Deletion of Crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack.

PubMed

Barata, Lidia; Miwa, Takashi; Sato, Sayaka; Kim, David; Mohammed, Imran; Song, Wen-Chao

2013-03-15

Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. Crry(-/-)DAF(-/-) mice were viable on a C3(-/-) background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF(-/-) mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre(+)-Crry(flox/flox) mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre(+)-Crry(flox/flox) bone marrows showed platelets from C3(-/-) but not C3(+/+) recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre(+)-Crry(flox/flox) mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre(+)-Crry(flox/flox) mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies.

A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yang, Junnian; Wang, Dayong

2016-03-01

The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms.

A MicroRNA-Mediated Insulin Signaling Pathway Regulates the Toxicity of Multi-Walled Carbon Nanotubes in Nematode Caenorhabditis elegans

PubMed Central

Zhao, Yunli; Yang, Junnian; Wang, Dayong

2016-01-01

The underlying mechanisms for functions of microRNAs (miRNAs) in regulating toxicity of nanomaterials are largely unclear. Using Illumina HiSeqTM 2000 sequencing technique, we obtained the dysregulated mRNA profiling in multi-walled carbon nanotubes (MWCNTs) exposed nematodes. Some dysregulated genes encode insulin signaling pathway. Genetic experiments confirmed the functions of these dysregulated genes in regulating MWCNTs toxicity. In the insulin signaling pathway, DAF-2/insulin receptor regulated MWCNTs toxicity by suppressing function of DAF-16/FOXO transcription factor. Moreover, we raised a miRNAs-mRNAs network involved in the control of MWCNTs toxicity. In this network, mir-355 might regulate MWCNTs toxicity by inhibiting functions of its targeted gene of daf-2, suggesting that mir-355 may regulate functions of the entire insulin signaling pathway by acting as an upregulator of DAF-2, the initiator of insulin signaling pathway, in MWCNTs exposed nematodes. Our results provides highlight on understanding the crucial role of miRNAs in regulating toxicity of nanomaterials in organisms. PMID:26984256

Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation.

PubMed

Li, Facai; Lok, James B; Gasser, Robin B; Korhonen, Pasi K; Sandeman, Mark R; Shi, Deshi; Zhou, Rui; Li, Xiangrui; Zhou, Yanqin; Zhao, Junlong; Hu, Min

2014-06-01

Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Plant-parasitic nematodes: towards understanding molecular players in stress responses

PubMed Central

Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair

2017-01-01

Background Plant–parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant–nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Scope Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1, which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. Conclusion DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. PMID:28087659

Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress.

PubMed

Lamitina, S Todd; Strange, Kevin

2005-02-01

All cells adapt to hypertonic stress by regulating their volume after shrinkage, by accumulating organic osmolytes, and by activating mechanisms that protect against and repair hypertonicity-induced damage. In mammals and nematodes, inhibition of signaling from the DAF-2/IGF-1 insulin receptor activates the DAF-16/FOXO transcription factor, resulting in increased life span and resistance to some types of stress. We tested the hypothesis that inhibition of insulin signaling in Caenorhabditis elegans also increases hypertonic stress resistance. Genetic inhibition of DAF-2 or its downstream target, the AGE-1 phosphatidylinositol 3-kinase, confers striking resistance to a normally lethal hypertonic shock in a DAF-16-dependent manner. However, insulin signaling is not inhibited by or required for adaptation to hypertonic conditions. Microarray studies have identified 263 genes that are transcriptionally upregulated by DAF-16 activation. We identified 14 DAF-16-upregulated genes by RNA interference screening that are required for age-1 hypertonic stress resistance. These genes encode heat shock proteins, proteins of unknown function, and trehalose synthesis enzymes. Trehalose levels were elevated approximately twofold in age-1 mutants, but this increase was insufficient to prevent rapid hypertonic shrinkage. However, age-1 animals unable to synthesize trehalose survive poorly under hypertonic conditions. We conclude that increased expression of proteins that protect eukaryotic cells against environmental stress and/or repair stress-induced molecular damage confers hypertonic stress resistance in C. elegans daf-2/age-1 mutants. Elevated levels of solutes such as trehalose may also function in a cytoprotective manner. Our studies provide novel insights into stress resistance in animal cells and a foundation for new studies aimed at defining molecular mechanisms underlying these essential processes.

daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

PubMed

Lin, K; Dorman, J B; Rodan, A; Kenyon, C

1997-11-14

The wild-type Caenorhabditis elegans nematode ages rapidly, undergoing development, senescence, and death in less than 3 weeks. In contrast, mutants with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, age more slowly than normal and live more than twice as long. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3 (HNF-3)/forkhead family of transcriptional regulators. In humans, insulin down-regulates the expression of certain genes by antagonizing the activity of HNF-3, raising the possibility that aspects of this regulatory system have been conserved.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

PubMed

Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.

PubMed

Jensen, Victor L; Simonsen, Karina T; Lee, Yu-Hui; Park, Donha; Riddle, Donald L

2010-12-31

The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27°C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production.

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo

PubMed Central

HARRIS, C L; WILLIAMS, A S; LINTON, S M; MORGAN, B P

2002-01-01

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function. PMID:12165074

The Application of Architecture Frameworks to Modelling Exploration Operations Costs

NASA Technical Reports Server (NTRS)

Shishko, Robert

2006-01-01

Developments in architectural frameworks and system-of-systems thinking have provided useful constructs for systems engineering. DoDAF concepts, language, and formalisms, in particular, provide a natural way of conceptualizing an operations cost model applicable to NASA's space exploration vision. Not all DoDAF products have meaning or apply to a DoDAF inspired operations cost model, but this paper describes how such DoDAF concepts as nodes, systems, and operational activities relate to the development of a model to estimate exploration operations costs. The paper discusses the specific implementation to the Mission Operations Directorate (MOD) operational functions/activities currently being developed and presents an overview of how this powerful representation can apply to robotic space missions as well.

C. elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity

PubMed Central

Zhang, Yanmei; Xu, Jinling; Puscau, Cristina; Kim, Yongsoon; Wang, Xi; Alam, Hena; Hu, Patrick J.

2008-01-01

SUMMARY Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals. PMID:18241854

Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

PubMed Central

Büchter, Christian; Ackermann, Daniela; Havermann, Susannah; Honnen, Sebastian; Chovolou, Yvonni; Fritz, Gerhard; Kampkötter, Andreas; Wätjen, Wim

2013-01-01

Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue) and SKN-1 (Nrf2 homologue), which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS) detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038). Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid. PMID:23736695

Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways.

PubMed

Perrin, A J; Gunda, M; Yu, B; Yen, K; Ito, S; Forster, S; Tissenbaum, H A; Derry, W B

2013-01-01

The insulin/IGF-1 pathway controls a number of physiological processes in the nematode worm Caenorhabditis elegans, including development, aging and stress response. We previously found that the Akt/PKB ortholog AKT-1 dampens the apoptotic response to genotoxic stress in the germline by negatively regulating the p53-like transcription factor CEP-1. Here, we report unexpected rearrangements to the insulin/IGF-1 pathway, whereby the insulin-like receptor DAF-2 and 3-phosphoinositide-dependent protein kinase PDK-1 oppose AKT-1 to promote DNA damage-induced apoptosis. While DNA damage does not affect phosphorylation at the PDK-1 site Thr350/Thr308 of AKT-1, it increased phosphorylation at Ser517/Ser473. Although ablation of daf-2 or pdk-1 completely suppressed akt-1-dependent apoptosis, the transcriptional activation of CEP-1 was unaffected, suggesting that daf-2 and pdk-1 act independently or downstream of cep-1 and akt-1. Ablation of the akt-1 paralog akt-2 or the downstream target of the insulin/IGF-1 pathway daf-16 (a FOXO transcription factor) restored sensitivity to damage-induced apoptosis in daf-2 and pdk-1 mutants. In addition, daf-2 and pdk-1 mutants have reduced levels of phospho-MPK-1/ERK in their germ cells, indicating that the insulin/IGF-1 pathway promotes Ras signaling in the germline. Ablation of the Ras effector gla-3, a negative regulator of mpk-1, restored sensitivity to apoptosis in daf-2 mutants, suggesting that gla-3 acts downstream of daf-2. In addition, the hypersensitivity of let-60/Ras gain-of-function mutants to damage-induced apoptosis was suppressed to wild-type levels by ablation of daf-2. Thus, insulin/IGF-1 signaling selectively engages AKT-2/DAF-16 to promote DNA damage-induced germ cell apoptosis downstream of CEP-1 through the Ras pathway.

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

PubMed Central

Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca EW; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D

2017-01-01

daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant. PMID:29063832

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.

PubMed

Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca Ew; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D; Baugh, L Ryan

2017-10-24

daf-16 /FoxO is required to survive starvation in Caenorhabditis elegans , but how daf-16I FoxO promotes starvation resistance is unclear. We show that daf-16 /FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16 /FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.

A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development.

PubMed

Ames, Kristina; Da Cunha, Dayse S; Gonzalez, Brenda; Konta, Marina; Lin, Feng; Shechter, Gabriel; Starikov, Lev; Wong, Sara; Bülow, Hannes E; Meléndez, Alicia

2017-03-20

The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16.2/ATG16L, atg-18/WIPI1/2, and atg-7/ATG7 are required for the late larval expansion of germline stem cell progenitors in the C. elegans gonad. We further show that BEC-1/BECN1/Beclin1 acts independently of the GLP-1/Notch or DAF-7/TGF-β pathways but together with the DAF-2/insulin IGF-1 receptor (IIR) signaling pathway to promote germline stem cell proliferation. Similar to DAF-2/IIR, BEC-1/BECN1/Beclin1, ATG-18/WIPI1/2, and ATG-16.2/ATG16L all promote cell-cycle progression and are negatively regulated by the phosphatase and tensin homolog DAF-18/PTEN. However, whereas BEC-1/BECN1/Beclin1 acts through the transcriptional regulator SKN-1/Nrf1, ATG-18/WIPI1/2 and ATG-16.2/ATG16L exert their function through the DAF-16/FOXO transcription factor. In contrast, ATG-7 functions in concert with the DAF-7/TGF-β pathway to promote germline proliferation and is not required for cell-cycle progression. Finally, we report that BEC-1/BECN1/Beclin1 functions non-cell-autonomously to facilitate cell-cycle progression and stem cell proliferation. Our findings demonstrate a novel non-autonomous role for BEC-1/BECN1/Beclin1 in the control of stem cell proliferation and cell-cycle progression, which may have implications for the understanding and development of therapies against malignant cell growth in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pristionchus pacificus daf-16 is essential for dauer formation but dispensable for mouth form dimorphism.

PubMed

Ogawa, Akira; Bento, Gilberto; Bartelmes, Gabi; Dieterich, Christoph; Sommer, Ralf J

2011-04-01

The nematode Pristionchus pacificus shows two forms of phenotypic plasticity: dauer formation and dimorphism of mouth form morphologies. It can therefore serve as a model for studying the evolutionary mechanisms that underlie phenotypic plasticity. Formation of dauer larvae is observed in many other species and constitutes one of the most crucial survival strategies in nematodes, whereas the mouth form dimorphism is an evolutionary novelty observed only in P. pacificus and related nematodes. We have previously shown that the same environmental cues and steroid signaling control both dauer formation and mouth form dimorphism. Here, we examine by mutational analysis and whole-genome sequencing the function of P. pacificus (Ppa) daf-16, which encodes a forkhead transcription factor; in C. elegans, daf-16 is the target of insulin signaling and plays important roles in dauer formation. We found that mutations in Ppa-daf-16 cause strong dauer formation-defective phenotypes, suggesting that Ppa-daf-16 represents one of the evolutionarily conserved regulators of dauer formation. Upon strong dauer induction with lophenol, Ppa-daf-16 individuals formed arrested larvae that partially resemble wild-type dauer larvae, indicating that Ppa-daf-16 is also required for dauer morphogenesis. By contrast, regulation of mouth form dimorphism was unaffected by Ppa-daf-16 mutations and mutant animals responded normally to environmental cues. Our results suggest that mechanisms for dauer formation and mouth form regulation overlap partially, but not completely, and one of two key transcriptional regulators of the dauer regulatory network was either independently co-opted for, or subsequently lost by, the mouth form regulatory network.

Redox regulation, gene expression and longevity.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-07-01

Lifespan can be lengthened by genetic and environmental modifications. Study of these might provide valuable insights into the mechanism of aging. Low doses of radiation and short-term exposure to heat and high concentrations of oxygen prolong the lifespan of the nematode Caenorhabditis elegans. These might be caused by adaptive responses to harmful environmental conditions. Single-gene mutations have been found to extend lifespan in C. elegans, Drosophila and mice. So far, the best-characterized system is the C. elegans mutant in the daf-2, insulin/IGF-I receptor gene that is the component of the insulin/IGF-I signaling pathway. The mutant animals live twice as long as the wild type. The insulin/IGF-I signaling pathway regulates the activity of DAF-16, a FOXO transcription factor. However, the unified explanation for the function of DAF-16 transcription targets in the lifespan extension is not yet fully established. As both of the Mn superoxide dismutase (MnSOD) isoforms (sod-2 and sod-3) are found to be targets of DAF-16, we attempted to assess their functions in regulating lifespan and oxidative stress responsivity. We show that the double deletions of sod-2 and sod-3 genes induced oxidative-stress sensitivity but do not shorten lifespan in the daf-2 mutant background, indicating that oxidative stress is not necessarily a limiting factor for longevity. Furthermore, the deletion in the sod-3 gene lengthens lifespan in the daf-2 mutant. We conclude that the MnSOD systems in C. elegans fine-tune the insulin/IGF-I-signaling based regulation of longevity by acting not as anti-oxidants but as physiological-redox-signaling modulators.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans.

PubMed

Reis Rodrigues, Pedro; Kaul, Tiffany K; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B; Held, Jason M; Bohn, Laura M; Gill, Matthew S

2016-06-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. Copyright © 2016 Rodrigues et al.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans

PubMed Central

Reis Rodrigues, Pedro; Kaul, Tiffany K.; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B.; Held, Jason M.; Bohn, Laura M.; Gill, Matthew S.

2016-01-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. PMID:27172180

Genes that regulate both development and longevity in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, P.L.; Albert, P.S.; Riddle, D.L.

1995-04-01

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determinationmore » of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. 47 refs., 7 figs., 5 tabs.« less

Simultaneous determination of reactive oxygen and nitrogen species in mitochondrial compartments of apoptotic HepG2 cells and PC12 cells based on microchip electrophoresis-laser-induced fluorescence.

PubMed

Chen, Zhenzhen; Li, Qingling; Sun, Qianqian; Chen, Hao; Wang, Xu; Li, Na; Yin, Miao; Xie, Yanxia; Li, Hongmin; Tang, Bo

2012-06-05

Determination of intracellular bioactive species will afford beneficial information related to cell metabolism, signal transduction, cell function, and disease treatment. In this study, the first application of a microchip electrophoresis-laser-induced fluorescence (MCE-LIF) method for concurrent determination of reactive oxygen species (ROS) and reactive nitrogen species (RNS), i.e., superoxide (O(2)(-•)) and nitric oxide (NO) in mitochondria, was developed using fluorescent probes 2-chloro-1,3-dibenzothiazolinecyclohexene (DBZTC) and 3-amino,4-aminomethyl-2',7'-difluorescein (DAF-FM), respectively. Potential interference of intracellular dehydroascorbic acid (DHA) and ascorbic acid (AA) for NO detection with DAF-FM was eliminated through oxidation of AA with the addition of ascorbate oxidase, followed by subsequent MCE separation. Fluorescent products of O(2)(-•) and NO, DBZTC oxide (DBO), and DAF-FM triazole (DAF-FMT) showed excellent baseline separation within 1 min with a running buffer of 40 mM Tris solution (pH 7.4) and a separating electric field of 500 V/cm. The levels of DBO and DAF-FMT in mitochondria isolated from normal HepG2 cells and PC12 cells were evaluated using this method. Furthermore, the changes of DBO and DAF-FMT levels in mitochondria isolated from apoptotic HepG2 cells and PC12 cells could also be detected. The current approach was proved to be simple, fast, reproducible, and efficient. Measurement of the two species with the method will be beneficial to understand ROS/RNS distinctive functions. In addition, it will provide new insights into the role that both species play in biological systems.

dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

PubMed

Kaplan, Rebecca E W; Chen, Yutao; Moore, Brad T; Jordan, James M; Maxwell, Colin S; Schindler, Adam J; Baugh, L Ryan

2015-12-01

Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.

dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest

PubMed Central

Moore, Brad T.; Jordan, James M.; Maxwell, Colin S.; Schindler, Adam J.; Baugh, L. Ryan

2015-01-01

Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This “L1 arrest” (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development. PMID:26656736

Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation

PubMed Central

Lavitrano, Marialuisa; Bacci, Maria Laura; Forni, Monica; Lazzereschi, Davide; Di Stefano, Carla; Fioretti, Daniela; Giancotti, Paola; Marfé, Gabriella; Pucci, Loredana; Renzi, Luigina; Wang, Hongjun; Stoppacciaro, Antonella; Stassi, Giorgio; Sargiacomo, Massimo; Sinibaldi, Paola; Turchi, Valeria; Giovannoni, Roberto; Della Casa, Giacinto; Seren, Eraldo; Rossi, Giancarlo

2002-01-01

A large number of hDAF transgenic pigs to be used for xenotransplantation research were generated by using sperm-mediated gene transfer (SMGT). The efficiency of transgenesis obtained with SMGT was much greater than with any other method. In the experiments reported, up to 80% of pigs had the transgene integrated into the genome. Most of the pigs carrying the hDAF gene transcribed it in a stable manner (64%). The great majority of pigs that transcribed the gene expressed the protein (83%). The hDAF gene was transmitted to progeny. Expression was stable and found in caveolae as it is in human cells. The expressed gene was functional based on in vitro experiments performed on peripheral blood mononuclear cells. These results show that our SMGT approach to transgenesis provides an efficient procedure for studies involving large animal models. PMID:12393815

Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

PubMed

Gaglia, Marta M; Jeong, Dae-Eun; Ryu, Eun-A; Lee, Dongyeop; Kenyon, Cynthia; Lee, Seung-Jae

2012-01-01

The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

Gravity Force Transduced by the MEC-4/MEC-10 DEG/ENaC Channel Modulates DAF-16/FoxO Activity in Caenorhabditis elegans

PubMed Central

Kim, Nahui; Dempsey, Catherine M.; Kuan, Chih-Jen; Zoval, Jim V.; O'Rourke, Eyleen; Ruvkun, Gary; Madou, Marc J.; Sze, Ji Y.

2007-01-01

The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16∷GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16∷GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16∷GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses. PMID:17720915

Unexpected role for dosage compensation in the control of dauer arrest, insulin-like signaling, and FoxO transcription factor activity in Caenorhabditis elegans.

PubMed

Dumas, Kathleen J; Delaney, Colin E; Flibotte, Stephane; Moerman, Donald G; Csankovszki, Gyorgyi; Hu, Patrick J

2013-07-01

During embryogenesis, an essential process known as dosage compensation is initiated to equalize gene expression from sex chromosomes. Although much is known about how dosage compensation is established, the consequences of modulating the stability of dosage compensation postembryonically are not known. Here we define a role for the Caenorhabditis elegans dosage compensation complex (DCC) in the regulation of DAF-2 insulin-like signaling. In a screen for dauer regulatory genes that control the activity of the FoxO transcription factor DAF-16, we isolated three mutant alleles of dpy-21, which encodes a conserved DCC component. Knockdown of multiple DCC components in hermaphrodite and male animals indicates that the dauer suppression phenotype of dpy-21 mutants is due to a defect in dosage compensation per se. In dpy-21 mutants, expression of several X-linked genes that promote dauer bypass is elevated, including four genes encoding components of the DAF-2 insulin-like pathway that antagonize DAF-16/FoxO activity. Accordingly, dpy-21 mutation reduced the expression of DAF-16/FoxO target genes by promoting the exclusion of DAF-16/FoxO from nuclei. Thus, dosage compensation enhances dauer arrest by repressing X-linked genes that promote reproductive development through the inhibition of DAF-16/FoxO nuclear translocation. This work is the first to establish a specific postembryonic function for dosage compensation in any organism. The influence of dosage compensation on dauer arrest, a larval developmental fate governed by the integration of multiple environmental inputs and signaling outputs, suggests that the dosage compensation machinery may respond to external cues by modulating signaling pathways through chromosome-wide regulation of gene expression.

Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

PubMed

Furuhashi, Tsubasa; Sakamoto, Kazuichi

2016-03-25

The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging in Caenorhabditis elegans.

PubMed

Baxi, Kunal; Ghavidel, Ata; Waddell, Brandon; Harkness, Troy A; de Carvalho, Carlos E

2017-09-01

Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signaling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity-a critical regulator of the proteolytic output of these organelles-as a novel biomarker of aging in C. elegans The increase in lysosomal pH in older worms is not a passive consequence of aging, but instead is timed with the cessation of reproduction, and correlates with the reduction in proteostasis in early adult life. Our results further implicate the steroid signaling pathway and DAF-16 in dynamically regulating lysosomal pH in the intestine of wild-type worms in response to the reproductive cycle. In the intestine of reproducing worms, DAF-16 promotes acidic lysosomes by upregulating the expression of v-ATPase genes. These findings support a model in which protein clearance in the soma is linked to reproduction in the gonad via the active regulation of lysosomal acidification. Copyright © 2017 by the Genetics Society of America.

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

A pilot randomized controlled trial of the Occupational Goal Intervention method for the improvement of executive functioning in patients with treatment-resistant schizophrenia.

PubMed

Vizzotto, Adriana D B; Celestino, Diego L; Buchain, Patricia C; Oliveira, Alexandra M; Oliveira, Graça M R; Di Sarno, Elaine S; Napolitano, Isabel C; Elkis, Helio

2016-11-30

Schizophrenia is a chronic disabling mental disorder that involves impairments in several cognitive domains, especially in executive functions (EF), as well as impairments in functional performance. This is particularly true in patients with Treatment-Resistant Schizophrenia (TRS). The aim of this study was to test the efficacy of the Occupational Goal Intervention (OGI) method for the improvement of EF in patients with TRS. In this randomized, controlled, single-blind pilot study, 25 TRS patients were randomly assigned to attend 30 sessions of either OGI or craft activities (control) over a 15-week period and evaluated by the Behavioural Assessment of the Dysexecutive Syndrome (BADS) as the primary outcome and the Direct Assessment of Functional Status (DAFS-BR) as well as the Independent Living Skills Survey (ILSS-BR) as secondary outcomes, all adapted for the Brazilian population. The Positive and Negative Syndrome Scale (PANSS) was used for monitoring symptom severity. Results showed significant statistical differences, favoring the OGI group in terms of improvement on the BADS, both in subtests (Action Program and Key Search) and the total score. Improvements in EFs were observed by families in various dimensions as measured by different subtests of the ILSS-BR inventory. The OGI group showed no significant results in secondary outcomes (DAFS-BR) except in terms of improvement of communication skills. Although preliminary, our results indicate that the OGI method is efficacious and effective for patients with TRS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

PubMed

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.

