26 results on '"Onken B"'
Search Results
2. 367 Regulating Livestock Waste in Nebraska – a Brief Overview.
- Author
-
Onken, B, primary
- Published
- 2018
- Full Text
- View/download PDF
3. Technik und Innovation des Imperium Romanum im Spiegel der epigraphischen Denkmäler
- Author
-
Onken, B, Rhode, D, Onken, B ( B ), Rhode, D ( D ), Kolb, A; https://orcid.org/0009-0004-4776-2421, Onken, B, Rhode, D, Onken, B ( B ), Rhode, D ( D ), and Kolb, A; https://orcid.org/0009-0004-4776-2421
- Published
- 2011
4. AERIALLY RELEASED SPRAY PENETRATION IN A TALL CONIFEROUS FOREST CANOPY.
- Author
-
Thistle, H. W., Reardon, R. C., Bonds, J. A. S., Fritz, B. L., Hoffmann, W. C., Kees, G. J., Grob, I. J., Hewitt, A. J., O'Donnell, C. C., Felton, K. D., and Onken, B. P.
- Published
- 2016
- Full Text
- View/download PDF
5. Evaluation of Corn Grain Yield and Water Use Efficiency Using Subsurface Drip Irrigation
- Author
-
Pablo, R. G., primary, O'Neill, M. K., additional, McCaslin, B. D., additional, Remmenga, M. D., additional, Keenan, J. G., additional, and Onken, B. M., additional
- Published
- 2007
- Full Text
- View/download PDF
6. Comparison of Aerially-Applied Gypchek Strains Against Gypsy Moth (Lepidoptera: Lymantriidae) in the Presence of an Entomophaga maimaiga Epizootic
- Author
-
Webb, R. E., primary, White, G. B., primary, Podgwaite, J. D., primary, D'Amico, V., primary, Slavicek, J., primary, Swearingen, J., primary, Onken, B., primary, and Thorpe, K. W., primary
- Published
- 2005
- Full Text
- View/download PDF
7. Arsenic Availability in Soil with Time under Saturated and Subsaturated Conditions
- Author
-
Onken, B. M., primary and Adriano, D. C., additional
- Published
- 1997
- Full Text
- View/download PDF
8. The Sorption of Nonionic Organic Solutes to Humic Acid‐Mineral Complexes: Effect of Cosolutes
- Author
-
Onken, B. M., primary and Traina, S. J., additional
- Published
- 1997
- Full Text
- View/download PDF
9. The Sorption of Pyrene and Anthracene to Humic Acid‐Mineral Complexes: Effect of Fractional Organic Carbon Content
- Author
-
Onken, B. M., primary and Traina, S. J., additional
- Published
- 1997
- Full Text
- View/download PDF
10. Determination of Arsenic Species in Soil Solution under Flooded Conditions
- Author
-
Onken, B. M., primary and Hossner, L. R., additional
- Published
- 1996
- Full Text
- View/download PDF
11. Plant Uptake and Determination of Arsenic Species in Soil Solution under Flooded Conditions
- Author
-
Onken, B. M., primary and Hossner, L. R., additional
- Published
- 1995
- Full Text
- View/download PDF
12. Plant uptake and determination of arsenic species in soil solution under flooded conditions
- Author
-
Hossner, L. R. and Onken, B. M.
- Subjects
PLANTS ,SOIL chemistry ,ARSENIC - Published
- 1995
13. Technik und Innovation des Imperium Romanum im Spiegel der epigraphischen Denkmäler
- Author
-
Kolb, A, University of Zurich, Onken, B, Rhode, D, and Kolb, A
- Subjects
10109 Institute of History ,900 History - Published
- 2011
14. The coupling between healthspan and lifespan in Caenorhabditis depends on complex interactions between compound intervention and genetic background.
