524, and hif-1(ia04. Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113 fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813 and osm-7(n1515, were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

International Nuclear Information System (INIS)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Active Hexose Correlated Compound Extends the Lifespan and Increases the Thermotolerance of Nematodes

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Tetsuya Okuyama

2013-06-01

of the heat shock genes, which are the targets of HSF-1. Similarly, the expression of hsf-1 mRNA was elevated following AHCC treatment. Recently, natural antisense transcripts were shown to regulate mRNA stability at the posttranscriptional level. In nematodes, AHCC increased the natural antisense transcript of the hsf-1 gene.Conclusion: AHCC conferred lifespan extension and thermotolerance to C. elegans. Our analyses suggest that the beneficial effects of AHCC on longevity are involved in the activation of at least two transcription factors, DAF-16 and HSF-1, most likely through an antisense transcript-mediated mechanism.Keywords: longevity, heat stress resistance, HSF, FOXO, heat shock gene

NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration

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Ilias Kounatidis

2017-04-01

Full Text Available During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that “age well” from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.

A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

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Arjumand Ghazi

2009-09-01

Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

International Nuclear Information System (INIS)

Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

2012-01-01

Highlights: ► Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. ► Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. ► Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation – when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

Energy Technology Data Exchange (ETDEWEB)

Khan, Maruf H. [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Hart, Matthew J., E-mail: HartMJ@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Rea, Shane L., E-mail: reas3@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper-Acidification of the Environment in Saccharomyces cerevisiae.

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Yo Maruyama

Full Text Available The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell-extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions.

Social consequences of Garona NPP lifespan extension issue

International Nuclear Information System (INIS)

Millan, Miguel A.

2010-01-01

On June 3, Spanish Nuclear Safety regulatory body, CSN, declared unanimously 'Santa Maria de Garona' nuclear power plant, a BWR reactor, as entirely compliant with all the safety requirements to extend its operation for the 2009-2019 period. Nevertheless, on July 3, Spanish government allowed Garona Nuclear Power Plant for 4 years more, two years more than the design life, 40 years. From June 3 until July 3 there were several public demonstrations in support of Garona continuity. Every day a lot of debates, interviews and articles, regarding Garona issue took place in TV channels, radio stations and newspapers. This paper shows all the activities that the owner, workers, unions and non-profit associations carried out to show the good state of the facility, also includes a discussion regarding the data showed by the government to shut-down the facility eight years before lifespan. And finally, what to do in those cases is discussed in this paper. (authors)

Lowbush cranberry acts through DAF-16/FOXO signaling to promote increased lifespan and axon branching in aging posterior touch receptor neurons.

Science.gov (United States)

Scerbak, Courtney; Vayndorf, Elena; Hernandez, Alicia; McGill, Colin; Taylor, Barbara

2018-05-01

Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments. DAF-16 is not observed in nuceli nor required for lifespan extension in lifespan-extending Alaskan blueberry treatments and, while DAF-16 is not visibly induced into the nucleus in lifespan-extending Alaskan chaga treatments, it is required for chaga-induced lifespan extension. These findings underscore the importance of DAF-16 in the aging of whole organisms and touch receptor neurons and also, importantly, indicate that this critical pathway is not always activated upon consumption of functional foods that impact aging.

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

2011-04-01

Highlights: {yields}We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. {yields} Deletion of the UGA1 or GAD1 genes extends replicative lifespan. {yields} Addition of GABA to wild-type cultures has no effect on lifespan. {yields} Intracellular GABA levels do not differ in longevity mutants and wild-type cells. {yields} Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for {gamma}-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The {Delta}uga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for {Delta}uga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of {sup 1}H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

International Nuclear Information System (INIS)

Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

2011-01-01

Highlights: →We demonstrate that two genes in the yeast GABA metabolism pathway affect aging. → Deletion of the UGA1 or GAD1 genes extends replicative lifespan. → Addition of GABA to wild-type cultures has no effect on lifespan. → Intracellular GABA levels do not differ in longevity mutants and wild-type cells. → Levels of tricarboxylic acid cycle intermediates positively correlate with lifespan. -- Abstract: Many of the genes involved in aging have been identified in organisms ranging from yeast to human. Our previous study showed that deletion of the UGA3 gene-which encodes a zinc-finger transcription factor necessary for γ-aminobutyric acid (GABA)-dependent induction of the UGA1 (GABA aminotransferase), UGA2 (succinate semialdehyde dehydrogenase), and UGA4 (GABA permease) genes-extends replicative lifespan in the budding yeast Saccharomycescerevisiae. Here, we found that deletion of UGA1 lengthened the lifespan, as did deletion of UGA3; in contrast, strains with UGA2 or UGA4 deletions exhibited no lifespan extension. The Δuga1 strain cannot deaminate GABA to succinate semialdehyde. Deletion of GAD1, which encodes the glutamate decarboxylase that converts glutamate into GABA, also increased lifespan. Therefore, two genes in the GABA metabolism pathway, UGA1 and GAD1, were identified as aging genes. Unexpectedly, intracellular GABA levels in mutant cells (except for Δuga2 cells) did not differ from those in wild-type cells. Addition of GABA to culture media, which induces transcription of the UGA structural genes, had no effect on replicative lifespan of wild-type cells. Multivariate analysis of 1 H nuclear magnetic resonance spectra for the whole-cell metabolite levels demonstrated a separation between long-lived and normal-lived strains. Gas chromatography-mass spectrometry analysis of identified metabolites showed that levels of tricarboxylic acid cycle intermediates positively correlated with lifespan extension. These results strongly suggest

NF-κB Immunity in the Brain Determines Fly Lifespan in Healthy Aging and Age-Related Neurodegeneration.

Science.gov (United States)

Kounatidis, Ilias; Chtarbanova, Stanislava; Cao, Yang; Hayne, Margaret; Jayanth, Dhruv; Ganetzky, Barry; Ligoxygakis, Petros

2017-04-25

During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Engineering Substantially Prolonged Human Lifespans: Biotechnological Enhancement and Ethics

NARCIS (Netherlands)

Derkx, P.H.J.M.

2006-01-01

Substantial extension of the human lifespan has recently become a subject of lively debate. One reason for this is the completion in 2001 of the Human Genome Project and the experimental avenues for biogerontological research it has opened. Another is recent theoretical progress in biogerontology.

No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

Directory of Open Access Journals (Sweden)

Janne M Toivonen

2007-06-01

Full Text Available To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans

DEFF Research Database (Denmark)

Mosbech, Mai-Britt; Kruse, Rikke; Harvald, Eva Bang

2013-01-01

Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2...... that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR......, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24), while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22). Here we show that functional loss of HYL-2 decreases lifespan, while loss...

Extensive interactions between HIV TAT and TAF(II)250.

Science.gov (United States)

Weissman, J D; Hwang, J R; Singer, D S

2001-03-09

The HIV transactivator, Tat, has been shown to be capable of potent repression of transcription initiation. Repression is mediated by the C-terminal segment of Tat, which binds the TFIID component, TAF(II)250, although the site(s) of interaction were not defined previously. We now report that the interaction between Tat and TAF(II)250 is extensive and involves multiple contacts between the Tat protein and TAF(II)250. The C-terminal domain of Tat, which is necessary for repression of transcription initiation, binds to a segment of TAF(II)250 that encompasses its acetyl transferase (AT) domain (885-1034 amino acids (aa)). Surprisingly, the N-terminal segment of Tat, which contains its activation domains, also binds to TAF(II)250 and interacts with two discontinuous segments of TAF(II)250 located between 885 and 984 aa and 1120 and 1279 aa. Binding of Tat to the 885-984 aa segment of TAF(II)250 requires the cysteine-rich domain of Tat, but not the acidic or glutamine-rich domains. Binding by the N-terminal domain of Tat to the 1120-1279 aa TAF(II)250 segment does not involve the acidic, cysteine- or glutamine-rich domains. Repression of transcription initiation by Tat requires functional TAF(II)250. We now demonstrate that transcription of the HIV LTR does not depend on TAF(II)250 which may account for its resistance to Tat mediated repression.

Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Seung-Il Oh

2015-05-01

Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans

Science.gov (United States)

Bolund, Elisabeth; Lummaa, Virpi; Smith, Ken R.; Hanson, Heidi A.; Maklakov, Alexei A.

2016-01-01

The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution. PMID:27087670

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

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Jitendra Kumar

Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

Science.gov (United States)

Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

2016-01-01

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

PXR as a mediator of herb–drug interaction

Directory of Open Access Journals (Sweden)

Brett C. Hogle

2018-04-01

Full Text Available Medicinal herbs have been a part of human medicine for thousands of years. The herb–drug interaction is an extension of drug–drug interaction, in which the consumptions of herbs cause alterations in the metabolism of drugs the patients happen to take at the same time. The pregnane X receptor (PXR has been established as one of the most important transcriptional factors that regulate the expression of phase I enzymes, phase II enzymes, and drug transporters in the xenobiotic responses. Since its initial discovery, PXR has been implicated in multiple herb–drug interactions that can lead to alterations of the drug's pharmacokinetic properties and cause fluctuating therapeutic efficacies, possibly leading to complications. Regions of the world that heavily incorporate herbalism into their primary health care and people turning to alternative medicines as a personal choice could be at risk for adverse reactions or unintended results from these interactions. This article is intended to highlight our understanding of the PXR-mediated herb–drug interactions. Keywords: Drug metabolism, Herb–drug interaction, PXR, St. John's Wort, Xenobiotics

Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

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Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

2017-05-06

Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Effects of fluctuating temperature and food availability on reproduction and lifespan.

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Schwartz, Tonia S; Pearson, Phillip; Dawson, John; Allison, David B; Gohlke, Julia M

2016-12-15

Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Lifespan extension and the doctrine of double effect.

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Capitaine, Laura; Devolder, Katrien; Pennings, Guido

2013-06-01

Recent developments in biogerontology--the study of the biology of ageing--suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan--a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the 'double effect argument', has gone unnoticed. This article exposes and critically evaluates this 'double effect argument'. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the 'double effect argument' is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning.

Meta-analysis of global transcriptomics reveals conserved genetic pathways of Quercetin and Tannic acid mediated longevity in C. elegans

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Kerstin ePietsch

2012-04-01

Full Text Available Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of C. elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to Quercetin or Tannic acid concentrations that are non-effective (in lifespan extension, lifespan extending or toxic. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published data sets derived from i longevity mutants or ii infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the formulation of mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling and the p38 MAPK pathway and Tannic acid’s impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, therefore seems to be a crucial regulator for both polyphenols.

Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity.

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Molina-Serrano, Diego; Schiza, Vassia; Demosthenous, Christis; Stavrou, Emmanouil; Oppelt, Jan; Kyriakou, Dimitris; Liu, Wei; Zisser, Gertrude; Bergler, Helmut; Dang, Weiwei; Kirmizis, Antonis

2016-12-01

Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

PXR as a mediator of herb-drug interaction.

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Hogle, Brett C; Guan, Xiudong; Folan, M Maggie; Xie, Wen

2018-04-01

Medicinal herbs have been a part of human medicine for thousands of years. The herb-drug interaction is an extension of drug-drug interaction, in which the consumptions of herbs cause alterations in the metabolism of drugs the patients happen to take at the same time. The pregnane X receptor (PXR) has been established as one of the most important transcriptional factors that regulate the expression of phase I enzymes, phase II enzymes, and drug transporters in the xenobiotic responses. Since its initial discovery, PXR has been implicated in multiple herb-drug interactions that can lead to alterations of the drug's pharmacokinetic properties and cause fluctuating therapeutic efficacies, possibly leading to complications. Regions of the world that heavily incorporate herbalism into their primary health care and people turning to alternative medicines as a personal choice could be at risk for adverse reactions or unintended results from these interactions. This article is intended to highlight our understanding of the PXR-mediated herb-drug interactions. Copyright © 2017. Published by Elsevier B.V.

Mitochondrial Respiratory Thresholds Regulate Yeast Chronological Lifespan and its Extension by Caloric Restriction

OpenAIRE

Ocampo, Alejandro; Liu, Jingjing; Schroeder, Elizabeth A.; Shadel, Gerald S.; Barrientos, Antoni

2012-01-01

We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases, and determining how this affects chronological lifespan (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS...

Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women.

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Kim, Soo Hyun; Sim, Mu Yul; Park, Sat Byul

2015-12-01

The benefit of estrogen therapy in postmenopausal women is still uncertain. Based upon extensive observational data, it was believed that estrogen was cardioprotective. The relationship between the period of exposure to endogenous estrogens and the risk of cardiovascular disease (CVD) has not been studied in Korean women. To assess associations between reproductive lifespan and CVD by using the Framingham risk score (FRS) in postmenopausal Korean women. This cross-sectional, population-based study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for the five years 2008-2012,after adjustment for relevant variables using complex sample analysis and data weighting. Among 25,534 women, 1973 women were enrolled, after excluding those 80 years of age (n=6194), those with diabetes, CVD or cancer (n=491), those with unrecorded physical measurements (n=7335), those with menarche age ≤8 years or ≥20 years (n=6194), and premenopausal women (n=3347). The FRS tended to show a significant negative correlation with the reproductive lifespan (preproductive lifespan and FRS (adjusted relative risk [RR] for reproductive years [shortest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], 1.2, p33 reproductive years [longest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], -0.42, p=0.011). A longer reproductive lifespan is associated with a lower estimated risk of CVD in the next 10 years in postmenopausal women. This result suggests that estrogen has a long-term protective effect against CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Animal lifespan and human influence

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Guo, Q.; Yang, S.

2002-01-01

Lifespan differs radically among organisms ever lived on earth, even among those roughly similar in size, shape, form, and physiology; Yet, in general, there exists a strong positive relationship between lifespan and body size. Although lifespans of humans and human-related (domestic) animals are becoming increasingly longer than that of other animals of similar sizes, the slope of the regression (lifespan-body size) line and the intercepts have been surprisingly stable over the course of the dramatic human population growth, indicating substantial depression in lifespans of many other animals probably due to shrunk and fragmented natural habitats. This article addresses two questions related to the lifespan-size relationship: (1) what caused the exceptions (e.g., a few remote human-related animals are also located above the regression line with great residuals) and why (e.g., could brain size or intelligence be a covariate in addition to body size in predicting lifespan?), and (2) whether continued human activities can eventually alter the ' natural' regression line in the future, and if so, how much. We also suggest similar research efforts to be extended to the plant world as well.

Histone modifications influence mediator interactions with chromatin

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Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

2011-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

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Claudiu Ramon D. BUTCULESCU

2014-05-01

Full Text Available Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

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Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

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Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

2017-07-01

The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

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Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

2018-05-02

DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

Neuromodulation and developmental contextual influences on neural and cognitive plasticity across the lifespan.

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Li, Shu-Chen

2013-11-01

Behavioral, cognitive, and motivational development entails co-constructive interactions between the environmental and social influences from the developmental context, on the one hand, and the individual's neurobiological inheritance, on the other hand. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines and acetylcholine). Thus, the maturation and senescence of neurotransmitter systems have direct implications for lifespan development. In addition to reviewing evidence on life age differences in dopaminergic modulation and cognitive development, this brief review selectively highlights recent findings on how important influences from the developmental context, such as reward-mediated motivational processes, transgenerational stress transmission, psychosocial stress, and cognitive interventions, may, in part, exert their effects on brain and behavioral development through their effects on neuromodulatory mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

The interplay between protein L-isoaspartyl methyltransferase activity and insulin-like signaling to extend lifespan in Caenorhabditis elegans.

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Shilpi Khare

Full Text Available The protein L-isoaspartyl-O-methyltransferase functions to initiate the repair of isomerized aspartyl and asparaginyl residues that spontaneously accumulate with age in a variety of organisms. Caenorhabditis elegans nematodes lacking the pcm-1 gene encoding this enzyme display a normal lifespan and phenotype under standard laboratory growth conditions. However, significant defects in development, egg laying, dauer survival, and autophagy have been observed in pcm-1 mutant nematodes when deprived of food and when exposed to oxidative stress. Interestingly, overexpression of this repair enzyme in both Drosophila and C. elegans extends adult lifespan under thermal stress. In this work, we show the involvement of the insulin/insulin-like growth factor-1 signaling (IIS pathway in PCM-1-dependent lifespan extension in C. elegans. We demonstrate that reducing the levels of the DAF-16 downstream transcriptional effector of the IIS pathway by RNA interference reduces the lifespan extension resulting from PCM-1 overexpression. Using quantitative real-time PCR analysis, we show the up-regulation of DAF-16-dependent stress response genes in the PCM-1 overexpressor animals compared to wild-type and pcm-1 mutant nematodes under mild thermal stress conditions. Additionally, similar to other long-lived C. elegans mutants in the IIS pathway, including daf-2 and age-1 mutants, PCM-1 overexpressor adult animals display increased resistance to severe thermal stress, whereas pcm-1 mutant animals survive less long under these conditions. Although we observe a higher accumulation of damaged proteins in pcm-1 mutant nematodes, the basal level of isoaspartyl residues detected in wild-type animals was not reduced by PCM-1 overexpression. Our results support a signaling role for the protein L-isoaspartyl methyltransferase in lifespan extension that involves the IIS pathway, but that may be independent of its function in overall protein repair.

Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a Drosophila Model of Leigh Syndrome.

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Loewen, Carin A; Ganetzky, Barry

2018-04-01

Proper mitochondrial activity depends upon proteins encoded by genes in the nuclear and mitochondrial genomes that must interact functionally and physically in a precisely coordinated manner. Consequently, mito-nuclear allelic interactions are thought to be of crucial importance on an evolutionary scale, as well as for manifestation of essential biological phenotypes, including those directly relevant to human disease. Nonetheless, detailed molecular understanding of mito-nuclear interactions is still lacking, and definitive examples of such interactions in vivo are sparse. Here we describe the characterization of a mutation in Drosophila ND23 , a nuclear gene encoding a highly conserved subunit of mitochondrial complex 1. This characterization led to the discovery of a mito-nuclear interaction that affects the ND23 mutant phenotype. ND23 mutants exhibit reduced lifespan, neurodegeneration, abnormal mitochondrial morphology, and decreased ATP levels. These phenotypes are similar to those observed in patients with Leigh syndrome, which is caused by mutations in a number of nuclear genes that encode mitochondrial proteins, including the human ortholog of ND23 A key feature of Leigh syndrome, and other mitochondrial disorders, is unexpected and unexplained phenotypic variability. We discovered that the phenotypic severity of ND23 mutations varies depending on the maternally inherited mitochondrial background. Sequence analysis of the relevant mitochondrial genomes identified several variants that are likely candidates for the phenotypic interaction with mutant ND23 , including a variant affecting a mitochondrially encoded component of complex I. Thus, our work provides an in vivo demonstration of the phenotypic importance of mito-nuclear interactions in the context of mitochondrial disease. Copyright © 2018 by the Genetics Society of America.

Parametric and non-parametric models for lifespan modeling of insulation systems in electrical machines

OpenAIRE

Salameh , Farah; Picot , Antoine; Chabert , Marie; Maussion , Pascal

2017-01-01

International audience; This paper describes an original statistical approach for the lifespan modeling of electric machine insulation materials. The presented models aim to study the effect of three main stress factors (voltage, frequency and temperature) and their interactions on the insulation lifespan. The proposed methodology is applied to two different insulation materials tested in partial discharge regime. Accelerated ageing tests are organized according to experimental optimization m...

Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome.

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Ohtsuka, Hokuto; Takinami, Masahiro; Shimasaki, Takafumi; Hibi, Takahide; Murakami, Hiroshi; Aiba, Hirofumi

2017-07-01

Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1 + gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner. © 2017 John Wiley & Sons Ltd.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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Nicole M. Templeman

2017-07-01

Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

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Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

2017-07-11

The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

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Paola V Castro

Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

Causal mediation analysis with multiple causally non-ordered mediators.

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Taguri, Masataka; Featherstone, John; Cheng, Jing

2018-01-01

In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

Vitellogenin-RNAi and ovariectomy each increase lifespan, increase protein storage, and decrease feeding, but are not additive in grasshoppers.

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Tetlak, Alicia G; Burnett, Jacob B; Hahn, Daniel A; Hatle, John D

2015-12-01

Reduced reproduction has been shown to increase lifespan in many animals, yet the mechanisms behind this trade-off are unclear. We addressed this question by combining two distinct, direct means of life-extension via reduced reproduction, to test whether they were additive. In the lubber grasshopper, Romalea microptera, ovariectomized (OVX) individuals had a ~20% increase in lifespan and a doubling of storage relative to controls (Sham operated). Similarly, young female grasshoppers treated with RNAi against vitellogenin (the precursor to egg yolk protein) had increased fat body mass and halted ovarian growth. In this study, we compared VgRNAi to two control groups that do not reduce reproduction, namely buffer injection (Buffer) and injection with RNAi against a hexameric storage protein (Hex90RNAi). Each injection treatment was tested with and without ovariectomy. Hence, we tested feeding, storage, and lifespans in six groups: OVX and Buffer, OVX and Hex90RNAi, OVX and VgRNAi, Sham and Buffer, Sham and Hex90RNAi, and Sham and VgRNAi. Ovariectomized grasshoppers and VgRNAi grasshoppers each had similar reductions in feeding (~40%), increases in protein storage in the hemolymph (150-300%), and extensions in lifespan (13-21%). Ovariectomized grasshoppers had higher vitellogenin protein levels than did VgRNAi grasshoppers. Last but not least, when ovariectomy and VgRNAi were applied together, there was no greater effect on feeding, protein storage, or longevity. Hence, feeding regulation, and protein storage in insects, may be conserved components of life-extension via reduced reproduction.

The Yang-Tonifying Herbal Medicine Cynomorium songaricum Extends Lifespan and Delays Aging in Drosophila

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Hsin-Ping Liu

2012-01-01

Full Text Available Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases.

Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

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Baraldi, Claudio

2009-01-01

This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…

A realistic extension of gauge-mediated SUSY-breaking model with superconformal hidden sector

International Nuclear Information System (INIS)

Asano, Masaki; Hisano, Junji; Okada, Takashi; Sugiyama, Shohei

2009-01-01

The sequestering of supersymmetry (SUSY) breaking parameters, which is induced by superconformal hidden sector, is one of the solutions for the μ/B μ problem in gauge-mediated SUSY-breaking scenario. However, it is found that the minimal messenger model does not derive the correct electroweak symmetry breaking. In this Letter we present a model which has the coupling of the messengers with the SO(10) GUT-symmetry breaking Higgs fields. The model is one of the realistic extensions of the gauge mediation model with superconformal hidden sector. It is shown that the extension is applicable for a broad range of conformality breaking scale

The normative dimensions of extending the human lifespan by age-related biomedical innovations.

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Ehni, Hans-Joerg; Marckmann, Georg

2008-10-01

The current normative debate on age-related biomedical innovations and the extension of the human lifespan has important shortcomings. Mainly, the complexity of the different normative dimensions relevant for ethical and/or juridicial norms is not fully developed and the normative quality of teleological and deontological arguments is not properly distinguished. This article addresses some of these shortcomings and develops the outline of a more comprehensive normative framework covering all relevant dimensions. Such a frame necessarily has to include conceptions of a good life on the individual and societal levels. Furthermore, as a third dimension, a model for the access to and the just distribution of age-related biomedical innovations and technologies extending the human lifespan will be developed. It is argued that such a model has to include the different levels of the general philosophical theories of distributive justice, including social rights and theories of just health care. Furthermore, it has to show how these theories can be applied to the problem area of aging and extending the human lifespan.

Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan.

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Speakman, John R; Hambly, Catherine

2007-04-01

Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

Magpies and mirrors : identity as a mediator of music preferences across the lifespan

OpenAIRE

Leadbeater, Richard; Marsden, Alan

2014-01-01

This thesis examines the role of identity on the development and trajectory of music preferences across the lifespan. The focus of interest in recent empirical research has been to predict music preferences using adolescent individual differences. It is widely recognized that adolescents use music to help them deal with a number of psychosocial and emotional challenges, which often arise during this critical period of identity development. There has been little study whether adults similarly ...

Volatile-mediated interactions in the rhizosphere

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Cordovez da Cunha, Viviane

2016-01-01

Plants and microorganisms are constantly engaged in highly dynamic interactions both above- and belowground. Several of these interactions are mediated by volatile organic compounds (VOCs), small carbon-based compounds with high vapor pressure at ambient temperature. In the rhizosphere, VOCs have

Proteinaceous molecules mediating Bifidobacterium-host interactions

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Lorena Ruiz

2016-08-01

Full Text Available Bifidobacteria are commensal microoganisms found in the gastrointestinal tract.Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.

Emotional Egocentricity Bias across the life-span

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Federica eRiva

2016-04-01

Full Text Available In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB, has been found to occur in young adults and, to a greater extent, in children. However, how EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults to examine EEB age-related changes. Participants were administered with a paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of EEB. Results highlighted a U-shaped relation between age and EEB, revealing higher emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG. This is an area that reaches full maturation only by the end of adolescence, and displays an early decay in older age. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

Strain mediated interaction of adatom dimers

OpenAIRE

Kappus, Wolfgang

2013-01-01

An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

A Novel Physiology-Based Mathematical Model to Estimate Red Blood Cell Lifespan in Different Human Age Groups.

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An, Guohua; Widness, John A; Mock, Donald M; Veng-Pedersen, Peter

2016-09-01

Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.

Deliberate utilization of interaction torques brakes elbow extension in a fast throwing motion.

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Hore, Jon; Debicki, Derek B; Gribble, Paul L; Watts, Sherry

2011-05-01

We tested the hypothesis that in fast arm movements the CNS deliberately utilizes interaction torques to decelerate (brake) joint rotations. Twelve subjects performed fast 2-D overarm throws in which large elbow extension velocities occurred. Joint motions were computed from recordings made with search coils; joint torques were calculated using inverse dynamics. After ball release, a large follow-through shoulder extension acceleration occurred that was initiated by shoulder extensor muscle torque. This shoulder acceleration produced a flexor interaction torque at the elbow that initiated elbow deceleration (braking). An instantaneous mechanical interaction of passive torques then occurred between elbow and shoulder, i.e., elbow extension deceleration produced a large shoulder extensor interaction torque that contributed to the shoulder extension acceleration which, simultaneously, produced a large elbow flexor interaction torque that contributed to elbow extension deceleration, and so on. Late elbow flexor muscle torque also contributed to elbow deceleration. The interaction of passive torques between shoulder and elbow was braked by shoulder flexor muscle torque. In this mechanism, shoulder musculature contributed to braking elbow extension in two ways: shoulder extensors initiated the mechanical interaction of passive torques between shoulder and elbow and shoulder flexors dissipated kinetic energy from elbow braking. It is concluded that, in fast 2-D throws, the CNS deliberately utilizes powerful interaction torques between shoulder and elbow to brake motion at the elbow.

Synchronous Computer-Mediated Communication and Interaction

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Ziegler, Nicole

2016-01-01

The current study reports on a meta-analysis of the relative effectiveness of interaction in synchronous computer-mediated communication (SCMC) and face-to-face (FTF) contexts. The primary studies included in the analysis were journal articles and dissertations completed between 1990 and 2012 (k = 14). Results demonstrate that interaction in SCMC…

Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans.

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Zheng, Jolene; Gao, Chenfei; Wang, Mingming; Tran, Phuongmai; Mai, Nancy; Finley, John W; Heymsfield, Steven B; Greenway, Frank L; Li, Zhaoping; Heber, David; Burton, Jeffrey H; Johnson, William D; Laine, Roger A

2017-05-04

Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P Glucose reduced lifespan (P fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

Gender separation increases somatic growth in females but does not affect lifespan in Nothobranchius furzeri.

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Michael Graf

2010-08-01

Full Text Available According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.

EFFECT ON LIFESPAN OF HIGH YIELD NONMYELOABLATING TRANSPLANTATION OF BONE MARROW FROM YOUNG TO OLD MICE

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Marina eKovina

2013-08-01

Full Text Available Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SC. An interesting question is whether donor stem cells are capable to prolong the lifespan of an ageing organism by tissue renewal.. In this work we investigated the possible use of bone marrow SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting bone marrow from young 1.5-month donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5×108 cells, that is, about 25 % of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (± 0.1 months for the control and experimental groups, respectively, corresponding to a 39% ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation a considerably smaller quantity of donor cells (5×106 was used, about 1 % of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals X-ray dose which eliminated the possibility of studying the lifespan extension by this method.

Weak Molecular Interactions in Clathrin-Mediated Endocytosis

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Sarah M. Smith

2017-11-01

Full Text Available Clathrin-mediated endocytosis is a process by which specific molecules are internalized from the cell periphery for delivery to early endosomes. The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. This review discusses the structural and functional data that have improved our knowledge and understanding of the main weak molecular interactions implicated in clathrin-mediated endocytosis, with a particular focus on the two key proteins: AP2 and clathrin.

A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.

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Cavuoto, Paul; Fenech, Michael F

2012-10-01

Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Minority Stress across the Career-Lifespan Trajectory

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Dispenza, Franco; Brown, Colton; Chastain, Taylor E.

2016-01-01

Sexual minority persons (e.g., lesbian, gay, bisexual, and queer) are likely to encounter "minority stress", such as discrimination, concealment, expectation of rejection, and internalized heterosexism. Minority stress occurs alongside one's lifespan and has considerable implications in the context of the career lifespan trajectory.…

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

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Yoko Honda

2015-01-01

Full Text Available Royal jelly (RJ produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA, the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS, indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling.

Science.gov (United States)

Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

2015-01-01

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS), indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR) components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

NARCIS (Netherlands)

Doroszuk, A.; Jonker, M.J.; Pul, N.; Breit, T.M.; Zwaan, B.J.

2012-01-01

Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of

Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model

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Virk Bhupinder

2012-07-01

Full Text Available Abstract Background Gut microbes influence animal health and thus, are potential targets for interventions that slow aging. Live E. coli provides the nematode worm Caenorhabditis elegans with vital micronutrients, such as folates that cannot be synthesized by animals. However, the microbe also limits C. elegans lifespan. Understanding these interactions may shed light on how intestinal microbes influence mammalian aging. Results Serendipitously, we isolated an E. coli mutant that slows C. elegans aging. We identified the disrupted gene to be aroD, which is required to synthesize aromatic compounds in the microbe. Adding back aromatic compounds to the media revealed that the increased C. elegans lifespan was caused by decreased availability of para-aminobenzoic acid, a precursor to folate. Consistent with this result, inhibition of folate synthesis by sulfamethoxazole, a sulfonamide, led to a dose-dependent increase in C. elegans lifespan. As expected, these treatments caused a decrease in bacterial and worm folate levels, as measured by mass spectrometry of intact folates. The folate cycle is essential for cellular biosynthesis. However, bacterial proliferation and C. elegans growth and reproduction were unaffected under the conditions that increased lifespan. Conclusions In this animal:microbe system, folates are in excess of that required for biosynthesis. This study suggests that microbial folate synthesis is a pharmacologically accessible target to slow animal aging without detrimental effects.

Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

NARCIS (Netherlands)

Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

2014-01-01

Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways

Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs.

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Susan Broughton

Full Text Available The insulin/IGF-like signalling (IIS pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dInR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.

A Motivational Theory of Life-Span Development

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Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

Pollinator-mediated interactions in experimental arrays vary with neighbor identity.

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Ha, Melissa K; Ivey, Christopher T

2017-02-01

Local ecological conditions influence the impact of species interactions on evolution and community structure. We investigated whether pollinator-mediated interactions between coflowering plants vary with plant density, coflowering neighbor identity, and flowering season. We conducted a field experiment in which flowering time and floral neighborhood were manipulated in a factorial design. Early- and late-flowering Clarkia unguiculata plants were placed into arrays with C. biloba neighbors, noncongeneric neighbors, additional conspecific plants, or no additional plants as a density control. We compared whole-plant pollen limitation of seed set, pollinator behavior, and pollen deposition among treatments. Interactions mediated by shared pollinators depended on the identity of the neighbor and possibly changed through time, although flowering-season comparisons were compromised by low early-season plant survival. Interactions with conspecific neighbors were likely competitive late in the season. Interactions with C. biloba appeared to involve facilitation or neutral interactions. Interactions with noncongeners were more consistently competitive. The community composition of pollinators varied among treatment combinations. Pollinator-mediated interactions involved competition and likely facilitation, depending on coflowering neighbor. Experimental manipulation helped to reveal context-dependent variation in indirect biotic interactions. © 2017 Botanical Society of America.

Sex-specific lifespan and its evolution in nematodes.