Molecular Basis for Antioxidant Enzymes in Mediating Copper Detoxification in the Nematode Caenorhabditis elegans

PubMed Central

Song, Shaojuan; Zhang, Xueyao; Wu, Haihua; Han, Yan; Zhang, Jianzhen; Ma, Enbo; Guo, Yaping

2014-01-01

Antioxidant enzymes play a major role in defending against oxidative damage by copper. However, few studies have been performed to determine which antioxidant enzymes respond to and are necessary for copper detoxification. In this study, we examined both the activities and mRNA levels of SOD, CAT, and GPX under excessive copper stress in Caenorhabditis elegans, which is a powerful model for toxicity studies. Then, taking advantage of the genetics of this model, we assessed the lethal concentration (LC50) values of copper for related mutant strains. The results showed that the SOD, CAT, and GPX activities were significantly greater in treated groups than in controls. The mRNA levels of sod-3, sod-5, ctl-1, ctl-2, and almost all gpx genes were also significantly greater in treated groups than in controls. Among tested mutants, the sod-5, ctl-1, gpx-3, gpx-4, and gpx-6 variants exhibited hypersensitivity to copper. The strains with SOD or CAT over expression were reduced sensitive to copper. Mutations in daf-2 and age-1, which are involved in the insulin/insulin-like growth factor-1 signaling pathway, result in reduced sensitivity to stress. Here, we showed that LC50 values for copper in daf-2 and age-1 mutants were significantly greater than in N2 worms. However, the LC50 values in daf-16;daf-2 and daf-16;age-1 mutants were significantly reduced than in daf-2 and age-1 mutants, implying that reduced copper sensitivity is influenced by DAF-16-related functioning. SOD, CAT, and GPX activities and the mRNA levels of the associated copper responsive genes were significantly increased in daf-2 and age-1 mutants compared to N2. Additionally, the activities of SOD, CAT, and GPX were greater in these mutants than in N2 when treated with copper. Our results not only support the theory that antioxidant enzymes play an important role in copper detoxification but also identify the response and the genes involved in these processes. PMID:25243607

Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.

PubMed

Mansfeld, Johannes; Urban, Nadine; Priebe, Steffen; Groth, Marco; Frahm, Christiane; Hartmann, Nils; Gebauer, Juliane; Ravichandran, Meenakshi; Dommaschk, Anne; Schmeisser, Sebastian; Kuhlow, Doreen; Monajembashi, Shamci; Bremer-Streck, Sibylle; Hemmerich, Peter; Kiehntopf, Michael; Zamboni, Nicola; Englert, Christoph; Guthke, Reinhard; Kaleta, Christoph; Platzer, Matthias; Sühnel, Jürgen; Witte, Otto W; Zarse, Kim; Ristow, Michael

2015-12-01

Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.

Branched-chain amino acid catabolism is a conserved regulator of physiological ageing

PubMed Central

Mansfeld, Johannes; Urban, Nadine; Priebe, Steffen; Groth, Marco; Frahm, Christiane; Hartmann, Nils; Gebauer, Juliane; Ravichandran, Meenakshi; Dommaschk, Anne; Schmeisser, Sebastian; Kuhlow, Doreen; Monajembashi, Shamci; Bremer-Streck, Sibylle; Hemmerich, Peter; Kiehntopf, Michael; Zamboni, Nicola; Englert, Christoph; Guthke, Reinhard; Kaleta, Christoph; Platzer, Matthias; Sühnel, Jürgen; Witte, Otto W.; Zarse, Kim; Ristow, Michael

2015-01-01

Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan. PMID:26620638

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration* ♦

PubMed Central

Koenig, Patrick; Lee, Chingwei V.; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F.; Fuh, Germaine

2015-01-01

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

Breeding new seedless grape by means of in vitro embryo rescue.

PubMed

Ji, W; Li, Z-Q; Zhou, Q; Yao, W-K; Wang, Y-J

2013-03-26

This project aimed at breeding new seedless grape cultivars by embryo rescue through three hybridization methods: 1) using cross-breeding between seedless Vitis vinifera cultivars and wild Chinese Vitis spp; 2) crossing with two seedless cultivars, and 3) hybridization between grapes of different ploidy. Genotype, sampling times, and media were confirmed to play important roles in this system. Among the different genotypes, the productions of hybrid plants were significantly different, ranging from 23.0% (Ruby Seedless x Black Olympia) to only 1.1% (Pink Seedless x Beichun), except for the combinations from which no surviving seedlings were obtained. We got the best sampling times, in days after flowering (DAF), from the following different combinations: 'Flame Seedless x Beichun' (39 DAF); 'Blush Seedless x Shuangyou' (54 DAF); 'Pink Seedless x Beichun' (54 DAF); 'DA7 x Shuangyou' (44 DAF); 'Blush Seedless x Thompson Seedless (54 DAF)'; 'Pink Seedless x Flame Seedless' (54 DAF); 'DA7 x Blush Seedless' (44 DAF); 'Ruby Seedless x Black Olympia' (63 DAF); 'DA7 x Jingyou' (44 DAF); 'Flame Seedless x Fujiminori' (39 DAF), and 'Big Black x Kyoho' (72 DAF). The highest rates of embryo formation (13.2%) and plant development (90.1%) were found when ovules were cultured in MM4 with 500 mg/L mashed banana. Conversely, they were reduced by addition of plant growth regulators. Seven new hybrids were successfully obtained. As a result of early nuclear-free character and ploidy level identification, 11 seedless grape lines, and 3 triploid and 2 haploid grape lines were obtained.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 restrictionmore » (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.« less

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway

PubMed Central

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O.

2017-01-01

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans. This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12–dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans. This finding suggests the existence of a conserved CYP4V2-POR–nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage. PMID:28760992

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

PubMed

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

2017-08-15

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

Role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of Dr+ Escherichia coli receptor protein Decay Accelerating Factor (DAF or CD55) by Nitric oxide

PubMed Central

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2012-01-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr+). The epithelial invasion of Dr+ E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by down-regulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5′-untranslated region and mapped NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5′-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3′-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. The NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. PMID:23176121

Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+ Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide.

PubMed

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2013-02-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr(+) ). The epithelial invasion of Dr(+) E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5'-untranslated region and mapped the NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5'-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3'-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to the AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. © 2012 The Authors Journal compilation © 2012 FEBS.

Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans

PubMed Central

Huang, Xiao-Bing; Mu, Xiao-Hui; Wan, Qin-Li; He, Xiao-Ming; Wu, Gui-Sheng

2017-01-01

Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan. PMID:28910305

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

PubMed Central

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

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration.

PubMed

Koenig, Patrick; Lee, Chingwei V; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F; Fuh, Germaine

2015-09-04

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Nitric Oxide (NO) Measurements in Stomatal Guard Cells.

PubMed

Agurla, Srinivas; Gayatri, Gunja; Raghavendra, Agepati S

2016-01-01

The quantitative measurement of nitric oxide (NO) in plant cells acquired great importance, in view of the multifaceted function and involvement of NO as a signal in various plant processes. Monitoring of NO in guard cells is quite simple because of the large size of guard cells and ease of observing the detached epidermis under microscope. Stomatal guard cells therefore provide an excellent model system to study the components of signal transduction. The levels and functions of NO in relation to stomatal closure can be monitored, with the help of an inverted fluorescence or confocal microscope. We can measure the NO in guard cells by using flouroprobes like 4,5-diamino fluorescein diacetate (DAF-2DA). This fluorescent dye, DAF-2DA, is cell permeable and after entry into the cell, the diacetate group is removed by the cellular esterases. The resulting DAF-2 form is membrane impermeable and reacts with NO to generate the highly fluorescent triazole (DAF-2T), with excitation and emission wavelengths of 488 and 530 nm, respectively. If time-course measurements are needed, the epidermis can be adhered to a cover-glass or glass slide and left in a small petri dishes. Fluorescence can then be monitored at required time intervals; with a precaution that excitation is done minimally, only when a fluorescent image is acquired. The present method description is for the epidermis of Arabidopsis thaliana and Pisum sativum and should work with most of the other dicotyledonous plants.

Clustering of Genetically Defined Allele Classes in the Caenorhabditis elegans DAF-2 Insulin/IGF-1 Receptor

PubMed Central

Patel, Dhaval S.; Garza-Garcia, Acely; Nanji, Manoj; McElwee, Joshua J.; Ackerman, Daniel; Driscoll, Paul C.; Gems, David

2008-01-01

The DAF-2 insulin/IGF-1 receptor regulates development, metabolism, and aging in the nematode Caenorhabditis elegans. However, complex differences among daf-2 alleles complicate analysis of this gene. We have employed epistasis analysis, transcript profile analysis, mutant sequence analysis, and homology modeling of mutant receptors to understand this complexity. We define an allelic series of nonconditional daf-2 mutants, including nonsense and deletion alleles, and a putative null allele, m65. The most severe daf-2 alleles show incomplete suppression by daf-18(0) and daf-16(0) and have a range of effects on early development. Among weaker daf-2 alleles there exist distinct mutant classes that differ in epistatic interactions with mutations in other genes. Mutant sequence analysis (including 11 newly sequenced alleles) reveals that class 1 mutant lesions lie only in certain extracellular regions of the receptor, while class 2 (pleiotropic) and nonconditional missense mutants have lesions only in the ligand-binding pocket of the receptor ectodomain or the tyrosine kinase domain. Effects of equivalent mutations on the human insulin receptor suggest an altered balance of intracellular signaling in class 2 alleles. These studies consolidate and extend our understanding of the complex genetics of daf-2 and its underlying molecular biology. PMID:18245374

Divisional Electronic Warfare Combat (DEWCOM) Model - User Manual.

DTIC Science & Technology

1980-09-01

ulated combat hours. DTIC TA% 1~ Il m I UNCLASSIFIED SIECURITY CLASSIFICATION Or THIS PAGEft7n Date Entered) 4 ’ ./ .7"* t l DIVISIONAL ELECTRONIC WARFARE...277 4.2.1 Report M (Unit Status) ....... .......................... 277 4.2.2 Report M2 (Link Status...NONE in the first 4 spaces. 27 Mai -RF DEWCOM M S aoNE_ DAF INPUT DATA PREPARATI toI 2 4 . 8 1() 1 12 ,1 14 15 1 1718 lq2n2122 21242526 2728293031 3233

RT 24 - Architecture, Modeling & Simulation, and Software Design

DTIC Science & Technology

2010-11-01

focus on tool extensions (UPDM, SysML, SoaML, BPMN ) Leverage “best of breed” architecture methodologies Provide tooling to support the methodology DoDAF...Capability 10 Example: BPMN 11 DoDAF 2.0 MetaModel BPMN MetaModel Mapping SysML to DoDAF 2.0 12 DoDAF V2.0 Models OV-2 SysML Diagrams Requirement

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

PubMed Central

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

2013-01-01

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 Ca2+/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 PMID:23805378

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model

PubMed Central

Gao, Chenfei; Gao, Zhanguo; Greenway, Frank L.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Chu, YiFang; Zheng, Jolene

2015-01-01

In addition to their fermentable dietary fiber and the soluble β-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1–like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P < .05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P < .05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P < .01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P < .01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P < .01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism. PMID:26253816

Hydrophobically-associating cationic polymers as micro-bubble surface modifiers in dissolved air flotation for cyanobacteria cell separation.

PubMed

Yap, R K L; Whittaker, M; Diao, M; Stuetz, R M; Jefferson, B; Bulmus, V; Peirson, W L; Nguyen, A V; Henderson, R K

2014-09-15

Dissolved air flotation (DAF), an effective treatment method for clarifying algae/cyanobacteria-laden water, is highly dependent on coagulation-flocculation. Treatment of algae can be problematic due to unpredictable coagulant demand during blooms. To eliminate the need for coagulation-flocculation, the use of commercial polymers or surfactants to alter bubble charge in DAF has shown potential, termed the PosiDAF process. When using surfactants, poor removal was obtained but good bubble adherence was observed. Conversely, when using polymers, effective cell removal was obtained, attributed to polymer bridging, but polymers did not adhere well to the bubble surface, resulting in a cationic clarified effluent that was indicative of high polymer concentrations. In order to combine the attributes of both polymers (bridging ability) and surfactants (hydrophobicity), in this study, a commercially-available cationic polymer, poly(dimethylaminoethyl methacrylate) (polyDMAEMA), was functionalised with hydrophobic pendant groups of various carbon chain lengths to improve adherence of polymer to a bubble surface. Its performance in PosiDAF was contrasted against commercially-available poly(diallyl dimethyl ammonium chloride) (polyDADMAC). All synthesised polymers used for bubble surface modification were found to produce positively charged bubbles. When applying these cationic micro-bubbles in PosiDAF, in the absence of coagulation-flocculation, cell removals in excess of 90% were obtained, reaching a maximum of 99% cell removal and thus demonstrating process viability. Of the synthesised polymers, the polymer containing the largest hydrophobic functionality resulted in highly anionic treated effluent, suggesting stronger adherence of polymers to bubble surfaces and reduced residual polymer concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of DAF in protecting against T-cell autoreactivity that leads to experimental autoimmune uveitis.

PubMed

An, Fengqi; Li, Qing; Tu, Zhidan; Bu, Hong; Chan, Chi-Chao; Caspi, Rachel R; Lin, Feng

2009-08-01

To investigate the role of decay-accelerating factor (DAF), a cell surface complement regulator that recently has been linked to T-cell responses and autoimmunity in the pathogenesis of experimental autoimmune uveitis (EAU). EAU was induced in wild-type (WT) and Daf1(-/-) mice, and their disease severities, IRBP specific Th1/Th17 responses, and cytokine expression profiles were compared. In a test of the efficacy of treatment with soluble mouse DAF protein, EAU was induced in disease-susceptible B10.RIII mice, and they were treated with 0.5 mg soluble DAF protein or equal volume of PBS IP every other day. Retinal histology and IRBP-specific T-cell responses were compared after 14 days. Both EAU incidence and histopathology scores were significantly greater in Daf1(-/-) mice. There was a >10-fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding, and photoreceptor cell layer destruction. There were 5- to 7-fold greater Th1 and 3- to 4-fold greater Th17 responses against IRBP in Daf1(-/-) mice with EAU, and they expressed significantly elevated levels of GM-CSF, IL-2, IL-3, and IFN-gamma. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP-specific Th1/Th17 responses and were protected from retinal injury compared with the mice that received PBS treatments. DAF significantly influences IRBP-specific Th1 and Th17 responses and disease severity in EAU. Systemic upregulation of DAF levels could be used to suppress retinal antigen(s)-specific autoimmunity to treat autoimmune posterior uveitis.

Bubble performance of a novel dissolved air flotation(DAF) unit.

PubMed

Chen, Fu-tai; Peng, Feng-xian; Wu, Xiao-qing; Luan, Zhao-kun

2004-01-01

ES-DAF, a novel DAF with low cost, high reliability and easy controllability, was studied. Without a costly air saturator, ES-DAF consists of an ejector and a static mixer between the pressure side and suction side of the recycle rotary pump. The bubble size distribution in this novel unit was studied in detail by using a newly developed CCD imagination through a microscope. Compared with M-DAF under the same saturation pressure, ES-DAF can produce smaller bubble size and higher bubble volume concentration, especially in lower pressure. In addition, the bubble size decreases with the increase of reflux ratio or decrease of superficial air-water ratio. These results suggested that smaller bubbles will be formed when the initial number of nucleation sites increases by enhancing the turbulence intensity in the saturation system.

The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

PubMed

Tu, C-F; Tai, H-C; Wu, C-P; Ho, L-L; Lin, Y-J; Hwang, C-S; Yang, T-S; Lee, J-M; Tseng, Y-L; Huang, C-C; Weng, C-N; Lee, P-H

2010-01-01

To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to <10% versus >40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC. Copyright 2010 Elsevier Inc. All rights reserved.

Randomized study combining interferon and glatiramer acetate in multiple sclerosis.

PubMed

Lublin, Fred D; Cofield, Stacey S; Cutter, Gary R; Conwit, Robin; Narayana, Ponnada A; Nelson, Flavia; Salter, Amber R; Gustafson, Tarah; Wolinsky, Jerry S

2013-03-01

A double-blind, randomized, controlled study was undertaken to determine whether combined use of interferon β-1a (IFN) 30 μg intramuscularly weekly and glatiramer acetate (GA) 20 mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis. A total of 1,008 participants were randomized and followed until the last participant enrolled completed 3 years. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score, and magnetic resonance imaging (MRI) metrics. Combination IFN+GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The combination was not better than either agent alone in lessening confirmed Expanded Disability Status Scale progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity-free status (DAFS) compared to either single arm, driven by the MRI results. Combining the 2 most commonly prescribed therapies for multiple sclerosis did not produce a significant clinical benefit over 3 years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address whether the observed differences in MRI and DAFS findings predict later clinical differences. Copyright © 2013 American Neurological Association.

A case study of dissolved air flotation for seasonal high turbidity water in Korea.

PubMed

Kwon, S B; Ahn, H W; Ahn, C J; Wang, C K

2004-01-01

A DAF (Dissolved-Air-Flotation) process has been designed considering raw water quality characteristics in Korea. Although direct filtration is usually operated, DAF is operated when freshwater algae blooms occur or raw water turbidity becomes high. Pre-sedimentation is operated in case when the raw water turbidity is very high due to rainstorms. A main feature of this plant is that the operation mode can be changed (controlled) based on the characteristics of the raw water to optimize the effluent quality and the operation costs. Treatment capacity (surface loading rate) and efficiency of DAF was found to be better than the conventional sedimentation process. Moreover, low-density particles (algae and alum flocs) are easily separated while the removal of them by sedimentation is more difficult. One of the main concerns for DAF operation is a high raw water turbidity. DAF is not adequate for raw water, which is more turbid than 100 NTU. In order to avoid this problem, pre-sedimentation basins are installed in the DAF plant to decrease the turbidity of the DAF inflow. For simulation of the actual operation, bench and full-scale tests were performed for highly turbid water conditions. Consequently, it is suggested that pre-sedimentation with optimum coagulation prior to DAF is the appropriate treatment scheme.

Porcine Knock-in Fibroblasts Expressing hDAF on α-1,3-Galactosyltransferase (GGTA1) Gene Locus.

PubMed

Kim, Ji Woo; Kim, Hye-Min; Lee, Sang Mi; Kang, Man-Jong

2012-10-01

The Galactose-α1,3-galactose (α1,3Gal) epitope is responsible for hyperacute rejection in pig-to-human xenotransplantation. Human decay-accelerating factor (hDAF) is a cell surface regulatory protein that serves as a complement inhibitor to protect self cells from complement attack. The generation of α1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a necessary step for their use as organ donors for humans. In this study, we established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was lower in the knock-in heterozygous cell line compared to the normal pig cell. Knock-in heterozygous cells afforded more effective protection against cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control cells. These cell lines may be used in the production of GGTA1 knock-out and DAF expression pigs for xenotransplantation.

Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs

PubMed Central

Gruner, Matthew; Nelson, Dru; Winbush, Ari; Hintz, Rebecca; Ryu, Leesun; Chung, Samuel H.; Kim, Kyuhyung; Gabel, Chrisopher V.; van der Linden, Alexander M.

2014-01-01

Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions. PMID:25357003

Coating of human decay accelerating factor (hDAF) onto medical devices to improve biocompatibility.

PubMed

Watkins, N J; Braidley, P; Bray, C J; Savill, C M; White, D J

1997-12-01

In passing blood through an artificial circulatory system, the blood is exposed to surfaces that result in activation of the complement system. The consequences of the activation of complement can be extremely serious for the patient ranging from mild discomfort to respiratory distress and even anaphylaxis. An entirely novel approach was to express recombinant GPI anchored human decay accelerating factor (hDAF) using the baculovirus system and then coat the recombinant protein onto the surfaces of these materials to reduce complement activation. Expression of hDAF in Sf9 cells was shown by ELISA, FACS analysis, and Western blot. Functional activity was tested by CH50 assay. For the coating experiments a small scale model of a cardiovascular bypass circuit constructed from COBE tubing was used. hDAF was either coated onto the circuit using adsorption or covalently linked via the photoreactive crosslinker, p-azidobenzoyl hydrazide. After coating, heparinised human blood was pumped around the circuit and samples were collected into EDTA collection tubes at different time points. Complement activation was measured using a Quidel C3a-des-arg EIA. The photolinked circuits gave a reduction in C3a production of 20-50%, compared to 10-20% seen with an absorbed hDAF circuit. Furthermore, the inhibition of complement was seen over the whole time scale of the photolinked circuit, 60-90 min, whilst in the adsorbed circuit inhibition was not seen to a significant degree after 60 min. The time scale of a standard cardiac bypass is 45-90 min, therefore, the photolinked circuit results are encouraging, as significant inhibition of complement activation is seen within this time frame.

Community environmental factors are associated with disability in older adults with functional limitations: the MOST study.

PubMed

Keysor, Julie J; Jette, Alan M; LaValley, Michael P; Lewis, Cora E; Torner, James C; Nevitt, Michael C; Felson, Dave T

2010-04-01

There is limited evidence supporting the hypothesized environment-disability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations. Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF. Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2-3.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.3-0.8) but not with DAF in adjusted models. People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently.

Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.

PubMed

Luciani, Genna M; Magomedova, Lilia; Puckrin, Rachel; Urbanus, Malene L; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Cummins, Carolyn L; Roy, Peter J

2011-11-06

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

EFFECT OF DELAYED AUDITORY FEEDBACK, SPEECH RATE, AND SEX ON SPEECH PRODUCTION.

PubMed

Stuart, Andrew; Kalinowski, Joseph

2015-06-01

Perturbations in Delayed Auditory Feedback (DAF) and speech rate were examined as sources of disruptions in speech between men and women. Fluent adult men (n = 16) and women (n = 16) spoke at a normal and an imposed fast rate of speech with 0, 25, 50, 100, and 200 msec. DAF. The syllable rate significantly increased when participants were instructed to speak at a fast rate, and the syllable rate decreased with increasing DAF delays. Men's speech rate was significantly faster during the fast speech rate condition with a 200 msec. DAF. Disfluencies increased with increasing DAF delay. Significantly more disfluency occurred at delays of 25 and 50 msec. at the fast rate condition, while more disfluency occurred at 100 and 200 msec. in normal rate conditions. Men and women did not display differences in the number of disfluencies. These findings demonstrate sex differences in susceptibility to perturbations in DAF and speech rate suggesting feedforward/feedback subsystems that monitor vocalizations may be different between sexes.

Decay-accelerating factor 1 deficiency exacerbates Trypanosoma cruzi-induced murine chronic myositis.

PubMed

Solana, María E; Ferrer, María F; Novoa, María Mercedes; Song, Wen-Chao; Gómez, Ricardo M

2012-10-01

Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T-cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance murine T-cell responses and autoimmunity. To determine whether Daf1 deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice were inoculated with 5 × 10(4) trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T-cell expansion were studied in the acute and chronic stages. DAF(-/-) mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells. An enhanced CD8(+) T-cell immune-specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a useful model to study T-cell mediated immunity in skeletal muscle tissues. Copyright © 2012 Wiley Periodicals, Inc.

The South Circumpolar Dorsa Argentea Formation and the Noachian-Hesperian Climate of Mars

NASA Astrophysics Data System (ADS)

Head, J. W., III; Scanlon, K. E.; Fastook, J.; Wordsworth, R. D.