- Author
-
Banse SA, Jackson EG, Sedore CA, Onken B, Hall D, Coleman-Hulbert A, Huynh P, Garrett T, Johnson E, Harinath G, Inman D, Guo S, Morshead M, Xue J, Falkowski R, Chen E, Herrera C, Kirsch AJ, Perez VI, Guo M, Lithgow GJ, Driscoll M, and Phillips PC
- Subjects
- Animals, Resveratrol pharmacology, Aging drug effects, Aging genetics, Genetic Background, Swimming, Piperazines pharmacology, Stilbenes pharmacology, Longevity drug effects, Longevity genetics, Oxidative Stress drug effects, Caenorhabditis elegans drug effects, Caenorhabditis elegans genetics, Caenorhabditis elegans physiology
- Abstract
Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Caenorhabditis Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol. Overall, we find the relationships among median lifespan, oxidative stress resistance, thermotolerance, and mobility vigor to be complex. We show that oxidative stress resistance and thermotolerance vary with compound intervention, genetic background, and age. The effects of tested compounds on swimming locomotion, in contrast, are largely species-specific. In this study, thermotolerance, but not oxidative stress or swimming ability, correlates with lifespan. Notably, some compounds exert strong impact on some health measures without an equally strong impact on lifespan. Our results demonstrate the importance of assessing health and lifespan across genetic backgrounds in the effort to identify reproducible anti-aging interventions, with data underscoring how personalized treatments might be required to optimize health benefits.
- Published
- 2024
- Full Text
- View/download PDF
15. Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.
- Author
-
Banse SA, Sedore CA, Johnson E, Coleman-Hulbert AL, Onken B, Hall D, Jackson EG, Huynh P, Foulger AC, Guo S, Garrett T, Xue J, Inman D, Morshead ML, Plummer WT, Chen E, Bhaumik D, Chen MK, Harinath G, Chamoli M, Quinn RP, Falkowski R, Edgar D, Schmidt MO, Lucanic M, Guo M, Driscoll M, Lithgow GJ, and Phillips PC
- Subjects
- Animals, Humans, Aged, Masoprocol pharmacology, Masoprocol metabolism, Caenorhabditis elegans genetics, Longevity, Health Promotion, Plant Extracts pharmacology, Tea metabolism, Mammals, Antioxidants pharmacology, Caenorhabditis
- Abstract
The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies-for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
16. Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes.
- Author
-
Onken B, Sedore CA, Coleman-Hulbert AL, Hall D, Johnson E, Jones EG, Banse SA, Huynh P, Guo S, Xue J, Chen E, Harinath G, Foulger AC, Chao EA, Hope J, Bhaumik D, Plummer T, Inman D, Morshead M, Guo M, Lithgow GJ, Phillips PC, and Driscoll M
- Subjects
- Animals, Humans, Hypoglycemic Agents pharmacology, Metformin pharmacology, Treatment Outcome, Aging genetics, Caenorhabditis elegans drug effects, Hypoglycemic Agents therapeutic use, Longevity genetics, Metformin therapeutic use
- Abstract
Metformin, the most commonly prescribed anti-diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti-aging drug-the Targeting Aging with Metformin (TAME) program. Genetic variation will likely influence outcomes when studying metformin health effects in human populations. To test for metformin impact in diverse genetic backgrounds, we measured lifespan and healthspan effects of metformin treatment in three Caenorhabditis species representing genetic variability greater than that between mice and humans. We show that metformin increases median survival in three C. elegans strains, but not in C. briggsae and C. tropicalis strains. In C. briggsae, metformin either has no impact on survival or decreases lifespan. In C. tropicalis, metformin decreases median survival in a dose-dependent manner. We show that metformin prolongs the period of youthful vigor in all C. elegans strains and in two C. briggsae strains, but that metformin has a negative impact on the locomotion of C. tropicalis strains. Our data demonstrate that metformin can be a robust promoter of healthy aging across different genetic backgrounds, but that genetic variation can determine whether metformin has positive, neutral, or negative lifespan/healthspan impact. These results underscore the importance of tailoring treatment to individuals when testing for metformin health benefits in diverse human populations., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
17. Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension.