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Ancell, Henry; Pires-daSilva, Andre

2017-10-01

Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to study variation in sex-specific lifespan patterns associated with shifts in life history and mating strategy. Although the plasticity of these sex differences will make it challenging to generalize from invertebrate to vertebrate systems, studies in nematodes have enabled empirical evaluation of predictions regarding the evolution of lifespan. These studies have highlighted how natural and sexual selection can generate divergent patterns of lifespan if the sexes are subject to different rates or sources of mortality, or if trade-offs between complex traits and longevity are resolved differently in each sex. Here, we integrate evidence derived mainly from nematodes that addresses the molecular and evolutionary basis of sex-specific aging and lifespan. Ultimately, we hope to generate a clearer picture of current knowledge in this area, and also highlight the limitations of our understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Young children accessing the learning of others: mediation through the ‘witnessing’ of others’ gestural interactions

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Karl Wall

2006-05-01

Full Text Available Contextualisation Children’s interactions in the classroom arguably underpin many of the learning events and activities they experience. These may involve their classroom teacher, teaching assistants, other adults (including, in the primary school, context, parents / carers, their peers or other children entering the room where they are working. The paper that follows, reflects on the nature of such interactions, focusing on gestural behaviours, observed as part of a programme of doctoral study. It explores the notion of how the ‘witnessing’ of others’ interactions may contribute to and inform the behaviour, understanding and learning of a child, as they work with their peers and a teacher on a grouped task. In so doing, it re-examines the notion of the more experienced other, associated with Vygotsky’s ideas on social interaction in a pedagogic context and draws on a range of disciplines for both practical and theoretical inspiration. Abstract: Arising from a study of grouped 5-6 year olds’ gestural interactions, an extension to Vygotskian notions of mediation is proposed. This is developed through a consideration of ideas grounded in: cultural psychology, situated learning, distributed cognition , the analysis of ‘task affordances’. The potential significance and role of a child’s ‘witnessing’ of the mediational interactions of others is discussed informed by data drawn from the author’s current research. The implications for teachers’ practice as a more ‘experienced other’, in such interactions, are briefly discussed.

Extension of lattice cluster theory to strongly interacting, self-assembling polymeric systems.

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Freed, Karl F

2009-02-14

A new extension of the lattice cluster theory is developed to describe the influence of monomer structure and local correlations on the free energy of strongly interacting and self-assembling polymer systems. This extension combines a systematic high dimension (1/d) and high temperature expansion (that is appropriate for weakly interacting systems) with a direct treatment of strong interactions. The general theory is illustrated for a binary polymer blend whose two components contain "sticky" donor and acceptor groups, respectively. The free energy is determined as an explicit function of the donor-acceptor contact probabilities that depend, in turn, on the local structure and both the strong and weak interactions.

Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans.

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Shane L Rea

2007-10-01

Full Text Available Prior studies have shown that disruption of mitochondrial electron transport chain (ETC function in the nematode Caenorhabditis elegans can result in life extension. Counter to these findings, many mutations that disrupt ETC function in humans are known to be pathologically life-shortening. In this study, we have undertaken the first formal investigation of the role of partial mitochondrial ETC inhibition and its contribution to the life-extension phenotype of C. elegans. We have developed a novel RNA interference (RNAi dilution strategy to incrementally reduce the expression level of five genes encoding mitochondrial proteins in C. elegans: atp-3, nuo-2, isp-1, cco-1, and frataxin (frh-1. We observed that each RNAi treatment led to marked alterations in multiple ETC components. Using this dilution technique, we observed a consistent, three-phase lifespan response to increasingly greater inhibition by RNAi: at low levels of inhibition, there was no response, then as inhibition increased, lifespan responded by monotonically lengthening. Finally, at the highest levels of RNAi inhibition, lifespan began to shorten. Indirect measurements of whole-animal oxidative stress showed no correlation with life extension. Instead, larval development, fertility, and adult size all became coordinately affected at the same point at which lifespan began to increase. We show that a specific signal, initiated during the L3/L4 larval stage of development, is sufficient for initiating mitochondrial dysfunction-dependent life extension in C. elegans. This stage of development is characterized by the last somatic cell divisions normally undertaken by C. elegans and also by massive mitochondrial DNA expansion. The coordinate effects of mitochondrial dysfunction on several cell cycle-dependent phenotypes, coupled with recent findings directly linking cell cycle progression with mitochondrial activity in C. elegans, lead us to propose that cell cycle checkpoint control

Dark matter self-interactions from a general spin-0 mediator

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Kahlhoefer, Felix; Schmidt-Hoberg, Kai; Wild, Sebastian

2017-04-15

Dark matter particles interacting via the exchange of very light spin-0 mediators can have large self-interaction rates and obtain their relic abundance from thermal freeze-out. At the same time, these models face strong bounds from direct and indirect probes of dark matter as well as a number of constraints on the properties of the mediator. We investigate whether these constraints can be consistent with having observable effects from dark matter self-interactions in astrophysical systems. For the case of a mediator with purely scalar couplings we point out the highly relevant impact of low-threshold direct detection experiments like CRESST-II, which essentially rule out the simplest realization of this model. These constraints can be significantly relaxed if the mediator has CP-violating couplings, but then the model faces strong constraints from CMB measurements, which can only be avoided in special regions of parameter space.

Dark matter self-interactions from a general spin-0 mediator

International Nuclear Information System (INIS)

Kahlhoefer, Felix; Schmidt-Hoberg, Kai; Wild, Sebastian

2017-01-01

Dark matter particles interacting via the exchange of very light spin-0 mediators can have large self-interaction rates and obtain their relic abundance from thermal freeze-out. At the same time, these models face strong bounds from direct and indirect probes of dark matter as well as a number of constraints on the properties of the mediator. We investigate whether these constraints can be consistent with having observable effects from dark matter self-interactions in astrophysical systems. For the case of a mediator with purely scalar couplings we point out the highly relevant impact of low-threshold direct detection experiments like CRESST-II, which essentially rule out the simplest realization of this model. These constraints can be significantly relaxed if the mediator has CP-violating couplings, but then the model faces strong constraints from CMB measurements, which can only be avoided in special regions of parameter space.

Dark matter self-interactions from a general spin-0 mediator

Energy Technology Data Exchange (ETDEWEB)

Kahlhoefer, Felix; Schmidt-Hoberg, Kai; Wild, Sebastian, E-mail: felix.kahlhoefer@desy.de, E-mail: kai.schmidt-hoberg@desy.de, E-mail: sebastian.wild@desy.de [DESY, Notkestraße 85, D-22607 Hamburg (Germany)

2017-08-01

Dark matter particles interacting via the exchange of very light spin-0 mediators can have large self-interaction rates and obtain their relic abundance from thermal freeze-out. At the same time, these models face strong bounds from direct and indirect probes of dark matter as well as a number of constraints on the properties of the mediator. We investigate whether these constraints can be consistent with having observable effects from dark matter self-interactions in astrophysical systems. For the case of a mediator with purely scalar couplings we point out the highly relevant impact of low-threshold direct detection experiments like CRESST-II, which essentially rule out the simplest realization of this model. These constraints can be significantly relaxed if the mediator has CP-violating couplings, but then the model faces strong constraints from CMB measurements, which can only be avoided in special regions of parameter space.

Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions.

Science.gov (United States)

Bellavia, Andrea; Valeri, Linda

2018-06-01

Mediation analysis allows decomposing a total effect into a direct effect of the exposure on the outcome and an indirect effect operating through a number of possible hypothesized pathways. Recent studies have provided formal definitions of direct and indirect effects when multiple mediators are of interest and have described parametric and semiparametric methods for their estimation. Investigating direct and indirect effects with multiple mediators, however, can be challenging in the presence of multiple exposure-mediator and mediator-mediator interactions. In this paper we derive a decomposition of the total effect that unifies mediation and interaction when multiple mediators are present. We illustrate the properties of the proposed framework in a secondary analysis of a pragmatic trial for the treatment of schizophrenia. The decomposition is employed to investigate the interplay of side effects and psychiatric symptoms in explaining the effect of antipsychotic medication on quality of life in schizophrenia patients. Our result offers a valuable tool to identify the proportions of total effect due to mediation and interaction when more than one mediator is present, providing the finest decomposition of the total effect that unifies multiple mediators and interactions.

Injuries can prolong lifespan in Drosophila melanogaster males

DEFF Research Database (Denmark)

Henten, Anne Marie Vestergaard; Loeschcke, Volker; Pedersen, Jørgen Granfeldt

2016-01-01

Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected...

Water-mediated ionic interactions in protein structures

Indian Academy of Sciences (India)

ISHWARYA( R SARANI( M KIRTI VAISHNAVI and K SEKAR. Supplementary table 1. List of complete water-mediated ionic interactions formed by different combinations of charged atoms and their corresponding occurrences. S. No. Type.

Autism through the Lifespan

Science.gov (United States)

... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Autism through the Lifespan Home / Living with Autism / ...

Brain structure across the lifespan: the influence of stress and mood

Directory of Open Access Journals (Sweden)

Jose Miguel Soares

2014-11-01

Full Text Available Normal brain aging is an inevitable and heterogeneous process characterized by a selective pattern of structural changes. Such heterogeneity arises as a consequence of cumulative effects over the lifespan, including stress and mood effects, which drive different micro- and macro-structural alterations in the brain. Investigating these differences in healthy age-related changes is a major challenge for the comprehension of the cognitive status. Herein we addressed the impact of normal aging, stress, mood and their interplay in the brain gray and white matter structure. We showed the critical impact of age in the white matter volume and how stress and mood influence brain volumetry across the lifespan. Moreover, we found a more profound effect of the interaction of aging/stress/mood on structures located in the left hemisphere. These findings help to clarify some divergent results associated with the aging decline and to enlighten the association between abnormal volumetric alterations and several states that may lead to psychiatric disorders.

Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals "aging factors" and mechanism of lifespan asymmetry.

Science.gov (United States)

Yang, Jing; McCormick, Mark A; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K; Li, Hao

2015-09-22

Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials ("aging factors") through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms.

Singlet deflected anomaly/gauge mediation

International Nuclear Information System (INIS)

Blas, J. de; Delgado, A.

2012-01-01

We study an extension of the standard anomaly/gauge mediation scenario where the messenger fields have direct interactions with an extra gauge singlet. This realizes a phenomenologically viable NMSSM-like scenario free of the μ-b μ problem. Current cosmological constraints imply a small size for the anomaly-mediation contributions, unless some source of R-parity violation is permitted. In the latter case the allowed regions in the parameter space can be substantially larger than in the corresponding gauge-mediation scenario.

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

OpenAIRE

Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

2015-01-01

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA f...

Measurement of lifespan in Drosophila melanogaster.

Science.gov (United States)

Linford, Nancy J; Bilgir, Ceyda; Ro, Jennifer; Pletcher, Scott D

2013-01-07

Aging is a phenomenon that results in steady physiological deterioration in nearly all organisms in which it has been examined, leading to reduced physical performance and increased risk of disease. Individual aging is manifest at the population level as an increase in age-dependent mortality, which is often measured in the laboratory by observing lifespan in large cohorts of age-matched individuals. Experiments that seek to quantify the extent to which genetic or environmental manipulations impact lifespan in simple model organisms have been remarkably successful for understanding the aspects of aging that are conserved across taxa and for inspiring new strategies for extending lifespan and preventing age-associated disease in mammals. The vinegar fly, Drosophila melanogaster, is an attractive model organism for studying the mechanisms of aging due to its relatively short lifespan, convenient husbandry, and facile genetics. However, demographic measures of aging, including age-specific survival and mortality, are extraordinarily susceptible to even minor variations in experimental design and environment, and the maintenance of strict laboratory practices for the duration of aging experiments is required. These considerations, together with the need to practice careful control of genetic background, are essential for generating robust measurements. Indeed, there are many notable controversies surrounding inference from longevity experiments in yeast, worms, flies and mice that have been traced to environmental or genetic artifacts(1-4). In this protocol, we describe a set of procedures that have been optimized over many years of measuring longevity in Drosophila using laboratory vials. We also describe the use of the dLife software, which was developed by our laboratory and is available for download (http://sitemaker.umich.edu/pletcherlab/software). dLife accelerates throughput and promotes good practices by incorporating optimal experimental design, simplifying

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans.

Science.gov (United States)

Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Bowman, Megan J; Winn, Mary E; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2017-07-01

Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticipated Ongoing Interaction versus Channel Effects of Relational Communication in Computer-Mediated Interaction.

Science.gov (United States)

Walther, Joseph B.

1994-01-01

Assesses the related effects of anticipated future interaction and different communication media (computer-mediated versus face-to-face communication) on the communication of relational intimacy and composure. Shows that the assignment of long-term versus short-term partnerships has a larger impact on anticipated future interaction reported by…

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan.

Directory of Open Access Journals (Sweden)

Rodrigo Dutra Nunes

2016-10-01

Full Text Available Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols.Here, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK. AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus.The present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan

DEFF Research Database (Denmark)

Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina

2014-01-01

cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND.......6 × 10(-6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans...... by 150% (p = 5.3 × 10(-8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can...

Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

Science.gov (United States)

Yang, Jing; McCormick, Mark A.; Zheng, Jiashun; Xie, Zhengwei; Tsuchiya, Mitsuhiro; Tsuchiyama, Scott; El-Samad, Hana; Ouyang, Qi; Kaeberlein, Matt; Kennedy, Brian K.; Li, Hao

2015-01-01

Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials (“aging factors”) through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms. PMID:26351681

Strain mediated tri- and quattro- interactions of adatoms

OpenAIRE

Kappus, Wolfgang

2016-01-01

Lateral interactions of oxygen adatoms derived from first-principles calculations of the O-Pd(100) system had been claimed to include trio- and quattro terms beside pair interactions. This paper is dedicated to extend an earlier model for substrate strain mediated interactions between adatom pairs to include trio- and quattro terms. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress. The requirement...

Frequency of interaction-mediated triggering of antibiotic production among soil bacteria

Directory of Open Access Journals (Sweden)

Olaf eTyc

2014-10-01

Full Text Available Certain bacterial species produce antimicrobial compounds only in the presence of a competing species. However little is known on the frequency of interaction-mediated induction of antibiotic compound production in natural communities of soil bacteria. Here we developed a high-throughput method to screen for the production of antimicrobial activity by monocultures and pair-wise combinations of 146 phylogenetically different bacteria isolated from similar soil habitats. Growth responses of two human pathogenic model organisms, Escherichia coli WA321 and Staphylococcus aureus 533R4, were used to monitor antimicrobial activity. From all isolates, 33% showed antimicrobial activity only in monoculture and 42% showed activity only when tested in interactions. More bacterial isolates were active against S. aureus than against E. coli. The frequency of interaction-mediated induction of antimicrobial activity was 6% (154 interactions out of 2798 indicating that only a limited set of species combinations showed such activity. The screening revealed also interaction-mediated suppression of antimicrobial activity for 22% of all combinations tested. Whereas all patterns of antimicrobial activity (non-induced production, induced production and suppression were seen for various bacterial classes, interaction-mediated induction of antimicrobial activity was more frequent for combinations of Flavobacteria and alpha- Proteobacteria. The results of our study give a first indication on the frequency of interference competitive interactions in natural soil bacterial communities which may forms a basis for selection of bacterial groups that are promising for the discovery of novel, cryptic antibiotics.

Self-interacting dark matter with a stable vector mediator

OpenAIRE

Duerr, Michael; Schmidt-Hoberg, Kai; Wild, Sebastian

2018-01-01

Light vector mediators can naturally induce velocity-dependent dark matter self-interactions while at the same time allowing for the correct dark matter relic abundance via thermal freeze-out. If these mediators subsequently decay into Standard Model states such as electrons or photons however, this is robustly excluded by constraints from the Cosmic Microwave Background. We study to what extent this conclusion can be circumvented if the vector mediator is stable and hence contributes to the ...

The Disclosure-Intimacy Link in Computer-Mediated Communication: An Attributional Extension of the Hyperpersonal Model

Science.gov (United States)

Jiang, L. Crystal; Bazarova, Natalie N.; Hancock, Jeffrey T.

2011-01-01

The present research investigated whether the attribution process through which people explain self-disclosures differs in text-based computer-mediated interactions versus face to face, and whether differences in causal attributions account for the increased intimacy frequently observed in mediated communication. In the experiment participants…

Real-time Control Mediation in Agile Distributed Software Development

DEFF Research Database (Denmark)

Persson, John Stouby; Aaen, Ivan; Mathiassen, Lars

2008-01-01

Agile distributed environments pose particular challenges related to control of quality and collaboration in software development. Moreover, while face-to-face interaction is fundamental in agile development, distributed environments must rely extensively on mediated interactions. On this backdrop...... control was mediated over distance by technology through real-time exchanges. Contrary to previous research, the analysis suggests that both formal and informal elements of real-time mediated control were used; that evolving goals and adjustment of expectations were two of the main issues in real......-time mediated control exchanges; and, that the actors, despite distances in space and culture, developed a clan-like pattern mediated by technology to help control quality and collaboration in software development....

Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tai, Akiko; Dakeyama, Shota; Yamamoto, Kaori; Inoue, Yamato; Kishimoto, Yoshifumi; Ohara, Hiroya; Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp

2015-07-31

Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be the potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.

Developing novel extensions to support prototyping for interactive social robots

NARCIS (Netherlands)

Bhömer, ten M.; Bartneck, C.; Hu, J.; Ahn, R.M.C.; Tuyls, K.P.; Delbressine, F.L.M.; Feijs, L.M.G.

2009-01-01

Lego Mindstorms NXT is a platform highly suitable for prototyping in the field of interactive social robotics. During a technology masterclass at Eindhoven University of Technology students from the department of Industrial Design have developed five novel extensions (sensors and actuators) for the

The Lifespan of Ornaments

DEFF Research Database (Denmark)

Munch, Anders V.; Riisberg, Vibeke

? In this paper we will look at contemporary use of ornament in different scales and contexts – from fashion textiles and interior objects to architecture. The lifespan of a building is different from that of a fashion dress or a plate, but with the digital era it seems like the concern of appropriateness...

Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity [v1; ref status: indexed, http://f1000r.es/3ac

Directory of Open Access Journals (Sweden)

Yingxue Ren

2014-06-01

Full Text Available One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites.  In honey bees (Apis mellifera, Vitellogenin (Vg, a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg-like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age-specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies.

A reduction in age-enhanced gluconeogenesis extends lifespan.

Science.gov (United States)

Hachinohe, Mayumi; Yamane, Midori; Akazawa, Daiki; Ohsawa, Kazuhiro; Ohno, Mayumi; Terashita, Yuzu; Masumoto, Hiroshi

2013-01-01

The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

A reduction in age-enhanced gluconeogenesis extends lifespan.

Directory of Open Access Journals (Sweden)

Mayumi Hachinohe

Full Text Available The regulation of energy metabolism, such as calorie restriction (CR, is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

Neurodevelopmental origins of lifespan changes in brain and cognition

Science.gov (United States)

Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

2016-01-01

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

QUANTIFYING LIFE STYLE IMPACT ON LIFESPAN

Directory of Open Access Journals (Sweden)

Antonello Lorenzini

2012-12-01

Full Text Available A healthy diet, physical activity and avoiding dangerous habits such as smoking are effective ways of increasing health and lifespan. Although a significant portion of the world's population still suffers from malnutrition, especially children, the most common cause of death in the world today is non-communicable diseases. Overweight and obesity significantly increase the relative risk for the most relevant non communicable diseases: cardiovascular disease, type II diabetes and some cancers. Childhood overweight also seems to increase the likelihood of disease in adulthood through epigenetic mechanisms. This worrisome trend now termed "globesity" will deeply impact society unless preventive strategies are put into effect. Researchers of the basic biology of aging have clearly established that animals with short lifespans live longer when their diet is calorie restricted. Although similar experiments carried on rhesus monkeys, a longer-lived species more closely related to humans, yielded mixed results, overall the available scientific data suggest keeping the body mass index in the "normal" range increases the chances of living a longer, healthier life. This can be successfully achieved both by maintaining a healthy diet and by engaging in physical activity. In this review we will try to quantify the relative impact of life style choices on lifespan.

Listening comprehension across the adult lifespan.

Science.gov (United States)

Sommers, Mitchell S; Hale, Sandra; Myerson, Joel; Rose, Nathan; Tye-Murray, Nancy; Spehar, Brent

2011-01-01

Although age-related declines in perceiving spoken language are well established, the primary focus of research has been on perception of phonemes, words, and sentences. In contrast, relatively few investigations have been directed at establishing the effects of age on the comprehension of extended spoken passages. Moreover, most previous work has used extreme-group designs in which the performance of a group of young adults is contrasted with that of a group of older adults and little if any information is available regarding changes in listening comprehension across the adult lifespan. Accordingly, the goals of the current investigation were to determine whether there are age differences in listening comprehension across the adult lifespan and, if so, whether similar trajectories are observed for age-related changes in auditory sensitivity and listening comprehension. This study used a cross-sectional lifespan design in which approximately 60 individuals in each of 7 decades, from age 20 to 89 yr (a total of 433 participants), were tested on three different measures of listening comprehension. In addition, we obtained measures of auditory sensitivity from all participants. Changes in auditory sensitivity across the adult lifespan exhibited the progressive high-frequency loss typical of age-related hearing impairment. Performance on the listening comprehension measures, however, demonstrated a very different pattern, with scores on all measures remaining relatively stable until age 65 to 70 yr, after which significant declines were observed. Follow-up analyses indicated that this same general pattern was observed across three different types of passages (lectures, interviews, and narratives) and three different question types (information, integration, and inference). Multiple regression analyses indicated that low-frequency pure-tone average was the single largest contributor to age-related variance in listening comprehension for individuals older than 65 yr, but

The long-term effects of a life-prolonging heat treatment on the Drosophila melanogaster transcriptome suggest that heat shock proteins extend lifespan

DEFF Research Database (Denmark)

Sarup, Pernille Merete; Sørensen, Peter; Loeschcke, Volker

2014-01-01

Heat-induced hormesis, i.e. the beneficial effect of mild heat-induced stress, increases the average lifespan of many organisms. This effect, which depends on the heat shock factor, decreases the log mortality rate weeks after the stress has ceased. To identify candidate genes that mediate......-treated flies. Several hsp70 probe sets were up-regulated 1.7–2-fold in the mildly stressed flies weeks after the last heat treatment (P shock protein, Hsp70, is reported to return to normal levels of expression shortly after heat stress. We...... conclude that the heat shock response, and Hsp70 in particular, may be central to the heat-induced increase in the average lifespan in flies that are exposed to mild heat stress early in life....

Different neural processes accompany self-recognition in photographs across the lifespan: an ERP study using dizygotic twins.

Science.gov (United States)

Butler, David L; Mattingley, Jason B; Cunnington, Ross; Suddendorf, Thomas

2013-01-01

Our appearance changes over time, yet we can recognize ourselves in photographs from across the lifespan. Researchers have extensively studied self-recognition in photographs and have proposed that specific neural correlates are involved, but few studies have examined self-recognition using images from different periods of life. Here we compared ERP responses to photographs of participants when they were 5-15, 16-25, and 26-45 years old. We found marked differences between the responses to photographs from these time periods in terms of the neural markers generally assumed to reflect (i) the configural processing of faces (i.e., the N170), (ii) the matching of the currently perceived face to a representation already stored in memory (i.e., the P250), and (iii) the retrieval of information about the person being recognized (i.e., the N400). There was no uniform neural signature of visual self-recognition. To test whether there was anything specific to self-recognition in these brain responses, we also asked participants to identify photographs of their dizygotic twins taken from the same time periods. Critically, this allowed us to minimize the confounding effects of exposure, for it is likely that participants have been similarly exposed to each other's faces over the lifespan. The same pattern of neural response emerged with only one exception: the neural marker reflecting the retrieval of mnemonic information (N400) differed across the lifespan for self but not for twin. These results, as well as our novel approach using twins and photographs from across the lifespan, have wide-ranging consequences for the study of self-recognition and the nature of our personal identity through time.

Different neural processes accompany self-recognition in photographs across the lifespan: an ERP study using dizygotic twins.

Directory of Open Access Journals (Sweden)

David L Butler

Full Text Available Our appearance changes over time, yet we can recognize ourselves in photographs from across the lifespan. Researchers have extensively studied self-recognition in photographs and have proposed that specific neural correlates are involved, but few studies have examined self-recognition using images from different periods of life. Here we compared ERP responses to photographs of participants when they were 5-15, 16-25, and 26-45 years old. We found marked differences between the responses to photographs from these time periods in terms of the neural markers generally assumed to reflect (i the configural processing of faces (i.e., the N170, (ii the matching of the currently perceived face to a representation already stored in memory (i.e., the P250, and (iii the retrieval of information about the person being recognized (i.e., the N400. There was no uniform neural signature of visual self-recognition. To test whether there was anything specific to self-recognition in these brain responses, we also asked participants to identify photographs of their dizygotic twins taken from the same time periods. Critically, this allowed us to minimize the confounding effects of exposure, for it is likely that participants have been similarly exposed to each other's faces over the lifespan. The same pattern of neural response emerged with only one exception: the neural marker reflecting the retrieval of mnemonic information (N400 differed across the lifespan for self but not for twin. These results, as well as our novel approach using twins and photographs from across the lifespan, have wide-ranging consequences for the study of self-recognition and the nature of our personal identity through time.

Trickle-down effects of supervisor perceptions of interactional justice: a moderated mediation approach.

Science.gov (United States)

Ambrose, Maureen L; Schminke, Marshall; Mayer, David M

2013-07-01

Supervisors' perceptions of how fairly they are treated by their own supervisors can influence their subordinates' perceptions, attitudes, and behavior. We present a moderated mediation model that demonstrates how work group structure can enhance or constrain these effects. Results show supervisors' perceptions of the fairness of the interactional treatment they receive relate to their subordinates' perceptions of interactional justice climate, and this relationship is stronger in work groups with more organic structures. Furthermore, consistent with the moderated mediation prediction, interactional justice climate mediates the relationship between supervisors' perceptions of interactional justice and outcomes when work group structures are more organic. We discuss the implications of the findings for research on justice and trickle-down effects. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Why do lifespan variability trends for the young and old diverge? A perturbation analysis

Directory of Open Access Journals (Sweden)

Michal Engelman

2014-05-01

Full Text Available Background: Variation in lifespan has followed strikingly different trends for the young and old: while overall lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the underlying demographic parameters determining age-specific mortality. Objective: We ask why the variation in the adult ages at death has followed a different trend than the variation at younger ages, and aim to explain the diverging patterns in terms of historical changes in the age schedule of mortality. Methods: Using simulations, we show that the empirical trends in lifespan variation are well characterized using the Siler model, which describes the mortality hazard across the full lifespan using functions representing early-life, later-life, and background mortality. We then obtain maximum likelihood estimates of the Siler parameters over time. Finally, we express lifespan variation in terms of a Markov chain model, and apply matrix calculus perturbation analysis to compute the sensitivity of age-specific lifespan variance trends to the changing Siler model parameters. Results: Our analysis produces a detailed quantification of the impact of changing demographic parameters on the pattern of lifespan variability at all ages, highlighting the impact of declining childhood mortality on the reduction of lifespan variability and the impact of improved survival in adulthood on the rising variability of lifespans at older ages. Conclusions: These findings provide insight into the dynamic relationship between the age pattern of survival improvements and time trends in lifespan variability.

CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

Directory of Open Access Journals (Sweden)

O.Popescu

1999-01-01

Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

Molecular simulations of lipid-mediated protein-protein interactions

NARCIS (Netherlands)

de Meyer, F.J.M.; Venturoli, M.; Smit, B.

2008-01-01

Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

Directory of Open Access Journals (Sweden)

Liangping Su

2018-03-01

Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

Understanding retirement: the promise of life-span developmental frameworks.

Science.gov (United States)

Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

Root signals that mediate mutualistic interactions in the rhizosphere.

Science.gov (United States)

Rasmann, Sergio; Turlings, Ted Cj

2016-08-01

A recent boom in research on belowground ecology is rapidly revealing a multitude of fascinating interactions, in particular in the rhizosphere. Many of these interactions are mediated by photo-assimilates that are excreted by plant roots. Root exudates are not mere waste products, but serve numerous functions to control abiotic and biotic processes. These functions range from changing the chemical and physical properties of the soil, inhibiting the growth of competing plants, combatting herbivores, and regulating the microbial community. Particularly intriguing are root-released compounds that have evolved to serve mutualistic interactions with soil-dwelling organisms. These mutually beneficial plant-mediated signals are not only of fundamental ecological interest, but also exceedingly important from an agronomical perspective. Here, we attempt to provide an overview of the plant-produced compounds that have so far been implicated in mutualistic interactions. We propose that these mutualistic signals may have evolved from chemical defenses and we point out that they can be (mis)used by specialized pathogens and herbivores. We speculate that many more signals and interactions remain to be uncovered and that a good understanding of the mechanisms and ecological implications can be the basis for exploitation and manipulation of the signals for crop improvement and protection. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Path to Competence: A Lifespan Developmental Perspective on Reading

Science.gov (United States)

Alexander, Patricia A.

2012-01-01

The purpose of this document is to present a developmental model of reading that encompasses changes across the lifespan. The need for such a lifespan orientation toward reading within our educational institutions is great. Until we adopt this lifelong perspective, we continue to run the risk of turning out undeveloped, unmotivated, and uncritical…

MC EMiNEM maps the interaction landscape of the Mediator.

Directory of Open Access Journals (Sweden)

Theresa Niederberger

Full Text Available The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs, a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC sampling with an Expectation-Maximization (EM algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

MC EMiNEM maps the interaction landscape of the Mediator.

Science.gov (United States)

Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C; Martin, Dietmar E; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

2012-01-01

The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between proteins that have pleiotropic effects on mRNA transcription. MC EMiNEM is based on Nested Effects Models (NEMs), a class of probabilistic graphical models that extends the idea of hierarchical clustering. It combines mode-hopping Monte Carlo (MC) sampling with an Expectation-Maximization (EM) algorithm for NEMs to increase sensitivity compared to existing methods. A meta-analysis of four Mediator perturbation studies in Saccharomyces cerevisiae, three of which are unpublished, provides new insight into the Mediator signaling network. In addition to the known modular organization of the Mediator subunits, MC EMiNEM reveals a hierarchical ordering of its internal information flow, which is putatively transmitted through structural changes within the complex. We identify the N-terminus of Med7 as a peripheral entity, entailing only local structural changes upon perturbation, while the C-terminus of Med7 and Med19 appear to play a central role. MC EMiNEM associates Mediator subunits to most directly affected genes, which, in conjunction with gene set enrichment analysis, allows us to construct an interaction map of Mediator subunits and transcription factors.

Exploring the Mediating Effect of E-social Capital Between Community Members Interaction and Consumer Engagement

OpenAIRE

Yan Bingsheng; Li Lihua; Sun Hongtao

2017-01-01

This article explored the effect of instrumental interaction and relational interaction on consumer engagement (community engagement and brand engagement) among community members. The mediating effect of E-social capital was investigated as well. The research results showed that: both instrumental interaction and interpersonal interaction promote the formation of E-social capital (online trust and online reciprocity); online trust plays a partial mediating role between community interaction (...

iELM—a web server to explore short linear motif-mediated interactions

Science.gov (United States)

Weatheritt, Robert J.; Jehl, Peter; Dinkel, Holger; Gibson, Toby J.

2012-01-01

The recent expansion in our knowledge of protein–protein interactions (PPIs) has allowed the annotation and prediction of hundreds of thousands of interactions. However, the function of many of these interactions remains elusive. The interactions of Eukaryotic Linear Motif (iELM) web server provides a resource for predicting the function and positional interface for a subset of interactions mediated by short linear motifs (SLiMs). The iELM prediction algorithm is based on the annotated SLiM classes from the Eukaryotic Linear Motif (ELM) resource and allows users to explore both annotated and user-generated PPI networks for SLiM-mediated interactions. By incorporating the annotated information from the ELM resource, iELM provides functional details of PPIs. This can be used in proteomic analysis, for example, to infer whether an interaction promotes complex formation or degradation. Furthermore, details of the molecular interface of the SLiM-mediated interactions are also predicted. This information is displayed in a fully searchable table, as well as graphically with the modular architecture of the participating proteins extracted from the UniProt and Phospho.ELM resources. A network figure is also presented to aid the interpretation of results. The iELM server supports single protein queries as well as large-scale proteomic submissions and is freely available at http://i.elm.eu.org. PMID:22638578

The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response

DEFF Research Database (Denmark)

Jakobsen, Henrik; Bojer, Martin Saxtorph; Marinus, Martin G.

2013-01-01

pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity....... Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.......The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin...

Testing Left-Right extensions of the standard model of electroweak interactions with double-beta decay and LHC measurements

Science.gov (United States)

Civitarese, O.; Suhonen, J.; Zuber, K.

2015-07-01

The minimal extension of the standard model of electroweak interactions allows for massive neutrinos, a massive right-handed boson WR, and a left-right mixing angle ζ. While an estimate of the light (electron) neutrino can be extracted from the non-observation of the neutrinoless double beta decay, the limits on the mixing angle and the mass of the righthanded (RH) boson may be extracted from a combined analysis of the double beta decay measurements (GERDA, EXO-200 and KamLAND-Zen collaborations) and ATLAS data on the two-jets two-leptons signals following the excitation of a virtual RH boson mediated by a heavy-mass neutrino. In this work we shall compare results of both types of experiments, and show that the estimates are not in tension.

Parent-child mediated learning interactions as determinants of cognitive modifiability: recent research and future directions.