2017-12-01

The Dorsa Argentea Formation (DAF), a set of geomorphologic units covering 1.5 · 106 km2 in the south circumpolar region of Mars with lobes extending along the 0° and 90°W meridians, has been interpreted as the remnants of a large Noachian-Hesperian ice sheet. Determining the extent and thermal regime of the DAF ice sheet, and the controls on its development, can therefore provide insight into the ancient martian climate. We used the Laboratoire de Météorologie Dynamique early Mars global climate model (GCM) and the University of Maine Ice Sheet Model (UMISM) glacial flow model to constrain climates that would permit both development of a south polar ice sheet of DAF-like size and shape and melting consistent with observed eskers and channels. An asymmetric south polar cold trap is a robust feature of GCM simulations with spin-axis obliquity of 15° or 25° and a 600 - 1000 mb CO2 atmosphere. The shape results from the strong dependence of surface temperature on altitude in a thicker atmosphere. Of the scenarios considered here, the shape and extent of the modeled DAF ice sheet in UMISM simulations most closely match those of the DAF when the surface water ice inventory of Mars is 20 · 106 km3 and obliquity is 15°. In climates warmed only by CO2, basal melting does not occur except when the ice inventory is larger than most estimates for early Mars. In this case, the extent of the ice sheet is also much larger than that of the DAF, and melting is more widespread than observed landforms indicate. When an idealized greenhouse gas warms the surface by at least 20° near the poles relative to CO2 alone, the extent of the ice sheet is less than that of the DAF, but strong basal melting occurs, with maxima in the locations where eskers and channels are observed. We conclude that the glaciofluvial landforms in the DAF implicate warming by a gas other than CO2 alone. Previously published exposure ages of eskers in the DAF indicate that eskers were being exposed as activity was ceasing in the equatorial valley networks, suggesting that the warming that allowed basal melting of the DAF ice sheet was broadly contemporaneous with development of the valley networks. Elevated Tharsis topography is required to produce an ice sheet with the shape of the DAF. Thus, our results are not consistent with the DAF (and the valley networks) forming before Tharsis, as recently suggested.

Insulin/Insulin-like growth factor signaling controls non-Dauer developmental speed in the nematode Caenorhabditis elegans.

PubMed

Ruaud, Anne-Françoise; Katic, Iskra; Bessereau, Jean-Louis

2011-01-01

Identified as a major pathway controlling entry in the facultative dauer diapause stage, the DAF-2/Insulin receptor (InsR) signaling acts in multiple developmental and physiological regulation events in Caenorhabditis elegans. Here we identified a role of the insulin-like pathway in controlling developmental speed during the C. elegans second larval stage. This role relies on the canonical DAF-16/FOXO-dependent branch of the insulin-like signaling and is largely independent of dauer formation. Our studies provide further evidence for broad conservation of insulin/insulin-like growth factor (IGF) functions in developmental speed control.

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

PubMed

Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

A Conserved PHD Finger Protein and Endogenous RNAi Modulate Insulin Signaling in Caenorhabditis elegans

PubMed Central

Hoersch, Sebastian; Jensen, Morten B.; Kawli, Trupti; Kennedy, Lisa M.; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D.; Grishok, Alla

2011-01-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16–dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes. PMID:21980302

A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans.

PubMed

Mansisidor, Andres R; Cecere, Germano; Hoersch, Sebastian; Jensen, Morten B; Kawli, Trupti; Kennedy, Lisa M; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D; Grishok, Alla

2011-09-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

PubMed Central

Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

2006-01-01

Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. Conclusion A screen for suppressors of PI3K mutant phenotypes identified activating mutations in two known pathway components, providing insights into their regulation. In particular, the interdependence of akt-1 and pdk-1, even in activated forms, supports the existence of AGE-1-independent pathways for these phospholipid-dependent kinases. Phenotypic analysis of these alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable in these mutants. PMID:17020605

Dissolved air flotation and me.

PubMed

Edzwald, James K

2010-04-01

This paper is mainly a critical review of the literature and an assessment of what we know about dissolved air flotation (DAF). A few remarks are made at the outset about the author's personal journey in DAF research, his start and its progression. DAF has been used for several decades in drinking water treatment as an alternative clarification method to sedimentation. DAF is particularly effective in treating reservoir water supplies; those supplies containing algae, natural color or natural organic matter; and those with low mineral turbidity. It is more efficient than sedimentation in removing turbidity and particles for these type supplies. Furthermore, it is more efficient in removing Giardia cysts and Cryptosporidium oocysts. In the last 20 years, fundamental models were developed that provide a basis for understanding the process, optimizing it, and integrating it into water treatment plants. The theories were tested through laboratory and pilot-plant studies. Consequently, there have been trends in which DAF pretreatment has been optimized resulting in better coagulation and a decrease in the size of flocculation tanks. In addition, the hydraulic loading rates have increased reducing the size of DAF processes. While DAF has been used mainly in conventional type water plants, there is now interest in the technology as a pretreatment step in ultrafiltration membrane plants and in desalination reverse osmosis plants. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes

PubMed Central

Wang, Zhu; Stoltzfus, Jonathan; You, Young-jai; Ranjit, Najju; Tang, Hao; Xie, Yang; Lok, James B.; Mangelsdorf, David J.; Kliewer, Steven A.

2015-01-01

Appropriate nutrient response is essential for growth and reproduction. Under favorable nutrient conditions, the C. elegans nuclear receptor DAF-12 is activated by dafachronic acids, hormones that commit larvae to reproductive growth. Here, we report that in addition to its well-studied role in controlling developmental gene expression, the DAF-12 endocrine system governs expression of a gene network that stimulates the aerobic catabolism of fatty acids. Thus, activation of the DAF-12 transcriptome coordinately mobilizes energy stores to permit reproductive growth. DAF-12 regulation of this metabolic gene network is conserved in the human parasite, Strongyloides stercoralis, and inhibition of specific steps in this network blocks reproductive growth in both of the nematodes. Our study provides a molecular understanding for metabolic adaptation of nematodes to their environment, and suggests a new therapeutic strategy for treating parasitic diseases. PMID:25774872

A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.

PubMed

Goszczynski, Barbara; Captan, Vasile V; Danielson, Alicia M; Lancaster, Brett R; McGhee, James D

2016-05-01

The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-β/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental. Copyright © 2016 Elsevier Inc. All rights reserved.

A pilot plant study using conventional and advanced water treatment processes: Evaluating removal efficiency of indicator compounds representative of pharmaceuticals and personal care products.

PubMed

Zhang, Shuangyi; Gitungo, Stephen; Axe, Lisa; Dyksen, John E; Raczko, Robert F

2016-11-15

With widespread occurrence of pharmaceuticals and personal care products (PPCPs) in the water cycle, their presence in source water has led to the need to better understand their treatability and removal efficiency in treatment processes. Fifteen indicator compounds were identified to represent the large number of PPCPs reported worldwide. Criteria applied to determine the indicator compounds included PPCPs widely used, observed at great frequency in aqueous systems, resistant to treatment, persistent in the environment, and representative of classes of organics. Through a pilot plant investigation to understand the optimal combination of unit process for treating PPCPs, 12 treatment trains with their additive and synergistic contributions were investigated; processes included dissolved air flotation (DAF), pre- and intermediate-ozonation with and without H 2 O 2 , intermediate chlorination, dual media filtration, granular activated carbon (GAC), and UV/H 2 O 2 . Treatment trains that achieved the greatest removals involved 1. DAF followed by intermediate ozonation, dual media filtration, and virgin GAC; 2. pre-ozonation followed by DAF, dual media filtration, and virgin GAC; and, 3. DAF (with either pre- or intermediate oxidation) followed by dual media filtration and UV/H 2 O 2 . Results revealed significant removal efficiencies for virgin GAC (preceded by DAF and intermediate ozonation) and UV/H 2 O 2 with an intensity of 700 mJ/cm 2 , where more than 12 of the compounds were removed by greater than 90%. Reduced PPCP removals were observed with virgin GAC preceded by pre-ozonation and DAF. Intermediate ozonation was more effective than using pre-ozonation, demonstrating the importance of this process targeting PPCPs after treatment of natural organic matter. Removal efficiencies of indicator compounds through ozonation were found to be a function of the O 3 rate constants (k O3 ). For compounds with low O 3 rate constants (k O3  < 10 M -1 s -1 ), H 2 O 2 addition in the O 3 reactor was required. Of the 15 indicator compounds, tri(2-chloroethyl) phosphate (TCEP) and cotinine were observed to be the most recalcitrant. Although UV/H 2 O 2 with elevated intensity (700 mJ/cm 2 ) was effective for PPCP removals, energy requirements far exceed intensities applied for disinfection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective expression of a splice variant of decay-accelerating factor in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandt, Burkhard; Mikesch, Jan-Hendrik; Simon, Ronald

2005-04-01

By differential-display-PCR a subclone of the SK-BR-3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of a new alternative splice variant of decay-accelerating factor (DAF). DAF seems to play an important role in some malignant tumours since on the one hand the expression of complement inhibitors on the surface of tumour cells prevents the accumulation of complement factors and in consequence cell lysis. On the other hand, DAF has been identified as a ligand for the CD97 surface receptor which induces cell migration. Immunofluorescence procedures, Western blot analyses, and cDNA clone sequencing were employedmore » to confirm the expression of DAF restricted to invasive tumour cells. Using a radioactive RNA-in situ hybridisation on freshly frozen tissue microarrays and RT-PCR on native tumour tissue, the expression of alternative spliced DAF mRNA was demonstrated in invasive breast cancer. Due to the fact that it could thereby not be detected in normal mammary tissues, it has to be confirmed in larger studies that the DAF splice variant might be a specific tumour marker for invasive breast cancer.« less

Concentration kinetics of secoisolariciresinol diglucoside and its biosynthetic precursor coniferin in developing flaxseed.

PubMed

Fang, Jingjing; Ramsay, Aina; Paetz, Christian; Tatsis, Evangelos C; Renouard, Sullivan; Hano, Christophe; Grand, Eric; Fliniaux, Ophélie; Roscher, Albrecht; Mesnard, Francois; Schneider, Bernd

2013-01-01

In the plant kingdom, flaxseed (Linum usitatissimum L.) is the richest source of secoisolariciresinol diglucoside (SDG), which is of great interest because of its potential health benefits for human beings. The information about the kinetics of SDG formation during flaxseed development is rare and incomplete. In this study, a reversed-phase high-performance liquid chromatography-diode array detection (HPLC-DAD) method was developed to quantify SDG and coniferin, a key biosynthetic precursor of SDG in flaxseed. Seeds from different developmental stages, which were scaled by days after flowering (DAF), were harvested. After alkaline hydrolysis, the validated HPLC method was applied to determine SDG and coniferin concentrations of flaxseed from different developing stages. Coniferin was found in the entire capsule as soon as flowering started and became undetectable 20 DAF. SDG was detected 6 DAF, and the concentration increased until maturity. On the other hand, the SDG amount in a single flaxseed approached the maximum around 25 DAF, before desiccation started. Concentration increase between 25 DAF and 35 DAF can be attributed to corresponding seed weight decrease. The biosynthesis of coniferin is not synchronous with that of SDG. Hence, the concentrations of SDG and coniferin change during flaxseed development. Copyright © 2012 John Wiley & Sons, Ltd.

The Dorsa Argentea Formation and the Noachian-Hesperian climate transition

NASA Astrophysics Data System (ADS)

Scanlon, K. E.; Head, J. W.; Fastook, J. L.; Wordsworth, R. D.

2018-01-01

The Dorsa Argentea Formation (DAF), a set of geomorphologic units covering ∼1.5 million square kilometers in the south circumpolar region of Mars, has been interpreted as the remnants of a large south polar ice sheet that formed near the Noachian-Hesperian boundary and receded in the early Hesperian. Determining the extent and thermal regime of the DAF ice sheet, as well as the mechanism and timing of its recession, can therefore provide insight into the ancient martian climate and the timing of the transition from a presumably thicker CO2 atmosphere to the present climate. We used the Laboratoire de Météorologie Dynamique (LMD) early Mars global climate model (GCM) and the University of Maine Ice Sheet Model (UMISM) glacial flow model to constrain climates allowing development of a south polar ice sheet of DAF-like size and shape. In addition, we modeled basal melting of this ice sheet in amounts and locations consistent with observed glaciofluvial landforms. A large, asymmetric region of ice stability surrounding the south pole is a robust feature of GCM simulations with spin-axis obliquity of 15° or 25° and a 600-1000 mb CO2 atmosphere. The shape results from the large-scale south polar topography of Mars and the strong dependence of surface temperature on altitude under a thicker atmosphere. Of the scenarios considered in this study, the extent of the modeled DAF ice sheet in UMISM simulations most closely matches that of the DAF when the surface water ice inventory of Mars is a ∼137 m global equivalent layer (GEL) and spin-axis obliquity is 15°. In climates warmed only by CO2, significant basal melting does not occur except when the ice inventory is larger than plausible estimates for early Mars. In this case, the extent of the south polar ice sheet is also much larger than that of the DAF, and basal melting is more widespread than observed landforms indicate. When an idealized greenhouse gas warms the surface by at least 20°C near the poles relative to CO2 alone, the stable extent of the ice sheet is less than that of the DAF units, but widespread basal melting occurs, with maxima in the locations where eskers are currently observed. We therefore conclude that warming by a gas other than CO2 alone was necessary to enable the construction of glaciofluvial landforms in the DAF. Previously published crater exposure ages of eskers in the DAF indicate that eskers were being exposed as activity was ceasing in the equatorial valley networks, suggesting that the warming that allowed basal melting at the edges of the DAF ice sheet were broadly contemporaneous with those in which the valley networks were carved. Finally, elevated Tharsis topography is required to produce an ice sheet with the shape of the DAF. Thus, our results are not consistent with the DAF (and the valley networks) forming before the emplacement of Tharsis, as recently suggested.

Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection.

PubMed

Cohen, Ehud; Du, Deguo; Joyce, Derek; Kapernick, Erik A; Volovik, Yuli; Kelly, Jeffery W; Dillin, Andrew

2010-04-01

Toxic protein aggregation (proteotoxicity) is a unifying feature in the development of late-onset human neurodegenerative disorders. Reduction of insulin/IGF-1 signaling (IIS), a prominent lifespan, developmental and reproductive regulatory pathway, protects worms from proteotoxicity associated with the aggregation of the Alzheimer's disease-linked Abeta peptide. We utilized transgenic nematodes that express human Abeta and found that late life IIS reduction efficiently protects from Abeta toxicity without affecting development, reproduction or lifespan. To alleviate proteotoxic stress in the animal, the IIS requires heat shock factor (HSF)-1 to modulate a protein disaggregase, while DAF-16 regulates a presumptive active aggregase, raising the question of how these opposing activities could be co-regulated. One possibility is that HSF-1 and DAF-16 have distinct temporal requirements for protection from proteotoxicity. Using a conditional RNAi approach, we found an early requirement for HSF-1 that is distinct from the adult functions of DAF-16 for protection from proteotoxicity. Our data also indicate that late life IIS reduction can protect from proteotoxicity when it can no longer promote longevity, strengthening the prospect that IIS reduction might be a promising strategy for the treatment of neurodegenerative disorders caused by proteotoxicity.

Inertial attitude control of a bat-like morphing-wing air vehicle.

PubMed

Colorado, J; Barrientos, A; Rossi, C; Parra, C

2013-03-01

This paper presents a novel bat-like unmanned aerial vehicle inspired by the morphing-wing mechanism of bats. The goal of this paper is twofold. Firstly, a modelling framework is introduced for analysing how the robot should manoeuvre by means of changing wing morphology. This allows the definition of requirements for achieving forward and turning flight according to the kinematics of the wing modulation. Secondly, an attitude controller named backstepping+DAF is proposed. Motivated by biological evidence about the influence of wing inertia on the production of body accelerations, the attitude control law incorporates wing inertia information to produce desired roll (ϕ) and pitch (θ) acceleration commands (desired angular acceleration function (DAF)). This novel control approach is aimed at incrementing net body forces (F(net)) that generate propulsion. Simulations and wind-tunnel experimental results have shown an increase of about 23% in net body force production during the wingbeat cycle when the wings are modulated using the DAF as a part of the backstepping control law. Results also confirm accurate attitude tracking in spite of high external disturbances generated by aerodynamic loads at airspeeds up to 5 ms⁻¹.

pkc-1 regulates daf-2 insulin/IGF signalling-dependent control of dauer formation in Caenorhabditis elegans.

PubMed

Monje, José M; Brokate-Llanos, Ana M; Pérez-Jiménez, Mercedes M; Fidalgo, Manuel A; Muñoz, Manuel J

2011-12-01

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Measurement of intracellular nitric oxide (NO) production in shrimp haemocytes by flow cytometry.

PubMed

Xian, Jian-An; Guo, Hui; Li, Bin; Miao, Yu-Tao; Ye, Jian-Min; Zhang, Sheng-Peng; Pan, Xun-Bin; Ye, Chao-Xia; Wang, An-Li; Hao, Xuan-Ming

2013-12-01

A flow cytometric method to measure the production of intracellular nitric oxide (NO) was adapted for use with shrimp haemocytes. We applied fluorescent probe 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) for NO detection in haemocytes from the tiger shrimp Penaeus monodon, and used flow cytometry to quantify fluorescence intensity in individual haemocyte. The optimized protocol for intracellular NO analysis consists to incubate haemocytes with DAF-FM DA at 10 μM for 60 min to determine the mean fluorescence intensity. Result showed that NO was also produced in the untreated shrimp haemocytes. NO level in granular cells and semigranular cells were much higher than that in hyaline cells. Defined by different characteristic of NO content, three subsets of haemocytes were observed. Zymosan A at dose of 10 or 100 particles per haemocyte triggered higher DAF-FM fluorescence intensity in granular and semigranular cells, than PMA that had no significant impact on all three cell types. These results indicate that granular and semigranular cells are the primary cells for NO generation. Cytochalasin B significantly inhibited the NO level induced by zymosan A. NG-Monomethyl-L-arginine (L-NMMA) and diphenylene iodonium chloride (DPI) significantly suppressed the DAF-FM fluorescence in haemocytes, but apocynin could not modulate it, indicating that the DAF-FM fluorescence was closely related to the activity of NO-synthase pathway. The NO donor sodium nitroprusside (SNP) improved the DAF-FM fluorescence in haemocytes, while the NO scavenger C-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) significantly decreased the fluorescence, demonstrating that the fluorescence intensity of DAF-FM is mainly dependent on the intracellular NO level.

Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms

PubMed Central

2011-01-01

Background Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. Results In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. Conclusions C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity. PMID:21749693

A C. elegans mutant that lives twice as long as wild type.

PubMed

Kenyon, C; Chang, J; Gensch, E; Rudner, A; Tabtiang, R

1993-12-02

We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans.

PubMed

Miyata, Sachiko; Begun, Jakob; Troemel, Emily R; Ausubel, Frederick M

2008-02-01

To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.

Flotation of algae for water reuse and biomass production: role of zeta potential and surfactant to separate algal particles.

PubMed

Kwak, Dong-Heui; Kim, Mi-Sug

2015-01-01

The effect of chemical coagulation and biological auto-flocculation relative to zeta potential was examined to compare flotation and sedimentation separation processes for algae harvesting. Experiments revealed that microalgae separation is related to auto-flocculation of Anabaena spp. and requires chemical coagulation for the whole period of microalgae cultivation. In addition, microalgae separation characteristics which are associated with surfactants demonstrated optimal microalgae cultivation time and separation efficiency of dissolved CO2 flotation (DCF) as an alternative to dissolved air flotation (DAF). Microalgae were significantly separated in response to anionic surfactant rather than cationic surfactant as a function of bubble size and zeta potential. DAF and DCF both showed slightly efficient flotation; however, application of anionic surfactant was required when using DCF.

Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism.

PubMed

Fan, Lavender Yuen-Nam; Saavedra-García, Paula; Lam, Eric Wing-Fai

2017-04-01

The data presented in this article are related to the review article entitled 'Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis' (Saavedra-Garcia et al., 2017) [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

TATN-1 Mutations Reveal a Novel Role for Tyrosine as a Metabolic Signal That Influences Developmental Decisions and Longevity in Caenorhabditis elegans

PubMed Central

Ferguson, Annabel A.; Dumas, Kathleen J.; Ritov, Vladimir B.; Matern, Dietrich; Hu, Patrick J.; Fisher, Alfred L.

2013-01-01

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. PMID:24385923

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva.

PubMed

Colella, Eileen; Li, Shaolin; Roy, Richard

2016-08-01

When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFβ, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFβ in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. Copyright © 2016 by the Genetics Society of America.

Identification of Late Larval Stage Developmental Checkpoints in Caenorhabditis elegans Regulated by Insulin/IGF and Steroid Hormone Signaling Pathways

PubMed Central

Schindler, Adam J.; Baugh, L. Ryan; Sherwood, David R.

2014-01-01

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint. PMID:24945623

Function of RSKS-1-AAK-2-DAF-16 signaling cascade in enhancing toxicity of multi-walled carbon nanotubes can be suppressed by mir-259 activation in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhuang, Ziheng; Li, Min; Liu, Hui; Luo, Libo; Gu, Weidong; Wu, Qiuli; Wang, Dayong

2016-08-01

Caenorhabditis elegans is an important non-mammalian alternative assay model for toxicological study. Previous study has indicated that exposure to multi-walled carbon nanotubes (MWCNTs) dysregulated the transcriptional expression of mir-259. In this study, we examined the molecular basis for mir-259 in regulating MWCNTs toxicity in nematodes. Mutation of mir-259 induced a susceptible property to MWCNTs toxicity, and MWCNTs exposure induced a significant increase in mir-259::GFP in pharyngeal/intestinal valve and reproductive tract, implying that mir-259 might mediate a protection mechanisms for nematodes against MWCNTs toxicity. RSKS-1, a putative ribosomal protein S6 kinase, acted as the target for mir-259 in regulating MWCNTs toxicity, and mutation of rsks-1 suppressed the susceptible property of mir-259 mutant to MWCNTs toxicity. Moreover, mir-259 functioned in pharynx-intestinal valve and RSKS-1 functioned in pharynx to regulate MWCNTs toxicity. Furthermore, RSKS-1 regulated MWCNTs toxicity by suppressing the function of AAK-2-DAF-16 signaling cascade. Our results will strengthen our understanding the microRNAs mediated protection mechanisms for animals against the toxicity from certain nanomaterials.

MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

PubMed Central

Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M.A.; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F.; Hellberg, Josephine; Thornton, Janet M.; Gems, David

2014-01-01

In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality. PMID:24531613

Integrated processes for produced water polishing: Enhanced flotation/sedimentation combined with advanced oxidation processes.

PubMed

Jiménez, Silvia; Micó, María M; Arnaldos, Marina; Ferrero, Enrique; Malfeito, Jorge J; Medina, Francisco; Contreras, Sandra

2017-02-01

In this study, bench scale dissolved air flotation (DAF) and settling processes have been studied and compared to a novel flotation technology based on the use of glass microspheres of limited buoyancy and its combination with conventional DAF, (Enhanced DAF or E-DAF). They were evaluated as pretreatments for advanced oxidation processes (AOPs) to polish produced water (PW) for reuse purposes. Settling and E-DAF without air injection showed adequate turbidity and oil and grease (O&G) removals, with eliminations higher than 87% and 90% respectively, employing 70 mg L -1 of FeCl 3 and 83 min of settling time, and 57.9 mg L -1 of FeCl 3 , 300 mg L -1 of microspheres and a flocculation rate of 40 rpm in the E-DAF process. A linear correlation was observed between final O&G concentration and turbidity after E-DAF. In order to polish the O&G content of the effluent even further, to remove soluble compounds as phenol and to take advantage of residual iron after these treatments, Fenton and photo-Fenton reactions were essayed. After 6 h of the Fenton reaction at pH 3, the addition of 1660 mg L -1 of H 2 O 2 and 133 mg L -1 of iron showed a maximum O&G elimination of 57.6% and a phenol removal up to 80%. Photo-Fenton process showed better results after 3 h, adding 600 mg L -1 of H 2 O 2 and 300 mg L -1 of iron, at pH 3, with a higher fraction of elimination of the O&G content (73.7%) and phenol (95%) compared to the conventional Fenton process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Refolding of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) from urea.