- Author
-
Onken B, Kalinava N, and Driscoll M
- Subjects
- Animals, Caloric Restriction, Gene Expression Regulation, Developmental genetics, Glucose metabolism, Humans, Life Expectancy, Longevity genetics, Phosphoenolpyruvate Carboxykinase (ATP) genetics, Signal Transduction genetics, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Forkhead Transcription Factors genetics, Gluconeogenesis genetics, Healthy Aging genetics
- Abstract
High glucose diets are unhealthy, although the mechanisms by which elevated glucose is harmful to whole animal physiology are not well understood. In Caenorhabditis elegans, high glucose shortens lifespan, while chemically inflicted glucose restriction promotes longevity. We investigated the impact of glucose metabolism on aging quality (maintained locomotory capacity and median lifespan) and found that, in addition to shortening lifespan, excess glucose negatively impacts locomotory healthspan. Conversely, disrupting glucose utilization by knockdown of glycolysis-specific genes results in large mid-age physical improvements via a mechanism that requires the FOXO transcription factor DAF-16. Adult locomotory capacity is extended by glycolysis disruption, but maximum lifespan is not, indicating that limiting glycolysis can increase the proportion of life spent in mobility health. We also considered the largely ignored role of glucose biosynthesis (gluconeogenesis) in adult health. Directed perturbations of gluconeogenic genes that specify single direction enzymatic reactions for glucose synthesis decrease locomotory healthspan, suggesting that gluconeogenesis is needed for healthy aging. Consistent with this idea, overexpression of the central gluconeogenic gene pck-2 (encoding PEPCK) increases health measures via a mechanism that requires DAF-16 to promote pck-2 expression in specific intestinal cells. Dietary restriction also features DAF-16-dependent pck-2 expression in the intestine, and the healthspan benefits conferred by dietary restriction require pck-2. Together, our results describe a new paradigm in which nutritional signals engage gluconeogenesis to influence aging quality via DAF-16. These data underscore the idea that promotion of gluconeogenesis might be an unappreciated goal for healthy aging and could constitute a novel target for pharmacological interventions that counter high glucose consequences, including diabetes., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
- View/download PDF
18. Healthy lifespan extension mediated by oenothein B isolated from Eucalyptus grandis × Eucalyptus urophylla GL9 in Caenorhabditis elegans.
- Author
-
Chen Y, Onken B, Chen H, Zhang X, Driscoll M, Cao Y, and Huang Q
- Subjects
- Animals, Caenorhabditis elegans physiology, Hydrolyzable Tannins chemistry, Hydrolyzable Tannins isolation & purification, Oxidative Stress drug effects, Phytochemicals chemistry, Phytochemicals isolation & purification, Phytochemicals pharmacology, Caenorhabditis elegans drug effects, Eucalyptus chemistry, Hydrolyzable Tannins pharmacology, Longevity drug effects
- Abstract
Oenothein B (OEB) exhibits extensive biological activities, but few investigations have been carried out on the pharmacologic influence of OEB on longevity in any organism. To explore the potential pharmacological ability of OEB to postpone the progression of age-related degenerative processes and diseases, we monitored the effects of OEB isolated from Eucalyptus leaves on the lifespan of Caenorhabditis elegans (C. elegans) at four different concentrations. We found that OEB increased the median lifespan of worms by up to 22% in a dose-dependent manner. Further studies demonstrated that OEB significantly enhanced youthfulness (healthy lifespan) by increasing the whole adult life's locomotory mobility, reducing age pigment and reactive oxygen species (ROS) accumulation, and enhancing thermal stress resistance. Furthermore, the genes daf-16, age-1, eat-2, sir-2.1, and isp-1 were required for the healthy longevity benefits induced by OEB, but not the genes mev-1 and clk-1. Taken together, OEB might modulate multiple genetic pathways involved in insulin/IGF-1 signaling (IIS) via age-1 and daf-16, the dietary restriction (DR) pathway via eat-2 and sir-2.1, and the mitochondrial electron transport chain via isp-1 to promote healthy lifespan including the reduction of age pigment and ROS accumulation and the enhancement of locomotory mobility, thermal stress tolerance and lifespan. These findings indicated that OEB has the potential to be developed into the next generation of multi-target drugs for prolonging healthy lifespan and intervening in age-related diseases.
- Published
- 2020
- Full Text
- View/download PDF
19. Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.