Science.gov (United States)

Tzuriel, D

1999-05-01

The main objectives of this article are to describe the effects of mediated learning experience (MLE) strategies in mother-child interactions on the child's cognitive modifiability, the effects of distal factors (e.g., socioeconomic status, mother's intelligence, child's personality) on MLE interactions, and the effects of situational variables on MLE processes. Methodological aspects of measurement of MLE interactions and of cognitive modifiability, using a dynamic assessment approach, are discussed. Studies with infants showed that the quality of mother-infant MLE interactions predict later cognitive functioning and that MLE patterns and children's cognitive performance change as a result of intervention programs. Studies with preschool and school-aged children showed that MLE interactions predict cognitive modifiability and that distal factors predict MLE interactions but not the child's cognitive modifiability. The child's cognitive modifiability was predicted by MLE interactions in a structured but not in a free-play situation. Mediation for transcendence (e.g., teaching rules and generalizations) appeared to be the strongest predictor of children's cognitive modifiability. Discussion of future research includes the consideration of a holistic transactional approach, which refers to MLE processes, personality, and motivational-affective factors, the cultural context of mediation, perception of the whole family as a mediational unit, and the "mediational normative scripts."

A conserved pattern in plant-mediated interactions between herbivores

OpenAIRE

Lu Jing; Robert Christelle A. M.; Lou Yonggen; Erb Matthias

2016-01-01

Abstract Plant?mediated interactions between herbivores are important determinants of community structure and plant performance in natural and agricultural systems. Current research suggests that the outcome of the interactions is determined by herbivore and plant identity, which may result in stochastic patterns that impede adaptive evolution and agricultural exploitation. However, few studies have systemically investigated specificity versus general patterns in a given plant system by varyi...

HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1

DEFF Research Database (Denmark)

Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha

2017-01-01

In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically...... inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene...... of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1-deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins...

Landfill Lifespan Estimation: A Case Study

African Journals Online (AJOL)

Michael

2017-12-02

Dec 2, 2017 ... site selection, design, construction, operation and management. For this reason, it ... This research used the future value of money equation to estimate the lifespan of the ..... Geomatic Engineering, UMaT, Tarkwa, Ghana, pp.

Worker lifespan is an adaptive trait during colony establishment in the long-lived ant Lasius niger

NARCIS (Netherlands)

Kramer, Boris H.; Schaible, Ralf; Scheuerlein, Alexander

2016-01-01

Eusociality has been recognized as a strong driver of lifespan evolution. While queens show extraordinary lifespans of 20 years and more, worker lifespan is short and variable. A recent comparative study found that in eusocial species with larger average colony sizes the disparities in the lifespans

Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

Science.gov (United States)

2015-08-01

exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

Direct detection signatures of self-interacting dark matter with a light mediator

International Nuclear Information System (INIS)

Nobile, Eugenio Del; Kaplinghat, Manoj; Yu, Hai-Bo

2015-01-01

Self-interacting dark matter (SIDM) is a simple and well-motivated scenario that could explain long-standing puzzles in structure formation on small scales. If the required self-interaction arises through a light mediator (with mass ∼ 10 MeV) in the dark sector, this new particle must be unstable to avoid overclosing the universe. The decay of the light mediator could happen due to a weak coupling of the hidden and visible sectors, providing new signatures for direct detection experiments. The SIDM nuclear recoil spectrum is more peaked towards low energies compared to the usual case of contact interactions, because the mediator mass is comparable to the momentum transfer of nuclear recoils. We show that the SIDM signal could be distinguished from that of DM particles with contact interactions by considering the time-average energy spectrum in experiments employing different target materials, or the average and modulated spectra in a single experiment. Using current limits from LUX and SuperCDMS, we also derive strong bounds on the mixing parameter between hidden and visible sector

Surface-state mediated three-adsorbate interaction: exact and numerical results and simple asymptotic expression

International Nuclear Information System (INIS)

Hyldgaard, Per; Einstein, T.L.

2003-01-01

The interaction energy of three adsorbates on a surface consists of the sum of the three-pair interactions plus a trio contribution produced primarily by interference of electrons which traverse the entire perimeter, d 123 , of the three-adsorbate cluster. Here, we investigate this three-adatom interaction when mediated by the isotropic Shockley surface-state band found on noble-metal (1 1 1) surfaces, extending work on pair interactions. Our experimentally testable result depends on the s-wave phase-shift, characterizing the standing-wave patterns seen in scanning-tunneling microscopy (STM) images. Compared with the adsorbate-pair interactions, and in contrast to bulk-mediated interactions, the trio contribution exhibits a slightly weaker amplitude and a slightly faster asymptotic envelope decay, d 123 -5/2 . It also has a different but well-defined oscillation period dependent on d 123 and little dependence on the shape of the cluster. We finally compare the asymptotic description with exact model calculations assuming short-range interactions, which are viable even in the non-asymptotic range (when not outweighed by bulk-mediated interactions)

The addition of a developmental factor, unc-62, to already long-lived worms increases lifespan and healthspan

Directory of Open Access Journals (Sweden)

Dror Sagi

2017-12-01

Full Text Available Aging is a complex trait that is affected by multiple genetic pathways. A relatively unexplored approach is to manipulate multiple independent aging pathways simultaneously in order to observe their cumulative effect on lifespan. Here, we report the phenotypic characterization of a strain with changes in five aging pathways: (1 mitochondrial reactive oxygen species (ROS production, (2 innate immunity, (3 stress response, (4 metabolic control and (5 developmental regulation in old age. The quintuply modified strain has a lifespan that is 160% longer than the transgenic control strain. Additionally, the quintuply modified strain maintains several physiological markers of aging for a longer time than the transgenic control. Our results support a modular approach as a general scheme to study how multiple pathways interact to achieve extreme longevity.

Leptogenesis and composite heavy neutrinos with gauge-mediated interactions

Energy Technology Data Exchange (ETDEWEB)

Biondini, S. [University of Bern, AEC, Institute for Theoretical Physics, Bern (Switzerland); Panella, O. [Istituto Nazionale di Fisica Nucleare, Sezione di Perugia, Perugia (Italy)

2017-09-15

Leptogenesis is an appealing framework to account for the baryon asymmetry in the universe. To this end physics beyond the standard model is demanded. In this paper we investigate the possibility to attain successful leptogenesis with composite Majorana neutrinos. We work in the framework of effective gauge-mediated and contact interactions without any reference to an underlying compositeness theory. This approach is the one adopted in all current experimental searches for composite fermions at colliders. In the case of gauge-mediated interactions, we calculate the CP asymmetry in heavy composite neutrino decays. Both the direct and the indirect CP asymmetry are derived and resonant leptogenesis is also discussed. We find that the Sakharov conditions can be met and, for some choice of the parameters, the correct order of magnitude of the baryon asymmetry is reproduced. (orig.)

Trait-mediated trophic interactions: is foraging theory keeping up?

Science.gov (United States)

Railsback, Steven F; Harvey, Bret C

2013-02-01

Many ecologists believe that there is a lack of foraging theory that works in community contexts, for populations of unique individuals each making trade-offs between food and risk that are subject to feedbacks from behavior of others. Such theory is necessary to reproduce the trait-mediated trophic interactions now recognized as widespread and strong. Game theory can address feedbacks but does not provide foraging theory for unique individuals in variable environments. 'State- and prediction-based theory' (SPT) is a new approach that combines existing trade-off methods with routine updating: individuals regularly predict future food availability and risk from current conditions to optimize a fitness measure. SPT can reproduce a variety of realistic foraging behaviors and trait-mediated trophic interactions with feedbacks, even when the environment is unpredictable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Audiovisual Simultaneity Judgment and Rapid Recalibration throughout the Lifespan.

Science.gov (United States)

Noel, Jean-Paul; De Niear, Matthew; Van der Burg, Erik; Wallace, Mark T

2016-01-01

Multisensory interactions are well established to convey an array of perceptual and behavioral benefits. One of the key features of multisensory interactions is the temporal structure of the stimuli combined. In an effort to better characterize how temporal factors influence multisensory interactions across the lifespan, we examined audiovisual simultaneity judgment and the degree of rapid recalibration to paired audiovisual stimuli (Flash-Beep and Speech) in a sample of 220 participants ranging from 7 to 86 years of age. Results demonstrate a surprisingly protracted developmental time-course for both audiovisual simultaneity judgment and rapid recalibration, with neither reaching maturity until well into adolescence. Interestingly, correlational analyses revealed that audiovisual simultaneity judgments (i.e., the size of the audiovisual temporal window of simultaneity) and rapid recalibration significantly co-varied as a function of age. Together, our results represent the most complete description of age-related changes in audiovisual simultaneity judgments to date, as well as being the first to describe changes in the degree of rapid recalibration as a function of age. We propose that the developmental time-course of rapid recalibration scaffolds the maturation of more durable audiovisual temporal representations.

Telomeres and the natural lifespan limit in humans

DEFF Research Database (Denmark)

Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

2017-01-01

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

COCOA (Theobroma cacao) Polyphenol-Rich Extract Increases the Chronological Lifespan of Saccharomyces cerevisiae.

Science.gov (United States)

Baiges, I; Arola, L

2016-01-01

BACKGROUND: Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. OBJECTIVE: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. MEASUREMENTS: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. RESULTS : CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, (+)-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. CONCLUSION: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate

Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

DEFF Research Database (Denmark)

Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine

2009-01-01

Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...

Mediation Analysis: A Practitioner's Guide.

Science.gov (United States)

VanderWeele, Tyler J

2016-01-01

This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

Phytohormone mediation of interactions between herbivores and plant pathogens

NARCIS (Netherlands)

Lazebnik, J.; Frago, E.; Dicke, M.; Loon, van J.J.A.

2014-01-01

Induced plant defenses against either pathogens or herbivore attackers are regulated by phytohormones. These phytohormones are increasingly recognized as important mediators of interactions between organisms associated with plants. In this review, we discuss the role of plant defense hormones in

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

Science.gov (United States)

Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

2018-03-06

Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Loss of Ceramide Synthases Elicits a PHA-4/FoxA-, SKN-1-, and Autophagy-Dependent Lifespan Extension in C. elegans

DEFF Research Database (Denmark)

Jensen, Mai-Britt Mosbech; Færgeman, Nils J.; Ejsing, Christer S.

2011-01-01

, these lipid species are recognized as bioactive signalling molecules involved in regulation of cell growth, differentiation, senescence, and apoptosis, and thus a delicate equilibrium between the levels of these interconvertible lipid species underlies the balance between cell survival and death. The C....... elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. Here we show that functional loss of HYL-1 and LAGR-1 depletes 43:1;3 sphingolipids and extends lifespan in a PHA-4-, SKN-1-, and ATG-12-dependent manner. The transcription factors PHA-4 and SKN-1 as well as ATG-12, which...

Changes in Regenerative Capacity through Lifespan

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Maximina H. Yun

2015-10-01

Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

Social interaction in type 2 diabetes computer-mediated environments: How inherent features of the channels influence peer-to-peer interaction.

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Lewinski, Allison A; Fisher, Edwin B

2016-06-01

Interventions via the internet provide support to individuals managing chronic illness. The purpose of this integrative review was to determine how the features of a computer-mediated environment influence social interactions among individuals with type 2 diabetes. A combination of MeSH and keyword terms, based on the cognates of three broad groupings: social interaction, computer-mediated environments, and chronic illness, was used to search the PubMed, PsychInfo, Sociology Research Database, and Cumulative Index to Nursing and Allied Health Literature databases. Eleven articles met the inclusion criteria. Computer-mediated environments enhance an individual's ability to interact with peers while increasing the convenience of obtaining personalized support. A matrix, focused on social interaction among peers, identified themes across all articles, and five characteristics emerged: (1) the presence of synchronous and asynchronous communication, (2) the ability to connect with similar peers, (3) the presence or absence of a moderator, (4) personalization of feedback regarding individual progress and self-management, and (5) the ability of individuals to maintain choice during participation. Individuals interact with peers to obtain relevant, situation-specific information and knowledge about managing their own care. Computer-mediated environments facilitate the ability of individuals to exchange this information despite temporal or geographical barriers that may be present, thus improving T2D self-management. © The Author(s) 2015.

MC EMiNEM maps the interaction landscape of the Mediator

OpenAIRE

Niederberger, Theresa; Etzold, Stefanie; Lidschreiber, Michael; Maier, Kerstin C.; Martin, Dietmar E.; Fröhlich, Holger; Cramer, Patrick; Tresch, Achim

2012-01-01

The Mediator is a highly conserved, large multiprotein complex that is involved essentially in the regulation of eukaryotic mRNA transcription. It acts as a general transcription factor by integrating regulatory signals from gene-specific activators or repressors to the RNA Polymerase II. The internal network of interactions between Mediator subunits that conveys these signals is largely unknown. Here, we introduce MC EMiNEM, a novel method for the retrieval of functional dependencies between...

Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

Science.gov (United States)

Chen, Di; Li, Patrick Wai-Lun; Goldstein, Benjamin A; Cai, Waijiao; Thomas, Emma Lynn; Chen, Fen; Hubbard, Alan E; Melov, Simon; Kapahi, Pankaj

2013-12-26

Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Pomegranate juice enhances healthy lifespan in Drosophila melanogaster

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Padmavathy eVenkatasubramanian

2014-12-01

Full Text Available Exploring innovative ways to ensure healthy ageing of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of Pomegranate (Punica granatum L., a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly model. Supplementation of standard corn meal with 10% (v/v pomegranate juice (PJ extended the life-span of male and female flies by 18% and 8% respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8. MSD for control and resveratrol (RV groups was at 20.8 and 23.1 days respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in humans.

Transporter-mediated natural product–drug interactions for the treatment of cardiovascular diseases

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Weibin Zha

2018-04-01

Full Text Available The growing use of natural products in cardiovascular (CV patients has been greatly raising the concerns about potential natural product–CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product–CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product–drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins have been identified to be substrates and inhibitors of the solute carrier (SLC transporters and the ATP-binding cassette (ABC transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product–CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product–CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product–CV drug interactions and help public and physicians understand these type of interactions. Keywords: Cardiovascular drugs, Natural products, Drug transporters, Natural product–drug interaction, Pharmacokinetics

Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

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Fanhui Meng

2018-01-01

Full Text Available Gengnianchun (GNC, a traditional Chinese medicine (TCM, is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465, rsks-1 (ok1255, and glp-1 (e2144, suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370, age-1 (hx546, and daf-16 (mu86 mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

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Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael

2018-03-06

The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.

Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

Science.gov (United States)

Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

2016-09-28

Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators

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Corraini P

2017-06-01

Full Text Available Priscila Corraini,1 Morten Olsen,1 Lars Pedersen,1 Olaf M Dekkers,1,2 Jan P Vandenbroucke1–3 1Department of Clinical Epidemiology, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Leiden University Medical Center, Leiden, the Netherlands; 3Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK Abstract: We revisited the three interrelated epidemiological concepts of effect modification, interaction and mediation for clinical investigators and examined their applicability when using research databases. The standard methods that are available to assess interaction, effect modification and mediation are explained and exemplified. For each concept, we first give a simple “best-case” example from a randomized controlled trial, followed by a structurally similar example from an observational study using research databases. Our explanation of the examples is based on recent theoretical developments and insights in the context of large health care databases. Terminology is sometimes ambiguous for what constitutes effect modification and interaction. The strong assumptions underlying the assessment of interaction, and particularly mediation, require clinicians and epidemiologists to take extra care when conducting observational studies in the context of health care databases. These strong assumptions may limit the applicability of interaction and mediation assessments, at least until the biases and limitations of these assessments when using large research databases are clarified. Keywords: methods, epidemiology, effect modifiers, stratified analyses, health care administrative claims

Individual versus Interactive Task-Based Performance through Voice-Based Computer-Mediated Communication

Science.gov (United States)

Granena, Gisela

2016-01-01

Interaction is a necessary condition for second language (L2) learning (Long, 1980, 1996). Research in computer-mediated communication has shown that interaction opportunities make learners pay attention to form in a variety of ways that promote L2 learning. This research has mostly investigated text-based rather than voice-based interaction. The…

Testing the Effects of DL-Alpha-Tocopherol Supplementation on Oxidative Damage, Total Antioxidant Protection and the Sex-Specific Responses of Reproductive Effort and Lifespan to Dietary Manipulation in Australian Field Crickets (Teleogryllus commodus

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C. Ruth Archer

2015-12-01

Full Text Available The oxidative stress theory predicts that the accumulation of oxidative damage causes aging. More generally, oxidative damage could be a cost of reproduction that reduces survival. Both of these hypotheses have mixed empirical support. To better understand the life-history consequences of oxidative damage, we fed male and female Australian field crickets (Teleogryllus commodus four diets differing in their protein and carbohydrate content, which have sex-specific effects on reproductive effort and lifespan. We supplemented half of these crickets with the vitamin E isoform DL-alpha-tocopherol and measured the effects of nutrient intake on lifespan, reproduction, oxidative damage and antioxidant protection. We found a clear trade-off between reproductive effort and lifespan in females but not in males. In direct contrast to the oxidative stress theory, crickets fed diets that improved their lifespan had high levels of oxidative damage to proteins. Supplementation with DL-alpha-tocopherol did not significantly improve lifespan or reproductive effort. However, males fed diets that increased their reproductive investment experienced high oxidative damage to proteins. While this suggests that male reproductive effort could elevate oxidative damage, this was not associated with reduced male survival. Overall, these results provide little evidence that oxidative damage plays a central role in mediating life-history trade-offs in T. commodus.

Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

Science.gov (United States)

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros

Science.gov (United States)

Valeri, Linda; VanderWeele, Tyler J.

2012-01-01

Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this paper are several-fold. First we seek to bring the developments in mediation analysis for non linear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically and we compare the types of inferences about mediation that are allowed by a variety of software macros. PMID:23379553

Comparing the Developmental Genetics of Cognition and Personality over the Lifespan

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Briley, Daniel A.; Tucker-Drob, Elliot M.

2015-01-01

Objective Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. Method We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the lifespan, focusing particular attention on age trends in heritability and differential stability. Results Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. Conclusions We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. PMID:26045299

A Review of Peer-Mediated Social Interaction Interventions for Students with Autism in Inclusive Settings

Science.gov (United States)

Watkins, Laci; O'Reilly, Mark; Kuhn, Michelle; Gevarter, Cindy; Lancioni, Giulio E.; Sigafoos, Jeff; Lang, Russell

2015-01-01

This review addresses the use of peer-mediated interventions (PMI) to improve the social interaction skills of students with autism spectrum disorder (ASD) in inclusive settings. The purpose of this review is to (a) identify the characteristics and components of peer-mediated social interaction interventions, (b) evaluate the effectiveness of PMI…

Workplace flexibility across the lifespan

OpenAIRE

Bal, Pieter; Jansen, Paul G W

2016-01-01

As demographic changes impact the workplace, governments, organizations and workers arelooking for ways to sustain optimal working lives at higher ages. Workplace flexibility has beenintroduced as a potential way workers can have more satisfying working lives until theirretirement ages. This paper presents a critical review of the literature on workplace flexibilityacross the lifespan. It discusses how flexibility has been conceptualized across differentdisciplines, and postulates a definitio...

A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

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Yong-Jian Ma

2016-01-01

Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

PAI1 mediates fibroblast-mast cell interactions in skin fibrosis.

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Pincha, Neha; Hajam, Edries Yousaf; Badarinath, Krithika; Batta, Surya Prakash Rao; Masudi, Tafheem; Dey, Rakesh; Andreasen, Peter; Kawakami, Toshiaki; Samuel, Rekha; George, Renu; Danda, Debashish; Jacob, Paul Mazhuvanchary; Jamora, Colin

2018-05-01

Fibrosis is a prevalent pathological condition arising from the chronic activation of fibroblasts. This activation results from the extensive intercellular crosstalk mediated by both soluble factors and direct cell-cell connections. Prominent among these are the interactions of fibroblasts with immune cells, in which the fibroblast-mast cell connection, although acknowledged, is relatively unexplored. We have used a Tg mouse model of skin fibrosis, based on expression of the transcription factor Snail in the epidermis, to probe the mechanisms regulating mast cell activity and the contribution of these cells to this pathology. We have discovered that Snail-expressing keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which functions as a chemotactic factor to increase mast cell infiltration into the skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them competent to bind to mast cells. This heterotypic cell-cell adhesion, also observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal activation of both mast cells and fibroblasts, leading to the cascade of events that promote fibrogenesis. Thus, we have identified roles for PAI1 in the multifactorial program of fibrogenesis that expand its functional repertoire beyond its canonical role in plasmin-dependent processes.

Exploring the Mediating Effect of E-social Capital Between Community Members Interaction and Consumer Engagement

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Yan Bingsheng

2017-01-01

Full Text Available This article explored the effect of instrumental interaction and relational interaction on consumer engagement (community engagement and brand engagement among community members. The mediating effect of E-social capital was investigated as well. The research results showed that: both instrumental interaction and interpersonal interaction promote the formation of E-social capital (online trust and online reciprocity; online trust plays a partial mediating role between community interaction (instrumental interaction, relational interaction and community engagement, but the influence of online reciprocity on community engagement is not significant; community engagement leads to brand engagement. The findings enrich the theories of brand community and consumer engagement and contribute to the virtual community management.

Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

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Poon, Peter C; Kuo, Tsung-Han; Linford, Nancy J; Roman, Gregg; Pletcher, Scott D

2010-04-20

For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2)) affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2)) and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros.

Science.gov (United States)

Valeri, Linda; Vanderweele, Tyler J

2013-06-01

Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this article are several-fold. First we seek to bring the developments in mediation analysis for nonlinear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically, and we compare the types of inferences about mediation that are allowed by a variety of software macros. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Hurst Exponent Analysis of Resting-State fMRI Signal Complexity across the Adult Lifespan

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Jianxin Dong

2018-02-01

Full Text Available Exploring functional information among various brain regions across time enables understanding of healthy aging process and holds great promise for age-related brain disease diagnosis. This paper proposed a method to explore fractal complexity of the resting-state functional magnetic resonance imaging (rs-fMRI signal in the human brain across the adult lifespan using Hurst exponent (HE. We took advantage of the examined rs-fMRI data from 116 adults 19 to 85 years of age (44.3 ± 19.4 years, 49 females from NKI/Rockland sample. Region-wise and voxel-wise analyses were performed to investigate the effects of age, gender, and their interaction on complexity. In region-wise analysis, we found that the healthy aging is accompanied by a loss of complexity in frontal and parietal lobe and increased complexity in insula, limbic, and temporal lobe. Meanwhile, differences in HE between genders were found to be significant in parietal lobe (p = 0.04, corrected. However, there was no interaction between gender and age. In voxel-wise analysis, the significant complexity decrease with aging was found in frontal and parietal lobe, and complexity increase was found in insula, limbic lobe, occipital lobe, and temporal lobe with aging. Meanwhile, differences in HE between genders were found to be significant in frontal, parietal, and limbic lobe. Furthermore, we found age and sex interaction in right parahippocampal gyrus (p = 0.04, corrected. Our findings reveal HE variations of the rs-fMRI signal across the human adult lifespan and show that HE may serve as a new parameter to assess healthy aging process.

The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II

DEFF Research Database (Denmark)

Elmlund, Hans; Baraznenok, Vera; Lindahl, Martin

2006-01-01

CDK8 (cyclin-dependent kinase 8), along with CycC, Med12, and Med13, form a repressive module (the Cdk8 module) that prevents RNA polymerase II (pol II) interactions with Mediator. Here, we report that the ability of the Cdk8 module to prevent pol II interactions is independent of the Cdk8......-dependent kinase activity. We use electron microscopy and single-particle reconstruction to demonstrate that the Cdk8 module forms a distinct structural entity that binds to the head and middle region of Mediator, thereby sterically blocking interactions with pol II....

Intrathymic laminin-mediated interactions: role in T cell migration and development

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Wilson eSavino

2015-11-01

Full Text Available Intrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins, a heterotrimeric protein family of the extracellular matrix. Several laminins are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells. Also, thymocytes and epithelial cells express integrin-type laminin receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the laminin isoform 211 exhibits defective thymocyte differentiation. Several data show haptotactic effects of laminins upon thymocytes, as well as their adhesion on thymic epithelial cells; both effects being prevented by anti-laminin or anti-laminin receptor antibodies. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate laminin-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors in human thymic epithelial cells, modulates a large number of cell-migration related genes, and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic trafficking events.

Mediation Analysis with Multiple Mediators.

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VanderWeele, T J; Vansteelandt, S

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

Building lifespan: effect on the environmental impact of building components in a Danish perspective

DEFF Research Database (Denmark)

Marsh, Rob

2017-01-01

of building lifespan are inadequately addressed. The aim of this research is therefore to explore how environmental impact from building components is affected by building lifespans of 50, 80, 100 and 120 years in a Danish context. LCAs are undertaken for 792 parametric variations of typical construction...... solutions, covering all primary building components and based on contemporary practice. A full statistical analysis is carried out, which shows a significant statistical correlation between changes in building lifespan and environmental impact for all primary building components, except windows......Construction professionals must now integrate environmental concerns with life cycle assessment (LCA) early in the procurement process. Building lifespan is important to LCA, since results must be normalized on an annualized basis for comparison. However, the scientific literature shows that issues...

The Interaction of Ethanol Ingestion and Social Interaction with an Intoxicated Peer on the Odor-Mediated Response to the Drug in Adolescent Rats.

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Eade, Amber M; Youngentob, Lisa M; Youngentob, Steven L

2016-04-01

Using a social transmission of food preference paradigm in rats, we previously demonstrated that ethanol (EtOH) exposure during adolescence, as either an observer (interaction with an intoxicated conspecific) or demonstrator (intragastric infusion with EtOH), altered the reflexive odor-mediated responses to the drug. The 2 modes of exposure were equivalent in the magnitude of their effects. Human adolescents, however, are likely to experience the drug in a social setting as both an EtOH observer and demonstrator. That is, both interacting with an intoxicated peer and experiencing EtOH's postingestive consequences in conjunction with hematogenic olfaction. Therefore, we tested whether combined adolescent exposure as both an observer and demonstrator differed from either form of individual experience. Beginning on postnatal day (P) 29, naïve rats received EtOH or water exposures in a social interaction paradigm as either an observer, a demonstrator, or combined experience (where each animal in the interaction was, itself, an observer and demonstrator). Exposures occurred 4 times, once every 48 hours. On P37, the reflexive behavioral response to EtOH odor was tested, using whole-body plethysmography. The odor-mediated responses of adolescent EtOH observers, demonstrators, and combined exposure animals all significantly differed from controls. Compared to controls, however, the magnitude of the behavioral effect was greatest in the combined exposure animals. Moreover, combined exposure as both an EtOH observer and demonstrator significantly differed from either form of individual EtOH experience. EtOH's component chemosensory qualities are known to be central contributors to its acceptance and increases in the acceptability of EtOH's odor, resulting from a social transmission experience, are predictive of enhanced EtOH avidity in adolescence. Our findings demonstrate that combined exposure as an observer and demonstrator, within a socially relevant framework, may

Mechanisms of increased lifespan in hypoxia in the alfalfa leafcutting bee, Megachile rotundata

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Genetic variation accounts for a small amount of variation in lifespan, while environmental stressors are strong predictors. Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly understood. In the bee Megachile rotundata, lifespan doubles upo...

Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

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Yu, Suyeun [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Jang, Yeogil; Paik, Donggi [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Lee, Eunil, E-mail: eunil@korea.ac.kr [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Park, Joong-Jean, E-mail: parkjj@korea.ac.kr [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of)

2015-10-02

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

International Nuclear Information System (INIS)

Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong-Jean

2015-01-01

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

Integrated of Mobile Phone as Interactive Media in Extensive Listening

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Kodir Al-Baekani Abdul

2018-01-01

Full Text Available Learning English is the most difficult to learn by students, especially in learning of listening aspect. This research aims to investigate the process of listening activity in the classroom using mobile phone as interactive media in extensive listening and how the students’ responds of learning listening using mobile phone as an interactive media in extensive listening. Methodology of this research is descriptive qualitative. The subject of this research is Private Senior High School Muhammadiyah Karawang with 30 students as the sample of this research. The data analysis of this research uses the result of observation, interview, and documentation. Observation is used to know the learning process in classroom. Interview is used to know the students’ respond in learning process. While documentation is used to strengthen the data. The result of observation class shows that the process of teaching and learning listening as follows: (1 the teacher begins learning within 10 minutes, (2 the main activity using mobile phone in learning listening within 25 minutes, and (2 the final activity: the teacher gives a test to measure the students’ ability in listening comprehension. Meanwhile, the result of interview with the students shows that students mentioned convenience and interesting using mobile phone (37% and accessed in anywhere and anytime (30%, easiness (17%, authenticity (10%, and usefulness and fun (7% to use their mobile phone in English listening.

Med5(Nut1) and Med17(Srb4) Are Direct Targets of Mediator Histone H4 Tail Interactions

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Liu, Zhongle; Myers, Lawrence C.

2012-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct. PMID:22693636

Regional and longitudinal estimation of product lifespan distribution: a case study for automobiles and a simplified estimation method.

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Oguchi, Masahiro; Fuse, Masaaki

2015-02-03

Product lifespan estimates are important information for understanding progress toward sustainable consumption and estimating the stocks and end-of-life flows of products. Publications reported actual lifespan of products; however, quantitative data are still limited for many countries and years. This study presents regional and longitudinal estimation of lifespan distribution of consumer durables, taking passenger cars as an example, and proposes a simplified method for estimating product lifespan distribution. We estimated lifespan distribution parameters for 17 countries based on the age profile of in-use cars. Sensitivity analysis demonstrated that the shape parameter of the lifespan distribution can be replaced by a constant value for all the countries and years. This enabled a simplified estimation that does not require detailed data on the age profile. Applying the simplified method, we estimated the trend in average lifespans of passenger cars from 2000 to 2009 for 20 countries. Average lifespan differed greatly between countries (9-23 years) and was increasing in many countries. This suggests consumer behavior differs greatly among countries and has changed over time, even in developed countries. The results suggest that inappropriate assumptions of average lifespan may cause significant inaccuracy in estimating the stocks and end-of-life flows of products.

Effects of fluctuating temperature and food availability on reproduction and lifespan

OpenAIRE

Schwartz, Tonia S.; Pearson, Phillip; Dawson, John; Allison, David B.; Gohlke, Julia M.

2016-01-01

Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reprod...

Myc-dependent genome instability and lifespan in Drosophila.

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Christina Greer

Full Text Available The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs. In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

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Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

2008-12-01

Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

Interaction between mantle and crustal detachments: A nonlinear system controlling lithospheric extension

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Rosenbaum, Gideon; Regenauer-Lieb, Klaus; Weinberg, Roberto F.

2010-11-01

We use numerical modeling to investigate the development of crustal and mantle detachments during lithospheric extension. Our models simulate a wide range of extensional systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles as a response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation. Crustal detachments, here referred as low-angle normal decoupling horizons, are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW m-2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate heat flow (60-70 mW m-2). Results show a nonlinear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometimes unexpected switches in extension modes (e.g., from diffuse extensional deformation to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this nonlinearity to result from the interference of doming wavelengths in the presence of multiple necking instabilities. Disharmonic crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonic crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged history of extension prior to continental breakup.

Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

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Takeda, Toru; Tanabe, Hiroyuki

2016-03-18

The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Sex differences and stress across the lifespan

Science.gov (United States)

Bale, Tracy L; Epperson, C Neill

2015-01-01

Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan. PMID:26404716

Sex differences and stress across the lifespan.

Science.gov (United States)

Bale, Tracy L; Epperson, C Neill

2015-10-01

Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan.

Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

Directory of Open Access Journals (Sweden)

Peter C Poon

Full Text Available For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2 affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2 and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

DomPep--a general method for predicting modular domain-mediated protein-protein interactions.

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Lei Li

Full Text Available Protein-protein interactions (PPIs are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. Proteomic binding data were employed to determine a simple yet novel parameter Ligand-Binding Similarity which, in turn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental binding data and those without. Using the PDZ and SH2 domain families as test cases, we show that DomPep can predict PPIs with accuracies superior to existing methods. To evaluate DomPep as a discovery tool, we deployed DomPep to identify interactions mediated by three human PDZ domains. Subsequent in-solution binding assays validated the high accuracy of DomPep in predicting authentic PPIs at the proteome scale. Because DomPep makes use of only interaction data and the primary sequence of a domain, it can be readily expanded to include other types of modular domains.

Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

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Hans B Sieburg

2013-04-01

Full Text Available The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs. HSCs are functionally defined by their multi-potency and self-renewal capacity. Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans. However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic. Lifespan is here defined as the time a HSC gives rise to all mature blood cells. This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs. Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level. We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes. Thus, failure rates repeatedly increase during population-wide division events and are counteracted and decreased by repair processes. In the long-run, a crossover from anti-persistent to persistent behavior occurs. The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction. This suggests that the repair capacity of HSCs is self-limiting. Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics. Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations. A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.

Trait-mediated trophic interactions: is foraging theory keeping up?

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Steven F. Railsback; Bret C. Harvey

2013-01-01

Many ecologists believe that there is a lack of foraging theory that works in community contexts, for populations of unique individuals each making trade-offs between food and risk that are subject to feedbacks from behavior of others. Such theory is necessary to reproduce the trait-mediated trophic interactions now recognized as widespread and strong. Game theory can...

Negative Interpersonal Interactions and Dating Abuse Perpetration: The Mediating Role of Dispositional Forgivingness.