PubMed

Liu, H; Moreau, J F; Gualde, N; Fu, J

1997-04-01

The insoluble inclusion bodies of soluble leukemia inhibitory factor receptor fusion protein (gp 190 sol DAF) was solubilized in 8 M urea on the unfolding transitions, and several factors on the aggregate formation were indirectly analyzed for the refolding of gp 190 sol DAF. Results indicate that the refolding yield can be considerably increased at lowering concentration of the unfolding protein, a little soluble protein with the slow refolding appears in the process of the aggregate formation and the concentration of the denaturant must be down to a minimum level for its refolding.

Waste management in the meat processing industry: Conversion of paunch and DAF sludge into solid fuel.

PubMed

Hamawand, Ihsan; Pittaway, Pam; Lewis, Larry; Chakrabarty, Sayan; Caldwell, Justin; Eberhard, Jochen; Chakraborty, Arpita

2017-02-01

This article addresses the novel dewatering process of immersion-frying of paunch and dissolved air flotation (DAF) sludge to produce high energy pellets. Literature have been analysed to address the feasibility of replacing conventional boiler fuel at meat processing facilities with high energy paunch-DAF sludge pellets (capsules). The value proposition of pelleting and frying this mixture into energy pellets is based on a Cost-Benefit Analysis (CBA). The CBA is based on information derived from the literature and consultation with the Australian Meat Processing Industry. The calorific properties of a mixture of paunch cake solids and DAF sludge were predicted from literature and industry consultation to validate the product. This study shows that the concept of pelletizing and frying paunch is economically feasible. The complete frying and dewatering of the paunch and DAF sludge mixture produces pellets with energy content per kilogram equivalent to coal. The estimated cost of this new product is half the price of coal and the payback period is estimated to be between 1.8 and 3.2years. Further research is required for proof of concept, and to identify the technical challenges associated with integrating this technology into existing meat processing plants. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

REMOVAL OF HUMICSUBSTANCES AND ALGAE BY DISSOLVED AIR FLOTATION

EPA Science Inventory

Dissolved air flotation (DAF) is used in place of conventional gravity settling as a means to separate low density floc particles from water. The following objectives were: (1) to compare DAF to conventional water treatment of coagulation-flocculation followed by gravity settling...

Accumulation of long-lived mRNAs associated with germination in embryos during seed development of rice

PubMed Central

Sano, Naoto; Ono, Hanako; Murata, Kazumasa; Yamada, Tetsuya; Hirasawa, Tadashi; Kanekatsu, Motoki

2015-01-01

Mature dry seeds contain translatable mRNAs called long-lived mRNAs. Early studies have shown that protein synthesis during the initial phase of seed germination occurs from long-lived mRNAs, without de novo transcription. However, the gene expression systems that generate long-lived mRNAs in seeds are not well understood. To examine the accumulation of long-lived mRNAs in developing rice embryos, germination tests using the transcriptional inhibitor actinomycin D (Act D) were performed with the Japonica rice cultivar Nipponbare. Although over 70% of embryos at 10 days after flowering (DAF) germinated in the absence of the inhibitor, germination was remarkably impaired in embryos treated with Act D. In contrast, more than 70% of embryos at 20, 25, 30 and 40 DAF germinated in the presence of Act D. The same results were obtained when another cultivar, Koshihikari, was used, indicating that the long-lived mRNAs required for germination predominantly accumulate in embryos between 10 and 20 DAF during seed development. RNA-Seq identified 529 long-lived mRNA candidates, encoding proteins such as ABA, calcium ion and phospholipid signalling-related proteins, and HSP DNA J, increased from 10 to 20 DAF and were highly abundant in 40 DAF embryos of Nipponbare and Koshihikari. We also revealed that these long-lived mRNA candidates are clearly up-regulated in 10 DAF germinating embryos after imbibition, suggesting that the accumulation of these mRNAs in embryos is indispensable for the induction of germination. The findings presented here may facilitate in overcoming irregular seed germination or producing more vigorous seedlings. PMID:25941326

Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution.

PubMed

Bento, Gilberto; Ogawa, Akira; Sommer, Ralf J

2010-07-22

Morphological novelties are lineage-specific traits that serve new functions. Developmental polyphenisms have been proposed to be facilitators of phenotypic evolution, but little is known about the interplay between the associated genetic and environmental factors. Here, we study two alternative morphologies in the mouth of the nematode Pristionchus pacificus and the formation of teeth-like structures that are associated with bacteriovorous feeding and predatory behaviour on fungi and other worms. These teeth-like denticles represent an evolutionary novelty, which is restricted to some members of the nematode family Diplogastridae but is absent from Caenorhabditis elegans and related nematodes. We show that the mouth dimorphism is a polyphenism that is controlled by starvation and the co-option of an endocrine switch mechanism. Mutations in the nuclear hormone receptor DAF-12 and application of its ligand, the sterol hormone dafachronic acid, strongly influence this switch mechanism. The dafachronic acid-DAF-12 module has been shown to control the formation of arrested dauer larvae in both C. elegans and P. pacificus, as well as related life-history decisions in distantly related nematodes. The comparison of dauer formation and mouth morphology switch reveals that different thresholds of dafachronic acid signalling provide specificity. This study shows how hormonal signalling acts by coupling environmental change and genetic regulation and identifies dafachronic acid as a key hormone in nematode evolution.

Biosynthesis of the Caenorhabditis elegans dauer pheromone.

PubMed

Butcher, Rebecca A; Ragains, Justin R; Li, Weiqing; Ruvkun, Gary; Clardy, Jon; Mak, Ho Yi

2009-02-10

To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human d-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.

Functional Identification and Characterization of the Brassica Napus Transcription Factor Gene BnAP2, the Ortholog of Arabidopsis Thaliana APETALA2

PubMed Central

Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered. PMID:22479468

Functional identification and characterization of the Brassica napus transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.

PubMed

Yan, Xiaohong; Zhang, Lei; Chen, Bo; Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered.

Stuttering adults' lack of pre-speech auditory modulation normalizes when speaking with delayed auditory feedback.

PubMed

Daliri, Ayoub; Max, Ludo

2018-02-01

Auditory modulation during speech movement planning is limited in adults who stutter (AWS), but the functional relevance of the phenomenon itself remains unknown. We investigated for AWS and adults who do not stutter (AWNS) (a) a potential relationship between pre-speech auditory modulation and auditory feedback contributions to speech motor learning and (b) the effect on pre-speech auditory modulation of real-time versus delayed auditory feedback. Experiment I used a sensorimotor adaptation paradigm to estimate auditory-motor speech learning. Using acoustic speech recordings, we quantified subjects' formant frequency adjustments across trials when continually exposed to formant-shifted auditory feedback. In Experiment II, we used electroencephalography to determine the same subjects' extent of pre-speech auditory modulation (reductions in auditory evoked potential N1 amplitude) when probe tones were delivered prior to speaking versus not speaking. To manipulate subjects' ability to monitor real-time feedback, we included speaking conditions with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF). Experiment I showed that auditory-motor learning was limited for AWS versus AWNS, and the extent of learning was negatively correlated with stuttering frequency. Experiment II yielded several key findings: (a) our prior finding of limited pre-speech auditory modulation in AWS was replicated; (b) DAF caused a decrease in auditory modulation for most AWNS but an increase for most AWS; and (c) for AWS, the amount of auditory modulation when speaking with DAF was positively correlated with stuttering frequency. Lastly, AWNS showed no correlation between pre-speech auditory modulation (Experiment II) and extent of auditory-motor learning (Experiment I) whereas AWS showed a negative correlation between these measures. Thus, findings suggest that AWS show deficits in both pre-speech auditory modulation and auditory-motor learning; however, limited pre-speech modulation is not directly related to limited auditory-motor adaptation; and in AWS, DAF paradoxically tends to normalize their otherwise limited pre-speech auditory modulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of inclined plate sedimentation and dissolved air flotation for the minimisation of subsequent nitrogenous disinfection by-product formation.

PubMed

Chu, Wen-Hai; Gao, Nai-Yun; Templeton, Michael R; Yin, Da-Qiang

2011-04-01

The formation of disinfection by-products (DBPs), including both nitrogenous disinfection by-products (N-DBPs) and carbonaceous disinfection by-products (C-DBPs), was investigated upon chlorination of water samples following two treatment processes: (i) coagulation-inclined plate sedimentation (IPS)-filtration and (ii) coagulation-dissolved air flotation (DAF)-filtration. The removal of algae, dissolved organic nitrogen (DON), dissolved organic carbon (DOC) and UV(254) by coagulation-DAF-filtration was superior to coagulation-IPS-filtration. On average, 53%, 53% and 31% of DOC, DON and UV(254) were removed by coagulation-DAF-filtration process, which were higher than 47%, 31% and 27% of that by coagulation-IPS-filtration process. Additionally, coagulation-IPS-filtration performed less well at removing the low molecular weight organics than coagulation-DAF-filtration process. The concentrations of chloroform, dichloroacetamide (DCAcAm) and dichloroacetonitrile (DCAN) formed during chlorination after coagulation-DAF-filtration reached their maximum values of 13, 1.5 and 4.7μgL(-1), respectively, and were lower than those after coagulation-IPS-filtration with the maximum detected levels of 17, 2.9 and 6.3μgL(-1). However, the trichloronitromethane (TCNM) concentration after the two processes was similar, suggesting that DON may have less of a contribution to TCNM formation than DCAcAm and DCAN. Copyright © 2011 Elsevier Ltd. All rights reserved.

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

PubMed Central

2015-01-01

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity. PMID:24555535

TsDAF-21/Hsp90 is expressed in all examined stages of Trichinella spiralis

USDA-ARS?s Scientific Manuscript database

Trichinella is an important parasitic nematode of animals worldwide. Heat shock proteins are ubiquitous in nature and allow organisms to quickly respond to environmental stress. A portion of the Tsdaf-21 gene, a Caenorhabditis elegans daf-21 homologue encoding heat-shock protein 90 (Hsp90) was clone...

Delayed Auditory Feedback and Movement

ERIC Educational Resources Information Center

Pfordresher, Peter Q.; Dalla Bella, Simone

2011-01-01

It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

Comparisons of Four Methods for Estimating a Dynamic Factor Model

ERIC Educational Resources Information Center

Zhang, Zhiyong; Hamaker, Ellen L.; Nesselroade, John R.

2008-01-01

Four methods for estimating a dynamic factor model, the direct autoregressive factor score (DAFS) model, are evaluated and compared. The first method estimates the DAFS model using a Kalman filter algorithm based on its state space model representation. The second one employs the maximum likelihood estimation method based on the construction of a…

Hydrothermal liquefaction of harvested high-ash low-lipid algal biomass from Dianchi Lake: effects of operational parameters and relations of products.

PubMed

Tian, Chunyan; Liu, Zhidan; Zhang, Yuanhui; Li, Baoming; Cao, Wei; Lu, Haifeng; Duan, Na; Zhang, Li; Zhang, Tingting

2015-05-01

Hydrothermal liquefaction (HTL) allows a direct conversion of algal biomass into biocrude oil, not only solving the environmental issues caused by the over-growing algae but also producing renewable energy. This study reports HTL of algae after separation from eutrophicated Dianchi Lake in China. Conversion efficiency was studied under different operational conditions via an orthogonal design, including holding temperature (HT) (260-340 °C), retention time (RT) (30-90 min) and total solid (TS) (10-20%). A highest biocrude oil yield (18.4%, dry ash-free basis, daf) was achieved at 300 °C, 60 min, and 20% (TS), due to the low contents of lipids (1.9%, daf) and proteins (24.8%, daf), and high contents of ash (41.6%, dry basis) and carbohydrates (71.8%, daf). Operational parameters significantly affected the biocrude yields, and chemical distribution of HTL products. The biocrude production also related to other HTL products, and involved chemical reactions, such as deoxygenation and/or denitrogenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans.

PubMed

Burnell, Ann M; Houthoofd, Koen; O'Hanlon, Karen; Vanfleteren, Jacques R

2005-11-01

When environmental conditions are unsuitable to support nematode reproduction, Caenorhabditis elegans arrests development before the onset of sexual maturity and specialised 'dauer' larvae, adapted for dispersal, and extended diapause are formed. Dauer larvae do not feed and their metabolism is dependent on internal food reserves. Adult worms which express defects in the insulin/insulin-like growth factor receptor DAF-2 also display enhanced longevity. Whole genome mRNA expression profiling has demonstrated that C. elegans dauer larvae and daf-2 adults have similar transcription profiles for a cohort of longevity genes. Important components of this enhanced longevity system are the alpha-crystallin family of small heat shock proteins, anti-ROS defence systems, increased activity of cellular detoxification processes and possibly also increased chromatin stability and decreased protein turnover. Anaerobic fermentation pathways are upregulated in dauer larvae, while long-lived daf-2 adults appear to have normal oxidative metabolism. Anabolic pathways are down regulated in dauer larvae (and possibly in daf-2 adults as well), and energy consumption appears to be diverted to enhanced cellular maintenance and detoxification processes in both systems.

Enterprise application architecture development based on DoDAF and TOGAF

NASA Astrophysics Data System (ADS)

Tao, Zhi-Gang; Luo, Yun-Feng; Chen, Chang-Xin; Wang, Ming-Zhe; Ni, Feng

2017-05-01

For the purpose of supporting the design and analysis of enterprise application architecture, here, we report a tailored enterprise application architecture description framework and its corresponding design method. The presented framework can effectively support service-oriented architecting and cloud computing by creating the metadata model based on architecture content framework (ACF), DoDAF metamodel (DM2) and Cloud Computing Modelling Notation (CCMN). The framework also makes an effort to extend and improve the mapping between The Open Group Architecture Framework (TOGAF) application architectural inputs/outputs, deliverables and Department of Defence Architecture Framework (DoDAF)-described models. The roadmap of 52 DoDAF-described models is constructed by creating the metamodels of these described models and analysing the constraint relationship among metamodels. By combining the tailored framework and the roadmap, this article proposes a service-oriented enterprise application architecture development process. Finally, a case study is presented to illustrate the results of implementing the tailored framework in the Southern Base Management Support and Information Platform construction project using the development process proposed by the paper.

Dissolved air flotation as a potential treatment process to remove Giardia cysts from anaerobically treated sewage.

PubMed

Santos, Priscila Ribeiro Dos; Daniel, Luiz Antonio

2017-10-01

Controlling Giardia cysts in sewage is an essential barrier for public health protection, reducing possible routes of protozoa transmission. The aim of this study was to evaluate the capability of dissolved air flotation (DAF), on a bench scale, to remove Giardia cysts from anaerobic effluent. Moreover, removals of indicator microorganisms and physical variables were also investigated. Flocculation conditions were studied, associating different flocculation times with different mean velocity gradients. DAF treatment achieved mean log removals in the range of 2.52-2.62 for Giardia cysts, depending on the flocculation condition. No statistical differences were observed among the flocculation conditions in terms of cyst removal. Low levels of turbidity and apparent color obtained from the treated effluent may indicate good treatment conditions for the DAF process in cyst removal. Indicator microorganisms were not able to predict the parasitological quality of the wastewater treated by flotation in terms of cyst concentrations. The DAF process provided an effective barrier to control cysts from sewage, which is an important parasite source.

Gender by assertiveness interaction in delayed auditory feedback.

PubMed

Elias, J W; Rosenzweig, C M; Dippel, R L

1981-04-01

The College Self-Expression and the Marlowe-Crowne Social Desirability Scales were given to 144 undergraduates. High (N; 10 M; 10 F) and Low (N; 10 M 10 F) Assertiveness Ss were given a DAF test with a 'Phonic Mirror" and the Stroop test (naming the color of a word printed in a different color). DAF performance did not differ among the 4 subgroups (M and F, High and Low Assertiveness), except that Low Assertiveness women showed significantly greater DAF interference than the other subgroups. There was no significant correlation between the continuous interference of the DAF vs the discontinuous of the Stroop test. The difference may reside in the time available and the consequent reduction in anxiety, for the next stimulus in the Stroop test. These data show that, under certain circumstances, personality factors such as assertiveness can interact with gender to affect speech fluency and production. The ability to overcome feedback-related disfluencies in speech may be partially aided by improvement in self-concept or specific training in such behaviors as assertiveness, and this may be more important for females than males.

LC-MS Proteomics Analysis of the Insulin/IGF-1 Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depuydt, Geert G.; Xie, Fang; Petyuk, Vladislav A.

2014-02-20

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity and metabolism in C. elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass-spectrometry (LC-MS) based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2); daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the up-regulation of many core intermediarymore » metabolic pathways. These include, glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complex I, II, III and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative for spatio-temporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves, possibly also shunting metabolites through alternative energy-generating pathways, in order to sustain longevity.« less

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.

2014-04-04

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediarymore » metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. Finally, this restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity.« less

Release of complement regulatory proteins from ocular surface cells in infections.

PubMed

Cocuzzi, E; Guidubaldi, J; Bardenstein, D S; Chen, R; Jacobs, M R; Medof, E M

2000-11-01

The decay accelerating factor (DAF or CD55) and the membrane inhibitor of reactive lysis (MIRL or CD59), two complement regulatory proteins that protect self cells from autologous complement-mediated injury, are attached to corneal and cqonjunctival epithelial cells by glycosylphos-phatidylinositol (GPI) anchors. We sought to 1) determine the frequency with which bacteria recovered from patients with infections of the eye elaborate factors that can remove these surface proteins from ocular cells, 2) determine the spectrum of bacteria from other sites that have similar effects, and 3) establish the time interval required for reconstitution of the two regulators. Culture supernatants of 18 ocular isolates [P. aeruginosa (n = 3), S. marcescens (n = 1), S. epidermidis (n = 9), and S. aureus (n = 5)], and > 100 other clinical specimens isolated in the hospital's microbiology laboratory [P. mirabilis (n = 1), S. aureus (n = 65), S. epidermidis (n = 24), B. cereus (n = 12), H. influenzae (n = 15), and Enterobacter sp. (n = 21)] were incubated at 37 degrees C for various times with conjunctival epithelial cells, conjunctival fibroblasts or HeLa cells and the release of DAF and CD59 proteins from the surfaces of the cells analyzed by 2-site immunoradiometric assays and by Western blotting. The kinetics of recovery of DAF and CD59 expression on the cells was measured by flow cytometry. DAF and/or CD59 release from the cell monolayers varied from < 5% to > 99% at as much as a 1:81 dilution of the supernatant from some bacteria. On conjunctival epithelial cells, more than 8 hr was required for 44% recovery of DAF expression and for 50% recovery of CD59 expression. Bacteria produce phospholipases and/or other enzymes which can efficiently remove DAF and CD59 from ocular cell surfaces. This phenomenon may correlate with their in vivo pathogenicity.

Trehalose extends longevity in the nematode Caenorhabditis elegans.

PubMed

Honda, Yoko; Tanaka, Masashi; Honda, Shuji

2010-08-01

Trehalose is a disaccharide of glucose found in diverse organisms and is suggested to act as a stress protectant against heat, cold, desiccation, anoxia, and oxidation. Here, we demonstrate that treatment of Caenorhabditis elegans with trehalose starting from the young-adult stage extended the mean life span by over 30% without any side effects. Surprisingly, trehalose treatment starting even from the old-adult stage shortly thereafter retarded the age-associated decline in survivorship and extended the remaining life span by 60%. Demographic analyses of age-specific mortality rates revealed that trehalose extended the life span by lowering age-independent vulnerability. Moreover, trehalose increased the reproductive span and retarded the age-associated decrease in pharyngeal-pumping rate and the accumulation of lipofuscin autofluorescence. Trehalose also enhanced thermotolerance and reduced polyglutamine aggregation. These results suggest that trehalose suppressed aging by counteracting internal or external stresses that disrupt protein homeostasis. On the other hand, the life span-extending effect of trehalose was abolished in long-lived insulin/IGF-1-like receptor (daf-2) mutants. RNA interference-mediated inactivation of the trehalose-biosynthesis genes trehalose-6-phosphate synthase-1 (tps-1) and tps-2, which are known to be up-regulated in daf-2 mutants, decreased the daf-2 life span. These findings indicate that a reduction in insulin/IGF-1-like signaling extends life span, at least in part, through the aging-suppressor function of trehalose. Trehalose may be a lead compound for potential nutraceutical intervention of the aging process.

Individual Variability in Delayed Auditory Feedback Effects on Speech Fluency and Rate in Normally Fluent Adults

ERIC Educational Resources Information Center

Chon, HeeCheong; Kraft, Shelly Jo; Zhang, Jingfei; Loucks, Torrey; Ambrose, Nicoline G.

2013-01-01

Purpose: Delayed auditory feedback (DAF) is known to induce stuttering-like disfluencies (SLDs) and cause speech rate reductions in normally fluent adults, but the reason for speech disruptions is not fully known, and individual variation has not been well characterized. Studying individual variation in susceptibility to DAF may identify factors…

Delayed Auditory Feedback in the Treatment of Stuttering: Clients as Consumers

ERIC Educational Resources Information Center

Van Borsel, John; Reunes, Gert; Van den Bergh, Nathalie

2003-01-01

Purpose: To investigate the effect of repeated exposure to delayed auditory feedback (DAF) during a 3-month period outside a clinical environment and with only minimal clinical guidance on speech fluency in people who stutter. Method: A pretest-post-test design was used with repeated exposure to DAF during 3 months as the independent variable.…

The Future of Architecture Collaborative Information Sharing: DoDAF Version 2.03 Updates

DTIC Science & Technology

2012-04-30

Salamander x Select Solution Factory Select Business Solutions BPMN , UML x SimonTool Simon Labs x SimProcess CACI BPMN x System Architecture Management...for DoDAF Mega UML x Metastorm ProVision Metastorm BPMN x Naval Simulation System - 4 Aces METRON x NetViz CA x OPNET OPNET x Tool Name Vendor Primary

Energy status of ripening and postharvest senescent fruit of litchi (Litchi chinensis Sonn.)

PubMed Central

2013-01-01

Background Recent studies have demonstrated that cellular energy is a key factor switching on ripening and senescence of fruit. However, the factors that influence fruit energy status remain largely unknown. Results HPLC profiling showed that ATP abundance increased significantly in developing preharvest litchi fruit and was strongly correlated with fruit fresh weight. In contrast, ATP levels declined significantly during postharvest fruit senescence and were correlated with the decrease in the proportion of edible fruit. The five gene transcripts isolated from the litchi fruit pericarp were highly expressed in vegetative tissues and peaked at 70 days after flowering (DAF) consistent with fruit ADP concentrations, except for uncoupling mitochondrial protein 1 (UCP1), which was predominantly expressed in the root, and ATP synthase beta subunit (AtpB), which was up-regulated significantly before harvest and peaked 2 days after storage. These results indicated that the color-breaker stage at 70 DAF and 2 days after storage may be key turning points in fruit energy metabolism. Transcript abundance of alternative oxidase 1 (AOX1) increased after 2 days of storage to significantly higher levels than those of LcAtpB, and was down-regulated significantly by exogenous ATP. ATP supplementation had no significant effect on transcript abundance of ADP/ATP carrier 1 (AAC1) and slowed the changes in sucrose non-fermenting-1-related kinase 2 (SnRK2) expression, but maintained ATP and energy charge levels, which were correlated with delayed senescence. Conclusions Our results suggest that senescence of litchi fruit is closely related with energy. A surge of LcAtpB expression marked the beginning of fruit senescence. The findings may provide a new strategy to extend fruit shelf life by regulating its energy level. PMID:23547657

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.

2015-06-27

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified C. elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols was rich in fatty acid species obtained from the dietary E. coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a relative decrease of MDT-28 abundance in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans.« less

Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans.