- Author
-
Banse SA, Lucanic M, Sedore CA, Coleman-Hulbert AL, Plummer WT, Chen E, Kish JL, Hall D, Onken B, Presley MP, Jones EG, Blue BW, Garrett T, Abbott M, Xue J, Guo S, Johnson E, Foulger AC, Chamoli M, Falkowski R, Melentijevic I, Harinath G, Huynh P, Patel S, Edgar D, Jarrett CM, Guo M, Kapahi P, Lithgow GJ, Driscoll M, and Phillips PC
- Subjects
- Animals, Caenorhabditis elegans drug effects, Caenorhabditis elegans radiation effects, Lasers, Longevity radiation effects, Photic Stimulation, Biological Assay methods, Caenorhabditis elegans growth & development, Ketoglutaric Acids pharmacology, Longevity drug effects
- Abstract
The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.
- Published
- 2019
- Full Text
- View/download PDF
20. Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects.
- Author
-
Lucanic M, Plummer WT, Chen E, Harke J, Foulger AC, Onken B, Coleman-Hulbert AL, Dumas KJ, Guo S, Johnson E, Bhaumik D, Xue J, Crist AB, Presley MP, Harinath G, Sedore CA, Chamoli M, Kamat S, Chen MK, Angeli S, Chang C, Willis JH, Edgar D, Royal MA, Chao EA, Patel S, Garrett T, Ibanez-Ventoso C, Hope J, Kish JL, Guo M, Lithgow GJ, Driscoll M, and Phillips PC
- Subjects
- Animals, Benzothiazoles, Caenorhabditis classification, Caenorhabditis genetics, Caenorhabditis elegans drug effects, Caenorhabditis elegans genetics, Dose-Response Relationship, Drug, Fertility drug effects, Fertility genetics, Longevity genetics, Reproducibility of Results, Species Specificity, Thiazoles pharmacology, Caenorhabditis drug effects, Genetic Background, Longevity drug effects, Organic Chemicals pharmacology
- Abstract
Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.
- Published
- 2017
- Full Text
- View/download PDF
21. Mechanism of longevity extension of Caenorhabditis elegans induced by pentagalloyl glucose isolated from eucalyptus leaves.
- Author
-
Chen Y, Onken B, Chen H, Xiao S, Liu X, Driscoll M, Cao Y, and Huang Q
- Subjects
- Animals, Caenorhabditis elegans drug effects, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Female, Gene Expression drug effects, Hydrolyzable Tannins isolation & purification, Male, Plant Extracts isolation & purification, Plant Leaves chemistry, Caenorhabditis elegans physiology, Eucalyptus chemistry, Hydrolyzable Tannins pharmacology, Longevity drug effects, Plant Extracts pharmacology
- Abstract
The multicellular model organism Caenorhabditis elegans (C. elegans) was used to identify the anti-aging effect of pentagalloyl glucose (PGG) isolated from Eucalyptus leaves at four different concentrations. For 160 μM PGG, the median lifespan of C. elegans was found to increase by 18%, and the thermal stress resistance was also increased. The anti-aging effect of PGG did not cause side effects on the physiological functions including the reproduction, pharyngeal pumping rate, age pigments accumulation, and locomotion ability. The life extension induced by PGG was found to rely on genes daf-16, age-1, eat-2, sir-2.1, and isp-1 but did not rely on genes mev-1 and clk-1. These findings suggested that the insulin/IGF-1 signaling pathway, dietary restriction, Sir-2.1 signaling, and mitochondrial electron transport chain became partly involved with the mechanism of lifespan extension mediated by PGG. Our results provided an insight into the mechanism of longevity extension mediated by PGG in C. elegans, which might be developed into a new generation of multitarget drug to prolong lifespan.
- Published
- 2014
- Full Text
- View/download PDF
22. Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan.