Science.gov (United States)

Garthe, Rachel C; Griffin, Brandon J; Worthington, Everett L; Goncy, Elizabeth A; Sullivan, Terri N; Coleman, Jennifer A; Davis, Don E; Kwakye-Nuako, Charlotte O; Mokushane, Thapelo; Makola, Solomon; Anakwah, Nkansah

2017-06-01

Theory and research suggest that an individual's negative interactions with his or her parents or romantic partner are associated with the perpetration of dating abuse. Research is beginning to explore the role of forgivingness within abusive romantic relationships, and these preliminary findings suggest that dispositional forgivingness might mediate the relations between negative interpersonal interactions and dating abuse. The current study assessed negative interactions with one's parents and one's romantic partner, the frequency of dating abuse perpetration, and dispositional forgivingness of others and oneself among a sample of emerging adults in college ( n = 421). Dispositional forgivingness of others was negatively associated with the perpetration of emotional/verbal dating abuse and threatening behaviors, and it mediated relations between negative interpersonal interactions and dating abuse perpetration. Our findings suggest that the tendency to forgive others may explain why some individuals who experience negative interpersonal interactions with parents or romantic partners do not escalate to perpetration of abuse within their romantic relationships. Implications for future research and application are discussed.

Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions

DEFF Research Database (Denmark)

Zhu, Xuefeng; Wirén, Marianna; Sinha, Indranil

2006-01-01

Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use chromatin immunoprecipitation (ChIP) and DNA microarrays...... to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts...... with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator...

Med5(Nut1 and Med17(Srb4 are direct targets of mediator histone H4 tail interactions.

Directory of Open Access Journals (Sweden)

Zhongle Liu

Full Text Available The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct.

Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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Takayuki Kondo

2014-08-01

Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response.

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Henrik Jakobsen

Full Text Available The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.

The alkaloid compound harmane increases the lifespan of Caenorhabditis elegans during bacterial infection, by modulating the nematode's innate immune response.

Science.gov (United States)

Jakobsen, Henrik; Bojer, Martin S; Marinus, Martin G; Xu, Tao; Struve, Carsten; Krogfelt, Karen A; Løbner-Olesen, Anders

2013-01-01

The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs.

Experiential Avoidance as a Mediator between Rejection Sensitivity and Social Interaction Anxiety

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Marcella L. Sintos

2017-12-01

Full Text Available Due to the overarching and related concepts involved in interpersonal sensitivity, this study aimed to look at the differences between, and relationships of, some of its concepts by explaining the mediating effect of experiential avoidance on rejection sensitivity and social interaction anxiety. One hundred fifty-nine undergraduates within the National Capital Region, aged 16 to 40 (M = 19.29, SD = 2.89, and comprising 89 females and 70 males participated in the study. Results show that both rejection sensitivity and experiential avoidance significantly affect social interaction anxiety. Also, a full mediation occurs when experiential avoidance serves as a mediator. This is explained through the occurrence of habitual coping, whereby the cognitive aspect of behavior (in this case, rejection sensitivity becomes dormant and unnecessary. Some variables which may have possibly accounted for the relationship between these concepts may be considered for future research to validate and better understand the findings of this study.

A dwarf mouse model with decreased GH/IGF-1 activity that does not experience life-span extension: potential impact of increased adiposity, leptin, and insulin with advancing age.

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Berryman, Darlene E; Lubbers, Ellen R; Magon, Vishakha; List, Edward O; Kopchick, John J

2014-02-01

Reduced growth hormone (GH) action is associated with extended longevity in many vertebrate species. GH receptor (GHR) null (GHR(-)(/-)) mice, which have a disruption in the GHR gene, are a well-studied example of mice that are insulin sensitive and long lived yet obese. However, unlike other mouse lines with reduced GH action, GH receptor antagonist (GHA) transgenic mice have reduced GH action yet exhibit a normal, not extended, life span. Understanding why GHA mice do not have extended life span though they share many physiological attributes with GHR(-)(/-) mice will help provide clues about how GH influences aging. For this study, we examined age- and sex-related changes in body composition, glucose homeostasis, circulating adipokines, and tissue weights in GHA mice and littermate controls. Compared with previous studies with GHR(-)(/-) mice, GHA mice had more significant increases in fat mass with advancing age. The increased obesity resulted in significant adipokine changes. Euglycemia was maintained in GHA mice; however, hyperinsulinemia developed in older male GHA mice. Overall, GHA mice experience a more substantial, generalized obesity accompanied by altered adipokine levels and glucose homeostasis than GHR(-)(/-) mice, which becomes more exaggerated with advancing age and which likely contributes to the lack of life-span extension in these mice.

Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

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Adam J. Dobson

2017-01-01

Full Text Available Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

The K Domain Mediates Homologous and Heterologous Interactions Between FLC and SVP Proteins of Brassica juncea

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Ma Guanpeng

2015-07-01

Full Text Available The transcription factors FLOWERING LOCUS C (FLC and SHORT VEGETATIVE PHASE (SVP can interact to form homologous and heterologous protein complexes that regulate flowering time in Brassica juncea Coss. (Mustard.Previous studies showed that protein interactions were mediated by the K domain, which contains the subdomains K1, K2 and K3. However, it remains unknown how the subdomains mediate the interactions between FLC and SVP. In the present study, we constructed several mutants of subdomains K1–K3 and investigated the mechanisms involved in the heterologous interaction of BjFLC/BjSVP and in the homologous interaction of BjFLC/BjFLC or BjSVP/BjSVP. Yeast two-hybrid and β-Galactosidase activity assays showed that the 19 amino acids of the K1 subdomain in BjSVP and the 17 amino acids of the K1 subdomain in BjFLC were functional subdomains that interact with each other to mediate hetero-dimerization. The heterologous interaction was enhanced by the K2 subdomain of BjSVP protein, but weakened by its interhelical domain L2. The heterologous interaction was also enhanced by the K2 subdomain of BjFLC protein, but weakened by its K3 subdomain. The homologous interaction of BjSVP was mediated by the full K-domain. However, the homologous interaction of BjFLC was regulated only by its K1 and weakened by its K2 and K3 subdomains. The results provided new insights into the interactions between FLC and SVP, which will be valuable for further studies on the molecular regulation mechanisms of the regulation of flowering time in B. juncea and other Brassicaceae.

Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.

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Dunn, Cory D

2011-10-01

Mitochondrial DNA (mtDNA) mutations escalate with increasing age in higher organisms. However, it has so far been difficult to experimentally determine whether mtDNA mutation merely correlates with age or directly limits lifespan. A recent study shows that budding yeast can also lose functional mtDNA late in life. Interestingly, independent studies of replicative lifespan (RLS) and of mtDNA-deficient cells show that the same mutations can increase both RLS and the division rate of yeast lacking the mitochondrial genome. These exciting, parallel findings imply a potential causal relationship between mtDNA mutation and replicative senescence. Furthermore, these results suggest more efficient methods for discovering genes that determine lifespan. Copyright © 2011 WILEY Periodicals, Inc.

Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in yeast

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Srinivas eAyyadevara

2014-08-01

Full Text Available A quantitative trait locus (QTL in the nematode C. elegans, lsq4, was recently implicated by mapping longevity genes. QTLs for lifespan and 3 stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing expression of sperm-specific genes, suggesting effects on spermatogenesis. Quantitation of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin reduced its transcripts 4-fold, to a level similar to the longer-lived strain, and extended lifespan 25–26% whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency, traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased leaky expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as nondisjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741 by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, reflecting antagonistic pleiotropy and/or balancing selection.

Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix.

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Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève

2002-03-05

Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPB(KKK-), a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of alpha4beta1 and alpha4beta7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB-GAG interaction in the chemokine-like activity of this protein.

Explanation in causal inference methods for mediation and interaction

CERN Document Server

VanderWeele, Tyler

2015-01-01

A comprehensive examination of methods for mediation and interaction, VanderWeele's book is the first to approach this topic from the perspective of causal inference. Numerous software tools are provided, and the text is both accessible and easy to read, with examples drawn from diverse fields. The result is an essential reference for anyone conducting empirical research in the biomedical or social sciences.

Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

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Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

2009-06-19

NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

Protein-Protein Interactions Prediction Based on Iterative Clique Extension with Gene Ontology Filtering

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Lei Yang

2014-01-01

Full Text Available Cliques (maximal complete subnets in protein-protein interaction (PPI network are an important resource used to analyze protein complexes and functional modules. Clique-based methods of predicting PPI complement the data defection from biological experiments. However, clique-based predicting methods only depend on the topology of network. The false-positive and false-negative interactions in a network usually interfere with prediction. Therefore, we propose a method combining clique-based method of prediction and gene ontology (GO annotations to overcome the shortcoming and improve the accuracy of predictions. According to different GO correcting rules, we generate two predicted interaction sets which guarantee the quality and quantity of predicted protein interactions. The proposed method is applied to the PPI network from the Database of Interacting Proteins (DIP and most of the predicted interactions are verified by another biological database, BioGRID. The predicted protein interactions are appended to the original protein network, which leads to clique extension and shows the significance of biological meaning.

Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

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Roshina, Natalia V; Symonenko, Alexander V; Krementsova, Anna V; Trostnikov, Mikhail V; Pasyukova, Elena G

2014-12-01

Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

Lifespan and reproduction of isoclonal individual E.coli in different environments

DEFF Research Database (Denmark)

Jouvet, Lionel; Steiner, Ulrich

Lifespan and reproduction are key fitness components, both of which are influences by genetics and the environment. Tracking large numbers of genotypically known individuals throughout their lives in known environments has been challenging. Here we show for isogenic individual E. coli bacteria...... under controlled environments how demographic parameters and distributions in reproduction and survival change across environments. We achieve this by using a microfluidic device that traps thousands of individual E. coli cells and tracks their division (reproduction) over their lifespan. Our results...

Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

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Fiske, Amy; O'Riley, Alisa A

2016-01-01

Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

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Laurent Kappeler

2008-10-01

Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

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Schroeder, Elizabeth A; Shadel, Gerald S

2014-01-01

Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Investigations of interactions mediated by neutral currents

International Nuclear Information System (INIS)

Witek, M.

2007-03-01

The report is devoted to four-fermion interactions mediated by the neutral currents. The results from the second phase of LEP are presented, when the production of two massive bosons was possible with the increased energy of the e + e - collisions. It enabled for a direct test of nonabelian structure of the electroweak theory. The results concern the four-fermion production of the pairs of the ZZ bosons, single Z and Zγ * production as well as search for anomalous gauge bosons couplings. The large part of the report is devoted to experimental techniques, physics analyses and discussion of results. (author)

The Alkaloid Compound Harmane Increases the Lifespan of Caenorhabditis elegans during Bacterial Infection, by Modulating the Nematode’s Innate Immune Response

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Marinus, Martin G.; Xu, Tao; Struve, Carsten; Krogfelt, Karen A.; Løbner-Olesen, Anders

2013-01-01

The nematode Caenorhabditis elegans has in recent years been proven to be a powerful in vivo model for testing antimicrobial compounds. We report here that the alkaloid compound Harmane (2-methyl-β-carboline) increases the lifespan of nematodes infected with a human pathogen, the Shiga toxin-producing Escherichia coli O157:H7 strain EDL933 and several other bacterial pathogens. This was shown to be unrelated to the weak antibiotic effect of Harmane. Using GFP-expressing E. coli EDL933, we showed that Harmane does not lower the colonization burden in the nematodes. We also found that the expression of the putative immune effector gene F35E12.5 was up-regulated in response to Harmane treatment. This indicates that Harmane stimulates the innate immune response of the nematode; thereby increasing its lifespan during bacterial infection. Expression of F35E12.5 is predominantly regulated through the p38 MAPK pathway; however, intriguingly the lifespan extension resulting from Harmane was higher in p38 MAPK-deficient nematodes. This indicates that Harmane has a complex effect on the innate immune system of C. elegans. Harmane could therefore be a useful tool in the further research into C. elegans immunity. Since the innate immunity of C. elegans has a high degree of evolutionary conservation, drugs such as Harmane could also be possible alternatives to classic antibiotics. The C. elegans model could prove to be useful for selection and development of such drugs. PMID:23544153

Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

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Störmer, Viola; Eppinger, Ben; Li, Shu-Chen

2014-06-01

Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

Lymphocyte mediators of delayed hypersensitivity; the early phase cells

Energy Technology Data Exchange (ETDEWEB)

Lefford, M J; McGregor, D D [Trudeau Inst., Saranac Lake, N.Y. (USA)

1978-04-01

Inbred rats were immunized with living Bacillus Calmette-Guerin (BCG) and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen, and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated /sup 3/HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

Hedonic Benefits of Close and Distant Interaction Partners: The Mediating Roles of Social Approval and Authenticity.

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Venaglia, Rachel B; Lemay, Edward P

2017-09-01

The current research utilized ecological momentary assessment methodology to examine affective responses to interacting with close versus distant interaction partners during naturally occurring social interactions, and to test predictions regarding the mediating roles of perceived social approval and authenticity. Analysis of 4,602 social interactions reported by 176 participants suggested that, relative to interactions with distant partners, interactions with close partners were characterized by more positive affect. This effect was mediated by perceived social approval and authenticity. These findings suggest that social interactions with close others confer greater hedonic benefits relative to interactions with distant partners due to greater confidence in social approval and feelings of authenticity. Exploratory analyses suggested that interactions with close partners featured warmer and less shy behavior, and that participants who placed more importance on close relationships (as measured by high relational-interdependent self-construal) experienced more approval and authenticity in their interactions, particularly with distant partners.

Generalized causal mediation and path analysis: Extensions and practical considerations.

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Albert, Jeffrey M; Cho, Jang Ik; Liu, Yiying; Nelson, Suchitra

2018-01-01

Causal mediation analysis seeks to decompose the effect of a treatment or exposure among multiple possible paths and provide casually interpretable path-specific effect estimates. Recent advances have extended causal mediation analysis to situations with a sequence of mediators or multiple contemporaneous mediators. However, available methods still have limitations, and computational and other challenges remain. The present paper provides an extended causal mediation and path analysis methodology. The new method, implemented in the new R package, gmediation (described in a companion paper), accommodates both a sequence (two stages) of mediators and multiple mediators at each stage, and allows for multiple types of outcomes following generalized linear models. The methodology can also handle unsaturated models and clustered data. Addressing other practical issues, we provide new guidelines for the choice of a decomposition, and for the choice of a reference group multiplier for the reduction of Monte Carlo error in mediation formula computations. The new method is applied to data from a cohort study to illuminate the contribution of alternative biological and behavioral paths in the effect of socioeconomic status on dental caries in adolescence.

Mechanisms and ecological implications of plant-mediated interactions between belowground and aboveground insect herbivores

NARCIS (Netherlands)

Papadopoulou, G.V.; Dam, N.M. van

2017-01-01

Plant-mediated interactions between belowground (BG) and aboveground (AG) herbivores have received increasing interest recently. However, the molecular mechanisms underlying ecological consequences of BG–AG interactions are not fully clear yet. Herbivore-induced plant defenses are complex and

Interactive uncertainty reduction strategies and verbal affection in computer-mediated communication

NARCIS (Netherlands)

Antheunis, M.L.; Schouten, A.P.; Valkenburg, P.M.; Peter, J.

2012-01-01

The goal of this study was to investigate the language-based strategies that computer-mediated communication (CMC) users employ to reduce uncertainty in the absence of nonverbal cues. Specifically, this study investigated the prevalence of three interactive uncertainty reduction strategies (i.e.,

The First International Mini-Symposium on Methionine Restriction and Lifespan

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Gene eAbles

2014-05-01

Full Text Available It has been 20 years since the Orentreich Foundation for the Advancement of Science, under the leadership Dr. Norman Orentreich, first reported that low methionine (Met ingestion by rats extends lifespan [1]. Since then, several studies have replicated the effects of dietary methionine restriction (MR in delaying age-related diseases [2–5]. We report the abstracts from the First International Mini-Symposium on Methionine Restriction and Lifespan held in Tarrytown, NY last September 2013. The goals were 1 to gather researchers with an interest in methionine restriction and lifespan, 2 to exchange knowledge, 3 to generate ideas for future investigations, and 4 to strengthen relationships within this community. The presentations highlighted the importance of research on cysteine, growth hormone (GH, and ATF4 in the paradigm of aging. In addition, the effects of dietary restriction or MR in the kidneys, liver, bones and the adipose tissue were discussed. The symposium also emphasized the value of other species, e.g. the naked mole rat, Brandt’s bat and drosophila in aging research. Overall, the symposium consolidated scientists with similar research interests and provided opportunities to conduct future collaborative studies.

TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants.

Science.gov (United States)

Khan, Maruf H; Ligon, Melissa; Hussey, Lauren R; Hufnal, Bryce; Farber, Robert; Munkácsy, Erin; Rodriguez, Amanda; Dillow, Andy; Kahlig, Erynn; Rea, Shane L

2013-10-01

While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.

The mediator complex in genomic and non-genomic signaling in cancer.

Science.gov (United States)

Weber, Hannah; Garabedian, Michael J

2018-05-01

Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

How sedimentation affects rift segment interaction during oblique extension: a 4D analogue modelling study

Science.gov (United States)

Zwaan, Frank; Schreurs, Guido; Adam, Jürgen

2017-04-01

During the early stages of rifting, rift segments may form along non-continuous and/or offset pre-existing weaknesses. It is important to understand how these initial rift segments interact and connect to form a continuous rift system. Previous modelling of rift interaction structures has shown the dominant influence of oblique extension, promoting rift segment linkage (e.g. Zwaan et al., 2016) and eventual continent break-up (Brune et al., 2012). However, these studies did not incorporate sedimentation, which can have important implications for rift evolution (e.g. Bialas and Buck, 2009). Here we present a series of analogue model experiments investigating the influence of sedimentation on rift interaction structures under oblique extension conditions. Our set-up involves a base of compressed foam and plexiglass that forces distributed extension in the overlying analogue materials when the model sidewalls move apart. A sand layer simulates the brittle upper crust and a viscous sand/silicone mixture the ductile lower crust. One of the underlying base plates can move laterally allowing oblique extension. Right-stepping offset and disconnected lines of silicone (seeds) on top of the basal viscous serve as inherited structures since the strong sand cover is locally thinner. We apply syn-rift sediments by filling in the developing rift and transfer zone basins with sand at fixed time steps. Models are run either with sedimentation or without to allow comparison. The first results suggest that the gross structures are similar with or without sedimentation. As seen by Zwaan et al. (2016), dextral oblique extension promotes rift linkage because rift propagation aligns itself perpendicular to the extension direction. This causes the rift segments to grow towards each other and to establish a continuous rift structure. However, the structures within the rift segments show quite different behaviour when sedimentation is applied. The extra sediment loading in the rift basin

Macronutrients mediate the functional relationship between Drosophila and Wolbachia

Science.gov (United States)

Ponton, Fleur; Wilson, Kenneth; Holmes, Andrew; Raubenheimer, David; Robinson, Katie L.; Simpson, Stephen J.

2015-01-01

Wolbachia are maternally inherited bacterial endosymbionts that naturally infect a diverse array of arthropods. They are primarily known for their manipulation of host reproductive biology, and recently, infections with Wolbachia have been proposed as a new strategy for controlling insect vectors and subsequent human-transmissible diseases. Yet, Wolbachia abundance has been shown to vary greatly between individuals and the magnitude of the effects of infection on host life-history traits and protection against infection is correlated to within-host Wolbachia abundance. It is therefore essential to better understand the factors that modulate Wolbachia abundance and effects on host fitness. Nutrition is known to be one of the most important mediators of host–symbiont interactions. Here, we used nutritional geometry to quantify the role of macronutrients on insect–Wolbachia relationships in Drosophila melanogaster. Our results show fundamental interactions between diet composition, host diet selection, Wolbachia abundance and effects on host lifespan and fecundity. The results and methods described here open a new avenue in the study of insect–Wolbachia relationships and are of general interest to numerous research disciplines, ranging from nutrition and life-history theory to public health. PMID:25520356

Nicotinamide extends replicative lifespan of human cells.

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Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

2006-10-01

We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

DEFF Research Database (Denmark)

Blažek, Radim; Polačik, Matej; Kačer, Petr

2017-01-01

intrinsic lifespans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intra-specific divergence in lifespan and ageing was not associated......Lifespan and ageing are substantially modified by natural selection. Across species, higher extrinsic (environmentally-related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid ageing. However, among populations within species, high extrinsic mortality can lead...... to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

Autonomic nervous system mediated effects of food intake. Interaction between gastrointestinal and cardiovascular systems.

NARCIS (Netherlands)

van Orshoven, N.P.

2008-01-01

The studies presented in this thesis focused on the autonomic nervous system mediated interactions between the gastrointestinal and cardiovascular systems in response to food intake and on potential consequences of failure of these interactions. The effects of food intake on cardiovascular

Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

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Leibrock, Christina B; Voelkl, Jakob; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Kuro-O, Makoto; Lang, Florian

2016-01-01

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. Copyright © 2016 the American Physiological Society.

p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6

Energy Technology Data Exchange (ETDEWEB)

Seibold, Kristina; Ehrenschwender, Martin, E-mail: martin.ehrenschwender@ukr.de

2015-08-14

CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. - Highlights: • CD40 activation triggers interaction of the adapter protein TRAF6 with p62. • TRAF6-p62 interaction regulates CD40-mediated NFκB signaling in macrophages. • Defective TRAF6-p62 interaction reduces CD40-mediated NFκB activation in macrophages.

(2012 30 Windsor Y B Access Just 103 A VIEW FROM WITHIN: RECONCEPTUALIZING MEDIATOR INTERACTIONS

Directory of Open Access Journals (Sweden)

Debbie De Girolamo

2012-10-01

Full Text Available This paper explores mediator interactions from within the mediation process. It is difficult to obtain access to mediations due to issues of confidentiality and litigation privilege, thus restricting direct empirical research. During a yearlong ethnographic study during which the author was a participant-observer of a number of commercial mediations, the nature of mediations was explored from an independent observational perspective – separate from the process yet within the process. In this study, real life patterns of interactions are examined through case study analysis. It offers a reconceptualization of the nature of mediator interventions, one that moves beyond the accepted understanding of third party intervention. It suggests that the mediator has a fugitive identity in mediation, reflecting a traditional neutral third party intervener role, a party role and an adviser role. Dans le présent document, l‟auteure explore les interactions des médiateurs dans le cadre du processus de médiation. Il est difficile d‟obtenir l‟accès aux séances de médiation en raison du secret professionnel et du privilège relatif au litige, et cette difficulté limite la recherche empirique directe. Au cours d‟une étude ethnographique qui s‟est déroulée sur une année et à laquelle l‟auteure a participé comme observatrice d‟un certain nombre de médiations commerciales, la nature des médiations a été explorée d‟un point de vue observationnel indépendant – distinct du processus bien qu‟au sein du processus. Dans la présente étude, des situations réelles d‟interaction sont examinées au moyen de l‟analyse d‟études de cas. L‟auteure offre une reconceptualisation de la nature des interventions du médiateur, qui va au-delà de ce qui est reconnu comme l‟intervention d‟une tierce partie. Le médiateur aurait une identité fugace dans le processus de médiation, cette identité s‟expliquant par un r

Focus on opportunities as a mediator of the relationship between business owners' age and venture growth

NARCIS (Netherlands)

Gielnik, Michael M.; Zacher, Hannes; Frese, Michael

Combining upper echelons and lifespan theories, we investigated the mediating effect of focus on opportunities on the negative relationship between business owners' age and venture growth. We also expected that mental health moderates the negative relationship between business owners' age and focus

Evidence for water-mediated mechanisms in coral–algal interactions

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Jorissen, Hendrikje; Skinner, Christina; Osinga, Ronald; de Beer, Dirk

2016-01-01

Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at the coral–algal interface vary with algal competitors and competitiveness. Using field observations and microsensor measurements in a flow chamber, we show that coral (massive Porites) interfaces with thick turf algae, macroalgae, and cyanobacteria, which are successful competitors against coral in the field, are characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces with crustose coralline algae, conspecifics, and thin turf algae, which are poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL thickness and hypoxia at the interface with turf decreased with increasing flow speed, but not when thick turf was upstream. Our results support the importance of water-mediated transport mechanisms in coral–algal interactions. Shifts towards algal dominance, particularly dense assemblages, may lead to thicker DBLs, higher hypoxia, and higher concentrations of harmful metabolites and pathogens along coral borders, which in turn may facilitate algal overgrowth of live corals. These effects may be mediated by flow speed and orientation. PMID:27512146

Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics.

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Walco, Gary A; Krane, Elliot J; Schmader, Kenneth E; Weiner, Debra K

2016-09-01

An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations. A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked. Copyright © 2016. Published by Elsevier Inc.

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

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Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

Science.gov (United States)

Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

2013-01-01

The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

Trade-off between reproduction and lifespan of the rotifer Brachionus plicatilis under different food conditions.

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Sun, Yunfei; Hou, Xinying; Xue, Xiaofeng; Zhang, Lu; Zhu, Xuexia; Huang, Yuan; Chen, Yafen; Yang, Zhou

2017-11-13

Phaeocystis globosa, one of the most typical red tide-forming species, is usually mixed in the food composition of rotifers. To explore how rotifers respond by adjusting life history strategy when feeding on different quality foods, we exposed the rotifer Brachionus plicatilis to cultures with 100% Chlorella, a mixture of 50% P. globosa and 50% Chlorella, or 100% P. globosa. Results showed that rotifers exposed to 100% Chlorella or to mixed diets produced more total offspring and had higher age-specific fecundity than those exposed to 100% P. globosa. Food combination significantly affected the net reproduction rates of rotifers. By contrast, rotifers that fed on 100% P. globosa or on mixed diets had a longer lifespan than those fed on 100% Chlorella. The overall performances (combining reproduction and lifespan together) of rotifers cultured in 100% Chlorella or mixed diets were significantly higher than those cultured in 100% P. globosa. In general, Chlorella favors rotifers reproduction at the cost of shorter lifespan, whereas P. globosa tends to extend the lifespan of rotifers with lower fecundity, indicating that trade-off exists between reproduction and lifespan under different food conditions. The present study also suggests that rotifers may have the potential to control harmful P. globosa.

Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

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Apfeld, Javier; Fontana, Walter

2017-12-23

It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

Phylogenetic relationship and Fourier-transform infrared spectroscopy-derived lipid determinants of lifespan parameters in the Saccharomyces cerevisiae yeast.

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Molon, Mateusz; Zebrowski, Jacek

2017-06-01

Yeast ageing has been gaining much attention in gerontology research, yet the process itself is still not entirely clear. One of the constraints related to the use of the Saccharomyces cerevisiae yeast in studies is the ambiguity of the results concerning ageing determinants for different genetic backgrounds. In this paper, we compare reproductive potentials and lifespans of seven widely used haploid laboratory strains differing in daughter cells production capabilities and highlight the importance of choosing an appropriate genotype for the studies on ageing. Moreover, we show here links between post-reproductive lifespan and lipid metabolism, as well as between reproductive potential, reproductive lifespan and phylogenetic relationship. Using FTIR spectroscopy that generated a biochemical fingerprint of cells, coupled with chemometrics, we found that the band of carbonyl (C = O) stretching vibration discriminates the strains according to post-reproductive lifespan. The results indicated that prolonged post-reproductive lifespan was associated with relatively lower amount of fatty acids esterified to phospholipids compared to a free acid pool, thus implying phospholipid metabolism for the post-reproductive lifespan of yeast. In addition, phylogenetic analysis showed a correlation between nucleotide similarity and the reproductive potential or reproductive lifespan, but not to the longevity expressed in time units. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evolution of product lifespan and implications for environmental assessment and management: a case study of personal computers in higher education.

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Babbitt, Callie W; Kahhat, Ramzy; Williams, Eric; Babbitt, Gregory A

2009-07-01

Product lifespan is a fundamental variable in understanding the environmental impacts associated with the life cycle of products. Existing life cycle and materials flow studies of products, almost without exception, consider lifespan to be constant over time. To determine the validity of this assumption, this study provides an empirical documentation of the long-term evolution of personal computer lifespan, using a major U.S. university as a case study. Results indicate that over the period 1985-2000, computer lifespan (purchase to "disposal") decreased steadily from a mean of 10.7 years in 1985 to 5.5 years in 2000. The distribution of lifespan also evolved, becoming narrower over time. Overall, however, lifespan distribution was broader than normally considered in life cycle assessments or materials flow forecasts of electronic waste management for policy. We argue that these results suggest that at least for computers, the assumption of constant lifespan is problematic and that it is important to work toward understanding the dynamics of use patterns. We modify an age-structured model of population dynamics from biology as a modeling approach to describe product life cycles. Lastly, the purchase share and generation of obsolete computers from the higher education sector is estimated using different scenarios for the dynamics of product lifespan.

Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Yoko Honda

Full Text Available One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5. pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS. pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA, which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical

How long do centenarians survive? Life expectancy and maximum lifespan.

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Modig, K; Andersson, T; Vaupel, J; Rau, R; Ahlbom, A

2017-08-01

The purpose of this study was to explore the pattern of mortality above the age of 100 years. In particular, we aimed to examine whether Scandinavian data support the theory that mortality reaches a plateau at particularly old ages. Whether the maximum length of life increases with time was also investigated. The analyses were based on individual level data on all Swedish and Danish centenarians born from 1870 to 1901; in total 3006 men and 10 963 women were included. Birth cohort-specific probabilities of dying were calculated. Exact ages were used for calculations of maximum length of life. Whether maximum age changed over time was analysed taking into account increases in cohort size. The results confirm that there has not been any improvement in mortality amongst centenarians in the past 30 years and that the current rise in life expectancy is driven by reductions in mortality below the age of 100 years. The death risks seem to reach a plateau of around 50% at the age 103 years for men and 107 years for women. Despite the rising life expectancy, the maximum age does not appear to increase, in particular after accounting for the increasing number of individuals of advanced age. Mortality amongst centenarians is not changing despite improvements at younger ages. An extension of the maximum lifespan and a sizeable extension of life expectancy both require reductions in mortality above the age of 100 years. © 2017 The Association for the Publication of the Journal of Internal Medicine.

The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

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Mittal, Nitish; Guimaraes, Joao C; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D; Aeschimann, Florian; Leidel, Sebastian A; Spang, Anne; Zavolan, Mihaela

2017-09-06

In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

Age-Related Changes in Binaural Interaction at Brainstem Level

NARCIS (Netherlands)

Yper, L.N. Van; Vermeire, K.; Vel, E.F. De; Beynon, A.J.; Dhooge, I.J.

2016-01-01

OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The

The Effect of Post-Reproductive Lifespan on the Fixation Probability of Beneficial Mutations

DEFF Research Database (Denmark)

Giaimo, Stefano; Baudisch, Annette

2015-01-01

Post-reproductive lifespan is a common trait among mammals and is usually considered to be neutral; i.e. with no influence on population dynamics. Here, we explore the role of post-reproductive lifespan in the fixation probability of beneficial genetic variation. We compare two separate, stationary...... populations living in a constant environment that are equivalent except for the average time their respective members spend in the post-reproductive stage of life. Using a recently derived approximation, we show that fixation of a beneficial mutation is more likely in the population with greater post......-reproductive longevity. This finding is surprising, as the population with more prolonged post-reproductive lifespan has smaller effective size and the classic population-genetic model would suggest that decreasing effective size reduces fixation chances of beneficial mutations. Yet, as we explain, in the age...

DIBS: a repository of disordered binding sites mediating interactions with ordered proteins.

Science.gov (United States)

Schad, Eva; Fichó, Erzsébet; Pancsa, Rita; Simon, István; Dosztányi, Zsuzsanna; Mészáros, Bálint

2018-02-01

Intrinsically Disordered Proteins (IDPs) mediate crucial protein-protein interactions, most notably in signaling and regulation. As their importance is increasingly recognized, the detailed analyses of specific IDP interactions opened up new opportunities for therapeutic targeting. Yet, large scale information about IDP-mediated interactions in structural and functional details are lacking, hindering the understanding of the mechanisms underlying this distinct binding mode. Here, we present DIBS, the first comprehensive, curated collection of complexes between IDPs and ordered proteins. DIBS not only describes by far the highest number of cases, it also provides the dissociation constants of their interactions, as well as the description of potential post-translational modifications modulating the binding strength and linear motifs involved in the binding. Together with the wide range of structural and functional annotations, DIBS will provide the cornerstone for structural and functional studies of IDP complexes. DIBS is freely accessible at http://dibs.enzim.ttk.mta.hu/. The DIBS application is hosted by Apache web server and was implemented in PHP. To enrich querying features and to enhance backend performance a MySQL database was also created. dosztanyi@caesar.elte.hu or bmeszaros@caesar.elte.hu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

Male lifespan and the secondary sex ratio.

Science.gov (United States)

Catalano, Ralph; Bruckner, Tim

2006-01-01

Literature speculating on the fetal origins of later life morbidity often invokes the "damaged cohort" theory, i.e., that maternal responses to exogenous shocks induce "stress reactivity" in fetuses and thereby shorten the lifespan of males in utero during stressful times. A rival, or "culled cohort," theory posits that exogenous shocks to gravid females induce spontaneous abortions of frail male fetuses, leaving relatively hardy survivors who enjoy, on average, lifespans longer than males in less stressed birth cohorts. A recent test based on archival data from Sweden supported the culled cohort theory. Several characteristics of the Swedish data, however, raise questions regarding the external validity of the findings. We repeat the test with data from Denmark, Iceland, and England and Wales. We use time-series methods that control for trends, seasonal cycles, and other forms of autocorrelation that could confound the test. None of the results supports the "damaged cohort" theory. Consistent with the Swedish findings and with evolutionary theory, we find support in Iceland and England and Wales for the "culled cohort" theory. We discuss the implications of our findings for basic research as well as for public health.