PubMed

Hannich, J Thomas; Entchev, Eugeni V; Mende, Fanny; Boytchev, Hristio; Martin, René; Zagoriy, Vyacheslav; Theumer, Gabriele; Riezman, Isabelle; Riezman, Howard; Knölker, Hans-Joachim; Kurzchalia, Teymuras V

2009-06-01

In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections.

Antioxidative Activities of Both Oleic Acid and Camellia tenuifolia Seed Oil Are Regulated by the Transcription Factor DAF-16/FOXO in Caenorhabditis elegans

PubMed Central

Wei, Chia-Cheng; Yen, Pei-Ling; Chang, Shang-Tzen; Cheng, Pei-Ling; Lo, Yi-Chen; Liao, Vivian Hsiu-Chuan

2016-01-01

Background Tea seed oil is a high quality edible oil, yet lacking sufficient scientific evidences to support the nutritional and medical purposes. We identified major and minor components in Camellia tenuifolia seed oil and investigated the antioxidative activity and its underlying mechanisms in Caenorhabditis elegans. Principal Findings The results showed that the major constitutes in C. tenuifolia seed oil were unsaturated fatty acids (~78.4%). Moreover, two minor compounds, β-amyrin and β-sitosterol, were identified and their antioxidative activity was examined. We found that oleic acid was the major constitute in C. tenuifolia seed oil and plays a key role in the antioxidative activity of C. tenuifolia seed oil in C. elegans. Conclusions This study found evidences that the transcription factor DAF-16/FOXO was involved in both oleic acid- and C. tenuifolia seed oil-mediated oxidative stress resistance in C. elegans. This study suggests the potential of C. tenuifolia seed oil as nutrient or functional foods. PMID:27275864

Removal of pharmaceutical residue in municipal wastewater by DAF (dissolved air flotation)-MBR (membrane bioreactor) and ozone oxidation.

PubMed

Choi, Miyoung; Choi, Dong Whan; Lee, Jung Yeol; Kim, Young Suk; Kim, Bun Su; Lee, Byoung Ho

2012-01-01

Growing attention is given to pharmaceutical residue in the water environment. It is known that pharmaceuticals are able to survive from a series of wastewater treatment processes. Concerns regarding pharmaceutical residues are attributed to the fact that they are being detected in water and sediment environment ubiquitously. Pharmaceutical treatment using a series of wastewater treatment processes of the DAF (dissolved air flotation)-MBR (membrane bioreactor)-ozone oxidation was conducted in the study. DAF, without addition of coagulant, could remove COD(cr) (chemical oxygen demand by Cr) up to over 70%, BOD 73%, SS 83%, T-N 55%, NH₄(+) 23%, and T-P 65% in influent of municipal wastewater. Average removal rates of water quality parameters by the DAF-MBR system were very high, e.g. COD(cr) 95.88%, BOD₅ 99.66%, COD(mn) (chemical oxygen demand by Mn) 93.63%, T-N 69.75%, NH₄-N 98.46%, T-P 78.23%, and SS 99.51%, which satisfy effluent water quality standards. Despite the high removal rate of the wastewater treatment system, pharmaceuticals were eliminated to be about 50-99% by the MBR system, depending on specific pharmaceuticals. Ibuprofen was well removed by MBR system up to over 95%, while removal rate of bezafibrate ranged between 50 and 90%. With over 5 mg/l of ozone oxidation, most pharmaceuticals which survived the DAF-MBR process were removed completely or resulted in very low survival rate within the range of few micrograms per litre. However, some pharmaceuticals such as bezafibrate and naproxen tended to be resistant to ozone oxidation.

Role of DAF-21protein in Caenorhabditis elegans immunity against Proteus mirabilis infection.

PubMed

JebaMercy, Gnanasekaran; Durai, Sellegounder; Prithika, Udayakumar; Marudhupandiyan, Shanmugam; Dasauni, Pushpanjali; Kundu, Suman; Balamurugan, Krishnaswamy

2016-08-11

Caenorhabditis elegans is emerging as one of the handy model for proteome related studies due to its simplest system biology. The present study, deals with changes in protein expression in C. elegans infected with Proteus mirabilis. Proteins were separated using two-dimensional differential gel electrophoresis (2D-DIGE) and identified using MALDI-TOF. Twelve distinctly regulated proteins identified in the infected worms, included heat shock proteins involved stress pathway (HSP-1 and HSP-6), proteins involved in immune response pathway (DAF-21), enzymes involved in normal cellular process (Eukaryotic translation Elongation Factor, actin family member, S-adenosyl homocysteine hydrolase ortholog, glutamate dehydrogenase and Vacuolar H ATPase family member) and few least characterized proteins (H28O16.1 and H08J11.2). The regulation of selected players at the transcriptional level during Proteus mirabilis infection was analyzed using qPCR. Physiological experiments revealed the ability of P. mirabilis to kill daf-21 mutant C. elegans significantly compared with the wild type. This is the first report studying proteome changes in C. elegans and exploring the involvement of MAP Kinase pathway during P. mirabilis infection. This is the first report studying proteome changes in C. elegans during P. mirabilis infection. The present study explores the role and contribution of MAP Kinase pathway and its regulator protein DAF-21 involvement in the immunity against opportunistic pathogen P. mirabilis infection. Manipulation of this DAF-21 protein in host, may pave the way for new drug development or disease control strategy during opportunistic pathogen infections. Copyright © 2016 Elsevier B.V. All rights reserved.

[Using delayed auditory feedback in the treatment of stuttering: evidence to consider].

PubMed

Van Borsel, John; Sierens, Sarah; Pereira, Mônica Medeiros de Britto

2007-01-01

There is some indication that the use of delayed auditory feedback (DAF) is a potentially helpful technique in the treatment of stuttering. Several devices for DAF are also commercially. However, not all individuals who stutter experience a positive effect on speech fluency when speaking under DAF. And those who do show a positive effect, may differ considerably as to the degree and the conditions in which the effect is seen. Therefore, the decision whether or not to attempt the use of DAF in an given client is usually not straightforward. Starting from a literature review, the present paper discusses and illustrates factors to take into account when considering the use of RAA in an individual client. Four types of factors are distinguished: factors inherent to the client such as gender, age, stuttering severity, dysfluency pattern, origin of stuttering, and biological subtype; factors outside the client including delay time, intensity, manner of delivery, speech mode, and speech situation; possible side-effects like a reduction in speech rate, an increase of speaking fundamental frequency and vocal intensity, lengthening of vowels, and a possible effect on speech naturalness; others namely cosmetics, finances, and the long-term effect. The review shows that most likely multiple factors play a role, but with the currently available data it is very hard to predict whether a given individual will or will not benefit from the use of DAF. Overall, the evidence for the influence of the different factors is still meager. Moreover, some studies present data of a quality that can hardly be considered "evidence".

Investigation of Poultry Waste for Anaerobic Digestion: A Case Study

NASA Astrophysics Data System (ADS)

Salam, Christopher R.

Anaerobic Digestion (AD) is a biological conversion technology which is being used to produce bioenergy all over the world. This energy is created from biological feedstocks, and can often use waste products from various food and agricultural processors. Biogas from AD can be used as a fuel for heating or for co-generation of electricity and heat and is a renewable substitute to using fossil fuels. Nutrient recycling and waste reduction are additional benefits, creating a final product that can be used as a fertilizer in addition to energy benefits. This project was conducted to investigate the viability of three turkey production wastes as AD feedstock: two turkey litters and a material separated from the turkey processing wastewater using dissolved air flotation (DAF) process. The DAF waste contained greases, oils and other non-commodity portions of the turkey. Using a variety of different process methods, types of bacteria, loading rates and food-to-microorganism ratios, optimal loading rates for the digestion of these three materials were obtained. In addition, the co-digestion of these materials revealed additional energy benefits. In this study, batch digestion tests were carried out to treat these three feedstocks, using mesophilic and thermophilic bacteria, using loading rates of 3 and 6 gVS/L They were tested separately and also as a mixture for co-digestion. The batch reactor used in this study had total and working volumes of 1130 mL and 500 mL, respectively. The initial organic loading was set to be 3 gVS/L, and the food to microorganism ratio was either 0.6 or 1.0 for different treatments based on the characteristics of each material. Only thermophilic (50 +/- 2ºC) temperatures were tested for the litter and DAF wastes in continuous digestion, but mesophilic and thermophilic batch digestion experiments were conducted. The optimum digestion time for all experiments was 14 days. The biogas yields of top litter, mixed litter, and DAF waste under mesophilic batch conditions all at 3 gVS/L loading were determined to be 148.6 +/- 7.82, 176.5 +/- 11.1 and 542.0 +/- 37.9 mL/ gVS, respectively and were 201.9 +/- 10.0, 210.4 +/- 29.3, and 419.3 +/- 12.1 mL/gVS, respectively, for initial loading of 6 gVS/L. Under thermophilic batch conditions, the top litter, mixed litter, and DAF waste had the biogas yields of 255.3 +/- 7.9, 313.4 +/- 30.1and 297.4 +/- 33.8 mL/gVS for loading rate of 3 gVS/L and 233.8 +/- 45.3, 306.5 +/- 11.8 and 185.1 +/- 0.85 mL/gVS for loading rate of 6 gVS/L. The biogas yields from co-digestion of the mixed litter and DAF waste at 3 gVS/L were 461.8 +/- 41.3 mL/gVS under thermophilic conditions. The results from batch anaerobic digestion tests were then used for designing continuous digestion experiments. All the continuous digestion experiments were conducted by using an Anaerobic Phase Solids (APS) digester system operated at a thermophilic temperature. The total volume of the continuous digester system was 4.8 L and the working volume was around 4.4 L. The APS digester system had two hydrolysis reactors and one biogasification reactor. Feedstock was loaded into the hydrolysis reactors in batches. The feedstock digestion time was 14 days and the average organic loading rate (OLR) of the system was 3 gVS/L/day. The experiment has three distinct feedstock stages, first with turkey litter waste, a co-digestion of DAF and turkey litter waste, followed by DAF waste. The biogas yields were determined to be 305.2 +/- 70.6 mL/gVS/d for turkey mixed litter, 455.8 +/- 77.2 mL/gVS/d during the mixture of mixed litter and DAF waste, and 382.0 +/- 39.6 mL/gVS for DAF waste. The biogas yields from the thermophilic batch test yields compare with that of the continuous digester yields. For experiments utilizing turkey litter, batch tests yielded 313.4 +/- 30.1mL/gVS biogas and 305.2 +/- 70.6 mL/gVS/d for continuous experiments. For experiments using codigestion of turkey litter and DAF waste, batches yielded 461.8 +/- 41.3 mL/gVS biogas comparing well to continuous digester operation that yielded 455.8 +/- 77.2 mL/gVS/d. It was mainly in the case for DAF that batch vs. continuous digester testing yielded a significant difference in performance. For experiments using DAF waste, batches yielded 297.4 +/- 33.8 mL/gVS biogas and continuous digester operation yielded 455.8 +/- 77.2 mL/gVS/d. For a case study on the APS digester system, mesophilic DAF waste was chosen as the optimum substrate. Using this material and reactor condition, a case study was built using provided information and experimental results to build a simulation. A reactor site needed to process 11,800 kgVS of DAF waste would require 4,800 m3 of tank volume, and use nearly 4,000 m3 as working volume. This reactor was modeled after a 2 stage APS reactor, with 2 hydrolysis reactors and 1 biogasification reactor, and had a 14 day retention time and a 3 gVS/L/d organic loading rate. The expected biogas output was 550 mL/gVS, and expected waste reduction was 20%. The reactor would produce 7,113 m3/d of biogas, and would be burned for 127,223 MJ/d.

Prevalence and Correlates of Drug/Alcohol-Facilitated and Incapacitated Sexual Assault in a Nationally Representative Sample of Adolescent Girls

ERIC Educational Resources Information Center

McCauley, Jenna L.; Conoscenti, Lauren M.; Ruggiero, Kenneth J.; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2009-01-01

Incapacitated/drug-alcohol facilitated sexual assault (IS/DAFS) is rapidly gaining recognition as a distinct form of assault with unique public health implications. This study reports the prevalence, case characteristics, and associated health risks of IS/DAFS using a large, nationally representative sample of 1,763 adolescent girls. Results…

A Proposed Pattern of Enterprise Architecture

DTIC Science & Technology

2013-02-01

consistent architecture descriptions. UPDM comprises extensions to both OMG’s Unified Modelling Language (UML) and Systems Modelling Language ( SysML ...those who use UML and SysML . These represent significant advancements that enable architecture trade-off analyses, architecture model execution...Language ( SysML ), and thus provides for architectural descriptions that contain a rich set of (formally) connected DoDAF/MoDAF viewpoints expressed

FOXO3a is broadly neuroprotective in vitro and in vivo against insults implicated in motor neuron diseases

PubMed Central

Mojsilovic-Petrovic, Jelena; Nedelsky, Natalia; Boccitto, Marco; Mano, Itzhak; Georgiades, Savvas N.; Zhou, Weiguo; Liu, Yuhong; Neve, Rachael L.; Taylor, J. Paul; Driscoll, Monica; Clardy, Jon; Merry, Diane; Kalb, Robert G.

2009-01-01

Aging is a risk factor for the development of adult-onset neuro-degenerative diseases. While some of the molecular pathways regulating longevity and stress resistance in lower organisms are defined (i.e., those activating the transcriptional regulators DAF-16 and HSF-1 in C. elegans), their relevance to mammals and disease susceptibility are unknown. We studied the signaling controlled by the mammalian homolog of DAF-16, FOXO3a, in model systems of motor neuron disease. Neuron death elicited in vitro by excitotoxic insult or the expression of mutant SOD1, mutant p150glued or polyQ expanded androgen receptor was abrogated by expression of nuclear-targeted FOXO3a. We identify a compound (Psammaplysene A, PA) that increases nuclear localization of FOXO3a in vitro and in vivo and show that PA also protects against these insults in vitro. Administration of PA to invertebrate model systems of neurodegeneration similarly blocked neuron death in a DAF-16/FOXO3a-dependent manner. These results indicate that activation of the DAF-16/FOXO3a pathway, genetically or pharmacologically, confers protection against the known causes of motor neuron diseases. PMID:19553463

Evaluation on simultaneous removal of particles and off-flavors using population balance for application of powdered activated carbon in dissolved air flotation process.

PubMed

Kwak, D H; Yoo, S J; Lee, E J; Lee, J W

2010-01-01

Most of the water treatment plants applying the DAF process are faced with off-flavors control problems. For simultaneous control of particles of impurities and dissolved organics that cause pungent taste and odor in water, an effective method would be the simple application of powdered activated carbon (PAC) in the DAF process. A series of experiments were carried out to explore the feasibility for simultaneous removal of kaolin particles and organic compounds that produce off-flavors (2-MIB and geosmin). In addition, the flotation efficiency of kaolin and PAC particles adsorbing organics in the DAF process was evaluated by employing the population balance theory. The removal efficiency of 2-MIB and geosmin under the treatment condition with kaolin particles for simultaneous treatment was lower than that of the individual treatment. The decrease in the removal efficiency was probably caused by 2-MIB and geosmin remaining in the PAC particle in the treated water of DAF after bubble flotation. Simulation results obtained by the population balance model indicate, that the initial collision-attachment efficiency of PAC particles was lower than that of kaolin particles.

Removal of iron ore slimes from a highly turbid water by DAF.

PubMed

Faustino, L M; Braga, A S; Sacchi, G D; Whitaker, W; Reali, M A P; Leal Filho, L S; Daniel, L A

2018-05-30

This paper addresses Dissolved Air Flotation (DAF) process variables, such as the flocculation parameters and the recycle water addition, as well as the pretreatment chemical variables (coagulation conditions), to determine the optimal values for the flotation of iron ore slimes found in a highly turbid water sample from the Gualaxo do Norte River, a tributary of the Doce River Basin in Minas Gerais, Brazil. This work was conducted using a flotatest batch laboratory-scale device to evaluate the effectiveness of DAF for cleaning the water polluted by the Samarco tailings dam leakage and determine the ability of DAF to reduce the water turbidity from 358 NTU to values below 100 NTU, aiming to comply with current legislation. The results showed that the four types of tested coagulants (PAC, ferric chloride, Tanfloc SG and Tanfloc SL) provided adequate conditions for coagulation, flocculation and flotation (in the range of 90-99.6% turbidity reduction). Although the process variables were optimized and low residual turbidity vales were achieved, results revealed that a portion of the flocs settled at the bottom of the flotatest columns, which indicated that the turbidity results represented removal caused by a combination of flotation and sedimentation processes simultaneously.

Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.

PubMed

Dansey, María V; Del Fueyo, María C; Veleiro, Adriana S; Di Chenna, Pablo H

2017-05-01

A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH 3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity. Copyright © 2017 Elsevier Inc. All rights reserved.

A physical map of the human regulator of complement activation gene cluster linking the complement genes CR1, CR2, DAF, and C4BP

PubMed Central

1988-01-01

We report the organization of the human genes encoding the complement components C4-binding protein (C4BP), C3b/C4b receptor (CR1), decay accelerating factor (DAF), and C3dg receptor (CR2) within the regulator of complement activation (RCA) gene cluster. Using pulsed field gel electrophoresis analysis these genes have been physically linked and aligned as CR1-CR2-DAF-C4BP in an 800-kb DNA segment. The very tight linkage between the CR1 and the C4BP loci, contrasted with the relative long DNA distance between these genes, suggests the existence of mechanisms interfering with recombination within the RCA gene cluster. PMID:2450163

Oscillographic and Physiological Measurements of Delayed Auditory Feedback and Anxiety Factors in Stutterers and Non-Stutterers.

ERIC Educational Resources Information Center

Timmons, Beverly A.; Boudreau, James P.

Reported are five studies on the use of delayed auditory feedback (DAF) with stutterers. The first study indicates that sex differences and age differences in temporal reaction were found when subjects (5-, 7-, 9-, 11-, and 13-years-old) recited a nursery rhyme under DAF and NAF (normal auditory feedback) conditions. The second study is reported…

A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

PubMed Central

Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

2016-01-01

Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID:27558892

A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

2016-08-01

Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.

Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.

PubMed

Legler, Daniel F; Doucey, Marie-Agnès; Schneider, Pascal; Chapatte, Laurence; Bender, Florent C; Bron, Claude

2005-01-01

Partitioning of proteins in cholesterol and sphingolipid enriched plasma membrane microdomains, called lipid rafts, is critical for many signal transduction and protein sorting events. Although raft partitioning of many signaling molecules remains to be determined, glycosylphosphatidyl-inositol (GPI)-anchored proteins possess high affinity for lipid rafts and are currently exploited as markers to investigate fundamental mechanisms in protein sorting and signal transduction events. In this study, we demonstrate that two recombinant GPI-anchored green fluorescent proteins (GFP-GPIs) that differ in their GPI signal sequence confer distinct localization in plasma membrane microdomains. GFP fused to the GPI signal of the decay accelerating factor GFP-GPI(DAF) partitioned exclusively in lipid rafts, whereas GFP fused to the GPI signal of TRAIL-R3, GFP-GPI(TRAIL-R3), associated only minimally with microdomains. In addition, we investigated the unique ability of purified GFP-GPIs to insert into membrane microdomains of primary lymphocytes. This cell surface painting allows rapid, stable, and functional association of the GPI-anchored proteins with the target cell plasma membrane. The distinct membrane localization of the two GFP-GPIs was observed irrespective of whether the GPI-anchored molecules were painted or transfected. Furthermore, we show that painted GFP-GPI(DAF) was totally dependent on the GPI anchor and that the membrane insertion was increased by the addition of raft-associated lipids such as cholesterol, sphingomyelin, and dipalmitoyl-phosphatidylethanolamine. Thus, this study provides evidence that different GPI signal sequences lead to distinct membrane microdomain localization and that painted GFP-GPI(DAF) serves as an excellent fluorescent marker for lipid rafts in live cells.

Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging.

PubMed

Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázs; Takács-Vellai, Krisztina; Vellai, Tibor

2012-11-01

Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

Mutant Transcriptome Sequencing Provides Insights into Pod Development in Peanut (Arachis hypogaea L.)

PubMed Central

Wan, Liyun; Li, Bei; Lei, Yong; Yan, Liying; Ren, Xiaoping; Chen, Yuning; Dai, Xiaofeng; Jiang, Huifang; Zhang, Juncheng; Guo, Wei; Chen, Ao; Liao, Boshou

2017-01-01

Pod size is the major yield component and a key target trait that is selected for in peanut breeding. However, although numerous quantitative trait loci (QTLs) for peanut pod size have been described, the molecular mechanisms underlying the development of this characteristic remain elusive. A peanut mutant with a narrower pod was developed in this study using ethyl methanesulfonate (EMS) mutagenesis and designated as the “pod width” mutant line (pw). The fresh pod weight of pw was only about 40% of that seen in the wild-type (WT) Zhonghua16, while the hull and seed filling of the mutant both also developed at earlier stages. Pods from both pw and WT lines were sampled 20, 40, and 60 days after flowering (DAF) and used for RNA-Seq analysis; the results revealed highly differentially expressed lignin metabolic pathway genes at all three stages, but especially at DAF 20 and DAF 40. At the same time, expression of genes related to auxin signal transduction was found to be significantly repressed during the pw early pod developmental stage. A genome-wide comparative analysis of expression profiles revealed 260 differentially expressed genes (DEGs) across all three stages, and two candidate genes, c26901_g1 (CAD) and c37339_g1 (ACS), responsible for pod width were identified by integrating expression patterns and function annotation of the common DEGs within the three stages. Taken together, the information provided in this study illuminates the processes underlying peanut pod development, and will facilitate further identification of causal genes and the development of improved peanut varieties with higher yields. PMID:29170673

The Caenorhabditis elegans DAF-12 nuclear receptor: structure, dynamics, and interaction with ligands.

PubMed

Alvarez, Lautaro D; Mañez, Pau Arroyo; Estrin, Darío A; Burton, Gerardo

2012-07-01

A structure for the ligand binding domain (LBD) of the DAF-12 receptor from Caenorhabditis elegans was obtained from the X-ray crystal structure of the receptor LBD from Strongyloides stercoralis bound to (25R)-Δ(7)-dafachronic acid (DA) (pdb:3GYU). The model was constructed in the presence of the ligand using a combination of Modeller, Autodock, and molecular dynamics (MD) programs, and then its dynamical behavior was studied by MD. A strong ligand binding mode (LBM) was found, with the three arginines in the ligand binding pocket (LBP) contacting the C-26 carboxylate group of the DA. The quality of the ceDAF-12 model was then evaluated by constructing several ligand systems for which the experimental activity is known. Thus, the dynamical behavior of the ceDAF-12 complex with the more active (25S)-Δ(7)-DA showed two distinct binding modes, one of them being energetically more favorable compared with the 25R isomer. Then the effect of the Arg564Cys and Arg598Met mutations on the (25R)-Δ(7)-DA binding was analyzed. The MD simulations showed that in the first case the complex was unstable, consistent with the lack of transactivation activity of (25R)-Δ(7)-DA in this mutant. Instead, in the case of the Arg598Met mutant, known to produce a partial loss of activity, our model predicted smaller effects on the LBM with a more stable MD trajectory. The model also showed that removal of the C-25 methyl does not impede the simultaneous strong interaction of the carboxylate with the three arginines, predicting that 27-nor-DAs are putative ceDAF-12 ligands. Copyright © 2012 Wiley Periodicals, Inc.

Lamella dissolved air flotation treatment of fish farming effluents as a part of an integrated farming and effluent treatment concept.