- Author
-
Vora M, Shah M, Ostafi S, Onken B, Xue J, Ni JZ, Gu S, and Driscoll M
- Subjects
- Animals, Caenorhabditis elegans physiology, Caenorhabditis elegans Proteins metabolism, Forkhead Transcription Factors, Gene Expression Regulation, Histone Acetyltransferases genetics, Histone Acetyltransferases metabolism, Sequence Deletion, Signal Transduction, Transcription Factors genetics, Transcription Factors metabolism, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Caloric Restriction, Longevity genetics, MicroRNAs genetics
- Abstract
Caloric/dietary restriction (CR/DR) can promote longevity and protect against age-associated disease across species. The molecular mechanisms coordinating food intake with health-promoting metabolism are thus of significant medical interest. We report that conserved Caenorhabditis elegans microRNA-80 (mir-80) is a major regulator of the DR state. mir-80 deletion confers system-wide healthy aging, including maintained cardiac-like and skeletal muscle-like function at advanced age, reduced accumulation of lipofuscin, and extended lifespan, coincident with induction of physiological features of DR. mir-80 expression is generally high under ad lib feeding and low under food limitation, with most striking food-sensitive expression changes in posterior intestine. The acetyltransferase transcription co-factor cbp-1 and interacting transcription factors daf-16/FOXO and heat shock factor-1 hsf-1 are essential for mir-80(Δ) benefits. Candidate miR-80 target sequences within the cbp-1 transcript may confer food-dependent regulation. Under food limitation, lowered miR-80 levels directly or indirectly increase CBP-1 protein levels to engage metabolic loops that promote DR., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2013
- Full Text
- View/download PDF
23. Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1.
- Author
-
Onken B and Driscoll M
- Subjects
- Animals, Insulin metabolism, Signal Transduction, Adenylate Kinase metabolism, Caenorhabditis elegans Proteins metabolism, Caloric Restriction, DNA-Binding Proteins metabolism, Hypoglycemic Agents pharmacology, Metformin pharmacology, Oxidative Stress, Transcription Factors metabolism
- Abstract
Metformin, a biguanide drug commonly used to treat type-2 diabetes, has been noted to extend healthspan of nondiabetic mice, but this outcome, and the molecular mechanisms that underlie it, have received relatively little experimental attention. To develop a genetic model for study of biguanide effects on healthspan, we investigated metformin impact on aging Caenorhabditis elegans. We found that metformin increases nematode healthspan, slowing lipofuscin accumulation, extending median lifespan, and prolonging youthful locomotory ability in a dose-dependent manner. Genetic data suggest that metformin acts through a mechanism similar to that operative in eating-impaired dietary restriction (DR) mutants, but independent of the insulin signaling pathway. Energy sensor AMPK and AMPK-activating kinase LKB1, which are activated in mammals by metformin treatment, are essential for health benefits in C. elegans, suggesting that metformin engages a metabolic loop conserved across phyla. We also show that the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2 is essential for metformin healthspan benefits in C. elegans, a mechanistic requirement not previously described in mammals. skn-1, which functions in nematode sensory neurons to promote DR longevity benefits and in intestines for oxidative stress resistance lifespan benefits, must be expressed in both neurons and intestines for metformin-promoted healthspan extension, supporting that metformin improves healthy middle-life aging by activating both DR and antioxidant defense longevity pathways. In addition to defining molecular players operative in metformin healthspan benefits, our data suggest that metformin may be a plausible pharmacological intervention to promote healthy human aging.
- Published
- 2010
- Full Text
- View/download PDF
24. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.
- Author
-
Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, and Kenyon C
- Subjects
- Animals, Animals, Genetically Modified, Autophagy genetics, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins antagonists & inhibitors, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins physiology, Diet, Genes, Helminth, Longevity genetics, Models, Biological, Mutation, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases physiology, Phosphoinositide-3 Kinase Inhibitors, Phosphotransferases (Alcohol Group Acceptor) genetics, Phosphotransferases (Alcohol Group Acceptor) physiology, RNA Interference, Receptor, Insulin genetics, Receptor, Insulin physiology, Receptors, Nicotinic genetics, Receptors, Nicotinic physiology, Trans-Activators antagonists & inhibitors, Trans-Activators genetics, Trans-Activators physiology, Vesicular Transport Proteins, rab GTP-Binding Proteins antagonists & inhibitors, rab GTP-Binding Proteins genetics, rab GTP-Binding Proteins physiology, Autophagy physiology, Caenorhabditis elegans growth & development, Caenorhabditis elegans physiology, Longevity physiology
- Abstract
In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins., Competing Interests: Competing interests. The authors have declared that no competing interests exist.