Separating monocular and binocular neural mechanisms mediating chromatic contextual interactions.

Science.gov (United States)

D'Antona, Anthony D; Christiansen, Jens H; Shevell, Steven K

2014-04-17

When seen in isolation, a light that varies in chromaticity over time is perceived to oscillate in color. Perception of that same time-varying light may be altered by a surrounding light that is also temporally varying in chromaticity. The neural mechanisms that mediate these contextual interactions are the focus of this article. Observers viewed a central test stimulus that varied in chromaticity over time within a larger surround that also varied in chromaticity at the same temporal frequency. Center and surround were presented either to the same eye (monocular condition) or to opposite eyes (dichoptic condition) at the same frequency (3.125, 6.25, or 9.375 Hz). Relative phase between center and surround modulation was varied. In both the monocular and dichoptic conditions, the perceived modulation depth of the central light depended on the relative phase of the surround. A simple model implementing a linear combination of center and surround modulation fit the measurements well. At the lowest temporal frequency (3.125 Hz), the surround's influence was virtually identical for monocular and dichoptic conditions, suggesting that at this frequency, the surround's influence is mediated primarily by a binocular neural mechanism. At higher frequencies, the surround's influence was greater for the monocular condition than for the dichoptic condition, and this difference increased with temporal frequency. Our findings show that two separate neural mechanisms mediate chromatic contextual interactions: one binocular and dominant at lower temporal frequencies and the other monocular and dominant at higher frequencies (6-10 Hz).

Cortical Changes Across the Autism Lifespan.

Science.gov (United States)

Osipowicz, Karol; Bosenbark, Danielle D; Patrick, Kristina E

2015-08-01

Although it is widely accepted that autism spectrum disorder (ASD) involves neuroanatomical abnormalities and atypical neurodevelopmental patterns, there is little consensus regarding the precise pattern of neuroanatomical differences or how these differences relate to autism symptomology. Furthermore, there is limited research related to neuroanatomical correlates of autism symptomology in individuals with ASD and the studies that do exist primarily include small samples. This study was the first to investigate gray matter (GM) changes throughout the ASD lifespan, using voxel-based morphometry to determine whether significant differences exist in the GM volumes of a large sample of individuals with ASD compared to age- and IQ-matched typical controls. We examined GM volume across the lifespan in 531 individuals diagnosed with ASD and 571 neurotypical controls, aged 7-64. We compared groups and correlated GM with age and autism severity in the ASD group. Findings suggest bilateral decreased GM volume for individuals with ASD in regions extending from the thalamus to the cerebellum, anterior medial temporal lobes, and orbitofrontal regions. Higher autism severity was associated with decreased GM volumes in prefrontal cortex, inferior parietal and temporal regions, and temporal poles. Similar relationships were found between GM volume and age. ASD diagnosis and severity were not associated with increased GM volumes in any region. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Interaction between mantle and crustal detachments: a non-linear system controlling lithospheric extension

Science.gov (United States)

Rosenbaum, G.; Regenauer-Lieb, K.; Weinberg, R. F.

2009-12-01

We use numerical modelling to investigate the development of crustal and mantle detachment faults during lithospheric extension. Our models simulate a wide range of rift systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles, which grow in response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation at different levels of the lithosphere. Crustal detachment faults are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW/m2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate (60-70 mW/m2) heat flow. Results show a non-linear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometime unexpected switches in extension modes (e.g. from diffuse rifting to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this non-linearity to result from the interference of doming wavelengths. Disharmony of crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonious crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged rifting history prior to continental breakup.

Effect of gamma irradiation on lifespan and offspring physiology of male drosophila melanogaster

International Nuclear Information System (INIS)

Hou Jiangyu; Gu Wei; Jiang Fangping; Han Hetong

2010-01-01

This study aimed to investigate the effects of γ-rays irradiation on adult longevity and physiological changes in F 1 generation.Male Drosophila melanogaster at 1 ∼ 2 days old were irradiated by γ-rays with doses of 5, 10, 15 and 30 Gy. In all experimental groups, mean lifespan, maximum lifespan and 90% of lethaldeath irradiated flies were reduced(at P 1 generation of irradiated group, body weight increased, but the capacity of physiological stress declined. (authors)

Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

Science.gov (United States)

Razquin Navas, Patricia; Thedieck, Kathrin

2017-07-15

Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Telomerase levels control the lifespan of human T lymphocytes

NARCIS (Netherlands)

Roth, Alexander; Yssel, Hans; Pene, Jerome; Chavez, Elizabeth A.; Schertzer, Mike; Lansdorp, Peter M.; Spits, Hergen; Luiten, Rosalie M.

2003-01-01

The loss of telomeric DNA with each cell division contributes to the limited replicative lifespan of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have previously shown that immortalization of human

Materialism across the lifespan : An age-period-cohort analysis

NARCIS (Netherlands)

Jaspers, Esther; Pieters, Rik

This research examined the development of materialism across the lifespan. Two initial studies revealed that: 1) lay beliefs were that materialism declines with age; and 2) previous research findings also implied a modest, negative relationship between age and materialism. Yet, previous research has

Axino dark matter in mirage mediation

International Nuclear Information System (INIS)

Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

2009-01-01

The mirage mediation of supersymmetry breaking is a phenomenologically quite interesting possibility, however, it suffers from two major problems: the moduli-induced gravitino problem and the μ-Bμ problem. In this paper, we propose that the axionic extension of mirage mediation, axionic mirage mediation can solve both problems simultaneously. We address the cosmological consequences of the scenario extensively.

Estimation of adult and neonatal RBC lifespans in anemic neonates using RBCs labeled at several discrete biotin densities.

Science.gov (United States)

Kuruvilla, Denison J; Widness, John A; Nalbant, Demet; Schmidt, Robert L; Mock, Donald M; An, Guohua; Veng-Pedersen, Peter

2017-06-01

Prior conclusions that autologous neonatal red blood cells (RBC) have substantially shorter lifespans than allogeneic adult RBCs were not based on direct comparison of autologous neonatal vs. allogeneic adult RBCs performed concurrently in the same infant. Biotin labeling of autologous neonatal RBCs and allogeneic adult donor RBCs permits concurrent direct comparison of autologous vs. allogeneic RBC lifespan. RBCs from 15 allogeneic adult donors and from 15 very-low-birth-weight (VLBW) neonates were labeled at separate biotin densities and transfused simultaneously into the 15 neonates. Two mathematical models that account for the RBC differences were employed to estimate lifespans for the two RBC populations. Mean ± SD lifespan for adult allogeneic RBC was 70.1 ± 19.1 d, which is substantially shorter than the 120 d lifespan of both autologous and adult allogeneic RBC in healthy adults. Mean ± SD lifespan for neonatal RBC was 54.2 ± 11.3 d, which is only about 30% shorter than that of the adult allogeneic RBCs. This study provides evidence that extrinsic environmental factors primarily determine RBC survival (e.g., small bore of the capillaries of neonates, rate of oxygenation/deoxygenation cycles) rather than factors intrinsic to RBC.

Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction.

Science.gov (United States)

Nishikawa, Joy L; Boeszoermenyi, Andras; Vale-Silva, Luis A; Torelli, Riccardo; Posteraro, Brunella; Sohn, Yoo-Jin; Ji, Fei; Gelev, Vladimir; Sanglard, Dominique; Sanguinetti, Maurizio; Sadreyev, Ruslan I; Mukherjee, Goutam; Bhyravabhotla, Jayaram; Buhrlage, Sara J; Gray, Nathanael S; Wagner, Gerhard; Näär, Anders M; Arthanari, Haribabu

2016-02-25

Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of detailed molecular knowledge of the mechanisms of gene activation by disease-associated transcription activators. We previously identified an activator-targeted three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11/Med15 Mediator subunits in fungi. The Gal11/Med15 KIX domain engages pleiotropic drug resistance transcription factor (Pdr1) orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae and in the clinically important human pathogen Candida glabrata. The prevalence of C. glabrata is rising, partly owing to its low intrinsic susceptibility to azoles, the most widely used antifungal agent. Drug-resistant clinical isolates of C. glabrata most commonly contain point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway represents a linchpin in C. glabrata multidrug resistance. Here we perform sequential biochemical and in vivo high-throughput screens to identify small-molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Determining the NMR structure of the C. glabrata Gal11A KIX domain provides a detailed understanding of the molecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1. We have demonstrated the feasibility of small-molecule targeting of a

Implications of Methodist clergies' average lifespan and missional ...

African Journals Online (AJOL)

2015-06-09

Jun 9, 2015 ... The author of Genesis 5 paid meticulous attention to the lifespan of several people ... of Southern Africa (MCSA), and to argue that memories of the ... average ages at death were added up and the sum was divided by 12 (which represents the 12 ..... not explicit in how the departed Methodist ministers were.

A 2D suspension of active agents: the role of fluid mediated interactions

International Nuclear Information System (INIS)

Behmadi, Hojjat; Najafi, Ali; Fazli, Zahra

2017-01-01

Taking into account both the Vicsek short-range ordering and the far-field hydrodynamic interactions mediated by the ambient fluid, we investigate the role of long-range interactions in the ordering phenomena in a quasi 2-dimensional active suspension. By studying the number fluctuations, the velocity correlation functions and cluster size distribution function, we show that depending on the number density of swimmers and the strength of noise, the hydrodynamic interactions can have significant effects in a suspension. For a fixed value of noise, at larger density of particles, long-range interactions enhance the particle pairing and cluster formation in the system. (paper)

Lepton-mediated electroweak baryogenesis

International Nuclear Information System (INIS)

Chung, Daniel J. H.; Garbrecht, Bjorn; Ramsey-Musolf, Michael J.; Tulin, Sean

2010-01-01

We investigate the impact of the tau and bottom Yukawa couplings on the transport dynamics for electroweak baryogenesis in supersymmetric extensions of the standard model. Although it has generally been assumed in the literature that all Yukawa interactions except those involving the top quark are negligible, we find that the tau and bottom Yukawa interaction rates are too fast to be neglected. We identify an illustrative 'lepton-mediated electroweak baryogenesis' scenario in which the baryon asymmetry is induced mainly through the presence of a left-handed leptonic charge. We derive analytic formulas for the computation of the baryon asymmetry that, in light of these effects, are qualitatively different from those in the established literature. In this scenario, for fixed CP-violating phases, the baryon asymmetry has opposite sign compared to that calculated using established formulas.

A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity

Directory of Open Access Journals (Sweden)

Clarissa Bohlmann

2017-12-01

Full Text Available Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM, while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable.

A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity.

Science.gov (United States)

Bohlmann, Clarissa; Rauch, Andreas; Zacher, Hannes

2017-01-01

Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM), while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable.

A Lifespan Perspective on Entrepreneurship: Perceived Opportunities and Skills Explain the Negative Association between Age and Entrepreneurial Activity

Science.gov (United States)

Bohlmann, Clarissa; Rauch, Andreas; Zacher, Hannes

2017-01-01

Researchers and practitioners are increasingly interested in entrepreneurship as a means to fight youth unemployment and to improve financial stability at higher ages. However, only few studies so far have examined the association between age and entrepreneurial activity. Based on theories from the lifespan psychology literature and entrepreneurship, we develop and test a model in which perceived opportunities and skills explain the relationship between age and entrepreneurial activity. We analyzed data from the 2013 Global Entrepreneurship Monitor (GEM), while controlling for gender and potential variation between countries. Results showed that age related negatively to entrepreneurial activity, and that perceived opportunities and skills for entrepreneurship mediated this relationship. Overall, these findings suggest that entrepreneurship research should treat age as a substantial variable. PMID:29250004

Connectivity trajectory across lifespan differentiates the precuneus from the default network.

Science.gov (United States)

Yang, Zhi; Chang, Catie; Xu, Ting; Jiang, Lili; Handwerker, Daniel A; Castellanos, F Xavier; Milham, Michael P; Bandettini, Peter A; Zuo, Xi-Nian

2014-04-01

The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding

Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly.

Science.gov (United States)

Chereji, Razvan V; Bharatula, Vasudha; Elfving, Nils; Blomberg, Jeanette; Larsson, Miriam; Morozov, Alexandre V; Broach, James R; Björklund, Stefan

2017-09-06

Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes. We have combined biochemical purification of the Saccharomyces cerevisiae Mediator from chromatin with chromatin immunoprecipitation in order to reveal Mediator occupancy on DNA genome-wide, and to identify proteins interacting specifically with Mediator on the chromatin template. Tandem mass spectrometry of proteins in immunoprecipitates of mediator complexes revealed specific interactions between Mediator and the RSC, Arp2/Arp3, CPF, CF 1A and Lsm complexes in chromatin. These factors are primarily involved in chromatin remodeling, actin assembly, mRNA 3'-end processing, gene looping and mRNA decay, but they have also been shown to enter the nucleus and participate in Pol II transcription. Moreover, we have found that Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. This suggests that Mediator plays a significant role in higher-order genome organization. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

Science.gov (United States)

Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

2015-06-01

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans.

Science.gov (United States)

Senchuk, Megan M; Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Madaj, Zachary B; Bowman, Megan J; Winn, Mary E; Van Raamsdonk, Jeremy M

2018-03-01

Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2. We show that DAF-16 and multiple DAF-16 interacting proteins (MATH-33, IMB-2, CST-1/2, BAR-1) are required for the full longevity of all three mitochondrial mutants. Our results suggest that the activation of DAF-16 in these mutants results from elevated levels of reactive oxygen species. Overall, this work reveals an overlapping genetic pathway required for longevity in three mitochondrial mutants, and, combined with previous work, demonstrates that DAF-16 is a downstream mediator of lifespan extension in multiple pathways of longevity.

Effects of an unusual poison identify a lifespan role for Topoisomerase 2 in Saccharomyces cerevisiae.

Science.gov (United States)

Tombline, Gregory; Millen, Jonathan I; Polevoda, Bogdan; Rapaport, Matan; Baxter, Bonnie; Van Meter, Michael; Gilbertson, Matthew; Madrey, Joe; Piazza, Gary A; Rasmussen, Lynn; Wennerberg, Krister; White, E Lucile; Nitiss, John L; Goldfarb, David S

2017-01-05

A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates aging without affecting proliferative growth or viability. Genetic and biochemical criteria reveal LS1 to be a weak Top2 poison. Top2 poisons induce the accumulation of covalent Top2-linked DNA double strand breaks that, if left unrepaired, lead to genome instability and death. LS1 is toxic to cells deficient in homologous recombination, suggesting that the damage it induces is normally mitigated by genome maintenance systems. The essential roles of yTop2 in proliferating cells may come with a fitness trade-off in older cells that are less able to sense or repair yTop2-mediated DNA damage. Consistent with this idea, cells live longer when yTop2 expression levels are reduced. These results identify intrinsic yTop2-mediated DNA damage as potentially manageable cause of aging.

Constraining flavor changing interactions from LHC Run-2 dilepton bounds with vector mediators

Directory of Open Access Journals (Sweden)

Farinaldo S. Queiroz

2016-12-01

Full Text Available Within the context of vector mediators, is a new signal observed in flavor changing interactions, particularly in the neutral mesons systems K0−K¯0, D0−D¯0 and B0−B0¯, consistent with dilepton resonance searches at the LHC? In the attempt to address this very simple question, we discuss the complementarity between flavor changing neutral current (FCNC and dilepton resonance searches at the LHC run 2 at 13 TeV with 3.2 fb−1 of integrated luminosity, in the context of vector mediators at tree level. Vector mediators, are often studied in the flavor changing framework, specially in the light of the recent LHCb anomaly observed at the rare B decay. However, the existence of stringent dilepton bound severely constrains flavor changing interactions, due to restrictive limits on the Z′ mass. We discuss this interplay explicitly in the well motivated framework of a 3-3-1 scheme, where fermions and scalars are arranged in the fundamental representation of the weak SU(3 gauge group. Due to the paucity of relevant parameters, we conclude that dilepton data leave little room for a possible new physics signal stemming from these systems, unless a very peculiar texture parametrization is used in the diagonalization of the CKM matrix. In other words, if a signal is observed in such flavor changing interactions, it unlikely comes from a 3-3-1 model.

Topological organization of the human brain functional connectome across the lifespan

Directory of Open Access Journals (Sweden)

Miao Cao

2014-01-01

Full Text Available Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions. Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

Toehold-mediated internal control to probe the near-field interaction between the metallic nanoparticle and the fluorophore

Science.gov (United States)

Ang, Y. S.; Yung, L. Y. L.

2014-10-01

Metallic nanoparticles (MNPs) are known to alter the emission of vicinal fluorophores through the near-field interaction, leading to either fluorescence quenching or enhancement. Much ambiguity remains in the experimental outcome of such a near-field interaction, particularly for bulk colloidal solution. It is hypothesized that the strong far-field interference from the inner filter effect of the MNPs could mask the true near-field MNP-fluorophore interaction significantly. Thus, in this work, a reliable internal control capable of decoupling the near-field interaction from far-field interference is established by the use of the DNA toehold concept to mediate the in situ assembly and disassembly of the MNP-fluorophore conjugate. A model gold nanoparticle (AuNP)-Cy3 system is used to investigate our proposed toehold-mediated internal control system. The maximum fluorescence enhancement is obtained for large-sized AuNP (58 nm) separated from Cy3 at an intermediate distance of 6.8 nm, while fluorescence quenching is observed for smaller-sized AuNP (11 nm and 23 nm), which is in agreement with the theoretical values reported in the literature. This work shows that the toehold-mediated internal control design can serve as a central system for evaluating the near-field interaction of other MNP-fluorophore combinations and facilitate the rational design of specific MNP-fluorophore systems for various applications.Metallic nanoparticles (MNPs) are known to alter the emission of vicinal fluorophores through the near-field interaction, leading to either fluorescence quenching or enhancement. Much ambiguity remains in the experimental outcome of such a near-field interaction, particularly for bulk colloidal solution. It is hypothesized that the strong far-field interference from the inner filter effect of the MNPs could mask the true near-field MNP-fluorophore interaction significantly. Thus, in this work, a reliable internal control capable of decoupling the near

Neoplastic and life-span effects of chronic exposure to tritium. II. Rats exposed in utero

International Nuclear Information System (INIS)

Cahill, D.F.; Wright, J.F.; Godbold, J.H.; Ward, J.M.; Laskey, J.W.; Tompkins, E.A.

1975-01-01

A study was conducted to determine the effects on neoplasia incidence and life-span of exposure in utero to a major environmental radionuclide. Sprague-Dawley rats were continuously exposed to tritiated water (HTO) from conception through birth in doses of 0, 1, 10, 50, and 100 μCi HTO/ml body water. HTO administration was terminated at birth. Calculated cumulative doses during gestation were approximately 0, 6.6, 66, 330, and 660 rads of total body irradiation. Under these exposure conditions, the two highest doses resulted in sterile offspring. Animals surviving through 30 days postnatally were defined as the study population and observed until their deaths. Intrauterine exposures to doses up to 66 rads had no significant effects on either sex with respect to lifespan, overall neoplasia incidence, incidence rate, or onset of mammary fibroadenomas. Females exposed to 330 or 660 rads were sterile and had lower incidence rates of mammary fibroadenomas than did controls; at 660 rads females had a lower incidence of overall neoplasia and reduced mean lifespans. Sterile male offspring had reduced mean longevity after irradiation at 660 rads. Regardless of dose group, females had significantly higher incidences of neoplasia and longer life-spans than males

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

Science.gov (United States)

Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

2013-12-01

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Azadirachtin interacts with retinoic acid receptors and inhibits retinoic acid-mediated biological responses.

Science.gov (United States)

Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B; Sureshkumar, Chitta; Manna, Sunil K

2011-02-11

Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies.

Azadirachtin Interacts with Retinoic Acid Receptors and Inhibits Retinoic Acid-mediated Biological Responses*

Science.gov (United States)

Thoh, Maikho; Babajan, Banaganapalli; Raghavendra, Pongali B.; Sureshkumar, Chitta; Manna, Sunil K.

2011-01-01

Considering the role of retinoids in regulation of more than 500 genes involved in cell cycle and growth arrest, a detailed understanding of the mechanism and its regulation is useful for therapy. The extract of the medicinal plant Neem (Azadirachta indica) is used against several ailments especially for anti-inflammatory, anti-itching, spermicidal, anticancer, and insecticidal activities. In this report we prove the detailed mechanism on the regulation of retinoic acid-mediated cell signaling by azadirachtin, active components of neem extract. Azadirachtin repressed all trans-retinoic acid (ATRA)-mediated nuclear transcription factor κB (NF-κB) activation, not the DNA binding but the NF-κB-dependent gene expression. It did not inhibit IκBα degradation, IκBα kinase activity, or p65 phosphorylation and its nuclear translocation but inhibited NF-κB-dependent reporter gene expression. Azadirachtin inhibited TRAF6-mediated, but not TRAF2-mediated NF-κB activation. It inhibited ATRA-induced Sp1 and CREB (cAMP-response element-binding protein) DNA binding. Azadirachtin inhibited ATRA binding with retinoid receptors, which is supported by biochemical and in silico evidences. Azadirachtin showed strong interaction with retinoid receptors. It suppressed ATRA-mediated removal of retinoid receptors, bound with DNA by inhibiting ATRA binding to its receptors. Overall, our data suggest that azadirachtin interacts with retinoic acid receptors and suppresses ATRA binding, inhibits falling off the receptors, and activates transcription factors like CREB, Sp1, NF-κB, etc. Thus, azadirachtin exerts anti-inflammatory and anti-metastatic responses by a novel pathway that would be beneficial for further anti-inflammatory and anti-cancer therapies. PMID:21127062

Drug synergy drives conserved pathways to increase fission yeast lifespan.

Directory of Open Access Journals (Sweden)

Xinhe Huang

Full Text Available Aging occurs over time with gradual and progressive loss of physiological function. Strategies to reduce the rate of functional loss and mitigate the subsequent onset of deadly age-related diseases are being sought. We demonstrated previously that a combination of rapamycin and myriocin reduces age-related functional loss in the Baker's yeast Saccharomyces cerevisiae and produces a synergistic increase in lifespan. Here we show that the same drug combination also produces a synergistic increase in the lifespan of the fission yeast Schizosaccharomyces pombe and does so by controlling signal transduction pathways conserved across a wide evolutionary time span ranging from yeasts to mammals. Pathways include the target of rapamycin complex 1 (TORC1 protein kinase, the protein kinase A (PKA and a stress response pathway, which in fission yeasts contains the Sty1 protein kinase, an ortholog of the mammalian p38 MAP kinase, a type of Stress Activated Protein Kinase (SAPK. These results along with previous studies in S. cerevisiae support the premise that the combination of rapamycin and myriocin enhances lifespan by regulating signaling pathways that couple nutrient and environmental conditions to cellular processes that fine-tune growth and stress protection in ways that foster long term survival. The molecular mechanisms for fine-tuning are probably species-specific, but since they are driven by conserved nutrient and stress sensing pathways, the drug combination may enhance survival in other organisms.

Interventional effects for mediation analysis with multiple mediators

OpenAIRE

Vansteelandt, Stijn; Daniel, Rhian M.

2017-01-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

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Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Plant-Mediated Systemic Interactions Between Pathogens, Parasitic Nematodes, and Herbivores Above- and Belowground

NARCIS (Netherlands)

Biere, A.; Goverse, A.

2016-01-01

Plants are important mediators of interactions between aboveground (AG) and belowground (BG) pathogens, arthropod herbivores, and nematodes (phytophages). We highlight recent progress in our understanding of within- and cross-compartment plant responses to these groups of phytophages in terms of

Plant-mediated systemic interactions between pathogens, parasitic nematodes, and herbivores above- and belowground

NARCIS (Netherlands)

Biere, A.; Goverse, Aska

2016-01-01

Plants are important mediators of interactions between aboveground (AG) and belowground (BG) pathogens, arthropod herbivores, and nematodes (phytophages). We highlight recent progress in our understanding of within and cross-compartment plant responses to these groups of phytophages in terms of

Toward an Integrative Science of Life-Span Development and Aging

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Piccinin, Andrea M.

2010-01-01

The study of aging demands an integrative life-span developmental framework, involving interdisciplinary collaborations and multiple methodological approaches for understanding how and why individuals change, in both normative and idiosyncratic ways. We highlight and summarize some of the issues encountered when conducting integrative research for understanding aging-related change, including, the integration of results across different levels of analysis; the integration of theory, design, and analysis; and the synthesis of results across studies of aging. We emphasize the necessity of longitudinal designs for understanding development and aging and discuss methodological issues that should be considered for achieving reproducible research on within-person processes. It will be important that current and future studies permit opportunities for quantitative comparison across populations given the extent to which historical shifts and cultural differences influence life-span processes and aging-related outcomes. PMID:20237144

Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

Directory of Open Access Journals (Sweden)

Cathy Slack

2010-03-01

Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

Learning Opportunities in Synchronous Computer-Mediated Communication and Face-to-Face Interaction

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Kim, Hye Yeong

2014-01-01

This study investigated how synchronous computer-mediated communication (SCMC) and face-to-face (F2F) oral interaction influence the way in which learners collaborate in language learning and how they solve their communicative problems. The findings suggest that output modality may affect how learners produce language, attend to linguistic forms,…

Two pion mediated scalar isoscalar NN interaction in the nuclear medium

International Nuclear Information System (INIS)

Kaskulov, Murat M.; Oset, E.; Vacas, M.J. Vicente

2006-01-01

We study the modification of the nucleon-nucleon interaction in a nuclear medium in the scalar isoscalar channel, mediated by the exchange of two correlated (σ channel) or uncorrelated pions. For this purpose we use a standard approach for the renormalization of pions in nuclei. The corrections obtained for the NN interaction in the medium in this channel are of the order of 20% of the free one in average, and the consideration of short-range correlations plays an important role in providing these moderate changes. Yet, the corrections are sizable enough to suggest further studies of the stability and properties of nuclear matter

Computational modeling identifies key gene regulatory interactions underlying phenobarbital-mediated tumor promotion

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Luisier, Raphaëlle; Unterberger, Elif B.; Goodman, Jay I.; Schwarz, Michael; Moggs, Jonathan; Terranova, Rémi; van Nimwegen, Erik

2014-01-01

Gene regulatory interactions underlying the early stages of non-genotoxic carcinogenesis are poorly understood. Here, we have identified key candidate regulators of phenobarbital (PB)-mediated mouse liver tumorigenesis, a well-characterized model of non-genotoxic carcinogenesis, by applying a new computational modeling approach to a comprehensive collection of in vivo gene expression studies. We have combined our previously developed motif activity response analysis (MARA), which models gene expression patterns in terms of computationally predicted transcription factor binding sites with singular value decomposition (SVD) of the inferred motif activities, to disentangle the roles that different transcriptional regulators play in specific biological pathways of tumor promotion. Furthermore, transgenic mouse models enabled us to identify which of these regulatory activities was downstream of constitutive androstane receptor and β-catenin signaling, both crucial components of PB-mediated liver tumorigenesis. We propose novel roles for E2F and ZFP161 in PB-mediated hepatocyte proliferation and suggest that PB-mediated suppression of ESR1 activity contributes to the development of a tumor-prone environment. Our study shows that combining MARA with SVD allows for automated identification of independent transcription regulatory programs within a complex in vivo tissue environment and provides novel mechanistic insights into PB-mediated hepatocarcinogenesis. PMID:24464994

Interaction Mortality: Senescence May Have Evolved because It Increases Lifespan

DEFF Research Database (Denmark)

Wensink, M. J.; Wrycza, T. F.; Baudisch, A.

2014-01-01

Given an extrinsic challenge, an organism may die or not depending on how the threat interacts with the organism's physiological state. To date, such interaction mortality has been only a minor factor in theoretical modeling of senescence. We describe a model of interaction mortality that does...... not involve specific functions, making only modest assumptions. Our model distinguishes explicitly between the physiological state of an organism and potential extrinsic, age-independent threats. The resulting mortality may change with age, depending on whether the organism's state changes with age. We find...... that depending on the physiological constraints, any outcome, be it 'no senescence' or 'high rate of senescence', can be found in any environment; that the highest optimal rate of senescence emerges for an intermediate physiological constraint, i.e. intermediate strength of trade-off; and that the optimal rate...

Lifespan Differences in the Social Networks of Prison Inmates

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Bond, Gary D.; Thompson, Laura A.; Malloy, Daniel M.

2005-01-01

Socioemotional Selectivity Theory (SST) (Carstensen, 1992, 1993) accounts for lifespan changes in human social networks and for the motivations which underlie those changes. SST is applied in this research with 256 prison inmates and non-inmates, ages 18-84, from Mississippi, Kansas, and New Mexico. Two research questions sought to identify (a)…

Holistic life-span health outcomes among elite intercollegiate student-athletes.

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Sorenson, Shawn C; Romano, Russell; Scholefield, Robin M; Martin, Brandon E; Gordon, James E; Azen, Stanley P; Schroeder, E Todd; Salem, George J

2014-01-01

Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). Cross-sectional study. A large Division I university. Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P students (P 99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable

Seasonal and scale-dependent variability in nutrient- and allelopathy-mediated macrophyte–phytoplankton interactions

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Lombardo P.

2013-08-01

Full Text Available macrophyte–phytoplankton interactions were investigated using a dual laboratory and field approach during a growing season, with responses quantified as changes in biomass. Short-term, close-range interactions in laboratory microcosms always led to mutual exclusion of macrophytes (Elodea canadensis or Ceratophyllum demersum and algae (Raphidocelis subcapitata, Fistulifera pelliculosa or cyanobacteria (Synechococcus leopoliensis, suggesting regulation by positive feedback mechanisms, progressively establishing and reinforcing a “stable state”. Laboratory results suggest that close-range regulation of R. subcapitata and F. pelliculosa by macrophytes was primarily via nutrient (N, P mediation. Sprig-produced allelochemicals may have contributed to inhibition of S. leopoliensis in C. demersum presence, while S. leopoliensis was apparently enhanced by nutrients leaked by subhealthy (discolored leaves; biomass loss E. canadensis. Seasonal changes in algal growth suppression were correlated with sprig growth. Marginal differences in in situ phytoplankton patterns inside and outside monospecific macrophyte stands suggest that the nutrient- and/or allelopathy-mediated close-range mechanisms observed in the laboratory did not propagate at the macrophyte-stand scale. Factors operating at a larger scale (e.g., lake trophic state, extent of submerged vegetation coverage appear to override in situ macrophyte–phytoplankton close-range interactions.

Social Skills as a Mediator between Anxiety Symptoms and Peer Interactions among Children and Adolescents

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Motoca, Luci M.; Williams, Sandra; Silverman, Wendy K.

2012-01-01

Objective The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as moderators. Method The sample consisted of 397 children and adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an anxiety disorders clinic. Anxiety symptoms, positive and negative peer interactions, and social skills were assessed using youth and parent ratings. Results Structural equation modeling results indicated that for youth ratings only, youth anxiety symptoms were negatively related to positive peer interactions controlling for primary social phobia and comorbid depressive disorders. For both youth and parent ratings, youth anxiety symptoms were positively related to negative peer interactions and negatively related to social skills. Also for both youth and parent ratings, social skills mediated the relations between youth anxiety symptoms and positive and negative peer interactions. For parent ratings only, the effects of youth anxiety symptoms and social skills on peer interactions were significantly moderated by youth age. Youth sex was not a significant moderator using youth and parent ratings. Conclusions Findings suggest difficulties with social skills and peer interactions are problematic features of youth referred for anxiety problems. Findings highlight the need to improve understanding of anxiety symptoms, social skills, and peer interactions in this population. PMID:22471319

Social skills as a mediator between anxiety symptoms and peer interactions among children and adolescents.

Science.gov (United States)

Motoca, Luci M; Williams, Sandra; Silverman, Wendy K

2012-01-01

The present study used a cross-sectional design to examine the relations among youth anxiety symptoms, positive and negative peer interactions, and social skills. Also examined was the mediating role of social skills in the relations between youth anxiety symptoms and positive and negative peer interactions. Youth sex and age were examined as moderators. The sample consisted of 397 children and adolescents (M = 10.11 years; 53.4% boys; 74.8% Hispanic Latino) referred to an anxiety disorders clinic. Anxiety symptoms, positive and negative peer interactions, and social skills were assessed using youth and parent ratings. Structural equation modeling results indicated that for youth ratings only, youth anxiety symptoms were negatively related to positive peer interactions controlling for primary social phobia and comorbid depressive disorders. For both youth and parent ratings, youth anxiety symptoms were positively related to negative peer interactions and negatively related to social skills. Also for both youth and parent ratings, social skills mediated the relations between youth anxiety symptoms and positive and negative peer interactions. For parent ratings only, the effects of youth anxiety symptoms and social skills on peer interactions were significantly moderated by youth age. Youth sex was not a significant moderator using youth and parent ratings. Findings suggest that difficulties with social skills and peer interactions are problematic features of youth referred for anxiety problems. Findings highlight the need to improve understanding of anxiety symptoms, social skills, and peer interactions in this population.