PubMed

Jokela, Petri; Lepistö, Raghida

2014-01-01

Nutrient emissions from fish farming can be reduced by a bag pen, i.e., a floating circular basin which serves simultaneously both as a fish cultivation tank and a swirl separation tank. Solid matter (excreta and uneaten feed) is collected at the bottom of the bag pen and pumped as an underflow to a dissolved air flotation (DAF) unit for nutrient removal. DAF equipped with lamella elements was studied in real conditions. Altogether 3000 rainbow trout females (2.0 kg each) were cultivated. Solid-water mixture was pumped from the bottom of the bag pen to an equalizing basin using a sequence of 2-min pumping followed by a 4-min pause. In some tests the influent was pumped directly and continuously from the bag pen to DAF. The influent quality changed substantially: average suspended solids (SS) and phosphorus (P) concentrations were 290 mg l⁻¹ ± 110 mg l⁻¹ and 3.2 mg l⁻¹ ± 1.2 mg l⁻¹, respectively. When the influent was fresh and P strongly associated with SS, DAF without precipitation chemicals produced up to 86% SS and 83% P removals. The influence of chemical doses was studied using 6.4-29.2 mg Fe l⁻¹ with hydraulic loadings (HLs) of 11.0-11.7 m h⁻¹. SS and P removal did not change substantially and the effluent concentration levelled at 30 mg SS l⁻¹ and 0.20-0.30 mg P l⁻¹, respectively. The lamella DAF, coupled with ferric precipitation, produced up to 90% P and 80% nitrogen reductions. HLs, excluding recycle water flow and lamella projection, up to 21 m h⁻¹ could be used.

Key Issues in the Application of Knowledge Management in Education

DTIC Science & Technology

2005-03-01

designed instructional programs are often outdated before they ever leave the design stage (DAF, 1994; DAF, 1993). Such programs are far too rigid...and end up drowning in raw facts and figures (Davenport, Harris, De Long & Jacobson, 2001). Information When relevance or context is applied to...of data to information can be categorized five ways (Davenport & Prusak, 1998; Davenport, Harris, De Long & Jacobson, 2001). 1. Contexualized

Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

DTIC Science & Technology

2011-07-01

Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.

Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomicsmore » also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.« less

Timing mechanism and effective activation energy concerned with aging and lifespan in the long-lived and thermosensory mutants of Caenorhabditis elegans.

PubMed

Suda, Hitoshi; Sato, Kazuya; Yanase, Sumino

2012-01-01

The lifespans of many poikilothermic animals, including the nematode Caenorhabditis elegans, depend significantly on environmental temperature. Using long-living, thermosensory mutants of C. elegans, we tested whether the temperature dependency of the mean lifespan is compatible with the Arrhenius equation, which typically represents one of the chemical reaction rate theories. The temperature dependency of C. elegans was the Arrhenius type or normal, but daf-2(e1370) mutants were quite different from the others. However, taking into account the effect of the thermal denaturation of DAF-2 with the temperature, we showed that our analyzed results are compatible with previous ones. We investigated the timing mechanism of one parameter (the onset of biodemographic aging (t(0))) in the lifespan equation by applying the RNAi feeding method to daf-2 mutants in order to suppress daf-16 activity at different times during the life cycle. In summary, we further deepened the biological role of two elements, t(0) and z (the inverse of the aging rate), in the lifespan equation and mean lifespan formulated by our diffusion model z(2) = 4Dt(0), where z is composed of t(0) and D (the diffusion constant). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

PubMed

Kennedy, Lisa M; Grishok, Alla

2014-05-01

Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

PubMed Central

Kennedy, Lisa M.; Grishok, Alla

2014-01-01

Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning. PMID:24558261

Removal of Anabaena flos-aquae in water treatment process using Moringa oleifera and assessment of fatty acid profile of generated sludge.

PubMed

Moreti, Livia O R; Coldebella, Priscila Ferri; Camacho, Franciele P; Carvalho Bongiovani, Milene; Pereira de Souza, Aloisio Henrique; Kirie Gohara, Aline; Matsushita, Makoto; Fernandes Silva, Marcela; Nishi, Letícia; Bergamasco, Rosângela

2016-01-01

This study aimed to evaluate the efficiency of the coagulation/flocculation/dissolved air flotation (C/F/DAF) process using the coagulant Moringa oleifera (MO) seed powder, and to analyse the profile of fatty acids present in the generated sludge after treatment. For the tests, deionized water artificially contaminated with cell cultures of Anabaena flos-aquae was used, with a cell density in the order of 10(4) cells mL(-1). C/F/DAF tests were conducted using 'Flotest' equipment. For fatty acid profile analyses, a gas chromatograph equipped with a flame ionization detector was used. It was seen that the optimal dosage (100 mg L(-1)) of MO used in the C/F/DAF process was efficient at removing nearly all A. flos-aquae cells (96.4%). The sludge obtained after treatment contained oleic acid (61.7%) and palmitic acid (10.8%). Thus, a water treatment process using C/F/DAF linked to integral MO powder seed was found to be efficient in removing cells of cyanobacteria, and produced a sludge rich in oleic acid that is a precursor favourable for obtaining quality biodiesel, thus becoming an alternative application for the recycling of such biomass.

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

PubMed Central

Yu, Ron X.; Liu, Jie; True, Nick; Wang, Wei

2008-01-01

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets. PMID:18350157

Critical evaluation and modeling of algal harvesting using dissolved air flotation. DAF Algal Harvesting Modeling

DOE PAGES

Zhang, Xuezhi; Hewson, John C.; Amendola, Pasquale; ...

2014-07-14

In our study, Chlorella zofingiensis harvesting by dissolved air flotation (DAF) was critically evaluated with regard to algal concentration, culture conditions, type and dosage of coagulants, and recycle ratio. Harvesting efficiency increased with coagulant dosage and leveled off at 81%, 86%, 91%, and 87% when chitosan, Al 3+, Fe 3+, and cetyl trimethylammonium bromide (CTAB) were used at dosages of 70, 180, 250, and 500 mg g -1, respectively. The DAF efficiency-coagulant dosage relationship changed with algal culture conditions. In evaluating the influence of the initial algal concentration and recycle ratio revealed that, under conditions typical for algal harvesting, wemore » found that it is possible that the number of bubbles is insufficient. A DAF algal harvesting model was developed to explain this observation by introducing mass-based floc size distributions and a bubble limitation into the white water blanket model. Moreover, the model revealed the importance of coagulation to increase floc-bubble collision and attachment, and the preferential interaction of bubbles with larger flocs, which limited the availability of bubbles to the smaller sized flocs. The harvesting efficiencies predicted by the model agree reasonably with experimental data obtained at different Al 3+ dosages, algal concentrations, and recycle ratios. Based on this modeling, critical parameters for efficient algal harvesting were identified.« less

Kinematic Analysis of Speech Sound Sequencing Errors Induced by Delayed Auditory Feedback.

PubMed

Cler, Gabriel J; Lee, Jackson C; Mittelman, Talia; Stepp, Cara E; Bohland, Jason W

2017-06-22

Delayed auditory feedback (DAF) causes speakers to become disfluent and make phonological errors. Methods for assessing the kinematics of speech errors are lacking, with most DAF studies relying on auditory perceptual analyses, which may be problematic, as errors judged to be categorical may actually represent blends of sounds or articulatory errors. Eight typical speakers produced nonsense syllable sequences under normal and DAF (200 ms). Lip and tongue kinematics were captured with electromagnetic articulography. Time-locked acoustic recordings were transcribed, and the kinematics of utterances with and without perceived errors were analyzed with existing and novel quantitative methods. New multivariate measures showed that for 5 participants, kinematic variability for productions perceived to be error free was significantly increased under delay; these results were validated by using the spatiotemporal index measure. Analysis of error trials revealed both typical productions of a nontarget syllable and productions with articulatory kinematics that incorporated aspects of both the target and the perceived utterance. This study is among the first to characterize articulatory changes under DAF and provides evidence for different classes of speech errors, which may not be perceptually salient. New methods were developed that may aid visualization and analysis of large kinematic data sets. https://doi.org/10.23641/asha.5103067.

Kinematic Analysis of Speech Sound Sequencing Errors Induced by Delayed Auditory Feedback

PubMed Central

Lee, Jackson C.; Mittelman, Talia; Stepp, Cara E.; Bohland, Jason W.

2017-01-01

Purpose Delayed auditory feedback (DAF) causes speakers to become disfluent and make phonological errors. Methods for assessing the kinematics of speech errors are lacking, with most DAF studies relying on auditory perceptual analyses, which may be problematic, as errors judged to be categorical may actually represent blends of sounds or articulatory errors. Method Eight typical speakers produced nonsense syllable sequences under normal and DAF (200 ms). Lip and tongue kinematics were captured with electromagnetic articulography. Time-locked acoustic recordings were transcribed, and the kinematics of utterances with and without perceived errors were analyzed with existing and novel quantitative methods. Results New multivariate measures showed that for 5 participants, kinematic variability for productions perceived to be error free was significantly increased under delay; these results were validated by using the spatiotemporal index measure. Analysis of error trials revealed both typical productions of a nontarget syllable and productions with articulatory kinematics that incorporated aspects of both the target and the perceived utterance. Conclusions This study is among the first to characterize articulatory changes under DAF and provides evidence for different classes of speech errors, which may not be perceptually salient. New methods were developed that may aid visualization and analysis of large kinematic data sets. Supplemental Material https://doi.org/10.23641/asha.5103067 PMID:28655038

Critical evaluation and modeling of algal harvesting using dissolved air flotation. DAF Algal Harvesting Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xuezhi; Hewson, John C.; Amendola, Pasquale

In our study, Chlorella zofingiensis harvesting by dissolved air flotation (DAF) was critically evaluated with regard to algal concentration, culture conditions, type and dosage of coagulants, and recycle ratio. Harvesting efficiency increased with coagulant dosage and leveled off at 81%, 86%, 91%, and 87% when chitosan, Al 3+, Fe 3+, and cetyl trimethylammonium bromide (CTAB) were used at dosages of 70, 180, 250, and 500 mg g -1, respectively. The DAF efficiency-coagulant dosage relationship changed with algal culture conditions. In evaluating the influence of the initial algal concentration and recycle ratio revealed that, under conditions typical for algal harvesting, wemore » found that it is possible that the number of bubbles is insufficient. A DAF algal harvesting model was developed to explain this observation by introducing mass-based floc size distributions and a bubble limitation into the white water blanket model. Moreover, the model revealed the importance of coagulation to increase floc-bubble collision and attachment, and the preferential interaction of bubbles with larger flocs, which limited the availability of bubbles to the smaller sized flocs. The harvesting efficiencies predicted by the model agree reasonably with experimental data obtained at different Al 3+ dosages, algal concentrations, and recycle ratios. Based on this modeling, critical parameters for efficient algal harvesting were identified.« less

Constitutive arginine-dependent nitric oxide synthase activity in different organs of pea seedlings during plant development.

PubMed

Corpas, Francisco J; Barroso, Juan B; Carreras, Alfonso; Valderrama, Raquel; Palma, José M; León, Ana M; Sandalio, Luisa M; del Río, Luis A

2006-07-01

Nitric oxide (NO) is an important signalling molecule in different animal and plant physiological processes. Little is known about its biological function in plants and on the enzymatic source or site of NO production during plant development. The endogenous NO production from L-arginine (NO synthase activity) was analyzed in leaves, stems and roots during plant development, using pea seedlings as a model. NOS activity was analyzed using a novel chemiluminescence-based assay which is more sensitive and specific than previous methods used in plant tissues. In parallel, NO accumulation was analyzed by confocal laser scanning microscopy using as fluorescent probes either DAF-2 DA or DAF-FM DA. A strong increase in NOS activity was detected in stems after 11 days growth, coinciding with the maximum stem elongation. The arginine-dependent NOS activity was constitutive and sensitive to aminoguanidine, a well-known irreversible inhibitor of animal NOS, and this NOS activity was differentially modulated depending on the plant organ and seedling developmental stage. In all tissues studied, NO was localized mainly in the vascular tissue (xylem) and epidermal cells and in root hairs. These loci of NO generation and accumulation suggest novel functions for NO in these cell types.

Low Temperature Extends the Lifespan of Bursaphelenchus xylophilus through the cGMP Pathway

PubMed Central

Wang, Bowen; Ma, Ling; Wang, Feng; Wang, Buyong; Hao, Xin; Xu, Jiayao; Ma, Yan

2017-01-01

The causal agent of pine wilt disease, pine wood nematode (PWN) (Bursaphelenchus xylophilus), revealed extended lifespan at low temperature. To discover the molecular mechanism of this phenomenon, we attempted to study the molecular characterization, transcript abundance, and functions of three genes of the cyclic guanosine monophosphate (cGMP) pathway from B. xylophilus. Three cGMP pathway genes were identified from B. xylophilus. Bioinformatic software was utilized to analyze the characteristics of the three putative proteins. Function of the three genes in cold tolerance was studied with RNA interference (RNAi). The results showed that the deduced protein of Bx-DAF-11 has an adenylate and guanylate cyclase catalytic domain, indicating an ability to bind to extracellular ligands and synthesizing cGMP. Both Bx-TAX-2 and Bx-TAX-4 have cyclic nucleotide-binding domains and ion transport protein domains, illustrating that they are cGMP-gated ion channels. The transcript level of Bx-daf-11, Bx-tax-2, and Bx-tax-4 increased at low temperature. The survival rates of three gene silenced B. xylophilus revealed a significant decrease at low temperature. This study illustrated that the cGMP pathway plays a key role in low-temperature-induced lifespan extension in B. xylophilus. PMID:29099744

Blockmodeling and the Estimation of Evolutionary Architectural Growth in Major Defense Acquisition Programs

DTIC Science & Technology

2016-04-30

Dabkowski, and Dixit (2015), we demonstrate that the DoDAF models required pre–MS A map to 14 of the 18 parameters of the Constructive Systems...engineering effort in complex systems. Saarbrücken, Germany: VDM Verlag. Valerdi, R., Dabkowski, M., & Dixit , I. (2015). Reliability improvement of...R., Dabkowski, M., & Dixit , I. (2015). Reliability Improvement of Major Defense Acquisition Program Cost Estimates – Mapping DoDAF to COSYSMO

Pilot testing of dissolved air flotation (DAF) in a highly effective coagulation-flocculation integrated (FRD) system.

PubMed

Wang, Yili; Guo, Jinlong; Tang, Hongxiao

2002-01-01

Factors of pretreatment coagulation/flocculation units were studied using raw water of low temperature and low turbidity. Aluminum sulfate (AS) and selected polyaluminium chlorides (PACls) were all effective in the DAF process when used under favorable conditions of coagulant addition, coagulation, flocculation and flotation units. Compared with the AS coagulant, PACls, at lower dosage, could give the same effective performance even with shorter coagulation/flocculation time or lower recycle ratio during the treatment of cold water. This is attributed to the higher-charged polymeric Al species, and the lower hydrophilic and more compact flocculated flocs of PACl coagulant. Based on results of pilot experiments, the goal of FRD system can be achieved by combining a DAF heterocoagulation reactor with PACl coagulant (F), an efficient flocculation reactor (R), as well as an economical auto-dosing system (D).

Effects of Lactobacillus salivarius, Lactobacillus reuteri, and Pediococcus acidilactici on the nematode Caenorhabditis elegans include possible antitumor activity.

PubMed

Fasseas, Michael K; Fasseas, Costas; Mountzouris, Konstantinos C; Syntichaki, Popi

2013-03-01

This study examined the effects of three lactic acid bacteria (LAB) strains on the nematode Caenorhabditis elegans. Lactobacillus salivarius, Lactobacillus reuteri, and Pediococcus acidilactici were found to inhibit the development and growth of the worm. Compared to Escherichia coli used as the control, L. reuteri and P. acidilactici reduced the lifespan of wild-type and short-lived daf-16 worms. On the contrary, L. salivarius extended the lifespan of daf-16 worms when used live, but reduced it as UV-killed bacteria. The three LAB induced the expression of genes involved in pathogen response and inhibited the growth of tumor-like germ cells, without affecting DAF16 localization or increasing corpse cells. Our results suggest the possible use of C. elegans as a model for studying the antitumor attributes of LAB. The negative effects of these LAB strains on the nematode also indicate their potential use against parasitic nematodes.

Generation of a felinized swine endothelial cell line by expression of feline decay-accelerating factor.

PubMed

Izuhara, Luna; Tatsumi, Norifumi; Miyagawa, Shuji; Iwai, Satomi; Watanabe, Masahito; Yamanaka, Shuichiro; Katsuoka, Yuichi; Nagashima, Hiroshi; Okano, Hirotaka J; Yokoo, Takashi

2015-01-01

Embryonic stem cell research has facilitated the generation of many cell types for the production of tissues and organs for both humans and companion animals. Because ≥30% of pet cats suffer from chronic kidney disease (CKD), xenotransplantation between pigs and cats has been studied. For a successful pig to cat xenotransplant, the immune reaction must be overcome, especially hyperacute rejection. In this study, we isolated the gene for feline decay-accelerating factor (fDAF), an inhibitor of complement proteins, and transfected a swine endothelial cell line with fDAF to "felinize" the pig cells. These fDAF-expressing cells were resistant to feline serum containing anti-pig antibodies, suggesting that felinized pig cells were resistant to hyperacute rejection. Our results suggest that a "felinized" pig kidney can be generated for the treatment of CKD in cats in the future.

Effect of delayed auditory feedback on normal speakers at two speech rates

NASA Astrophysics Data System (ADS)

Stuart, Andrew; Kalinowski, Joseph; Rastatter, Michael P.; Lynch, Kerry

2002-05-01

This study investigated the effect of short and long auditory feedback delays at two speech rates with normal speakers. Seventeen participants spoke under delayed auditory feedback (DAF) at 0, 25, 50, and 200 ms at normal and fast rates of speech. Significantly two to three times more dysfluencies were displayed at 200 ms (p<0.05) relative to no delay or the shorter delays. There were significantly more dysfluencies observed at the fast rate of speech (p=0.028). These findings implicate the peripheral feedback system(s) of fluent speakers for the disruptive effects of DAF on normal speech production at long auditory feedback delays. Considering the contrast in fluency/dysfluency exhibited between normal speakers and those who stutter at short and long delays, it appears that speech disruption of normal speakers under DAF is a poor analog of stuttering.

H3K4 demethylase activities repress proliferative and postmitotic aging

PubMed Central

Alvares, Stacy M; Mayberry, Gaea A; Joyner, Ebony Y; Lakowski, Bernard; Ahmed, Shawn

2014-01-01

Homeostasis of postmitotic and proliferating cells is maintained by pathways that repress stress. We found that the Caenorhabditis elegans histone 3 lysine 4 (H3K4) demethylases RBR-2 and SPR-5 promoted postmitotic longevity of stress-resistant daf-2 adults, altered pools of methylated H3K4, and promoted silencing of some daf-2 target genes. In addition, RBR-2 and SPR-5 were required for germ cell immortality at a high temperature. Transgenerational proliferative aging was enhanced for spr-5; rbr-2 double mutants, suggesting that these histone demethylases may function sequentially to promote germ cell immortality by targeting distinct H3K4 methyl marks. RBR-2 did not play a comparable role in the maintenance of quiescent germ cells in dauer larvae, implying that it represses stress that occurs as a consequence of germ cell proliferation, rather than stress that accumulates in nondividing cells. We propose that H3K4 demethylase activities promote the maintenance of chromatin states during stressful growth conditions, thereby repressing postmitotic aging of somatic cells as well as proliferative aging of germ cells. PMID:24134677

Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de

Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effectsmore » of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.« less

Immunogenicity of HILDA/LIF either in a soluble or in a membrane anchored form expressed in vivo by recombinant vaccinia viruses.

PubMed

Taupin, J L; Acres, B; Dott, K; Schmitt, D; Kieny, M P; Gualde, N; Moreau, J F

1993-09-01

Insertion of various cDNAs in the genome of the vaccinia virus (VV) enables the in vivo and in vitro study of the functional role and/or the immunogenicity of the virally encoded recombinant proteins. We have prepared a recombinant VV expressing the cDNA of the human cytokine HILDA/LIF (human interleukin for DA cells/leukaemia inhibitory factor), and used this virus to immunize mice against this protein, which is very homologous to its murine counterpart (approximately 80% homology). We also constructed and expressed by the same system a chimeric gene encoding the HILDA/LIF protein fused to the 37 COOH-terminal amino-acids of the human decay accelerating factor (DAF). This sequence proved to be sufficient for the targeting of the fusion protein to the cell membrane, where it is linked to the phosphatidylinositols. Both recombinant VVs induced cytokine-specific antibodies in mice as analysed with an ELISA where the recombinant HILDA/LIF was plastic-coated and a cytofluorometric assay where the LIF-DAF molecule was present at the cell surface of stably transfected P815. In the latter case HILDA/LIF remained biologically active suggesting that it was expressed in its native form. The LIF-DAF fusion protein was found to exhibit a better capacity to elicit an antibody response against the native form of the cytokine as detected in cytofluorometric assays. Whatever the recombinant virus used to immunize the mice, the MoAbs obtained were positive either in the ELISA or in the cytofluorometric assays but one, which suggested that the plastic coating induced a conformational change of HILDA/LIF.

Phenotyping of congenic dipeptidyl peptidase 4 (DP4) deficient Dark Agouti (DA) rats suggests involvement of DP4 in neuro-, endocrine, and immune functions.

PubMed

Frerker, Nadine; Raber, Kerstin; Bode, Felix; Skripuletz, Thomas; Nave, Heike; Klemann, Christian; Pabst, Reinhard; Stephan, Michael; Schade, Jutta; Brabant, Georg; Wedekind, Dirk; Jacobs, Roland; Jörns, Anne; Forssmann, Ulf; Straub, Rainer H; Johannes, Sigrid; Hoffmann, Torsten; Wagner, Leona; Demuth, Hans-Ulrich; von Hörsten, Stephan

2009-01-01

Treatment of diabetes type 2 using chronic pharmacological inhibition of dipeptidyl peptidase 4 (DP4) still requires an in-depth analysis of models for chronic DP4 deficiency, because adverse reactions induced by some DP4 inhibitors have been described. In the present study, a novel congenic rat model of DP4 deficiency on a "DP4-high" DA rat genetic background was generated (DA.F344-Dpp4(m)/ SvH rats) and comprehensively phenotyped. Similar to chronic pharmacological inhibition of DP4, DP4 deficient rats exhibited a phenotype involving reduced diet-induced body weight gain and improved glucose tolerance associated with increased levels of glucagon-like peptide-1 (GLP-1) and bound leptin as well as decreased aminotransferases and triglycerides. Additionally, DA.F344-Dpp4(m)/SvH rats showed anxiolytic-like and reduced stress-like responses, a phenomenon presently not targeted by DP4 inhibitors. However, several immune alterations, such as differential leukocyte subset composition at baseline, blunted natural killer cell and T-cell functions, and altered cytokine levels were observed. While this animal model confirms a critical role of DP4 in GLP-1-dependent glucose regulation, genetically induced chronic DP4 deficiency apparently also affects stress-regulatory and immuneregulatory systems, indicating that the use of chronic DP4 inhibitors might have the potential to interfere with central nervous system and immune functions in vivo.

Implications for Arms Control in Technology Transfer to Less Developed Countries (LDC’s). Volume I. Considerations in Controlling Dual-Use Technology Products: An Overview

DTIC Science & Technology

1980-09-01

Mitsubishi Brazil - Mercedes - Benz FranceNetherlands - DAF France - Hispani-Suiza, Sweden - Volvo-Penta SOFAM, Peugeot West Germany - Motor-Turbinen...Mitsubishi Brazil - Mercedes - Benz Netherlands - DAF France - Hispani-Suiza, Sweden - Volvo-Penta SOFAM, Peugeot West Germany - Motor-Turbinen... marketing practices as later described in pages 4-11. This paper examines likely LDC reactions to a situation in which for whatever reason they are

Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity in C. elegans model of Alzheimer's disease.