- Published
- 2008
- Full Text
- View/download PDF
25. Compartmentalized signaling of Ras in fission yeast.
- Author
-
Onken B, Wiener H, Philips MR, and Chang EC
- Subjects
- Animals, Cell Line, Cell Shape, Guanine Nucleotide Exchange Factors genetics, Guanine Nucleotide Exchange Factors metabolism, MAP Kinase Kinase Kinases genetics, MAP Kinase Kinase Kinases metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Schizosaccharomyces cytology, Schizosaccharomyces pombe Proteins genetics, Subcellular Fractions metabolism, Two-Hybrid System Techniques, ras Proteins genetics, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins metabolism, Signal Transduction physiology, ras Proteins metabolism
- Abstract
Compartment-specific Ras signaling is an emerging paradigm that may explain the multiplex outputs from a single GTPase. The fission yeast, Schizosaccharomyces pombe, affords a simple system in which to study Ras signaling because it has a single Ras protein, Ras1, that regulates two distinct pathways: one that controls mating through a Byr2-mitogen-activated protein kinase cascade and one that signals through Scd1-Cdc42 to maintain elongated cell morphology. We generated Ras1 mutants that are restricted to either the endomembrane or the plasma membrane. Protein binding studies showed that each could interact with the effectors of both pathways. However, when examined in ras1 null cells, endomembrane-restricted Ras1 supported morphology but not mating, and, conversely, plasma membrane-restricted Ras1 supported mating but did not signal to Scd1-Cdc42. These observations provide a striking demonstration of compartment-specific Ras signaling and indicate that spatial specificity in the Ras pathway is evolutionarily conserved.
- Published
- 2006
- Full Text
- View/download PDF
26. Two ras pathways in fission yeast are differentially regulated by two ras guanine nucleotide exchange factors.
- Author
-
Papadaki P, Pizon V, Onken B, and Chang EC
- Subjects
- ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism, Fungal Proteins genetics, Gene Deletion, Guanine Nucleotide Exchange Factors genetics, Mitogen-Activated Protein Kinases metabolism, Protein Structure, Tertiary, Schizosaccharomyces genetics, Signal Transduction, ras Proteins genetics, Cell Cycle Proteins metabolism, Fungal Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, MAP Kinase Kinase Kinases, Proto-Oncogene Proteins metabolism, Schizosaccharomyces metabolism, Schizosaccharomyces pombe Proteins, ras Proteins metabolism
- Abstract
How a given Ras prreotein coordinates multiple signaling inputs and outputs is a fundamental issue of signaling specificity. Schizosaccharomyces pombe contains one Ras, Ras1, that has two distinct outputs. Ras1 activates Scd1, a presumptive guanine nucleotide exchange factor (GEF) for Cdc42, to control morphogenesis and chromosome segregation, and Byr2, a component of a mitogen-activated protein kinase cascade, to control mating. So far there is only one established Ras1 GEF, Ste6. Paradoxically, ste6 null (ste6 Delta) mutants are sterile but normal in cell morphology. This suggests that Ste6 specifically activates the Ras1-Byr2 pathway and that there is another GEF capable of activating the Scd1 pathway. We thereby characterized a potential GEF, Efc25. Genetic data place Efc25 upstream of the Ras1-Scd1, but not the Ras1-Byr2, pathway. Like ras1 Delta and scd1 Delta, efc25 Delta is synthetically lethal with a deletion in tea1, a critical element for cell polarity control. Using truncated proteins, we showed that the C-terminal GEF domain of Efc25 is essential for function and regulated by the N terminus. We conclude that Efc25 acts as a Ras1 GEF specific for the Scd1 pathway. While ste6 expression is induced during mating, efc25 expression is constitutive. Moreover, Efc25 overexpression renders cells hyperelongated and sterile; the latter can be rescued by activated Ras1. This suggests that Efc25 can recruit Ras1 to selectively activate Scd1 at the expense of Byr2. Reciprocally, Ste6 overexpression can block Scd1 activation. We propose that external signals can partly segregate two Ras1 pathways by modulating GEF expression and that GEFs can influence how Ras is coupled to specific effectors.
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.