The reproductive lifespan of Onchocerca volvulus in West African savanna

NARCIS (Netherlands)

A.P. Plaisier (Anton); G.J. van Oortmarssen (Gerrit); J.H.F. Remme (Jan); J.D.F. Habbema (Dik)

1991-01-01

markdownabstractAbstract The epidemiological model ONCHOSIM — a model and computer simulation program for the transmission and control of onchocerciasis — has been used to determine the range of plausible values for the reproductive lifespan of Onchocerca volvulus. Model predictions based on

Mediated Windows: The Use of Framing and Transparency in Designing for Presence

Directory of Open Access Journals (Sweden)

Charlie Gullström

2014-07-01

Full Text Available This paper explores the fusion of architecture and media technology that facilitates collaborative practices across spatial extensions: video-mediated spaces. The example presented is a mediated extension of the Museum of National Antiquities in Stockholm to a neighbouring park area and archaeological excavation site in 2008, referred to as a mediated window, or a glass-door. The concepts framing and transparency are used to outline the significance of windows and glazing in architecture and art. The author then considers the potential contribution of architecture in representing the passage from indoors to outdoors and designing for presence. Presence design assumes a contribution from architects to presence research, a currently diversified field, spanning media-space research, cognitive science, interaction design, ubiquitous computing, second-order cybernetics, and computer-supported collaborative work, but in which architecture and artistic practices are less represented.The paper thereby addresses the potential of an extended architectural practice, which incorporates the design of mediated spaces, and outlines presence design as a transdisciplinary practice in which presence research meets architectural design, and spatial and aesthetic conceptual tools, derived from related visual practices, may be productively applied.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

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Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

What do we learn about hadronic interactions at ultrahigh energies from extensive air shower observations?

International Nuclear Information System (INIS)

Rebel, H.

2002-01-01

The interpretation of extensive air shower (EAS) observations needs a sufficiently accurate knowledge of the interactions driving the cascade development in the atmosphere. While the electromagnetic and weak interaction parts do not provide principal problems, the hadronic interaction is a subject of uncertainties and debates, especially in the ultrahigh energy region extending the energy limits of man made accelerators and experimental knowledge from collider experiments. Since the EAS development is dominantly governed by soft processes, which are presently not accessible to a perturbative QCD treatment, one has to rely on QCD inspired phenomenological interaction models, in particular on string-models based on the Gribov-Regge theory like QGSJET, VENUS and SYBILL. Recent results of the EAS experiments KASCADE are scrutinized in terms of such models used as generators in the Monte Carlo EAS simulation code CORSIKA. (author)

The Lifespan Self-Esteem Scale: Initial Validation of a New Measure of Global Self-Esteem.

Science.gov (United States)

Harris, Michelle A; Donnellan, M Brent; Trzesniewski, Kali H

2018-01-01

This article introduces the Lifespan Self-Esteem Scale (LSE), a short measure of global self-esteem suitable for populations drawn from across the lifespan. Many existing measures of global self-esteem cannot be used across multiple developmental periods due to changes in item content, response formats, and other scale characteristics. This creates a need for a new lifespan scale so that changes in global self-esteem over time can be studied without confounding maturational changes with alterations in the measure. The LSE is a 4-item measure with a 5-point response format using items inspired by established self-esteem scales. The scale is essentially unidimensional and internally consistent, and it converges with existing self-esteem measures across ages 5 to 93 (N = 2,714). Thus, the LSE appears to be a useful measure of global self-esteem suitable for use across the lifespan as well as contexts where a short measure is desirable, such as populations with short attention spans or large projects assessing multiple constructs. Moreover, the LSE is one of the first global self-esteem scales to be validated for children younger than age 8, which provides the opportunity to broaden the field to include research on early formation and development of global self-esteem, an area that has previously been limited.

Essential oil alloaromadendrene from mixed-type Cinnamomum osmophloeum leaves prolongs the lifespan in Caenorhabditis elegans.

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Yu, Chan-Wei; Li, Wen-Hsuan; Hsu, Fu-Lan; Yen, Pei-Ling; Chang, Shang-Tzen; Liao, Vivian Hsiu-Chuan

2014-07-02

Cinnamomum osmophloeum Kaneh. is an indigenous tree species in Taiwan. The present study investigates phytochemical characteristics, antioxidant activities, and longevity of the essential oils from the leaves of the mixed-type C. osmophloeum tree. We demonstrate that the essential oils from leaves of mixed-type C. osmophloeum exerted in vivo antioxidant activities on Caenorhabditis elegans. In addition, minor (alloaromadendrene, 5.0%) but not major chemical components from the leaves of mixed-type C. osmophloeum have a key role against juglone-induced oxidative stress in C. elegans. Additionally, alloaromadendrene not only acts protective against oxidative stress but also prolongs the lifespan of C. elegans. Moreover, mechanistic studies show that DAF-16 is required for alloaromadendrene-mediated oxidative stress resistance and longevity in C. elegans. The results in the present study indicate that the leaves of mixed-type C. osmophloeum and essential oil alloaromadendrene have the potential for use as a source for antioxidants or treatments to delay aging.

Water-mediated interactions between trimethylamine-N-oxide and urea.

Science.gov (United States)

Hunger, Johannes; Ottosson, Niklas; Mazur, Kamila; Bonn, Mischa; Bakker, Huib J

2015-01-07

The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in natural organisms, where it counteracts biochemical stress associated with urea in aqueous environments. Despite the important role of TMAO as osmoprotectant, the mechanism behind TMAO's action has remained elusive. Here, we study the interaction between urea, TMAO, and water in solution using broadband (100 MHz-1.6 THz) dielectric spectroscopy. We find that the previously reported tight hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of TMAO, remain intact at all investigated concentrations of urea, showing that no significant hydrogen bonding occurs between the two co-solutes. Despite the absence of direct TMAO-urea interactions, the solute reorientation times of urea and TMAO show an anomalous nonlinear increase with concentration, for ternary mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the reorientation correlates with changes in the viscosity, showing that the combination of TMAO and urea cooperatively enhances the hydrogen-bond structure of the ternary solutions. This nonlinear increase is indicative of water mediated interaction between the two solutes and is not observed if urea is combined with other amphiphilic solutes.

Variation in plant-mediated interactions between rhizobacteria and caterpillars: potential role of soil composition

NARCIS (Netherlands)

Pangesti, N.P.D.; Pineda Gomez, A.M.; Dicke, M.; Loon, van J.J.A.

2015-01-01

Selected strains of non-pathogenic rhizobacteria can trigger induced systemic resistance (ISR) in plants against aboveground insect herbivores. However, the underlying mechanisms of plant-mediated interactions between rhizobacteria and herbivorous insects are still poorly understood. Using

An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

Directory of Open Access Journals (Sweden)

Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

2015-09-01

Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

Mediation Analysis with Multiple Mediators

OpenAIRE

VanderWeele, T.J.; Vansteelandt, S.

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

A chemical arms race at sea mediates algal host-virus interactions.

Science.gov (United States)

Bidle, Kay D; Vardi, Assaf

2011-08-01

Despite the critical importance of viruses in shaping marine microbial ecosystems and lubricating upper ocean biogeochemical cycles, relatively little is known about the molecular mechanisms mediating phytoplankton host-virus interactions. Recent work in algal host-virus systems has begun to shed novel insight into the elegant strategies of viral infection and subcellular regulation of cell fate, which not only reveal tantalizing aspects of viral replication and host resistance strategies but also provide new diagnostic tools toward elucidating the impact of virus-mediated processes in the ocean. Widespread lateral gene transfer between viruses and their hosts plays a prominent role in host-virus diversification and in the regulation of host-virus infection mechanisms by allowing viruses to manipulate and 'rewire' host metabolic pathways to facilitate infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preschool Interactive Peer Play Mediates Problem Behavior and Learning for Low-Income Children

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Bulotsky-Shearer, Rebecca J.; Bell, Elizabeth R.; Romero, Sandy L.; Carter, Tracy M.

2012-01-01

The study employed a developmental, ecological, and resiliency framework to examine whether interactive peer play competencies mediated associations between teacher reported problem behavior and learning outcomes for a representative sample of urban low-income children (N = 507 across 46 Head Start classrooms). Structural equation models provided…

Life-span studies of inhaled plutonium in beagle dogs

International Nuclear Information System (INIS)

Bair, W.J.

1990-04-01

In 1970 a life-span study with over 300 beagle dogs was begun to gain an understanding of long-term health effects resulting from respiratory tract intakes of plutonium and to derive risk estimates that might be applied to plutonium and other transuranic elements. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. The objective of this paper is to give you a progress report on the current life-span studies of inhaled plutonium in beagle dogs at the Pacific Northwest Laboratory. I will describe the biokinetics of inhaled plutonium in dogs and the resulting health effects. I will also mention some studies directed towards understanding the mechanism leading to these effects. Finally, I will discuss the current risk estimates derived from these studies and how they might relate to plutonium exposures in humans. 5 refs., 13 figs., 4 tabs

On the genetic mechanisms of nutrient-dependent lifespan and reproduction

NARCIS (Netherlands)

Zandveld, Jelle

2017-01-01

Dietary restriction (DR), a moderate reduction in nutrient intake, improves health or extends lifespan across many species. Moreover, recent insights have shown that also the effects of specific nutrients are of importance for the beneficial effects of DR rather than intake alone. However, we

Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans.

Directory of Open Access Journals (Sweden)

Wai-Jiao Cai

Full Text Available Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ(1-42 proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS since the daf-16(mu86 and daf-2(e1370 failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.

CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

Science.gov (United States)

Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

2013-06-25

The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

Anisotropic Surface State Mediated RKKY Interaction Between Adatoms on a Hexagonal Lattice

Science.gov (United States)

Einstein, Theodore; Patrone, Paul

2012-02-01

Motivated by recent numerical studies of Ag on Pt(111), we derive a far-field expression for the RKKY interaction mediated by surface states on a (111) FCC surface, considering the effect of anisotropy in the Fermi edge. The main contribution to the interaction comes from electrons whose Fermi velocity vF is parallel to the vector R connecting the interacting adatoms; we show that in general, the corresponding Fermi wave-vector kF is not parallel to R. The interaction is oscillatory; the amplitude and wavelength of oscillations have angular dependence arising from the anisotropy of the surface state band structure. The wavelength, in particular, is determined by the component of the aforementioned kF that is parallel to R. Our analysis is easily generalized to other systems. For Ag on Pt(111), our results indicate that the RKKY interaction between pairs of adatoms should be nearly isotropic and so cannot account for the anisotropy found in the studies motivating our work.

The Insulation for Machines Having a High Lifespan Expectancy, Design, Tests and Acceptance Criteria Issues

Directory of Open Access Journals (Sweden)

Olivier Barré

2017-02-01

Full Text Available The windings insulation of electrical machines will remain a topic that is updated frequently. The criteria severity requested by the electrical machine applications increases continuously. Manufacturers and designers are always confronted with new requirements or new criteria with enhanced performances. The most problematic requirements that will be investigated here are the extremely long lifespan coupled to critical operating conditions (overload, supply grid instabilities, and critical operating environments. Increasing lifespan does not have a considerable benefit because the purchasing price of usual machines has to be compared to the purchasing price and maintenance price of long lifespan machines. A machine having a 40-year lifespan will cost more than twice the usual price of a 20-year lifetime machine. Systems which need a long lifetime are systems which are crucial for a country, and those for which outage costs are exorbitant. Nuclear power stations are such systems. It is certain that the used technologies have evolved since the first nuclear power plant, but they cannot evolve as quickly as in other sectors of activities. No-one wants to use an immature technology in such power plants. Even if the electrical machines have exceeded 100 years of age, their improvements are linked to a patient and continuous work. Nowadays, the windings insulation systems have a well-established structure, especially high voltage windings. Unfortunately, a high life span is not only linked to this result. Several manufacturers’ improvements induced by many years of experiment have led to the writing of standards that help the customers and the manufacturers to regularly enhance the insulation specifications or qualifications. Hence, in this publication, the authors will give a step by step exhaustive review of one insulation layout and will take time to give a detailed report on the standards that are linked to insulation systems. No standard can

Bacterial Respiration and Growth Rates Affect the Feeding Preferences, Brood Size and Lifespan of Caenorhabditis elegans

Science.gov (United States)

Yu, Li; Yan, Xiaomei; Ye, Chenglong; Zhao, Haiyan; Chen, Xiaoyun; Hu, Feng; Li, Huixin

2015-01-01

Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs) in soils, and influence nematodes behavior and physiology through their metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp. JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli OP50) and the typical BFN Caenorhabditis elegans were selected to study the effects of bacterial respiration and growth rates on the feeding preferences, brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were found to be more active, with high respiration and rapid growth, whereas B. amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C. elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously. Furthermore, worms that fed on these two active bacteria produced more offspring but had shorter lifespan, while inactive and less preferred bacteria had increased nematodes lifespan and decreased the brood size. Based on these results, we propose that the bacterial activity may influence the behavior and life traits of C. elegans in the following ways: (1) active bacteria reproduce rapidly and emit high levels of CO2 attracting C. elegans; (2) these active bacteria use more resources in the nematodes’ gut to sustain their survival and reproduction, thereby reducing the worm's lifespan; (3) inactive bacteria may provide less food for worms than active bacteria, thus increasing nematodes lifespan but decreasing their fertility. Nematodes generally require a balance between their preferred foods and beneficial foods, only preferred food may not be beneficial for nematodes. PMID:26222828

Search for gauge extensions of the MSSM at the LHC

International Nuclear Information System (INIS)

Ali, Ahmed; Demir, Durmus A.; Izmir Institute of Technology, IZTECH, Izmir; Frank, Mariana; Turan, Ismail

2009-02-01

The extensions of the minimal supersymmetric model (MSSM), driving mainly from the need to solve the μ problem, involve novel matter species and gauge groups. These extended MSSM models can be searched for at the LHC via the effects of the gauge and Higgs bosons or their fermionic partners. Traditionally, the focus has been on the study of the extra forces induced by the new gauge and Higgs bosons present in such models. An alternative way of studying such effects is through the superpartners of matter species and the gauge forces. We thus consider a U(1)' gauge extension of the MSSM, and perform an extensive study of the signatures of the model through the production and decays of the scalar quarks and gluino, which are expected to be produced copiously at the LHC. After a detailed study of the distinctive features of such models with regard to the signatures at the LHC, we carry out a detailed Monte Carlo analysis of the signals from the process pp→n leptons+m jets+E T , and compare the resulting distributions with those predicted by the MSSM. Our results show that the searches for the extra gauge interactions in the supersymmetric framework can proceed not only through the forces mediated by the gauge and Higgs bosons but also through the superpartner forces mediated by the gauge and Higgs fermions. Analysis of the events induced by the squark/gluino decays presented here is complementary to the direct Z' searches at the LHC. (orig.)

Search for gauge extensions of the MSSM at the LHC

Energy Technology Data Exchange (ETDEWEB)

Ali, Ahmed [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Demir, Durmus A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Izmir Institute of Technology, IZTECH, Izmir (Turkey). Dept. of Physics; Frank, Mariana; Turan, Ismail [Montreal Univ., PQ (Canada). Dept. of Physics

2009-02-15

The extensions of the minimal supersymmetric model (MSSM), driving mainly from the need to solve the {mu} problem, involve novel matter species and gauge groups. These extended MSSM models can be searched for at the LHC via the effects of the gauge and Higgs bosons or their fermionic partners. Traditionally, the focus has been on the study of the extra forces induced by the new gauge and Higgs bosons present in such models. An alternative way of studying such effects is through the superpartners of matter species and the gauge forces. We thus consider a U(1)' gauge extension of the MSSM, and perform an extensive study of the signatures of the model through the production and decays of the scalar quarks and gluino, which are expected to be produced copiously at the LHC. After a detailed study of the distinctive features of such models with regard to the signatures at the LHC, we carry out a detailed Monte Carlo analysis of the signals from the process pp{yields}n leptons+m jets+E{sub T}, and compare the resulting distributions with those predicted by the MSSM. Our results show that the searches for the extra gauge interactions in the supersymmetric framework can proceed not only through the forces mediated by the gauge and Higgs bosons but also through the superpartner forces mediated by the gauge and Higgs fermions. Analysis of the events induced by the squark/gluino decays presented here is complementary to the direct Z' searches at the LHC. (orig.)

Lectin receptor kinases participate in protein-protein interactions to mediate plasma membrane-cell wall adhesions in Arabidopsis

NARCIS (Netherlands)

Gouget, A.; Senchou, V.; Govers, F.; Sanson, A.; Barre, A.; Rougé, P.; Pont-Lezica, R.; Canut, H.

2006-01-01

Interactions between plant cell walls and plasma membranes are essential for cells to function properly, but the molecules that mediate the structural continuity between wall and membrane are unknown. Some of these interactions, which are visualized upon tissue plasmolysis in Arabidopsis

Toxic effect of visible light on Drosophila lifespan depending upon diet protein content.

Science.gov (United States)

Shen, Jie; Zhu, Xiang; Gu, Yitian; Zhang, Chiqian; Huang, Jiahong; Qing, Xiao

2018-03-01

We investigated the toxic effect of visible light on Drosophila lifespan in both sexes. The toxic effect of ultraviolet (UV) light on organisms is well known. However, the effects of illumination with visible light remain unclear. Here, we found that visible light could be toxic to Drosophila survival, depending on the protein content in diet. In addition, further analysis revealed significant interaction between light and sex, and showed that strong light shortened life span by causing opposite direction changes in mortality rate parameters in females versus males. Our findings suggest that photoageing may be a general phenomenon, and support the theory of sexual antagonistic pleiotropy in aging intervention. The results caution that exposure to visible light could be hazardous to life span and suggest that identification of the underlying mechanism would allow better understanding of aging intervention.

Uneven Futures of Human Lifespans: Reckonings from Gompertz Mortality Rates, Climate Change, and Air Pollution

OpenAIRE

Finch, Caleb E; Beltrán-Sánchez, Hiram; Crimmins, Eileen M

2013-01-01

The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit. We calc...

Lifespan trends of autobiographical remembering: episodicity and search for meaning.

Science.gov (United States)

Habermas, Tilmann; Diel, Verena; Welzer, Harald

2013-09-01

Autobiographical memories of older adults show fewer episodic and more non-episodic elements than those of younger adults. This semantization effect is attributed to a loss of episodic memory ability. However the alternative explanation by an increasing proclivity to search for meaning has not been ruled out to date. To test whether a decrease in episodicity and an increase in meaning-making in autobiographical narratives are related across the lifespan, we used different instructions, one focussing on specific episodes, the other on embedding events in life, in two lifespan samples. A continuous decrease of episodic quality of memory (memory specificity, narrative quality) was confirmed. An increase of search for meaning (interpretation, life story integration) was confirmed only up to middle adulthood. This non-inverse development of episodicity and searching for meaning in older age speaks for an autonomous semantization effect that is not merely due to an increase in interpretative preferences. Copyright © 2013 Elsevier Inc. All rights reserved.

Electrochemical DNA biosensor based on grafting-to mode of terminal deoxynucleoside transferase-mediated extension.

Science.gov (United States)

Chen, Jinyuan; Liu, Zhoujie; Peng, Huaping; Zheng, Yanjie; Lin, Zhen; Liu, Ailin; Chen, Wei; Lin, Xinhua

2017-12-15

Previously reported electrochemical DNA biosensors based on in-situ polymerization approach reveal that terminal deoxynucleoside transferase (TdTase) has good amplifying performance and promising application in the design of electrochemical DNA biosensor. However, this method, in which the background is significantly affected by the amount of TdTase, suffers from being easy to produce false positive result and poor stability. Herein, we firstly present a novel electrochemical DNA biosensor based on grafting-to mode of TdTase-mediated extension, in which DNA targets are polymerized in homogeneous solution and then hybridized with DNA probes on BSA-based DNA carrier platform. It is surprising to find that the background in the grafting-to mode of TdTase-based electrochemical DNA biosensor have little interference from the employed TdTase. Most importantly, the proposed electrochemical DNA biosensor shows greatly improved detection performance over the in-situ polymerization approach-based electrochemical DNA biosensor. Copyright © 2017 Elsevier B.V. All rights reserved.

A decrease in ubiquitination and resulting prolonged life-span of KIT underlies the KIT overexpression-mediated imatinib resistance of KIT mutation-driven canine mast cell tumor cells.

Science.gov (United States)

Kobayashi, Masato; Kuroki, Shiori; Kurita, Sena; Miyamoto, Ryo; Tani, Hiroyuki; Tamura, Kyoichi; Bonkobara, Makoto

2017-10-01

Overexpression of KIT is one of the mechanisms that contributes to imatinib resistance in KIT mutation-driven tumors. Here, the mechanism underlying this overexpression of KIT was investigated using an imatinib-sensitive canine mast cell tumor (MCT) line CoMS, which has an activating mutation in KIT exon 11. A KIT-overexpressing imatinib-resistant subline, rCoMS1, was generated from CoMS cells by their continuous exposure to increasing concentrations of imatinib. Neither a secondary mutation nor upregulated transcription of KIT was detected in rCoMS1 cells. A decrease in KIT ubiquitination, a prolonged KIT life-span, and KIT overexpression were found in rCoMS1 cells. These events were suppressed by withdrawal of imatinib and were re-induced by re‑treatment with imatinib. These findings suggest that imatinib elicited overexpression of KIT via suppression of its ubiquitination. These results also indicated that imatinib-induced overexpression of KIT in rCoMS1 cells was not a permanently acquired feature but was a reversible response of the cells. Moreover, the pan deubiquitinating enzyme inhibitor PR619 prevented imatinib induction of KIT overexpression, suggesting that the imatinib-induced decrease in KIT ubiquitination could be mediated by upregulation and/or activation of deubiquitinating enzyme(s). It may be possible that a similar mechanism of KIT overexpression underlies the acquisition of imatinib resistance in some human tumors that are driven by KIT mutation.

Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

Science.gov (United States)

Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

2017-01-01

The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans’ replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal’s effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells

Tunable-Range, Photon-Mediated Atomic Interactions in Multimode Cavity QED

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Varun D. Vaidya

2018-01-01

Full Text Available Optical cavity QED provides a platform with which to explore quantum many-body physics in driven-dissipative systems. Single-mode cavities provide strong, infinite-range photon-mediated interactions among intracavity atoms. However, these global all-to-all couplings are limiting from the perspective of exploring quantum many-body physics beyond the mean-field approximation. The present work demonstrates that local couplings can be created using multimode cavity QED. This is established through measurements of the threshold of a superradiant, self-organization phase transition versus atomic position. Specifically, we experimentally show that the interference of near-degenerate cavity modes leads to both a strong and tunable-range interaction between Bose-Einstein condensates (BECs trapped within the cavity. We exploit the symmetry of a confocal cavity to measure the interaction between real BECs and their virtual images without unwanted contributions arising from the merger of real BECs. Atom-atom coupling may be tuned from short range to long range. This capability paves the way toward future explorations of exotic, strongly correlated systems such as quantum liquid crystals and driven-dissipative spin glasses.

Sexual selection affects the evolution of lifespan and ageing in the decorated cricket Gryllodes sigillatus.

Science.gov (United States)

Archer, C R; Zajitschek, F; Sakaluk, S K; Royle, N J; Hunt, J

2012-10-01

Recent work suggests that sexual selection can influence the evolution of ageing and lifespan by shaping the optimal timing and relative costliness of reproductive effort in the sexes. We used inbred lines of the decorated cricket, Gryllodes sigillatus, to estimate the genetic (co)variance between age-dependent reproductive effort, lifespan, and ageing within and between the sexes. Sexual selection theory predicts that males should die sooner and age more rapidly than females. However, a reversal of this pattern may be favored if reproductive effort increases with age in males but not in females. We found that male calling effort increased with age, whereas female fecundity decreased, and that males lived longer and aged more slowly than females. These divergent life-history strategies were underpinned by a positive genetic correlation between early-life reproductive effort and ageing rate in both sexes, although this relationship was stronger in females. Despite these sex differences in life-history schedules, age-dependent reproductive effort, lifespan, and ageing exhibited strong positive intersexual genetic correlations. This should, in theory, constrain the independent evolution of these traits in the sexes and may promote intralocus sexual conflict. Our study highlights the importance of sexual selection to the evolution of sex differences in ageing and lifespan in G. sigillatus. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age.

Science.gov (United States)

Zou, Sige; Carey, James R; Liedo, Pablo; Ingram, Donald K; Yu, Binbing

2012-04-01

Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano-cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet supplemented with or without 2% OC. Lifespan and daily egg production of individual flies were recorded. The effect of short-term OC supplementation was evaluated by implementing the supplementation at three age intervals-young, middle, and old age. We found that OC increased lifespan of Mexflies on the full or DR diet when compared to their respective controls. OC increased reproduction of females on the full diet and, to a lesser extent, on the DR diet. Short-term OC supplementation was not sufficient to extend lifespan for males at all three age intervals nor for females at young and old age intervals. However, OC supplementation at the middle age interval was sufficient to extend lifespan in females, while only OC supplementation at the young age interval increased reproduction in females. Our findings suggest that OC extends lifespan and promotes reproduction partly through DR-independent pathways, and short-term supplementation have varied impact on longevity and reproduction. This also suggests a positive interaction between non-genetic interventions in promoting longevity and provides guidance for using botanicals as aging interventions in humans.

Advances in asthma 2015: Across the lifespan.

Science.gov (United States)

Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2016-08-01

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Plant-plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO

NARCIS (Netherlands)

Loon, Van Marloes P.; Rietkerk, Max; Dekker, Stefan C.; Hikosaka, Kouki; Ueda, Miki U.; Anten, Niels P.R.

2016-01-01

Background and Aims The rising atmospheric CO₂ concentration ([CO₂]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant-plant interactions could mediate the trajectory of vegetation responses to elevated

Steroids as central regulators of organismal development and lifespan.

Directory of Open Access Journals (Sweden)

Siu Sylvia Lee

Full Text Available Larvae of the nematode Caenorhabditis elegans must choose between reproductive development and dauer diapause. This decision is based on sensing of environmental inputs and dauer pheromone, a small molecule signal that serves to monitor population density. These signals are integrated via conserved neuroendocrine pathways that converge on steroidal ligands of the nuclear receptor DAF-12, a homolog of the mammalian vitamin D receptor and liver X receptor. DAF-12 acts as the main switch between gene expression programs that drive either reproductive development or dauer entry. Extensive studies in the past two decades demonstrated that biosynthesis of two bile acid-like DAF-12 ligands, named dafachronic acids (DA, controls developmental fate. In this issue of PLoS Biology, Wollam et al. showed that a conserved steroid-modifying enzyme, DHS-16, introduces a key feature in the structures of the DAF-12 ligands, closing a major gap in the DA biosynthesis pathway. The emerging picture of DA biosynthesis in C. elegans enables us to address a key question in the field: how are complex environmental signals integrated to enforce binary, organism-wide decisions on developmental fate? Schaedel et al. demonstrated that pheromone and DA serve as competing signals, and that a positive feedback loop based on regulation of DA biosynthesis ensures organism-wide commitment to reproductive development. Considering that many components of DA signaling are highly conserved, ongoing studies in C. elegans may reveal new aspects of bile acid function and lifespan regulation in mammals.

Analysis of the Varicella-Zoster Virus IE62 N-Terminal Acidic Transactivating Domain and Its Interaction with the Human Mediator Complex▿

OpenAIRE

Yamamoto, Shinobu; Eletsky, Alexander; Szyperski, Thomas; Hay, John; Ruyechan, William T.

2009-01-01

The varicella-zoster virus major transactivator, IE62, contains a potent N-terminal acidic transcriptional activation domain (TAD). Our experiments revealed that the minimal IE62 TAD encompasses amino acids (aa) 19 to 67. We showed that the minimal TAD interacts with the human Mediator complex. Site-specific mutations revealed residues throughout the minimal TAD that are important for both activation and Mediator interaction. The TAD interacts directly with aa 402 to 590 of the MED25 subunit,...

Metal-metal interaction mediates the iron induction of Drosophila MtnB

International Nuclear Information System (INIS)

Qiang, Wenjia; Huang, Yunpeng; Wan, Zhihui; Zhou, Bing

2017-01-01

Metallothionein (MT) protein families are a class of small and universal proteins rich in cysteine residues. They are synthesized in response to heavy metal stresses to sequester the toxic ions by metal-thiolate bridges. Five MT family members, namely MtnA, MtnB, MtnC, MtnD and MtnE, have been discovered and identified in Drosophila. These five isoforms of MTs are regulated by metal responsive transcription factor dMTF-1 and play differentiated but overlapping roles in detoxification of metal ions. Previous researches have shown that Drosophila MtnB responds to copper (Cu), cadmium (Cd) and zinc (Zn). Interestingly in this study we found that Drosophila MtnB expression also responds to elevated iron levels in the diet. Further investigations revealed that MtnB plays limited roles in iron detoxification, and the direct binding of MtnB to ferrous iron in vitro is also weak. The induction of MtnB by iron turns out to be mediated by iron interference of other metals, because EDTA at even a partial concentration of that of iron can suppress this induction. Indeed, in the presence of iron, zinc homeostasis is altered, as reflected by expression changes of zinc transporters dZIP1 and dZnT1. Thus, iron-mediated MtnB induction appears resulting from interrupted homeostasis of other metals such as zinc, which in turns induced MtnB expression. Metal-metal interaction may more widely exist than we expected. - Highlights: • Metallothionein B expression is regulated by iron in Drosophila melanogaster. • MtnB has limited physiological roles in iron detoxification. • Binding affinity of MtnB to iron is weak in vitro. • Induction of Drosophila MtnB by iron is mediated indirectly through metal-metal interaction.

The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

Directory of Open Access Journals (Sweden)

C. L. Hughes

2015-01-01

Full Text Available In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.

[Russian/German contacts in discussion on cellular mechanisms of aging and lifespan (author's transl)].

Science.gov (United States)

Duplenko, J K

1980-01-01

This is a brief review of the discussions which took place in natural literature at the end of XIX, and the beginning of XX century concerning the problems of cellular mechanism of aging, animal lifespan, death of metazoa and immortality of protozoa. The participation of German and Russian natural scientists in the discussion of cardinal gerontological questions is specially considered. The close relationship between the gerontological conceptions and the evolutionary ideas is emphasized. The author has established historical continuity of the above conceptions and modern evolutionary approaches to the predetermination of species' lifespan and mechanisms of aging.

DMPD: Signal transduction pathways mediated by the interaction of CpG DNA withToll-like receptor 9. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 14751759 Signal transduction pathways mediated by the interaction of CpG DNA withTo...;16(1):17-22. (.png) (.svg) (.html) (.csml) Show Signal transduction pathways mediated by the interaction of... CpG DNA withToll-like receptor 9. PubmedID 14751759 Title Signal transduction pathways media

Non-Identity-Mediated CRISPR-Bacteriophage Interaction Mediated via the Csy and Cas3 Proteins ▿#

Science.gov (United States)

Cady, Kyle C.; O'Toole, George A.

2011-01-01

Studies of the Escherichia, Neisseria, Thermotoga, and Mycobacteria clustered regularly interspaced short palindromic repeat (CRISPR) subtypes have resulted in a model whereby CRISPRs function as a defense system against bacteriophage infection and conjugative plasmid transfer. In contrast, we previously showed that the Yersinia-subtype CRISPR region of Pseudomonas aeruginosa strain UCBPP-PA14 plays no detectable role in viral immunity but instead is required for bacteriophage DMS3-dependent inhibition of biofilm formation by P. aeruginosa. The goal of this study is to define the components of the Yersinia-subtype CRISPR region required to mediate this bacteriophage-host interaction. We show that the Yersinia-subtype-specific CRISPR-associated (Cas) proteins Csy4 and Csy2 are essential for small CRISPR RNA (crRNA) production in vivo, while the Csy1 and Csy3 proteins are not absolutely required for production of these small RNAs. Further, we present evidence that the core Cas protein Cas3 functions downstream of small crRNA production and that this protein requires functional HD (predicted phosphohydrolase) and DEXD/H (predicted helicase) domains to suppress biofilm formation in DMS3 lysogens. We also determined that only spacer 1, which is not identical to any region of the DMS3 genome, mediates the CRISPR-dependent loss of biofilm formation. Our evidence suggests that gene 42 of phage DMS3 (DMS3-42) is targeted by CRISPR2 spacer 1 and that this targeting tolerates multiple point mutations between the spacer and DMS3-42 target sequence. This work demonstrates how the interaction between P. aeruginosa strain UCBPP-PA14 and bacteriophage DMS3 can be used to further our understanding of the diverse roles of CRISPR system function in bacteria. PMID:21398535

Impact of Service Extension and Services Interaction on B2b Sales: A Temporal Investigation Into Fuels’ Category

Directory of Open Access Journals (Sweden)

Marcos Inacio Severo de Almeida

2014-11-01

Full Text Available The scope of services marketing has a theoretical and empirical gap that refers to the impact of the provision of services on sales. This research opportunity is routinely highlighted in theoretical proposals such as the Augmented Service Offering (ASO, Innovation in Services (IS and Service Dominant Logic (SDL, which require alternative measures of combinations of product and service and the possible effects that these arrangements may cause. This article aims to investigate the impact of the extension and the interaction of services on Business to Business (B2B sales. Three hypotheses were tested with data from the fuel sector. Research was operationalized based on secondary data, ceded by an energy company, which comprise sales of regular and premium gasoline of this company to 19 gas stations along 27 months, totaling 513 observations. The study involved the construction of a generalized linear model with balanced, long and random effects panel structure. The three hypotheses were supported, identifying how the extensive principle of service contributes to the increased performance and conclude the existence of a direct, linear and positive impact of extension and interaction of services on B2B sales.