PubMed

Wang, Xiaoxia; Cao, Min; Dong, Yuqing

2016-08-23

Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the β-amyloid (Aβ) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of Aβ toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.

Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection

PubMed Central

Nguyen, Bao-Ngoc H.; Azimzadeh, Agnes M.; Schroeder, Carsten; Buddensick, Thomas; Zhang, Tianshu; Laaris, Amal; Cochrane, Megan; Schuurman, Henk-Jan; Sachs, David H.; Allan, James S.; Pierson, Richard N.

2012-01-01

Background Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection. Methods We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF+/+) pig lungs. Results GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild-type lungs (P = 0.001) and 45 ± 60 min for hDAF+/+ lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF+/+ lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF+/+ lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points. Conclusions In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms. PMID:21496117

Generation of sequence signatures from DNA amplification fingerprints with mini-hairpin and microsatellite primers.

PubMed

Caetano-Anollés, G; Gresshoff, P M

1996-06-01

DNA amplification fingerprinting (DAF) with mini-hairpins harboring arbitrary "core" sequences at their 3' termini were used to fingerprint a variety of templates, including PCR products and whole genomes, to establish genetic relationships between plant tax at the interspecific and intraspecific level, and to identify closely related fungal isolates and plant accessions. No correlation was observed between the sequence of the arbitrary core, the stability of the mini-hairpin structure and DAF efficiency. Mini-hairpin primers with short arbitrary cores and primers complementary to simple sequence repeats present in microsatellites were also used to generate arbitrary signatures from amplification profiles (ASAP). The ASAP strategy is a dual-step amplification procedure that uses at least one primer in each fingerprinting stage. ASAP was able to reproducibly amplify DAF products (representing about 10-15 kb of sequence) following careful optimization of amplification parameters such as primer and template concentration. Avoidance of primer sequences partially complementary to DAF product termini was necessary in order to produce distinct fingerprints. This allowed the combinatorial use of oligomers in nucleic acid screening, with numerous ASAP fingerprinting reactions based on a limited number of primer sequences. Mini-hairpin primers and ASAP analysis significantly increased detection of polymorphic DNA, separating closely related bermudagrass (Cynodon) cultivars and detecting putatively linked markers in bulked segregant analysis of the soybean (Glycine max) supernodulation (nitrate-tolerant symbiosis) locus.

Partial characterization of the cross-reacting determinant, a carbohydrate epitope shared by decay accelerating factor and the variant surface glycoprotein of the African Trypanosoma brucei.

PubMed

Shak, S; Davitz, M A; Wolinsky, M L; Nussenzweig, V; Turner, M J; Gurnett, A

1988-03-15

The variant surface glycoprotein (VSG) of the African trypanosome is anchored in the cell membrane by a complex glycan attached to phosphatidylinositol. The carboxyl terminal portion of VSG contains a cryptic carbohydrate epitope, the cross-reacting determinant (CRD), that is revealed only after removal of the diacylglycerol by phosphatidylinositol-specific phospholipase C (PIPLC) or VSG lipase. Recently, we have shown that after hydrolysis by PIPLC, decay-accelerating factor (DAF)--a mammalian phosphatidylinositol-anchored protein--also contains the CRD epitope. Using a two site immunoradiometric assay in which the capturing antibody is a monoclonal antibody to DAF and the revealing antibody is anti-CRD, we now show that sugar phosphates significantly inhibited the binding of anti-CRD antibody to DAF released by PIPLC. DL-myo-inositol 1,2-cyclic phosphate was the most potent inhibitor of binding (IC50 less than 10(-8) M). Other sugar phosphates, such as alpha-D-glucose-1-phosphate, which also possess adjacent hydroxyl and phosphate moieties in cis also inhibited binding at low concentrations (IC50 = 10(-5) to 10(-4) M). In contrast, sugar phosphates which do not possess adjacent hydroxyl and phosphate moieties in cis and simple sugars weakly inhibited binding (IC50 greater than 10(-3) M). These results suggest that myo-inositol 1,2-cyclic phosphate contributes significantly to the epitope recognized by the anti-CRD antibody and is consistent with analysis of the carboxyl terminus of VSG, which also suggested the presence of the cyclic inositol phosphate. In light of the recent findings that human serum contains a glycan-phosphatidyl-inositol-specific phospholipase D, which converts DAF from a hydrophobic to a hydrophilic form lacking the CRD, the observation that the phosphate is crucial for expression of the epitope may be relevant in understanding the origin of CRD-negative DAF in urine and plasma.

Investigation of the Low Power Stage of an 1178 nm Raman System

DTIC Science & Technology

2013-12-23

LEANNE HENRY, DR-III, DAF KENTON T. WOOD, DR-IV, DAF Work Unit Manager Chief, Laser Division This report is published in the...and 1069 nm pumped Raman laser system where the second Stokes is amplified in a 1121 nm resonator defined by high reflector fiber Bragg gratings (FBGs...the gratings was found to impact the performance of the laser and needs to be dealt with in order to obtain high 1178 nm output power levels. In order

Visual Search in the Detection of Retinal Injury: A Feasibility Study

DTIC Science & Technology

2013-04-01

D, Heyes A. et al. Mobility of people with retinitis pigmentosa as a function of vision and psychological variables. Optometry and Vision Science...AFRL-RH-FS-TR-2013-0019 Visual Search in the Detection of Retinal Injury: A Feasibility Study Thomas Kuyk TASC, Inc. Lei Liu The...Detection of Retinal Injury: A Feasibility Study" 2013 0019 LEON N. McLIN, JR., DR-III, DAF Work Unit Manager 711 HPW/ RHDO POLHAMUS.GARR ETT.D

FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

DOE PAGES

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; ...

2016-09-13

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.« less

Development of the Potential for Cyanogenesis in Maturing Black Cherry (Prunus serotina Ehrh.) Fruits 1

PubMed Central

Swain, Elisabeth; Li, Chun Ping; Poulton, Jonathan E.

1992-01-01

Biochemical changes related to cyanogenesis (hydrogen cyanide production) were monitored during maturation of black cherry (Prunus serotina Ehrh.) fruits. At weekly intervals from flowering until maturity, fruits (or selected parts thereof) were analyzed for (a) fresh and dry weights, (b) prunasin and amygdalin levels, and (c) levels of the catabolic enzymes amygdalin hydrolase, prunasin hydrolase, and mandelonitrile lyase. During phase I (0-28 days after flowering [DAF]), immature fruits accumulated prunasin (mean: 3 micromoles/fruit) but were acyanogenic because they lacked the above enzymes. Concomitant with cotyledon development during mid-phase II, the seeds began accumulating both amygdalin (mean: 3 micromoles/seed) and the catabolic enzymes and were highly cyanogenic upon tissue disruption. Meanwhile, prunasin levels rapidly declined and were negligible by maturity. During phases II (29-65 DAF) and III (66-81 DAF), the pericarp also accumulated amygdalin, whereas its prunasin content declined toward maturity. Lacking the catabolic enzymes, the pericarp remained acyanogenic throughout all developmental stages. ImagesFigure 2Figure 4 PMID:16668810

Integration of carbohydrate metabolism and redox state controls dauer larva formation in Caenorhabditis elegans.

PubMed

Penkov, Sider; Kaptan, Damla; Erkut, Cihan; Sarov, Mihail; Mende, Fanny; Kurzchalia, Teymuras V

2015-08-20

Under adverse conditions, Caenorhabditis elegans enters a diapause stage called the dauer larva. External cues signal the nuclear hormone receptor DAF-12, the activity of which is regulated by its ligands: dafachronic acids (DAs). DAs are synthesized from cholesterol, with the last synthesis step requiring NADPH, and their absence stimulates dauer formation. Here we show that NADPH levels determine dauer formation in a regulatory mechanism involving key carbohydrate and redox metabolic enzymes. Elevated trehalose biosynthesis diverts glucose-6-phosphate from the pentose phosphate pathway, which is the major source of cellular NADPH. This enhances dauer formation due to the decrease in the DA level. Moreover, DAF-12, in cooperation with DAF-16/FoxO, induces negative feedback of DA synthesis via activation of the trehalose-producing enzymes TPS-1/2 and inhibition of the NADPH-producing enzyme IDH-1. Thus, the dauer developmental decision is controlled by integration of the metabolic flux of carbohydrates and cellular redox potential.

Stable thermophilic anaerobic digestion of dissolved air flotation (DAF) sludge by co-digestion with swine manure.

PubMed

Creamer, K S; Chen, Y; Williams, C M; Cheng, J J

2010-05-01

Environmentally sound treatment of by-products in a value-adding process is an ongoing challenge in animal agriculture. The sludge produced as a result of the dissolved air flotation (DAF) wastewater treatment process in swine processing facilities is one such low-value residue. The objective of this study was to determine the fundamental performance parameters for thermophilic anaerobic digestion of DAF sludge. Testing in a semi-continuous stirred tank reactor and in batch reactors was conducted to determine the kinetics of degradation and biogas yield. Stable operation could not be achieved using pure DAF sludge as a substrate, possibly due to inhibition by long-chain fatty acids or to nutrient deficiencies. However, in a 1:1 ratio (w/w, dry basis) with swine manure, operation was both stable and productive. In the semi-continuous stirred reactor at 54.5 degrees Celsius, a hydraulic residence time of 10 days, and an organic loading rate of 4.68 gVS/day/L, the methane production rate was 2.19 L/L/day and the specific methane production rate was 0.47 L/gVS (fed). Maximum specific methanogenic activity (SMA) in batch testing was 0.15 mmoles CH(4) h(-1) gVS(-1) at a substrate concentration of 6.9 gVS L(-1). Higher substrate concentrations cause an initial lag in methane production, possibly due to long-chain fatty acid or nitrogen inhibition. Copyright 2009 Elsevier Ltd. All rights reserved.

Role of Caenorhabditis elegans AKT-1/2 and SGK-1 in Manganese Toxicity.

PubMed

Peres, Tanara V; Arantes, Leticia P; Miah, Mahfuzur R; Bornhorst, Julia; Schwerdtle, Tanja; Bowman, Aaron B; Leal, Rodrigo B; Aschner, Michael

2018-06-07

Excessive levels of the essential metal manganese (Mn) may cause a syndrome similar to Parkinson's disease. The model organism Caenorhabditis elegans mimics some of Mn effects in mammals, including dopaminergic neurodegeneration, oxidative stress, and increased levels of AKT. The evolutionarily conserved insulin/insulin-like growth factor-1 signaling pathway (IIS) modulates worm longevity, metabolism, and antioxidant responses by antagonizing the transcription factors DAF-16/FOXO and SKN-1/Nrf-2. AKT-1, AKT-2, and SGK-1 act upstream of these transcription factors. To study the role of these proteins in C. elegans response to Mn intoxication, wild-type N2 and loss-of-function mutants were exposed to Mn (2.5 to 100 mM) for 1 h at the L1 larval stage. Strains with loss-of-function in akt-1, akt-2, and sgk-1 had higher resistance to Mn compared to N2 in the survival test. All strains tested accumulated Mn similarly, as shown by ICP-MS. DAF-16 nuclear translocation was observed by fluorescence microscopy in WT and loss-of-function strains exposed to Mn. qRT-PCR data indicate increased expression of γ-glutamyl cysteine synthetase (GCS-1) antioxidant enzyme in akt-1 mutants. The expression of sod-3 (superoxide dismutase homologue) was increased in the akt-1 mutant worms, independent of Mn treatment. However, dopaminergic neurons degenerated even in the more resistant strains. Dopaminergic function was evaluated with the basal slowing response behavioral test and dopaminergic neuron integrity was evaluated using worms expressing green fluorescent protein (GFP) under the dopamine transporter (DAT-1) promoter. These results suggest that AKT-1/2 and SGK-1 play a role in C. elegans response to Mn intoxication. However, tissue-specific responses may occur in dopaminergic neurons, contributing to degeneration.

Business Case Analysis for the Versatile Depot Automated Test Station Used in the USAF Warner Robins Air Logistics Center Maintenance Depot

DTIC Science & Technology

2008-06-01

executes the avionics test) can run on the new ATS thus creating the common ATS framework . The system will also enable numerous new functional...Enterprise-level architecture that reflects corporate DoD priorities and requirements for business systems, and provides a common framework to ensure that...entire Business Mission Area (BMA) of the DoD. The BEA also contains a set of integrated Department of Defense Architecture Framework (DoDAF

Electroflotation

NASA Astrophysics Data System (ADS)

Chen, Xueming; Chen, Guohua

Electroflotation (EF) is the flotation using electrolytically generated bubbles of hydrogen and oxygen for separating suspended substances from aqueous phases. This process was first proposed by Elmore in 1905 for flotation of valuable minerals from ores. Compared with the conventional dissolved air flotation (DAF), EF has many advantages, including high flotation efficiency, compact units, easy operation, and less maintenance. Therefore, EF is an attractive alternative to DAF. This technique has been proven very effective in treating oily wastewater or oil-water emulsion, mining wastewater, groundwater, food processing wastewater, restaurant wastewater, industrial sewage, heavy metals containing effluent, and many other water and wastewaters.

Baseline tests of the C. H. Waterman DAF electric passenger vehicle

NASA Technical Reports Server (NTRS)

Sargent, N. B.; Maslowski, E. A.; Soltis, R. F.; Schuh, R. M.

1977-01-01

An electric vehicle was tested as part of an Energy Research Development Administration (ERDA) project to characterize the state-of-the-art of electric vehicles. The Waterman vehicle performance test results are presented in this report. The vehicle is a converted four-passenger DAF 46 sedan. It is powered by sixteen 6-volt traction batteries through a three-step contactor controller actuated by a foot throttle to change the voltage applied to the 6.7 kW motor. The braking system is a conventional hydraulic braking system.

3CE Methodology for Conducting a Modeling, Simulation, and Instrumentation Tool Capability Analysis

DTIC Science & Technology

2010-05-01

flRmurn I F )T:Ir,tir)l! MCr)lto.-lng DHin nttbli..’"Ollc:~ E,;m:a..liut .!,)’l’lt’Mn:l’lll.ll~ t Managemen t F unction a l Arem 1 .5 Toola na...a modeling, simulation, and instrumentation (MS&I) environment. This methodology uses the DoDAF product set to document operational and systems...engineering process were identified and resolved, such as duplication of data elements derived from DoDAF operational and system views used to

Study of vibrational modes and specific heat of wurtzite phase of BN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Daljit, E-mail: daljit.jt@gmail.com; Sinha, M. M.

2016-05-06

In these days of nanotechnology the materials like BN is of utmost importance as in hexagonal phase it is among hardest materials. The phonon mode study of the materials is most important factor to find structural and thermodynamcal properties. To study the phonons de launey angular force (DAF) constant model is best suited as it involves many particle interactions. Therefore in this presentation we have studied the lattice dynamical properties and specific heat of BN in wurtzite phase using DAF model. The obtained results are in excellent agreement with existing results.

Adaptation to delayed auditory feedback induces the temporal recalibration effect in both speech perception and production.

PubMed

Yamamoto, Kosuke; Kawabata, Hideaki

2014-12-01

We ordinarily speak fluently, even though our perceptions of our own voices are disrupted by various environmental acoustic properties. The underlying mechanism of speech is supposed to monitor the temporal relationship between speech production and the perception of auditory feedback, as suggested by a reduction in speech fluency when the speaker is exposed to delayed auditory feedback (DAF). While many studies have reported that DAF influences speech motor processing, its relationship to the temporal tuning effect on multimodal integration, or temporal recalibration, remains unclear. We investigated whether the temporal aspects of both speech perception and production change due to adaptation to the delay between the motor sensation and the auditory feedback. This is a well-used method of inducing temporal recalibration. Participants continually read texts with specific DAF times in order to adapt to the delay. Then, they judged the simultaneity between the motor sensation and the vocal feedback. We measured the rates of speech with which participants read the texts in both the exposure and re-exposure phases. We found that exposure to DAF changed both the rate of speech and the simultaneity judgment, that is, participants' speech gained fluency. Although we also found that a delay of 200 ms appeared to be most effective in decreasing the rates of speech and shifting the distribution on the simultaneity judgment, there was no correlation between these measurements. These findings suggest that both speech motor production and multimodal perception are adaptive to temporal lag but are processed in distinct ways.

Comparative Transcriptome Analysis Reveals Growth-Related Genes in Juvenile Chinese Sea Cucumber, Russian Sea Cucumber, and Their Hybrids.

PubMed

Wang, Zhicheng; Cui, Jun; Song, Jian; Wang, Haoze; Gao, Kailun; Qiu, Xuemei; Gou, Meng; Li, Xin; Hu, Ziwen; Wang, Xiuli; Chang, Yaqing

2018-04-01

Heterosis is important for sea cucumber breeding, but its molecular mechanism remains largely unexplored. In this study, parental lines of Apostichopus japonicus from Russia (R) and China (C) were used to construct hybrids (CR and RC) by reciprocal crossing. We examined the transcriptional profiles of the hybrids (CR and RC) and the purebreds (CC and RR) at different developmental times. A total of 60.27 Gb of clean data was obtained, and 176,649 unigenes were identified, of which 50,312 unigenes were annotated. A total of 414,536 SNPs were identified. A total of 7011 differentially expressed genes (DEGs) were obtained between the purebreds and hybrids at 45 days after fertilization (DAF), and a total of 8218 DEGs were obtained between the purebreds and hybrids at 75 DAF. In addition, a total of 7652 DEGs were obtained between 45 DAF and 75 DAF. The significant DEGs were mainly involved in the MAPK and FOXO signaling pathways, especially in the Ras-Raf-MEK1/2-ERK module, which may be a key regulator of development and growth in juvenile A. japonicus. In addition, we also identified key growth-related genes, such as fgfs, igfs, megfs and hgfs, which were upregulated in the hybrids (RC and CR); these genes may play important roles in heterosis in A. japonicus. Our study provides fundamental information on the molecular mechanisms underlying heterosis in sea cucumber and might suggest strategies for the selection of rapidly growing strains of sea cucumber in aquaculture.

Effects of a Caenorhabditis elegans dauer pheromone ascaroside on physiology and signal transduction pathways.

PubMed

Gallo, Marco; Riddle, Donald L

2009-02-01

Daumone is one of the three purified and artificially synthesized components of the Caenorhabditis elegans dauer pheromone. It affects the major signal transduction pathways known to discriminate between developmental arrest at the dauer stage and growth to the adult [the transforming growth factor beta (TGF-beta) and daf-2/IGF1R pathways], just as natural pheromone extracts do. Transcription of daf-7/TGF-beta is reduced in pre-dauer larvae, and nuclear localization of the DAF-16/FOXO transcription factor is increased in embryos and L1 larvae exposed to synthetic daumone. However, daumone does not require the cilia in the amphidial neurons to produce these effects nor does it require the Galpha protein GPA-3 to induce dauer entry, although GPA-3 is required for dauer induction by natural dauer pheromone extracts. Synthetic daumone has physiological effects that have not been observed with natural pheromone. It is toxic at the concentrations required for bioassay and is lethal to mutants with defective cuticles. The molecular and physiological effects of daumone and natural dauer pheromone are only partially overlapping.

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

PubMed Central

Chang, Jessica T; Kumsta, Caroline; Hellman, Andrew B; Adams, Linnea M; Hansen, Malene

2017-01-01

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan. DOI: http://dx.doi.org/10.7554/eLife.18459.001 PMID:28675140

Use of diaminofluoresceins to detect and measure nitric oxide in low level generating human immune cells.

PubMed

Tiscornia, Adriana; Cairoli, Ernesto; Marquez, Maria; Denicola, Ana; Pritsch, Otto; Cayota, Alfonso

2009-03-15

Nitric oxide ((*)NO) has been implicated in multiple physiological and pathological immune processes. Different methods have been developed to detect and quantify (*)NO, where one of the principal difficulties are the accurately detection in cellular system with low levels of (*)NO production. The choice of the (*)NO detection method to be used depends on the characteristics of the experimental system and the levels of (*)NO production which depend on either the organism source of samples or the experimental conditions. Recently, high sensitive methods to detect and image (*)NO have been reported using 4,5-diaminofluorescein-based fluorescent probes (DAF) and its derivate 4,5-diaminofluorescein diacetate (DAF-2 DA). This work was aimed to adapt and optimize the use of DAF probes to detect and quantify the (*)NO production in systems of high, moderate and low out-put production, especially in human PBMC and their subpopulations. Here, we report an original experimental design which is useful to detect and estimate (*)NO fluxes in human PBMC and their subpopulations with high specificity and sensitivity.

A conserved neuronal DAF-16/FoxO plays an important role in conveying pheromone signals to elicit repulsion behavior in Caenorhabditis elegans.

PubMed

Park, Donha; Hahm, Jeong-Hoon; Park, Saeram; Ha, Go; Chang, Gyeong-Eon; Jeong, Haelim; Kim, Heekyeong; Kim, Sunhee; Cheong, Eunji; Paik, Young-Ki

2017-08-03

Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood. Here, we show that pheromone signals perceived by GPA-3 is conveyed through glutamatergic neurotransmission in which neuronal DAF-16/FoxO plays an important modulatory role by controlling glutaminase gene expression. We further provide evidence that this modulatory role for DAF-16/FoxO seems to be conserved evolutionarily by electro-physiological study in mouse primary hippocampal neurons that are responsible for glutamatergic neurotransmission. These findings provide the basis for understanding the nematode pheromone signaling, which seems crucial for adaptation of adult hermaphrodites to changes in environmental condition for survival.

Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein

DOE PAGES

Vrablik, Tracy L.; Petyuk, Vladislav A.; Larson, Emily M.; ...

2015-06-27

Lipid droplets are cytoplasmic organelles that store neutral lipids for membrane synthesis and energy reserves. In this study, we characterized the lipid and protein composition of purified Caenorhabditis elegans lipid droplets. These lipid droplets are composed mainly of triacylglycerols, surrounded by a phospholipid monolayer composed primarily of phosphatidylcholine and phosphatidylethanolamine. The fatty acid composition of the triacylglycerols is rich in fatty acid species obtained from the dietary Escherichia coli, including cyclopropane fatty acids and cis-vaccenic acid. Unlike other organisms, C. elegans lipid droplets contain very little cholesterol or cholesterol esters. Comparison of the lipid droplet proteomes of wild type andmore » high-fat daf-2 mutant strains shows a very similar proteome in both strains, except that the most abundant protein in the C. elegans lipid droplet proteome, MDT-28, is relatively less abundant in lipid droplets isolated from daf-2 mutants. Functional analysis of lipid droplet proteins identified in our proteomic studies indicated an enrichment of proteins required for growth and fat homeostasis in C. elegans. Finally, we confirmed the localization of one of the newly identified lipid droplet proteins, ACS-4. We found that ACS-4 localizes to the surface of lipid droplets in the C. elegans intestine and skin. This study bolsters C. elegans as a model to study the dynamics and functions of lipid droplets in a multicellular organism.« less

Yellow Pigment Aurovertins Mediate Interactions between the Pathogenic Fungus Pochonia chlamydosporia and Its Nematode Host.