New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.

Directory of Open Access Journals (Sweden)

Malene Hansen

2005-07-01

Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

Directory of Open Access Journals (Sweden)

2005-07-01

Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

Increasing Responsive Parent–Child Interactions and Joint Engagement: Comparing the Influence of Parent-Mediated Intervention and Parent Psychoeducation

Science.gov (United States)

Gulsrud, Amanda; Kasari, Connie

2016-01-01

Enhancing immediate and contingent responding by caregivers to children’s signals is an important strategy to support social interactions between caregivers and their children with autism. Yet, there has been limited examination of parents’ responsive behaviour in association with children’s social behaviour post caregiver-mediated intervention. Eighty-five dyads were randomized to one of two 10-week caregiver-training interventions. Parent–child play interactions were coded for parental responsivity and children’s joint engagement. Significant gains in responsivity and time jointly engaged were found post JASPER parent-mediated intervention over a psychoeducation intervention. Further, combining higher levels of responsive behaviour with greater adoption of intervention strategies was associated with greater time jointly engaged. Findings encourage a focus on enhancing responsive behaviour in parent-mediated intervention models. PMID:26797940

Cultivating Composting Culture Activities among Citizens and Its Beneficial to Prolong the Landfill Lifespan

Science.gov (United States)

Azura Zakarya, Irnis; Azri Jamial, Khairul; Mat Tanda, Norazlinda

2018-03-01

Currently, the Ministry of Housing and Local Government manage solid waste in Malaysia, with the participation of the private sector. Food waste represents almost 60% of the total municipal solid waste disposed in the landfill. Material valorisation of food waste usually conducted by biological processes such as composting. Compost, an organic amendment, is the final product of the composting process. These processes are efficient, low cost and environmentally friendly alternative for managing food waste and are used extensively worldwide. Therefore, organic solid waste management practices program for the communities in Perlis was conducted. The main objective of this program was to instilling environment awareness especially among Perlis citizens. This study was investigated the impact of food waste or kitchen waste composting to the citizens in Perlis State and the beneficial of compost fertilizer to our environment especially in plant growth. Composting method was taught to the food premises owner, individuals, teachers, and students and their responses to the composting practices were then summarized. In future, we can prolong our landfill lifespan by practicing organic waste composting and can preserving our environment.

Cell-cell interactions mediate cytoskeleton organization and collective endothelial cell chemotaxis.

Science.gov (United States)

Shamloo, Amir

2014-09-01

This study investigates the role of cell-cell and cell-ligand interactions in cytoskeleton organization of endothelial cells (ECs) and their directional migration within a microfluidic device. The migration of ECs in response to a biochemical factor was studied. Mathematical analysis of the cell migration pathways and cellular cytoskeleton revealed that directional migration, migration persistence length, migration speed, and cytoskeletal stress fiber alignment can be mediated by the level of cell contacts as well as the presence or absence of a biochemical polarizing factor. It was shown that in the presence of a biochemical polarizing factor, higher cell density and more frequent cell contacts has a reinforcing effect on collective cell chemotaxis. In contrast, in the absence of a polarizing factor, high cell density can decrease or suppress the ability of the cells to migrate. Also, the correlation of actin stress fiber organization and alignment with directional migration of ECs was investigated. It was shown that in the presence of a biochemical polarizing factor, stress fibers within the cytoskeleton of ECs can be significantly aligned parallel to the gradient direction when the cells have higher level of contacts. The results also show that the organization and alignment of actin stress fibers is mediated by cell adhesion junctions during collective cell migration and introduce cell-cell interactions as a key factor during collective cell chemotaxis. © 2014 Wiley Periodicals, Inc.

Weight concern across the life-span: relationship to self-esteem and feminist identity.

Science.gov (United States)

Tiggemann, M; Stevens, C

1999-07-01

The aim of this study was to investigate the correlates of weight concern across the life-span. Questionnaires assessing weight concern, self-esteem, and feminist attitudes were completed in their homes by 180 women aged between 18 and 60 years. It was found that there was a negative relationship between weight concern and self-esteem for 30 to 49-year-old women, but not for younger or older women. A similar pattern held for feminist attitudes. Among 30 to 49-year-old women, a strong feminist orientation related to a lesser concern with weight. It was concluded that the meaning and experience of body weight and size change across the life-span.

Anisotropic surface-state-mediated RKKY interaction between adatoms on a hexagonal lattice

Science.gov (United States)

Patrone, Paul N.; Einstein, T. L.

2012-01-01

Motivated by recent numerical studies of Ag on Pt(111), we derive an expression for the RKKY interaction mediated by surface states, considering the effect of anisotropy in the Fermi edge. Our analysis is based on a stationary phase approximation. The main contribution to the interaction comes from electrons whose Fermi velocity vF is parallel to the vector R connecting the interacting adatoms; we show that, in general, the corresponding Fermi wave vector kF is not parallel to R. The interaction is oscillatory; the amplitude and wavelength of oscillations have angular dependence arising from the anisotropy of the surface-state band structure. The wavelength, in particular, is determined by the projection of this kF (corresponding to vF) onto the direction of R. Our analysis is easily generalized to other systems. For Ag on Pt(111), our results indicate that the RKKY interaction between pairs of adatoms should be nearly isotropic and so cannot account for the anisotropy found in the studies motivating our work. However, for metals with surface-state dispersions similar to Be(101¯0), we show that the RKKY interaction should have considerable anisotropy.

Mutually Beneficial Foreign Language Learning: Creating Meaningful Interactions through Video-Synchronous Computer-Mediated Communication

Science.gov (United States)

Kato, Fumie; Spring, Ryan; Mori, Chikako

2016-01-01

Providing learners of a foreign language with meaningful opportunities for interactions, specifically with native speakers, is especially challenging for instructors. One way to overcome this obstacle is through video-synchronous computer-mediated communication tools such as Skype software. This study reports quantitative and qualitative data from…

Stray current interaction in the system of two extensive underground conductors

International Nuclear Information System (INIS)

Machczynski, W.

1993-01-01

The important problem, technically, is to evaluate the harmful effects that an electrified railway has on nearby earth-return circuits (cables, pipelines). This paper considers the effects of a DC-electrified railway system on two extensive metal conductors buried in parallel in the vicinity of the tracks. The interaction between currents flowing in both underground conductors is taken into account, whereas the reaction of the conductors' currents on the track current is disregarded. The analysis given is applicable to any DC railway system in which tracks may be represented by a single earth return circuit with current energization. It is assumed in the paper that the system considered is linear and that the earth is homogeneous. The technical application of the method is illustrated by an example of computer simulation

Effect of RuCl{sub 3} Concentration on the Lifespan of Insoluble Anode for Cathodic Protection on PCCP

Energy Technology Data Exchange (ETDEWEB)

Cho, H. W.; Kim, Y. S. [Materials Research Center for Energy and Clean Technology, School of Materials Science and Engineering, Andong National University, Andong (Korea, Republic of); Chang, H. Y.; Lim, B. T.; Park, H. B. [Power Engineering Research Institute, KEPCO Engineering and Construction Company, Seongnam (Korea, Republic of)

2015-08-15

Prestressed Concrete steel Cylinder Pipe (PCCP) is extensively used as seawater pipes for cooling in nuclear power plants. The internal surface of PCCP is exposed to seawater, while the external surface is in direct contact with underground soil. Therefore, materials and strategies that would reduce the corrosion of its cylindrical steel body and external steel wiring need to be employed. To prevent against the failure of PCCP, operators provided a cathodic protection to the pre-stressing wires. The efficiency of cathodic protection is governed by the anodic performance of the system. A mixed metal oxide (MMO) electrode was developed to meet criteria of low over potential and high corrosion resistance. Increasing coating cycles improved the performance of the anode, but cycling should be minimized due to high materials cost. In this work, the effects of RuCl{sub 3} concentration on the electrochemical properties and lifespan of MMO anode were evaluated. With increasing concentration of RuCl{sub 3}, the oxygen evolution potential lowered and polarization resistance were also reduced but demonstrated an increase in passive current density and oxygen evolution current density. To improve the electrochemical properties of the MMO anode, RuCl{sub 3} concentration was increased. As a result, the number of required coating cycles were reduced substantially and the MMO anode achieved an excellent lifespan of over 80 years. Thus, we concluded that the relationship between RuCl{sub 3} concentration and coating cycles can be summarized as follows: No. of coating cycle = 0.48{sup *}[RuCl{sub 3} concentration, M]{sup -0.97}.

On the challenge of a century lifespan satellite

Science.gov (United States)

Gonzalo, Jesús; Domínguez, Diego; López, Deibi

2014-10-01

This paper provides a review of the main issues affecting satellite survivability, including a discussion on the technologies to mitigate the risks and to enhance system reliability. The feasibility of a 100-year lifespan space mission is taken as the guiding thread for the discussion. Such a mission, defined with a few preliminary requirements, could be used to deliver messages to our descendants regardless of the on-ground contingencies. After the analysis of the main threats for long endurance in space, including radiation, debris and micrometeoroids, atmospheric drag and thermal environment, the available solutions are investigated. A trade-off study analyses orbital profiles from the point of view of radiation, thermal stability and decay rate, providing best locations to maximize lifespan. Special attention is also paid to on-board power, in terms of energy harvesting and accumulation, highlighting the limitations of current assets, i.e. solar panels and batteries, and revealing possible future solutions. Furthermore, the review includes electronics, non-volatile memories and communication elements, which need extra hardening against radiation and thermal cycling if extra-long endurance is required. As a result of the analysis, a century-lifetime mission is depicted by putting together all the reviewed concepts. The satellite, equipped with reliability enhanced elements and system-level solutions such as smart hibernation policies, could provide limited but still useful performance after a 100-year flight.

Sex differences in facial emotion perception ability across the lifespan.

Science.gov (United States)

Olderbak, Sally; Wilhelm, Oliver; Hildebrandt, Andrea; Quoidbach, Jordi

2018-03-22

Perception of emotion in the face is a key component of human social cognition and is considered vital for many domains of life; however, little is known about how this ability differs across the lifespan for men and women. We addressed this question with a large community sample (N = 100,257) of persons ranging from younger than 15 to older than 60 years of age. Participants were viewers of the television show "Tout le Monde Joue", and the task was presented on television, with participants responding via their mobile devices. Applying latent variable modeling, and establishing measurement invariance between males and females and across age, we found that, for both males and females, emotion perception abilities peak between the ages of 15 and 30, with poorer performance by younger adults and declining performance after the age of 30. In addition, we show a consistent advantage by females across the lifespan, which decreases in magnitude with increasing age. This large scale study with a wide range of people and testing environments suggests these effects are largely robust. Implications are discussed.

Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis.

Directory of Open Access Journals (Sweden)

Zhengui Zheng

Full Text Available Mediator is a conserved multi-protein complex that plays an important role in regulating transcription by mediating interactions between transcriptional activator proteins and RNA polymerase II. Much evidence exists that Mediator plays a constitutive role in the transcription of all genes transcribed by RNA polymerase II. However, evidence is mounting that specific Mediator subunits may control the developmental regulation of specific subsets of RNA polymerase II-dependent genes. Although the Mediator complex has been extensively studied in yeast and mammals, only a few reports on Mediator function in flowering time control of plants, little is known about Mediator function in floral organ identity. Here we show that in Arabidopsis thaliana, MEDIATOR SUBUNIT 18 (MED18 affects flowering time and floral organ formation through FLOWERING LOCUS C (FLC and AGAMOUS (AG. A MED18 loss-of-function mutant showed a remarkable syndrome of later flowering and altered floral organ number. We show that FLC and AG mRNA levels and AG expression patterns are altered in the mutant. Our results support parallels between the regulation of FLC and AG and demonstrate a developmental role for Mediator in plants.

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults

Science.gov (United States)

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-01-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys (N=847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations. PMID:26113769

Life-Span Differences in the Uses and Gratifications of Tablets: Implications for Older Adults.

Science.gov (United States)

Magsamen-Conrad, Kate; Dowd, John; Abuljadail, Mohammad; Alsulaiman, Saud; Shareefi, Adnan

2015-11-01

This study extends Uses and Gratifications theory by examining the uses and gratifications of a new technological device, the tablet computer, and investigating the differential uses and gratifications of tablet computers across the life-span. First, we utilized a six-week tablet training intervention to adapt and extend existing measures to the tablet as a technological device. Next, we used paper-based and online surveys ( N =847), we confirmed four main uses of tablets: 1) Information Seeking, 2) Relationship Maintenance, 3) Style, 4) Amusement and Killing time, and added one additional use category 5) Organization. We discovered differences among the five main uses of tablets across the life-span, with older adults using tablets the least overall. Builders, Boomers, GenX and GenY all reported the highest means for information seeking. Finally, we used a structural equation model to examine how uses and gratifications predicts hours of tablet use. The study provides limitations and suggestions for future research and marketers. In particular, this study offers insight to the relevancy of theory as it applies to particular information and communication technologies and consideration of how different periods in the life-span affect tablet motivations.

FQC Dashboard: integrates FastQC results into a web-based, interactive, and extensible FASTQ quality control tool

Energy Technology Data Exchange (ETDEWEB)

Brown, Joseph; Pirrung, Meg; McCue, Lee Ann

2017-06-09

FQC is software that facilitates large-scale quality control of FASTQ files by carrying out a QC protocol, parsing results, and aggregating quality metrics within and across experiments into an interactive dashboard. The dashboard utilizes human-readable configuration files to manipulate the pages and tabs, and is extensible with CSV data.

Proliferative lifespan is conserved after nuclear transfer.

Science.gov (United States)

Clark, A John; Ferrier, Patricia; Aslam, Samena; Burl, Sarah; Denning, Chris; Wylie, Diana; Ross, Arlene; de Sousa, Paul; Wilmut, Ian; Cui, Wei

2003-06-01

Cultured primary cells exhibit a finite proliferative lifespan, termed the Hayflick limit. Cloning by nuclear transfer can reverse this cellular ageing process and can be accomplished with cultured cells nearing senescence. Here we describe nuclear transfer experiments in which donor cell lines at different ages and with different proliferative capacities were used to clone foetuses and animals from which new primary cell lines were generated. The rederived lines had the same proliferative capacity and rate of telomere shortening as the donor cell lines, suggesting that these are innate, genetically determined, properties that are conserved by nuclear transfer.

Modality Differences in Timing and Temporal Memory throughout the Lifespan

Science.gov (United States)

Lustig, Cindy; Meck, Warren H.

2011-01-01

The perception of time is heavily influenced by attention and memory, both of which change over the lifespan. In the current study, children (8 yrs), young adults (18-25 yrs), and older adults (60-75 yrs) were tested on a duration bisection procedure using 3 and 6-s auditory and visual signals as anchor durations. During test, participants were…

Sexuality and Developmental Disability: Obstacles to Healthy Sexuality throughout the Lifespan

Science.gov (United States)

Richards, Deborah; Miodrag, Nancy; Watson, Shelley L.

2006-01-01

This paper presents a lifespan perspective of sexuality issues for individuals with developmental disabilities. Individuals with developmental disabilities are human beings who have historically been denied the right to express their sexuality or engage in sexual relationships due to misconceptions or negative attitudes. Using a hypothetical case…

Collaboration of Extension and Grape Industry Members to Create a New Extension Publication

Science.gov (United States)

Stafne, Eric T.; Ingels, George; Ingels, Jane; Carroll, Becky

2016-01-01

Collaboration is an important part of the interaction between Extension and industry. Successful sharing of workload can provide benefits for both parties. A project to create a workbook to address vineyard sustainability was initiated by members of the Oklahoma grape industry with assistance from land-grant university Extension. Productive…

Control of intestinal bacterial proliferation in regulation of lifespan in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Portal-Celhay Cynthia

2012-03-01

Full Text Available Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

Tenebrio molitor Extracts Modulate the Response to Environmental Stressors and Extend Lifespan in Caenorhabditis elegans.

Science.gov (United States)

Won, Seong-Min; Cha, Hye-Uk; Yi, Sun Shin; Kim, Sung-Jo; Park, Sang-Kyu

2016-09-08

Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.

Lifespan estimation of seal welded super stainless steels for water condenser of nuclear power plants

Science.gov (United States)

Kim, Young Sik; Park, Sujin; Chang, Hyun Young

2014-01-01

When sea water was used as cooling water for water condenser of nuclear power plants, commercial stainless steels can not be applied because chloride concentration exceeds 20,000 ppm. There are many opinions for the materials selection of tube and tube sheets of a condenser. This work reviewed the application guide line of stainless steels for sea-water facilities and the estimation equations of lifespan were proposed from the analyses of both field data for sea water condenser and experimental results of corrosion. Empirical equations for lifespan estimation were derived from the pit initiation time and re-tubing time of stainless steel tubing in sea water condenser of nuclear power plants. The lifespan of seal-welded super austenitic stainless steel tube/tube sheet was calculated from these equations. Critical pitting temperature of seal-welded PRE 50 grade super stainless steel was evaluated as 60 °C. Using the proposed equation in engineering aspect, tube pitting corrosion time of seal-welded tube/tube sheet was calculated as 69.8 years and re-tubing time was estimated as 82.0 years.

New interactions in the dark sector mediated by dark energy

International Nuclear Information System (INIS)

Brookfield, Anthony W.; Bruck, Carsten van de; Hall, Lisa M. H.

2008-01-01

Cosmological observations have revealed the existence of a dark matter sector, which is commonly assumed to be made up of one particle species only. However, this sector might be more complicated than we currently believe: there might be more than one dark matter species (for example, two components of cold dark matter or a mixture of hot and cold dark matter) and there may be new interactions between these particles. In this paper we study the possibility of multiple dark matter species and interactions mediated by a dark energy field. We study both the background and the perturbation evolution in these scenarios. We find that the background evolution of a system of multiple dark matter particles (with constant couplings) mimics a single fluid with a time-varying coupling parameter. However, this is no longer true on the perturbative level. We study the case of attractive and repulsive forces as well as a mixture of cold and hot dark matter particles

Results from Pion-Carbon Interactions Measured by NA61/SHINE for Improved Understanding of Extensive Air Showers

CERN Document Server

Herve, Alexander

2015-07-21

The interpretation of extensive air shower measurements, produced by ultra-high energy cosmic rays, relies on the correct modeling of the hadron-air interactions that occur during the shower development. The majority of hadronic particles are produced at equivalent beam energies below the TeV range. NA61/SHINE is a fixed target experiment using secondary beams produced at CERN at the SPS. Hadron-hadron interactions have been recorded at beam momenta between 13 and 350 GeV/c with a wide-acceptance spectrometer. In this contribution we present measurements of the spectra of charged pions and the $\\rho^0$ production in pion-carbon interactions, which are essential for modeling of air showers.

Constraints on light mediators: confronting dark matter searches with B physics

CERN Document Server

Schmidt-Hoberg, Kai; Winkler, Martin Wolfgang

2013-01-01

Light scalars appear in many well-motivated extensions of the Standard Model including supersymmetric models with additional gauge singlets. Such scalars could mediate the interactions between dark matter and nuclei, giving rise to the tentative signals observed by several dark matter direct detection experiments including CDMS-Si. In this letter, we derive strong new limits on light scalar mediators by using the LHCb, Belle and BaBar searches for rare $\\Upsilon$ and B decays. These limits rule out significant parts of the parameter space favored by CDMS-Si. Nevertheless, as current searches are not optimized for investigating weakly coupled light scalars, a further increase in experimental sensitivity could be achieved by relaxing requirements in the event selection.

Constraints on light mediators. Confronting dark matter searches with B physics

Energy Technology Data Exchange (ETDEWEB)

Schmidt-Hoberg, Kai [European Organization for Nuclear Research (CERN), Geneva (Switzerland); Staub, Florian [Bonn Univ. (Germany). Bethe Center for Theoretical Physics; Bonn Univ. (Germany). Physikalisches Inst.; Winkler, Martin Wolfgang [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

2013-11-15

Light scalars appear in many well-motivated extensions of the Standard Model including supersymmetric models with additional gauge singlets. Such scalars could mediate the interactions between dark matter and nuclei, giving rise to the tentative signals observed by several dark matter direct detection experiments including CDMS-Si. In this letter, we derive strong new limits on light scalar mediators by using the LHCb, Belle and BaBar searches for rare {Upsilon} and B decays. These limits rule out significant parts of the parameter space favored by CDMS-Si. Nevertheless, as current searches are not optimized for investigating weakly coupled light scalars, a further increase in experimental sensitivity could be achieved by relaxing requirements in the event selection.

Homeless Aging Veterans in Transition: A Life-Span Perspective

Directory of Open Access Journals (Sweden)

Carla J. Thompson

2013-01-01

Full Text Available The need for counseling and career/educational services for homeless veterans has captured political and economic venues for more than 25 years. Veterans are three times more likely to become homeless than the general population if veterans live in poverty or are minority veterans. This mixed methods study emphasized a life-span perspective approach for exploring factors influencing normative aging and life-quality of 39 homeless veterans in Alabama and Florida. Seven descriptive quantitative and qualitative research questions framed the investigation. Study participants completed a quantitative survey reflecting their preferences and needs with a subset of the sample (N=12 also participating in individual qualitative interview sessions. Thirty-two service providers and stakeholders completed quantitative surveys. Empirical and qualitative data with appropriate triangulation procedures provided interpretive information relative to a life-span development perspective. Study findings provide evidence of the need for future research efforts to address strategies that focus on the health and economic challenges of veterans before they are threatened with the possibility of homelessness. Implications of the study findings provide important information associated with the premise that human development occurs throughout life with specific characteristics influencing the individual’s passage. Implications for aging/homelessness research are grounded in late-life transitioning and human development intervention considerations.

Stability and Change in Risk-Taking Propensity Across the Adult Lifespan

Science.gov (United States)

Josef, Anika K.; Richter, David; Samanez-Larkin, Gregory R.; Wagner, Gert G.; Hertwig, Ralph; Mata, Rui

2016-01-01

Can risk-taking propensity be thought of as a trait that captures individual differences across domains, measures, and time? Studying stability in risk-taking propensities across the lifespan can help to answer such questions by uncovering parallel, or divergent, trajectories across domains and measures. We contribute to this effort by using data from respondents aged 18 to 85 in the German Socio-Economic Panel Study (SOEP) and by examining (1) differential stability, (2) mean-level differences, and (3) individual-level changes in self-reported general (N = 44,076) and domain-specific (N =11,903) risk-taking propensities across adulthood. In addition, we investigate (4) the correspondence between cross-sectional trajectories of self-report and behavioral measures of social (trust game; N = 646) and nonsocial (monetary gamble; N = 433) risk taking. The results suggest that risk-taking propensity can be understood as a trait with moderate stability. Results show reliable mean-level differences across the lifespan, with risk-taking propensities typically decreasing with age, although significant variation emerges across domains and individuals. Interestingly, the mean-level trajectory for behavioral measures of social and nonsocial risk taking was similar to those obtained from self-reported risk, despite small correlations between task behavior and self-reports. Individual-level analyses suggest a link between changes in risk-taking propensities both across domains and in relation to changes in some of the Big Five personality traits. Overall, these results raise important questions concerning the role of common processes or events that shape the lifespan development of risk-taking across domains as well as other major personality facets. PMID:26820061

Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

Science.gov (United States)

Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

2017-10-01

The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

Interventional Effects for Mediation Analysis with Multiple Mediators.

Science.gov (United States)

Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

Directory of Open Access Journals (Sweden)

Felipe Merino

2015-06-01

Full Text Available Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

Ratio-of-Mediator-Probability Weighting for Causal Mediation Analysis in the Presence of Treatment-by-Mediator Interaction

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Hong, Guanglei; Deutsch, Jonah; Hill, Heather D.

2015-01-01

Conventional methods for mediation analysis generate biased results when the mediator--outcome relationship depends on the treatment condition. This article shows how the ratio-of-mediator-probability weighting (RMPW) method can be used to decompose total effects into natural direct and indirect effects in the presence of treatment-by-mediator…

Vicious vs. Virtuous Cycles of Turn Negotiation in Video-Mediated Telecollaboration: Interactional Sociolinguistics Perspective

Science.gov (United States)

Akiyama, Yuka

2016-01-01

To examine how participants' different eTandem experiences could be attributed to the way they co-constructed turns, this study analyzed turn negotiation practices of one dyad who engaged in video-mediated interaction between Japan and America. This dyad was chosen for analysis because they expressed the greatest frustration and required a…

Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive approaches

CSIR Research Space (South Africa)

Musee, N

2012-05-01

Full Text Available -1 NANOLCA Symposium, "Safety issues and regulatory challenges of nanomaterials", San Sebastian, Spain, 3-4 May 2012 Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive...

Phenotypic analysis of newly isolated short-lifespan Neurospora crassa mutant deficient in a high mobility group box protein.

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Yoshihara, Ryouhei; Li, ZhengHao; Ishimori, Keisuke; Kuwabara, Kazuki; Hatakeyama, Shin; Tanaka, Shuuitsu

2017-08-01

To elucidate genetic mechanisms affecting the lifespan of the filamentous fungus Neurospora crassa, we attempted to identify a gene of which a defect causes a short-lifespan. By screening a Neurospora knockout library, provided by the Fungal Genetics Stock Center at Kansas State University, several KO strains with a short-lifespan were isolated. FGSC#11693 is one of these, which shows similar phenotypes to known Neurospora short-lifespan mutants as follows: 1) hyphal growth ceases after about 2weeks of cultivation, despite that of the wild-type continuing for over 2years, 2) viability of conidia is lower than that of the wild-type, and 3) high sensitivity to mutagens such as methyl methanesulfonate, ultraviolet radiation, and hydroxyl urea is exhibited. The NCU number of the knocked-out gene in the KO strain is NCU02695, and recovery from the short-lifespan and mutagen sensitivity was achieved by the introduction of this gene from the wild-type. The putative amino acid sequence of the knocked-out gene contains two high mobility group box domains and a mitochondrial localization signal is found at the N-terminal of this sequence. Upon analyzing the subcellular localization of the gene product fused with GFP, GFP signals were detected in mitochondria. From these observations, the gene and KO strain were named mitochondrial high mobility group box protein 1 (MHG1) and mhg1 KO strain, respectively. The amount of mtDNA relative to the nuclear amount was lower in the mhg1 KO strain than in the wild-type. mtDNA aberration was also observed in the mhg1 KO strain. These results suggest that the MHG1 protein plays an important role in the maintenance of mitochondrial DNA, and mitochondrial abnormality caused by mtDNA aberration is responsible for the short-lifespan of the mhg1 KO strain. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterologous expression of tri5 gene in Trichoderma harzianum: Effect of trichodiene production on Trichoderma environmental interactions

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Terpenes form a large class of compounds that have a variety of roles in mediating antagonistic and beneficial interactions among organisms. The trichothecenes are phytotoxic sesquiterpenoid compounds that have been extensively studied, mainly in the genus Fusarium, that can act as virulence factors...

Entropy Generation and Human Aging: Lifespan Entropy and Effect of Physical Activity Level

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Silva, Carlos; Annamalai, Kalyan

2008-06-01

The first and second laws of thermodynamics were applied to biochemical reactions typical of human metabolism. An open-system model was used for a human body. Energy conservation, availability and entropy balances were performed to obtain the entropy generated for the main food components. Quantitative results for entropy generation were obtained as a function of age using the databases from the U.S. Food and Nutrition Board (FNB) and Centers for Disease Control and Prevention (CDC), which provide energy requirements and food intake composition as a function of age, weight and stature. Numerical integration was performed through human lifespan for different levels of physical activity. Results were presented and analyzed. Entropy generated over the lifespan of average individuals (natural death) was found to be 11,404 kJ/ºK per kg of body mass with a rate of generation three times higher on infants than on the elderly. The entropy generated predicts a life span of 73.78 and 81.61 years for the average U.S. male and female individuals respectively, which are values that closely match the average lifespan from statistics (74.63 and 80.36 years). From the analysis of the effect of different activity levels, it is shown that entropy generated increases with physical activity, suggesting that exercise should be kept to a “healthy minimum” if entropy generation is to be minimized.

Precise colocalization of interacting structural and pigmentary elements generates extensive color pattern variation in Phelsuma lizards

Science.gov (United States)

2013-01-01

Background Color traits in animals play crucial roles in thermoregulation, photoprotection, camouflage, and visual communication, and are amenable to objective quantification and modeling. However, the extensive variation in non-melanic pigments and structural colors in squamate reptiles has been largely disregarded. Here, we used an integrated approach to investigate the morphological basis and physical mechanisms generating variation in color traits in tropical day geckos of the genus Phelsuma. Results Combining histology, optics, mass spectrometry, and UV and Raman spectroscopy, we found that the extensive variation in color patterns within and among Phelsuma species is generated by complex interactions between, on the one hand, chromatophores containing yellow/red pteridine pigments and, on the other hand, iridophores producing structural color by constructive interference of light with guanine nanocrystals. More specifically, we show that 1) the hue of the vivid dorsolateral skin is modulated both by variation in geometry of structural, highly ordered narrowband reflectors, and by the presence of yellow pigments, and 2) that the reflectivity of the white belly and of dorsolateral pigmentary red marks, is increased by underlying structural disorganized broadband reflectors. Most importantly, these interactions require precise colocalization of yellow and red chromatophores with different types of iridophores, characterized by ordered and disordered nanocrystals, respectively. We validated these results through numerical simulations combining pigmentary components with a multilayer interferential optical model. Finally, we show that melanophores form dark lateral patterns but do not significantly contribute to variation in blue/green or red coloration, and that changes in the pH or redox state of pigments provide yet another source of color variation in squamates. Conclusions Precisely colocalized interacting pigmentary and structural elements generate extensive

The Effects of Leader-Member Exchanges on the Relationships Between Extension Agents and County Extension Directors in Florida

OpenAIRE

Matt Benge; Amy Harder

2017-01-01

The relationship between a supervisor and employee has a direct effect on the employee’s job satisfaction, work productivity, and efficiency. Understanding the interactions between Extension agents and County Extension Directors is critical to maintaining positive relationships and providing adequate support to Extension supervisors through professional development and training opportunities. This article examined the dyadic relationships between Extension agents and County Extension Direc...

Lifespan metabolic potential of the unicellular organisms expressed by Boltzmann constant, absolute temperature and proton mass

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Atanasov, Atanas Todorov

2016-12-01

The unicellular organisms and phages are the first appeared fundamental living organisms on the Earth. The total metabolic energy (Els, J) of these organisms can be expressed by their lifespan metabolic potential (Als, J/kg) and body mass (M, kg): Els =Als M. In this study we found a different expression - by Boltzmann's constant (k, J/K), nucleon mass (mp+, kg) of protons (and neutrons), body mass (M, kg) of organism or mass (Ms) of biomolecules (proteins, nucleotides, polysaccharides and lipids) building organism, and the absolute temperature (T, K). The found equations are: Els= (M/mp+)kT for phages and Els=(Ms/mp+)kT for the unicellular organisms. From these equations the lifespan metabolic potential can be expressed as: Als=Els/M= (k/mp+)T for phages and Als=Els/M= (k/3.3mp+)T for unicellular organisms. The temperature-normated lifespan metabolic potential (Als/T, J/K.kg) is equals to the ratio between Boltzmann's constant and nucleon mass: Als/T=k/mp+ for phages and Als/T=k/3.3mp+ for unicellular organisms. The numerical value of the k/mp+ ratio is equals to 8.254×103 J/K.kg, and the numerical value of k/3.3mp+ ratio is equal to 2.497×103 J/K.kg. These values of temperature-normated lifespan metabolic potential could be considered fundamental for the unicellular organisms.

Patterns of hippocampal-neocortical interactions in the retrieval of episodic autobiographical memories across the entire life-span of aged adults

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Viard, Armelle; Lebreton, Karine; Chételat, Gaël; Desgranges, Béatrice; Landeau, Brigitte; Young, Alan; De La Sayette, Vincent; Eustache, Francis; Piolino, Pascale

2010-01-01

We previously demonstrated that Episodic Autobiographical Memories (EAMs) rely on a network of brain regions comprising the medial temporal lobe (MTL) and distributed neocortical regions regardless of their remoteness. The findings supported the model of memory consolidation which proposes a permanent role of MTL during EAM retrieval (Multiple-Trace Theory or MTT) rather than a temporary role (standard model). Our present aim was to expand the results by examining the interactions between the MTL and neocortical regions (or MTL-neocortical links) during EAM retrieval with varying retention intervals. We used an experimental paradigm specially designed to engage aged participants in the recollection of EAMs, extracted from five different time-periods, covering their whole life-span, in order to examine correlations between activation in the MTL and neocortical regions. The nature of the memories was checked at debriefing by means of behavioral measures to control the degree of episodicity and properties of memories. Targeted correlational analyses carried out on the MTL, frontal, lateral temporal and posterior regions revealed strong links between the MTL and neocortex during the retrieval of both recent and remote EAMs, challenging the standard model of memory consolidation and supporting MTT instead. Further confirmation was given by results showing that activation in the left and right hippocampi significantly correlated during the retrieval of both recent and remote memories. Correlations among extra-MTL neocortical regions also emerged for all time-periods, confirming the critical role of the prefrontal, temporal (lateral temporal cortex and temporal pole), precuneus and posterior cingulate regions in EAM retrieval. Overall, this paper emphasizes the role of a bilateral network of MTL and neocortical areas whose activation correlate during the recollection of rich phenomenological recent and remote EAMs. PMID:19338022

Life-span radiation effects studies in animals: what can they tell us

International Nuclear Information System (INIS)

Thompson, R.C.

1984-05-01

Results from life-span studies in a variety of animal species have found relatively little application in the development of radiation risk factors for various organs of man. This paper discusses possible reasons for this situation and presents recommendations to correct it

Perceptions of love across the lifespan: differences in passion, intimacy, and commitment

NARCIS (Netherlands)

Sumter, S.R.; Valkenburg, P.M.; Peter, J.

2013-01-01

This study investigated perceptions of love across the lifespan using Sternberg’s triangular theory of love, which distinguishes between passion, intimacy, and commitment. The study aimed to (a) investigate the psychometric properties of the short Triangular Love Scale (TLS-short) in adolescents and

Do "big guys" really die younger? An examination of height and lifespan in former professional basketball players.

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Lemez, Srdjan; Wattie, Nick; Baker, Joseph

2017-01-01

While factors such as genetics may mediate the relationship between height and mortality, evidence suggests that larger body size may be an important risk indicator of reduced lifespan longevity in particular. This study critically examined this relationship in professional basketball players. We examined living and deceased players who have played in the National Basketball Association (debut between 1946-2010) and/or the American Basketball Association (1967-1976) using descriptive and Kaplan-Meier and Cox regression analyses. The cut-off date for death data collection was December 11, 2015. Overall, 3,901 living and deceased players were identified and had a mean height of 197.78 cm (± 9.29, Range: 160.02-231.14), and of those, 787 former players were identified as deceased with a mean height of 193.88 cm (± 8.83, Range: 167.6-228.6). Descriptive findings indicated that the tallest players (top 5%) died younger than the shortest players (bottom 5%) in all but one birth decade (1941-1950). Similarly, survival analyses showed a significant relationship between height and lifespan longevity when both dichotomizing [χ2 (1) = 13.04, p < .05] and trichotomizing [χ2 (2) = 18.05, p < .05] the predictor variable height per birth decade, where taller players had a significantly higher mortality risk compared to shorter players through median (HR: 1.30, 95% CI: 1.13-1.50, p < .05) and trichotomized tertile split (HR: 1.40, 95% CI: 1.18-1.68, p <. 05; tallest 33.3% compared to shortest 33.3%) analyses. The uniqueness of examining the height-longevity hypothesis in this relatively homogeneous sub-population should be considered when interpreting these results. Further understanding of the potential risks of early mortality can help generate discourse regarding potential at-risk cohorts of the athlete population.

Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

Energy Technology Data Exchange (ETDEWEB)

Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

2015-01-02

Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

Cognitive Creative Abilities and Self-Esteem across the Adult Life-Span.

Science.gov (United States)

Jaquish, Gail A.; Ripple, Richard E.

1981-01-01

Explored the relationship between divergent thinking and self-esteem across the adult lifespan. Subjects from 18 to 84 years of age responded to a self-esteem inventory and an exercise in divergent thinking. Self-esteem predicted divergent thinking across age groups, whereas age differences accounted for little variance in divergent thinking.…

Dance Talent Development across the Lifespan: A Review of Current Research

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Chua, Joey

2014-01-01

The aim of this study is to compile and synthesize empirically based articles published between 2000 and 2012 about the critical issues of developing dance talents across the lifespan of children, adolescents and adults. The present article updates and extends a review article related to the identification and development in dance written by…

Building and Managing Makerspaces in Extension

Science.gov (United States)

Francis, Dave; Hill, Paul; Graham, Dallini; Swadley, Emy; Esplin, Kaleb

2017-01-01

As traditional face-to-face Extension office interactions are supplanted by online education options, the makerspace offers a venue for authentic engagement between Extension and the community. In makerspaces, learners make and learn from one another in a cooperative learning environment. Through involvement in the maker movement, Extension has an…

Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan.

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Wolkow, Catherine A; Iser, Wendy B

2006-05-01

Uncoupling proteins (UCPs), which dissipate the mitochondrial proton gradient, have the ability to decouple mitochodrial respiration from ATP production. Since mitochondrial electron transport is a major source of free radical production, it is possible that UCP activity might impact free radical production. Free radicals can react with and damage cellular proteins, DNA and lipids. Accumulated damage from oxidative stress is believed to be a major contributor to cellular decline during aging. If UCP function were to impact mitochondrial free radical production, then one would expect to find a link between UCP activity and aging. This theory has recently been tested in a handful of organisms whose genomes contain UCP1 homologs. Interestingly, these experiments indicate that UCP homologs can affect lifespan, although they do not support a simple relationship between UCP activity and aging. Instead, UCP-like proteins appear to have a variety of effects on lifespan, and on pathways implicated in lifespan regulation. One possible explanation for this complex picture is that UCP homologs may have tissue-specific effects that complicate their effects on aging. Furthermore, the functional analysis of UCP1 homologs is incomplete. Thus, these proteins may perform functions in addition to, or instead of, mitochondrial uncoupling. Although these studies have not revealed a clear picture of UCP effects on aging, they have contributed to the growing knowledge base for these interesting proteins. Future biochemical and genetic investigation of UCP-like proteins will do much to clarify their functions and to identify the regulatory networks in which they are involved.

The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan.

Directory of Open Access Journals (Sweden)

Geilson Lima Santana

Full Text Available Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942. Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively, panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively, and panic was related to the transition from ideation to attempts (OR 2.7. Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively, and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8. In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology.

A methodology for the analysis of differential coexpression across the human lifespan.

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Gillis, Jesse; Pavlidis, Paul

2009-09-22

Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging, differential coexpression has not. Generalizing differential coexpression analysis to many time points presents a methodological challenge. Here we introduce a method for analyzing changes in coexpression across multiple ordered groups (e.g., over time) and extensively test its validity and usefulness. Our method is based on the use of the Haar basis set to efficiently represent changes in coexpression at multiple time scales, and thus represents a principled and generalizable extension of the idea of differential coexpression to life stage data. We used published microarray studies categorized by age to test the methodology. We validated the methodology by testing our ability to reconstruct Gene Ontology (GO) categories using our measure of differential coexpression and compared this result to using coexpression alone. Our method allows significant improvement in characterizing these groups of genes. Further, we examine the statistical properties of our measure of differential coexpression and establish that the results are significant both statistically and by an improvement in semantic similarity. In addition, we found that our method finds more significant changes in gene relationships compared to several other methods of expressing temporal relationships between genes, such as coexpression over time. Differential coexpression over age generates significant and biologically relevant information about the genes producing it. Our Haar basis methodology for determining age-related differential coexpression performs better than other tested methods. The Haar basis set also lends itself to ready interpretation

Pair Interactions and Mode of Communication: Comparing Face-to-Face and Computer Mediated Communication

Science.gov (United States)

Tan, Lan Liana; Wigglesworth, Gillian; Storch, Neomy

2010-01-01

In today's second language classrooms, students are often asked to work in pairs or small groups. Such collaboration can take place face-to-face, but now more often via computer mediated communication. This paper reports on a study which investigated the effect of the medium of communication on the nature of pair interaction. The study involved…

Oral Computer-Mediated Interaction Between L2 Learners: It’s About Time!

Directory of Open Access Journals (Sweden)

Yanguas, Íñigo

2010-10-01

Full Text Available This study explores task-based, synchronous oral computer-mediated communication (CMC among intermediate-level learners of Spanish. In particular, this paper examines (a how learners in video and audio CMC groups negotiate for meaning during task-based interaction, (b possible differences between both oral CMC modes and traditional face-to-face (FTF communication, and (c how this oral computer mediated negotiation compares to that found in the text-based CMC literature. Fifteen learner-to-learner dyads were randomly assigned to an audio group, a video group, and a FTF control group to complete a jigsaw task that was seeded with 16 unknown lexical items. Experimental groups used Skype, free online communication software, to carry out the task. The transcripts of the conversations reveal that oral CMC groups do indeed negotiate for meaning in this multimedia context when non-understanding occurs between speakers. In addition, results showed differences in the way audio and video groups carry out these negotiations, which were mainly due to the lack of visual contact in the audio group. No differences were found between video and FTF groups. Furthermore, oral CMC turn-taking patterns were shown to be very similar to FTF patterns but opposite to those found in written synchronous CMC. Oral CMC interaction patterns are shown to be more versatile.

Linking agricultural practices, mycorrhizal fungi, and traits mediating plant-insect interactions.

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Barber, Nicholas A; Kiers, E Toby; Theis, Nina; Hazzard, Ruth V; Adler, Lynn S

2013-10-01

Agricultural management has profound effects on soil communities. Activities such as fertilizer inputs can modify the composition of arbuscular mycorrhizal fungi (AMF) communities, which form important symbioses with the roots of most crop plants. Intensive conventional agricultural management may select for less mutualistic AMF with reduced benefits to host plants compared to organic management, but these differences are poorly understood. AMF are generally evaluated based on their direct growth effects on plants. However, mycorrhizal colonization also may alter plant traits such as tissue nutrients, defensive chemistry, or floral traits, which mediate important plant-insect interactions like herbivory and pollination. To determine the effect of AMF from different farming practices on plant performance and traits that putatively mediate species interactions, we performed a greenhouse study by inoculating Cucumis sativus (cucumber, Cucurbitaceae) with AMF from conventional farms, organic farms, and a commercial AMF inoculum. We measured growth and a suite of plant traits hypothesized to be important predictors of herbivore resistance and pollinator attraction. Several leaf and root traits and flower production were significantly affected by AMF inoculum. Both conventional and organic AMF reduced leaf P content but increased Na content compared to control and commercial AMF. Leaf defenses were unaffected by AMF treatments, but conventional AMF increased root cucurbitacin C, the primary defensive chemical of C. sativus, compared to organic AMF. These effects may have important consequences for herbivore preference and population dynamics. AMF from both organic and conventional farms decreased flower production relative to commercial and control treatments, which may reduce pollinator attraction and plant reproduction. AMF from both farm types also reduced seed germination, but effects on plant growth were limited. Our results suggest that studies only considering AMF

Mental health and illness in relation to physical health across the lifespan

NARCIS (Netherlands)

Lamers, S.M.A.; Westerhof, Gerben Johan; Bohlmeijer, Ernst Thomas; Keyes, Corey L.M.; Sinnott, J.D.

2013-01-01

This chapter addresses mental health as more than the absence of disease, also approaching it from a positive perspective as the presence of well-being across the lifespan. The study described in the chapter investigated the association of age with psychopathology and positive mental health,

Lifespan development of attentiveness in domestic dogs: drawing parallels with humans

Directory of Open Access Journals (Sweden)

Lisa Jessica Wallis

2014-02-01

Full Text Available Attention is pivotal to consciousness, perception, cognition, and working memory in all mammals, and therefore changes in attention over the lifespan are likely to influence development and aging of all of these functions. Due to their evolutionary and developmental history, the dog is being recognised as an important species for modelling human healthspan, aging and associated diseases. In this study, we investigated the normal lifespan development of attentiveness of pet dogs in naturalistic situations, and compared the resulting cross-sectional developmental trajectories with data from previous studies in humans. We tested a sample of 145 Border collies (six months to 14 years with humans and objects or food as attention attractors, in order to assess their attentional capture, sustained and selective attention and sensorimotor abilities. Our results reveal differences in task relevance in sustained attentional performance when watching a human or a moving object, which may be explained by life-long learning processes involving such stimuli. During task-switching we found that dogs’ selective attention and sensorimotor abilities showed differences between age groups, with performance peaking at middle age. Dogs’ sensorimotor abilities showed a quadratic distribution with age and were correlated with selective attention performance. Our results support the hypothesis that the development and senescence of sensorimotor and attentional control may be fundamentally interrelated. Additionally, attentional capture, sustained attention and sensorimotor control developmental trajectories paralleled those found in humans. Given that the development of attention is similar across humans and dogs, we propose that the same regulatory mechanisms are likely to be present in both species. Finally, this cross-sectional study provides the first description of age group changes in attention over the lifespan of pet dogs.

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

Science.gov (United States)

Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

2014-01-01

Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs.

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Fan, Rong; Olbricht, Gayla; Baker, Xavior; Hou, Chen

2016-12-08

Larger dog breeds live shorter than the smaller ones, opposite of the mass-lifespan relationship observed across mammalian species. Here we use data from 90 dog breeds and a theoretical model based on the first principles of energy conservation and life history tradeoffs to explain the negative correlation between longevity and body size in dogs. We found that the birth/adult mass ratio of dogs scales negatively with adult size, which is different than the weak interspecific scaling in mammals. Using the model, we show that this ratio, as an index of energy required for growth, is the key to understanding why the lifespan of dogs scales negatively with body size. The model also predicts that the difference in mass-specific lifetime metabolic energy usage between dog breeds is proportional to the difference in birth/adult mass ratio. Empirical data on lifespan, body mass, and metabolic scaling law of dogs strongly supports this prediction.

Yeast chronological lifespan and proteotoxic stress: is autophagy good or bad?

Science.gov (United States)

Sampaio-Marques, Belém; Felgueiras, Carolina; Silva, Alexandra; Rodrigues, Fernando; Ludovico, Paula

2011-10-01

Autophagy, a highly conserved proteolytic mechanism of quality control, is essential for the maintenance of metabolic and cellular homoeostasis and for an efficient cellular response to stress. Autophagy declines with aging and is believed to contribute to different aspects of the aging phenotype. The nutrient-sensing pathways PKA (protein kinase A), Sch9 and TOR (target of rapamycin), involved in the regulation of yeast lifespan, also converge on a common targeted process: autophagy. The molecular mechanisms underlying the regulation of autophagy and aging by these signalling pathways in yeast, with special attention to the TOR pathway, are discussed in the present paper. The question of whether or not autophagy could contribute to yeast cell death occurring during CLS (chronological lifespan) is discussed in the light of our findings obtained after autophagy activation promoted by proteotoxic stress. Autophagy progressively increases in cells expressing the aggregation-prone protein α-synuclein and seems to participate in the early cell death and shortening of CLS under these conditions, highlighting that autophagic activity should be maintained below physiological levels to exert its promising anti-aging effects.

Acoustically mediated long-range interaction among multiple spherical particles exposed to a plane standing wave

International Nuclear Information System (INIS)

Zhang, Shenwei; Qiu, Chunyin; Wang, Mudi; Ke, Manzhu; Liu, Zhengyou

2016-01-01

In this work, we study the acoustically mediated interaction forces among multiple well-separated spherical particles trapped in the same node or antinode plane of a standing wave. An analytical expression of the acoustic interaction force is derived, which is accurate even for the particles beyond the Rayleigh limit. Interestingly, the multi-particle system can be decomposed into a series of independent two-particle systems described by pairwise interactions. Each pairwise interaction is a long-range interaction, as characterized by a soft oscillatory attenuation (at the power exponent of n  = −1 or −2). The vector additivity of the acoustic interaction force, which is not well expected considering the nonlinear nature of the acoustic radiation force, is greatly useful for exploring a system consisting of a large number of particles. The capability of self-organizing a big particle cluster can be anticipated through such acoustically controllable long-range interaction. (paper)

Aberrant TAL1 activation is mediated by an interchromosomal interaction in human T-cell acute lymphoblastic leukemia.

Science.gov (United States)

Patel, B; Kang, Y; Cui, K; Litt, M; Riberio, M S J; Deng, C; Salz, T; Casada, S; Fu, X; Qiu, Y; Zhao, K; Huang, S

2014-02-01

Long-range chromatin interactions control metazoan gene transcription. However, the involvement of intra- and interchromosomal interactions in development and oncogenesis remains unclear. TAL1/SCL is a critical transcription factor required for the development of all hematopoietic lineages; yet, aberrant TAL1 transcription often occurs in T-cell acute lymphoblastic leukemia (T-ALL). Here, we report that oncogenic TAL1 expression is regulated by different intra- and interchromosomal loops in normal hematopoietic and leukemic cells, respectively. These intra- and interchromosomal loops alter the cell-type-specific enhancers that interact with the TAL1 promoter. We show that human SET1 (hSET1)-mediated H3K4 methylations promote a long-range chromatin loop, which brings the +51 enhancer in close proximity to TAL1 promoter 1 in erythroid cells. The CCCTC-binding factor (CTCF) facilitates this long-range enhancer/promoter interaction of the TAL1 locus in erythroid cells while blocking the same enhancer/promoter interaction of the TAL1 locus in human T-cell leukemia. In human T-ALL, a T-cell-specific transcription factor c-Maf-mediated interchromosomal interaction brings the TAL1 promoter into close proximity with a T-cell-specific regulatory element located on chromosome 16, activating aberrant TAL1 oncogene expression. Thus, our study reveals a novel molecular mechanism involving changes in three-dimensional chromatin interactions that activate the TAL1 oncogene in human T-cell leukemia.

Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals.

Science.gov (United States)

Paulmurugan, Ramasamy; Gambhir, Sanjiv S

2005-08-15

Networks of protein interactions execute many different intracellular pathways. Small molecules either synthesized within the cell or obtained from the external environment mediate many of these protein-protein interactions. The study of these small molecule-mediated protein-protein interactions is important in understanding abnormal signal transduction pathways in a variety of disorders, as well as in optimizing the process of drug development and validation. In this study, we evaluated the rapamycin-mediated interaction of the human proteins FK506-binding protein (FKBP12) rapamycin-binding domain (FRB) and FKBP12 by constructing a fusion of these proteins with a split-Renilla luciferase or a split enhanced green fluorescent protein (split-EGFP) such that complementation of the reporter fragments occurs in the presence of rapamycin. Different linker peptides in the fusion protein were evaluated for the efficient maintenance of complemented reporter activity. This system was studied in both cell culture and xenografts in living animals. We found that peptide linkers with two or four EAAAR repeat showed higher protein-protein interaction-mediated signal with lower background signal compared with having no linker or linkers with amino acid sequences GGGGSGGGGS, ACGSLSCGSF, and ACGSLSCGSFACGSLSCGSF. A 9 +/- 2-fold increase in signal intensity both in cell culture and in living mice was seen compared with a system that expresses both reporter fragments and the interacting proteins separately. In this fusion system, rapamycin induced heterodimerization of the FRB and FKBP12 moieties occurred rapidly even at very lower concentrations (0.00001 nmol/L) of rapamycin. For a similar fusion system employing split-EGFP, flow cytometry analysis showed significant level of rapamycin-induced complementation.

Which HRM practices enhance employee outcomes at work across the life-span?

NARCIS (Netherlands)

Veth, Klaske; Korzilius, Hubert P.L.M.; van der Heijden, Beatrice I.J.M.; Emans, Ben; de Lange, Annet H.

Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

Which HRM practices enhance employee outcomes at work across the life-span?

NARCIS (Netherlands)

Veth, K.N.; Korzilius, H.P.L.M.; Heijden, B.I.J.M. van der; Lange, A.H. de; Emans, B.J.M.

2017-01-01

Based on the social exchange theory and on ageing and life-span theories, this paper aims to examine: (1) the relationships between perceived availability and use of HRM practices, and employee outcomes (i.e. work engagement and employability); and (2) how employee age moderates these relationships.

Mental illness and mental health: The two continua model across the lifespan

NARCIS (Netherlands)

Westerhof, Gerben Johan; Keyes, Cory L.M.

2010-01-01

Mental health has long been defined as the absence of psychopathologies, such as depression and anxiety. The absence of mental illness, however, is a minimal outcome from a psychological perspective on lifespan development. This article therefore focuses on mental illness as well as on three core

From the discovery of the weak interactions to that of its mediators

International Nuclear Information System (INIS)

Conversi, M.

1985-01-01

After a brief outline of 'prehistory' of the field of weak interactions, this article recalls the main steps occurred, in our understanding of nature at the deepest level, in the fifty years elapsed between the 1933 discovery of the Fermi weak force and the 1983 discovery of its mediators at CERN, the European Organization for Nuclear Research. Emphasis is given, on one side, to the spectacular predicting power of the gauge theories which have unified electromagnetic and weak interactions, and, on the other side, to the exceptional achievement by the European Physics Community, which by developing a project of extreme technical complexity through a team work of unprecedented size, has made it possible to reveal the carriers of the weak force, the heaviest subnuclear objects thus far observed by man

From the discovery of the weak interactions to that of its mediators

Energy Technology Data Exchange (ETDEWEB)

Conversi, M

1985-01-01

After a brief outline of 'prehistory' of the field of weak interactions, this article recalls the main steps occurred, in our understanding of nature at the deepest level, in the fifty years elapsed between the 1933 discovery of the Fermi weak force and the 1983 discovery of its mediators at CERN, the European Organization for Nuclear Research. Emphasis is given, on one side, to the spectacular predicting power of the gauge theories which have unified electromagnetic and weak interactions, and, on the other side, to the exceptional achievement by the European Physics Community, which by developing a project of extreme technical complexity through a team work of unprecedented size, has made it possible to reveal the carriers of the weak force, the heaviest subnuclear objects thus far observed by man. 42 refs.

Self-consistent Dark Matter simplified models with an s-channel scalar mediator

Energy Technology Data Exchange (ETDEWEB)

Bell, Nicole F.; Busoni, Giorgio; Sanderson, Isaac W., E-mail: n.bell@unimelb.edu.au, E-mail: giorgio.busoni@unimelb.edu.au, E-mail: isanderson@student.unimelb.edu.au [ARC Centre of Excellence for Particle Physics at the Terascale, School of Physics, The University of Melbourne, Victoria 3010 (Australia)

2017-03-01

We examine Simplified Models in which fermionic DM interacts with Standard Model (SM) fermions via the exchange of an s -channel scalar mediator. The single-mediator version of this model is not gauge invariant, and instead we must consider models with two scalar mediators which mix and interfere. The minimal gauge invariant scenario involves the mixing of a new singlet scalar with the Standard Model Higgs boson, and is tightly constrained. We construct two Higgs doublet model (2HDM) extensions of this scenario, where the singlet mixes with the 2nd Higgs doublet. Compared with the one doublet model, this provides greater freedom for the masses and mixing angle of the scalar mediators, and their coupling to SM fermions. We outline constraints on these models, and discuss Yukawa structures that allow enhanced couplings, yet keep potentially dangerous flavour violating processes under control. We examine the direct detection phenomenology of these models, accounting for interference of the scalar mediators, and interference of different quarks in the nucleus. Regions of parameter space consistent with direct detection measurements are determined.

Self-consistent Dark Matter simplified models with an s-channel scalar mediator

International Nuclear Information System (INIS)

Bell, Nicole F.; Busoni, Giorgio; Sanderson, Isaac W.

2017-01-01

We examine Simplified Models in which fermionic DM interacts with Standard Model (SM) fermions via the exchange of an s -channel scalar mediator. The single-mediator version of this model is not gauge invariant, and instead we must consider models with two scalar mediators which mix and interfere. The minimal gauge invariant scenario involves the mixing of a new singlet scalar with the Standard Model Higgs boson, and is tightly constrained. We construct two Higgs doublet model (2HDM) extensions of this scenario, where the singlet mixes with the 2nd Higgs doublet. Compared with the one doublet model, this provides greater freedom for the masses and mixing angle of the scalar mediators, and their coupling to SM fermions. We outline constraints on these models, and discuss Yukawa structures that allow enhanced couplings, yet keep potentially dangerous flavour violating processes under control. We examine the direct detection phenomenology of these models, accounting for interference of the scalar mediators, and interference of different quarks in the nucleus. Regions of parameter space consistent with direct detection measurements are determined.

Entropy Generation and Human Aging: Lifespan Entropy and Effect of Physical Activity Level

Directory of Open Access Journals (Sweden)

Kalyan Annamalai

2008-06-01

Full Text Available The first and second laws of thermodynamics were applied to biochemical reactions typical of human metabolism. An open-system model was used for a human body. Energy conservation, availability and entropy balances were performed to obtain the entropy generated for the main food components. Quantitative results for entropy generation were obtained as a function of age using the databases from the U.S. Food and Nutrition Board (FNB and Centers for Disease Control and Prevention (CDC, which provide energy requirements and food intake composition as a function of age, weight and stature. Numerical integration was performed through human lifespan for different levels of physical activity. Results were presented and analyzed. Entropy generated over the lifespan of average individuals (natural death was found to be 11,404 kJ/ºK per kg of body mass with a rate of generation three times higher on infants than on the elderly. The entropy generated predicts a life span of 73.78 and 81.61 years for the average U.S. male and female individuals respectively, which are values that closely match the average lifespan from statistics (74.63 and 80.36 years. From the analysis of the effect of different activity levels, it is shown that entropy generated increases with physical activity, suggesting that exercise should be kept to a “healthy minimum” if entropy generation is to be minimized.

Shortened β-cell lifespan leads to β-cell deficit in a rodent model of type 2 diabetes

OpenAIRE

Manesso, Erica; Toffolo, Gianna M.; Butler, Alexandra E.; Butler, Peter C.; Cobelli, Claudio

2011-01-01

Since the fundamental defect in both type 1 and type 2 diabetes is β-cell failure, there is increasing interest in the capacity, if any, for β-cell regeneration. Insights into typical β-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for β-cell regeneration as means to reverse the deficit in β-cell mass in diabetes. We assessed the mean β-cell age and lifespan by the classical McKendrick-von Foester...

Radiation effects on lifespan of the fish Oryzias latipes

International Nuclear Information System (INIS)

Egami, N.

1979-01-01

The mortality rate of adult fish exposed to continuous γ-ray irradiation was examined and the results summarized. Initial results into the effects of low-dose γ-irradiation during early developmental stages (one day embryo - 3 month old young) on lifespan, indicate that in this fish the life-shortening effects of radiation are marked at high doses but not at low doses. Age-related histological changes in various tissues have been observed in both irradiated and non-irradiated fish. (Auth.)

SAD1, an RNA polymerase I subunit A34.5 of rice, interacts with Mediator and controls various aspects of plant development.

Science.gov (United States)

Li, Weiqiang; Yoshida, Akiko; Takahashi, Megumu; Maekawa, Masahiko; Kojima, Mikiko; Sakakibara, Hitoshi; Kyozuka, Junko

2015-01-01

The DWARF14 (D14) gene of rice functions within the signaling pathway of strigolactones, a group of plant hormones that inhibits shoot branching. We isolated a recessive mutant named super apical dormant (sad1-1) from a suppressor screen of d14-1. The growth of tillers (vegetative shoot branches) is suppressed in both the d14-1 sad1-1 double mutant and the sad1-1 single mutant. In addition, the sad1-1 mutant shows pleiotropic defects throughout development. SAD1 encodes an ortholog of RPA34.5, a subunit of RNA polymerase I (Pol I). Consequently, the level of ribosomal RNA (rRNA) is severely reduced in the sad1-1 mutant. These results indicate that proper ribosome function is a prerequisite for normal development in plants. The Arabidopsis ortholog of SAD1 was previously isolated as a Mediator-interacting protein. Here we show that SAD1 interacts physically with the Mediator complex through direct binding with OsMED4, a component of the middle module of the Mediator complex in rice. It is known that Mediator interacts with Pol II, which transcribes mRNAs and functions as a central regulator of transcription. This study indicates a novel aspect of Mediator function in Pol I-controlled rRNA transcription. TFIIF2 and RPC53 are the counterparts of RPA34.5 in Pol II and Pol III, respectively. We demonstrate that the rice orthologs of these proteins also interact with OsMED4. Our results suggest that interaction with MED4 in the Mediator complex is a common feature of the three types of RNA polymerases. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

A conserved mammalian protein interaction network.

Directory of Open Access Journals (Sweden)

Åsa Pérez-Bercoff

Full Text Available Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.

Qualitative Exploration of Acculturation and Life-Span Issues of Elderly Asian Americans

Science.gov (United States)

Lee, Jee Hyang; Heo, Nanseol; Lu, Junfei; Portman, Tarrell Awe Agahe

2013-01-01

Awareness of aging issues across diverse populations begins the journey toward counselors becoming culturally competent across client life spans. Understanding the life-span experiences of cultural groups is important for helping professionals. The purpose of this research was to gain insight into the qualitative experiences of Asian American…

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

Science.gov (United States)

van Rooij, Daan; Anagnostou, Evdokia; Arango, Celso; Auzias, Guillaume; Behrmann, Marlene; Busatto, Geraldo F; Calderoni, Sara; Daly, Eileen; Deruelle, Christine; Di Martino, Adriana; Dinstein, Ilan; Duran, Fabio Luis Souza; Durston, Sarah; Ecker, Christine; Fair, Damien; Fedor, Jennifer; Fitzgerald, Jackie; Freitag, Christine M; Gallagher, Louise; Gori, Ilaria; Haar, Shlomi; Hoekstra, Liesbeth; Jahanshad, Neda; Jalbrzikowski, Maria; Janssen, Joost; Lerch, Jason; Luna, Beatriz; Martinho, Mauricio Moller; McGrath, Jane; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan G M; O'Hearn, Kirsten; Oranje, Bob; Parellada, Mara; Retico, Alessandra; Rosa, Pedro; Rubia, Katya; Shook, Devon; Taylor, Margot; Thompson, Paul M; Tosetti, Michela; Wallace, Gregory L; Zhou, Fengfeng; Buitelaar, Jan K

2018-04-01

Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different

Age-related differences in cognition across the adult lifespan in autism spectrum disorder

NARCIS (Netherlands)

Lever, A.G.; Geurts, H.M.

It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is

Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

Science.gov (United States)

Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

2017-01-01

Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

Performing Re-mediation in Graphical Cyberspace: Mediating Agency, Body and Identity in Virtual Interactional Practices

DEFF Research Database (Denmark)

McIlvenny, Paul

and spectacular multi-media event raises many questions. How do we conceive of the recent developments in media technology and social computing that are impacting on what we have traditionally called 'the mass media'? How is interaction and talk mediated and adapted to new media genres? And how do participants......Promoted as the first academic conference to be held completely in graphical cyberspace, Avatars 98 took place in November 1998. The virtual conference site was built and inhabited using software that supports multi-party presence over the Internet in a simulated, navigable environment. During...... frameworks through the multimedia representations that were 'cast' and 'served' across the Internet. If such a ceremonial event had been broadcast through the institutional medium of television, broadcast talk would have been produced for an eavesdropping 'mass audience'. Instead, the digitally re...

DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16.

Science.gov (United States)

Huang, Lei; Li, Pengfei; Wang, Guan; Guan, Shuwen; Sun, Xiaoli; Wang, Liping

2013-04-01

Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

DOE life-span radiation effects studies at Pacific Northwest Laboratory

International Nuclear Information System (INIS)

Thompson, R.C.; Cross, F.T.; Dagle, G.E.; Park, J.F.; Sanders, C.L.

1986-01-01

Major life-span radiation effects studies at Pacific Northwest Laboratory fall into three categories: (1) studies with beagle dogs exposed to plutonium compounds via a single inhalation; (2) studies with dogs and rats exposed chronically via inhalation to various combinations and concentrations of radon, radon daughters, and other components of uranium mine atmospheres; and (3) a study in which rats are exposed via single inhalation, in very large numbers, to very low concentrations of 239 PuO 2 . Exposure of beagles currently on study was initiated in 1970 with 239 PuO 2 , in 1973 with 238 PuO 2 , and in 1976 with 239 Pu(NO 3 ) 4 . These experiments involve more than 500 animals, many of them still alive. Experiments seeking to explain the increased incidence of lung cancer in uranium miners have been in progress since 1966. Present emphasis is on studies with rats, in an attempt to define dose-effect relationships at the lowest feasible radon-daughter exposure levels. Our very-low-level experiment with inhaled 239 PuO 2 in rats, with exposures still under way, includes 1000 rats in the control group and 1000 rats in the lowest-exposure group, where life-span lung doses of <5 rads are anticipated

In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.

Science.gov (United States)

Acosta-Cabronero, Julio; Betts, Matthew J; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J

2016-01-13

Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)--a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20-79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM-age associations were identified in several deep-brain nuclei--chiefly the striatum and midbrain-and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions. This study used a whole--brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI analysis and prior knowledge

Perceptions of Love across the Lifespan: Differences in Passion, Intimacy, and Commitment

Science.gov (United States)

Sumter, Sindy R.; Valkenburg, Patti M.; Peter, Jochen

2013-01-01

This study investigated perceptions of love across the lifespan using Sternberg's triangular theory of love, which distinguishes between passion, intimacy, and commitment. The study aimed to (a) investigate the psychometric properties of the short Triangular Love Scale (TLS-short) in adolescents and adults (see Appendix), and (b) track age and…

Beat Synchronization across the Lifespan: Intersection of Development and Musical Experience

OpenAIRE

Thompson, Elaine C.; White-Schwoch, Travis; Tierney, Adam; Kraus, Nina

2015-01-01

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance ...

The Nature of Negotiations in Face-to-Face versus Computer-Mediated Communication in Pair Interactions

Science.gov (United States)

Rouhshad, Amir; Wigglesworth, Gillian; Storch, Neomy

2016-01-01

The Interaction Approach argues that negotiation for meaning and form is conducive to second language development. To date, most of the research on negotiations has been either in face-to-face (FTF) or text-based synchronous computer-mediated communication (SCMC) modes. Very few studies have compared the nature of negotiations across the modes.…