PubMed

Wang, Yan-li; Li, Lin-fang; Li, Dong-xian; Wang, Baile; Zhang, Keqin; Niu, Xuemei

2015-07-29

Nematophagous fungi are globally distributed soil fungi and well-known natural predators of soil-dwelling nematodes. Pochonia chlamydosporia can be found in diverse nematode-suppressive soils as a parasite of nematode eggs and is one of the most studied potential biological control agents of nematodes. However, little is known about the functions of small molecules in the process of infection of nematodes by this parasitic fungus or about small-molecule-mediated interactions between the pathogenic fungus and its host. Our recent study demonstrated that a P. chlamydosporia strain isolated from root knots of tobacco infected by the root-knot nematode Meloidogyne incognita produced a class of yellow pigment metabolite aurovertins, which induced the death of the free-living nematode Panagrellus redivevus. Here we report that nematicidal P. chlamydosporia strains obtained from the nematode worms tended to yield a total yellow pigment aurovertin production exceeding the inhibitory concentration shown in nematicidal bioassays. Aurovertin D was abundant in the pigment metabolites of P. chlamydosporia strains. Aurovertin D showed strong toxicity toward the root-knot nematode M. incognita and exerted profound and detrimental effects on the viability of Caenorhabditis elegans even at a subinhibitory concentration. Evaluation of the nematode mutation in the β subunit of F1-ATPase, together with the application of RNA interference in screening each subunit of F1FO-ATPase in the nematode worms, demonstrated that the β subunit of F1-ATPase might not be the specific target for aurovertins in nematodes. The resistance of C. elegans daf-2(e1370) and the hypersensitivity of C. elegans daf-16(mu86) to aurovertin D indicated that DAF-16/FOXO transcription factor in nematodes was triggered in response to the aurovertin attack. These findings advance our understanding of the roles of aurovertin production in the interactions between nematodes and the pathogen fungus P. chlamydosporia.

Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Yijun; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan; Pattnaik, Asit K.

2012-03-01

The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating thatmore » the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.« less

Effects of oxygen plasma treatment on domestic aramid fiber III reinforced bismaleimide composite interfacial properties

NASA Astrophysics Data System (ADS)

Shi, Chen; Wang, Jing; Chen, Ping; Feng, Jiayue; Cui, Jinyuan; Yang, Faze

2017-12-01

Domestic Aramid Fiber III (DAF III) was modified by oxygen plasma treatment. The fiber surface characteristics was observed by Scanning Electron Microscopy. The results showed that oxygen plasma treatment changed surface morphologies. The effects of oxygen plasma treatment on DAF III reinforced bismaleimides (BMI) composite bending and interfacial properties were investigated, respectively. The ILSS value increased from 49.3 MPa to 56.0 MPa (by 13.5%) after oxygen plasma treatment. The bending strength changed a little. Furthermore, the composite rupture mode changed from interfacial rupture to fiber or resin bulk rupture.

Transcriptomic basis of functional difference and coordination between seeds and the silique wall of Brassica napus during the seed-filling stage.

PubMed

Liu, Han; Yang, Qingyong; Fan, Chuchuan; Zhao, Xiaoqin; Wang, Xuemin; Zhou, Yongming

2015-04-01

The silique of oilseed rape (Brassica napus) is a composite organ including seeds and the silique wall (SW) that possesses distinctly physiological, biochemical and functional differentiations. Yet, the molecular events controlling such differences between the SW and seeds, as well as their coordination during silique development at transcriptional level are largely unknown. Here, we identified large sets of differentially expressed genes in the SW and seeds of siliques at 21-22 days after flowering with a Brassica 95K EST microarray. At this particular stage, there were 3278 SW preferentially expressed genes and 2425 seed preferentially expressed genes. Using the MapMan visualization software, genes differentially regulated in various metabolic pathways and sub-pathways between the SW and seeds were revealed. Photosynthesis and transport-related genes were more actively transcripted in the SW, while those involved in lipid metabolism were more active in seeds during the seed filling stage. On the other hand, genes involved in secondary metabolisms were selectively regulated in the SW and seeds. Large numbers of transcription factors were identified to be differentially expressed between the SW and seeds, suggesting a complex pattern of transcriptional control in these two organs. Furthermore, most genes discussed in categories or pathways showed a similar expression pattern through 21 DAF to 42 DAF. Our results thus provide insights into the coordination of seeds and the SW in the developing silique at the transcriptional levels, which will facilitate the functional studies of important genes for improving B. napus seed productivity and quality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Piracy of Decay-Accelerating Factor (CD55) Signal Transduction by the Diffusely Adhering Strain Escherichia coli C1845 Promotes Cytoskeletal F-Actin Rearrangements in Cultured Human Intestinal INT407 Cells

PubMed Central

Peiffer, Isabelle; Servin, Alain L.; Bernet-Camard, Marie-Françoise

1998-01-01

Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. PMID:9712744

Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins.

PubMed

Wang, Xiaoxia; Cook, Lauren F; Grasso, Lindsay M; Cao, Min; Dong, Yuqing

2015-07-01

Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of floc and bubble size on the efficiency of the dissolved air flotation (DAF) process.

PubMed

Han, Mooyoung; Kim, Tschung-il; Kim, Jinho

2007-01-01

Dissolved air flotation (DAF) is a method for removing particles from water using micro bubbles instead of settlement. The process has proved to be successful and, since the 1960s, accepted as an alternative to the conventional sedimentation process for water and wastewater treatment. However, limited research into the process, especially the fundamental characteristics of bubbles and particles, has been carried out. The single collector collision model is not capable of determining the effects of particular characteristics, such as the size and surface charge of bubbles and particles. Han has published a set of modeling results after calculating the collision efficiency between bubbles and particles by trajectory analysis. His major conclusion was that collision efficiency is maximum when the bubbles and particles are nearly the same size but have opposite charge. However, experimental verification of this conclusion has not been carried out yet. This paper describes a new method for measuring the size of particles and bubbles developed using computational image analysis. DAF efficiency is influenced by the effect of the recycle ratio on various average floc sizes. The larger the recycle ratio, the higher the DAF efficiency at the same pressure and particle size. The treatment efficiency is also affected by the saturation pressure, because the bubble size and bubble volume concentration are controlled by the pressure. The highest efficiency is obtained when the floc size is larger than the bubble size. These results, namely that the highest collision efficiency occurs when the particles and bubbles are about the same size, are more in accordance with the trajectory model than with the white water collector model, which implies that the larger the particles, the higher is the collision efficiency.

Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes.

PubMed

Yang, C; Jones, J L; Barnum, S R

1993-09-01

In this report, we have shown the expression of the complement regulatory proteins decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46) and CD59 on human D54-MG astroglioma cells by several methods, including immunofluorescence, flow cytometry and Western blotting and Northern blot analysis. These studies demonstrate that all three proteins are structurally and antigenically similar to their counterparts expressed on HepG2 and SW480 cells (hepatocyte and epithelial cell lines, respectively). D54-MG cells express mRNA for all three proteins of the appropriate size(s). The phosphatidylinositol-specific enzyme, PIPLC, cleaved DAF from the surface of D54-MG cells, demonstrating that DAF is linked by a glycophospholipid anchor as has been shown for other cell types. Flow cytometry demonstrates that primary rat astrocytes also constitutively express all three regulatory proteins. These data are the first to demonstrate the expression of CD59 on astrocytes, and the presence of all three regulatory proteins on astrocytes suggests that regulation of complement activation in the central nervous system is important in neural host defense mechanisms.

Nematode orphan genes are adopted by conserved regulatory networks and find a home in ecology.

PubMed

Mayer, Melanie G; Sommer, Ralf J

2015-01-01

Nematode dauer formation represents an essential survival and dispersal strategy and is one of a few ecologically relevant traits that can be studied in laboratory approaches. Under harsh environmental conditions, the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus arrest their development and induce the formation of stress-resistant dauer larvae in response to dauer pheromones, representing a key example of phenotypic plasticity. Previous studies have indicated that in P. pacificus, many wild isolates show cross-preference of dauer pheromones and compete for access to a limited food source. When investigating the genetic mechanisms underlying this intraspecific competition, we recently discovered that the orphan gene dauerless (dau-1) controls dauer formation by copy number variation. Our results show that dau-1 acts in parallel to or downstream of steroid hormone signaling but upstream of the nuclear hormone receptor daf-12, suggesting that DAU-1 represents a novel inhibitor of DAF-12. Phylogenetic analysis reveals that the observed copy number variation is part of a complex series of gene duplication events that occurred over short evolutionary time scales. Here, we comment on the incorporation of novel or fast-evolving genes into conserved genetic networks as a common principle for the evolution of phenotypic plasticity and intraspecific competition. We discuss the possibility that orphan genes might often function in the regulation and execution of ecologically relevant traits. Given that only few ecological processes can be studied in model organisms, the function of such genes might often go unnoticed, explaining the large number of uncharacterized genes in model system genomes.

Reporting Recommended Patch Density from Vehicle Panel Vibration Convergence Studies using both DAF and TBL Fits of the Spatial Correlation Function

NASA Technical Reports Server (NTRS)

Smith, Andrew M.; Davis, Robert Ben; LaVerde, Bruce T.; Jones, Douglas C.; Band, Jonathon L.

2012-01-01

Using the patch method to represent the continuous spatial correlation function of a phased pressure field over a structural surface is an approximation. The approximation approaches the continuous function as patches become smaller. Plotting comparisons of the approximation vs the continuous function may provide insight revealing: (1) For what patch size/density should the approximation be very good? (2) What the approximation looks like when it begins to break down? (3) What the approximation looks like when the patch size is grossly too large. Following these observations with a convergence study using one FEM may allow us to see the importance of patch density. We may develop insights that help us to predict sufficient patch density to provide adequate convergence for the intended purpose frequency range of interest

Expression and functional characterization of a C-7 cholesterol desaturase from Tetrahymena thermophila in an insect cell line.

PubMed

Poklepovich, Tomas J; Urtasun, Nicolás; Miranda, María V; Nusblat, Alejandro D; Nudel, Clara B

2015-04-01

Tetrahymena thermophila transforms exogenous cholesterol into pro-vitamin D3 (7-dehydrocholesterol) with remarkable efficiency in a one-step reaction carried out by a C-7 cholesterol desaturase. The enzyme DES7 is encoded by the gene TTHERM_00310640, identified with RNAi and gene knock-out experiments, but has not yet been heterologously expressed actively in any organism. A model derived from its amino acid sequence classified DES7p as a Rieske-type oxygenase with transmembrane localization. The protein has catalytic activity, sequence and topological similarity to DAF-36/Neverland proteins involved in the synthesis of steroid hormones in insects and nematodes. Due to their structural and functional similarity, we analyzed the expression of a codon optimized DES7 gene from Tetrahymena in the insect Sf9 cell line, identified and measured the steroid metabolites formed, and extended the actual knowledge on its localization. We found that the accumulation of 7-dehydrocholesterol could be increased 16-40-fold in Spodopterafrugiperda, depending on physiological conditions, by overexpression of T. thermophila DES7. The protein was detected in the microsomal fraction, in accordance with previous reports. Although the electron transfer chain for Des7p/DAF-36/Neverland Rieske-type oxygenases is presently unknown, we identified possible donors in the ciliate and insect genomes by bioinformatic analysis. In spite of the large evolutionary distance between S. frugiperda and T. thermophila, the results indicate that there is significant functional conservation of the electron donors, since the ciliate's sterol desaturase can function in the context of the insect electron transport system. The results achieved demonstrate that DES7 is the first gene from a ciliate, coding for a microsomal enzyme, expressed in active form in an insect cell line. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluate Rijsimulator-Instellingen Voor de DAF YA-4440 (Evaluation Drive Simulator Settings for DAF YA-4440)

DTIC Science & Technology

1991-10-01

waarbij: 0c1 staat voor de beginsnclhcid; cl = 24 K1 C= (3/25) K2 C= 5 K4 Merk op dat 0o cxponenticcl afhankelijk is van t. TNO-rapport Pagina 9 Voor (KI...gegeven: cgt) = sqrt(ci/C3)*tan(arctan(sqr((c 3/c1 )*w0 )) - sqrl(c1 *C3)*t/C4) ( 9 ) waarbij: cl= -24 K, C= 3 1(3/500 C4= 5 K4~ Merk op dat (o niet-lincair...wcrgegevcn. Omdat K, kiciner is dan K4 heeft con kicine absolute verandering in K, grotere gevolgen voor de UDB-uitrolcurve dan en kieinc verandoring in

Fruit coloration and anthocyanin biosynthesis after bag removal in non-red and red apples (Malus × domestica Borkh.).

PubMed

Liu, Yulian; Che, Fei; Wang, Lixin; Meng, Rui; Zhang, Xiaojun; Zhao, Zhengyang

2013-01-25

In the present study, evolution of apple color (L* and a/b), the accumulation of anthocyanins and the activity of the related enzymes, phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), dihydroflavonol4-reductase (DFR) and UDP-Glucose: flavonoid-3-O-galactosyl transferase (UFGT), were investigated in bagged non-red apple cultivars ('Granny Smith' and 'Golden Delicious') and red apple cultivars ('Starkrimon' and 'Pink Lady'). Young fruits were bagged 40-45 days after flowering (DAF), and fruits of 'Golden Delicious' and 'Starkrimon' were uncovered and exposed to light 120 DAF, while those of 'Granny Smith' and 'Pink Lady' were exposed for 160 DAF. Results showed that cyanidin 3-galactoside (cy3-gal) was the most abundant anthocyanin in both non-red and red cultivars. Level of anthocyanins was higher in 'Granny Smith' than in 'Golden Delicious', indicating that red color was easier to develop in green cultivar 'Granny Smith' than in yellow cultivar 'Golden Delicious' after bag removal. The cy3-gal accumulation of non-red cultivars tested was not significantly correlated with PAL, CHI and DFR activity, but was significantly correlated with UFGT activity. During the reddening of non-red apples, UFGT may be the more important factor in the anthocyanin biosynthesis.

Coagulation, flocculation, dissolved air flotation and filtration in the removal of Giardia spp. and Cryptosporidium spp. from water supply.

PubMed

Andreoli, Fernando César; Sabogal-Paz, Lyda Patricia

2017-11-15

Removing protozoa from a water supply using coagulation, flocculation, dissolved air flotation (DAF) and filtration on a bench scale was evaluated. Calcium carbonate flocculation with and without immunomagnetic separation (IMS) was chosen to detect Giardia spp. cysts and Cryptosporidium spp. oocysts in the studied samples. The results indicated that DAF removed between 1.31 log and 1.79 log of cysts and between 1.08 log and 1.42 log of oocysts. The performance was lower in filtration, with the removal of 1.07 log-1.44 log for cysts and 0.82 log-0.98 log for oocysts. The coagulation, flocculation, DAF and filtration steps removed more than 2.2 log of cysts and oocysts from the water studied. However, protozoa were detected in the filtered water, even with turbidity values of 0.2 NTU. The recovery of the detection method met the international criteria and was higher when there was no IMS. Including the third acid dissociation in the IMS was critical to improve the performance of the protocol tested. However, there was an increase in the technical and analytical complexity and costs. It was also observed that the efficiency of the treatment was linked to the performance of the selected method of detecting protozoa.

Highlighting the importance of transitional ventilation regimes in the management of Mediterranean show caves (Nerja-Pintada system, southern Spain).

PubMed

Liñán, C; Del Rosal, Y; Carrasco, F; Vadillo, I; Benavente, J; Ojeda, L

2018-08-01

This study shows the utilization of the air CO 2 exhaled by a very high number of visitors in the Nerja Cave as both a tracer and an additional tool to precisely evaluate the air circulation through the entire karst system, which includes non-touristic passages, originally free of anthropogenic CO 2 . The analysis of the temporal - spatial evolution of the CO 2 content and other monitoring data measured from January 2015 to December 2016 in the Nerja-Pintada system, including air microbiological controls, has allowed us to define a new general ventilation model, of great interest for the conservation of the subterranean environment. During the annual cycle four different ventilation regimes and two ventilation modes (UAF-mode and DAF-mode) exist which determine the significance of the anthropogenic impact within the caves. During the winter regime, the strong ventilation regime and the airflow directions from the lowest to the highest entrance (UAF-mode) contribute to the rapid elimination of anthropogenic CO 2 , and this affects the whole karstic system. During the summer regime the DAF-mode ventilation (with airflows from the highest to the lowest entrances) is activated. Although the number of visitors is maximum and the natural ventilation of the karstic system is the lowest of the annual cycle, the anthropogenic impact only affects the Tourist Galleries. The transitional ventilation regimes -spring and autumn- are the most complex of the annual cycle, with changing air-flow directions (from UAF-mode to DAF-mode and vice versa) at diurnal and poly diurnal scale, which conditions the range of the anthropogenic impact in each sector of the karst system. The activation of the DAF-mode has been observed when the temperature difference between the external and air cave is higher than 5°C. Copyright © 2018 Elsevier B.V. All rights reserved.

Combining sun-based technologies (microalgae and solar disinfection) for urban wastewater regeneration.

PubMed

Gutiérrez-Alfaro, Sergio; Rueda-Márquez, Juan J; Perales, José A; Manzano, Manuel A

2018-04-01

Solar disinfection (SODIS) of urban wastewater can be a suitable technology for improving the microbiological quality of reclaimed water as a complement to other extensive and environmentally friendly technologies such as microalgae biotreatment. The objective of this work is to evaluate the feasibility of incorporating the SODIS technology at the end of a pilot scale urban wastewater treatment plant (WWTP) where the processes are based on microalgae biotechnology and comprising three Upflow Anaerobic Sludge Blanket (UASB, 20m 3 each one) reactor, six High Rate Algal Ponds (HRAP, 32m 2 each one), and a Dissolved Air Flotation (DAF, 1m 3 ) unit. E. coli concentration was monitored at the effluent of the different units (UASB, HRAP, DAF) of the pilot WWTP. The efficiency of the SODIS process was studied for the inactivation of three of the commonly employed indicator microorganisms (Escherichia coli, Enterococcus spp. and Clostridium perfringens) using a compound parabolic collector (CPC) for five months under various conditions of irradiance and temperature. E. coli and Enterococcus spp. were more effectively disinfected by the SODIS unit (2.9 and 2.5 logarithms of reduction on average, respectively) than by the HRAP (2 and 1.1) or the DAF (0.9 and 0.1). On the contrary, the DAF technology achieved better reduction rates of C. perfringens (1.7) than the SODIS (0.9) and the HRAP (0.1). No regrowth of any microorganisms was detected during dark storage after the SODIS treatment. Incorporating a SODIS unit after the non-conventional WWTP processes substantially increases the possibilities for reuse of the treated water after receiving a cumulative UV radiation dose of 25W·h/m 2 (50min of normalized time of solar illumination). The surface requirement of the SODIS equipment would be 3.5 times smaller than the HRAP's surface. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

PubMed

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.

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

PubMed Central

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. PMID:25789174

Development of dissolved air flotation technology from the first generation to the newest (third) one (DAF in turbulent flow conditions).

PubMed

Kiuru, H J

2001-01-01

This paper gives a brief description of the development of dissolved air flotation DAF (or so-called high pressure flotation) as an unit operation for removal of solids in water and wastewater treatment during the last 80 years up to this time. The first DAF-systems used in the water industry were the ADKA and Sveen-Pedersen ones from the 1920s. Some of these are still in use. The tanks in which the flotation phenomenon takes place in these systems are very shallow and narrow as well as rather long. The flow rate of water is some 2-3 m/h (at most less than 5 m/h only) and there is a very thin micro-bubble blanket below the water surface between the dry sludge blanket on that and the clarified water which flows almost horizontally below the bubble blanket toward the end of the tanks to be taken out there from near the bottom. The second generation of DAF was introduced in the 1960s and these units are widely in use today. Their tanks are almost square ones having usually a little bit more length than breadth. They are rather deep, too. There is an under-flow wall in front of the back wall of the units having a narrow horizontal gap on the bottom of the tanks for letting out the clarified water from the flotation space. The flow rate of water is usually 5-7 m/h or at most less than 10 m/h. The direction of flow is 30-45 degrees below the horizontal. There is a rather thick micro-bubble bed at the beginning of the tank below the dry sludge blanket. This bubble-bed becomes clearly thinner, when going toward the end of the tank. There are also round DAF tanks which are based on the same hydraulic principles as the rectangular ones presented above. A special application of DAF called the flotation filter was invented at the very end of the 1960s. It is a combination of flotation and rapid sand filtration, both of those being placed in the same tank. Flotation takes place in the upper part of the tank and the filter has been placed in the lower part of it. The direction of water flow is now vertically down from the free surface of water in the tank toward the deep-bed filter. This controls the direction of flow in the flotation space of the tank above the filter bed. The flow rate of water in flotation filters may be 10-15 m/h, but the flow conditions are still laminar. It is the threat that the head-loss of filters would grow too rapidly which in practice is limiting the hydraulic flow rate of flotation filters in this area. The third generation of DAF has been developed at the end of the 1990s. The operational idea is based on that of the flotation filter. The filter bed on the bottom of the tank has been replaced by a thin stiff plate with plenty of round orifices throughout the plate. This plate, having a very much lower flowing resistance than a sand filter can have, controls the vertical flow of water in the flotation space above the plate and distributes it evenly throughout the horizontal cross-section of the tank. The flotation tank is almost square seen from above and its depth is clearly more than the length and breadth of it. This kind of flotation unit can be operated with flow rates of water in the range 25-40 m/l. Even a flow rate of more than 60 m/h has been reported from this kind of DAF-units. There is no risk of clogging of the plate by suspended solids which could limit the flow rate. This is to say that it is possible to operate DAF also in turbulent flow conditions. The depth of the micro-bubble bed below the surface of water can be 1.5-2.5 m. There actually is a continuously regenerated micro-bubble bed in the tank filtering water which is going through this bed. The lower surface of the micro-bubble bed is really a horizontal one a little bit above the plate controlling the flow in the flotation space. The clarified water below the micro-bubble bed is totally clear. It can be said that in this case the removal of suspended solids takes place much more by filtering water by a deep-bed micro-bubble filter than by attaching micro-bubbles onto solids, when both of these are mixed with each other in the inlet shaft of the flotation unit, because the retention time of water in the inlet shaft is very short indeed.

Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.

PubMed

Stoica, Sonia; Magoulas, George E; Antoniou, Antonia I; Suleiman, Sherif; Cassar, Analisse; Gatt, Lucienne; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Schembri-Wismayer, Pierre

2016-02-15

Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deployable Air Beam Fender System (DAFS): Energy Absorption Performance Analysis

DTIC Science & Technology

2007-03-30

impacts. The main energy-absorbing component of DAFS is the flexible cylindrical pressure vessel (figure 3), which is constructed of a woven, coated fabric...96Co60rfss ar Fiur 16.atca Normali"ed Volme Versusm Percen04-t DiamerlCmrsinCre o 5 2-Ft Dia 2- tFt -ia 4 ~6-ft Dia 0.75 47Il " - Ft13-4 iaa U +1.77 M...N .S.)2Is- Ol = X’Scot ,60O DLe4" e~~eoo Cnmlat~V~ aDxftcil Iffc /idaN 6-ft Die - 900 Bo 2-31S FtO ria LS135. 4- Dia60pi8fDa +oo 2:U13ý0 * X𔃼

Isolation of the endosperm-specific LPAAT gene promoter from coconut (Cocos nucifera L.) and its functional analysis in transgenic rice plants.

PubMed

Xu, Li; Ye, Rongjian; Zheng, Yusheng; Wang, Zhekui; Zhou, Peng; Lin, Yongjun; Li, Dongdong

2010-09-01

As one of the key tropical crops, coconut (Cocos nucifera L.) is a member of the monocotyledonous family Aracaceae (Palmaceae). In this study, we amplified the upstream region of an endosperm-specific expression gene, Lysophosphatidyl acyltransferase (LPAAT), from the coconut genomic DNA by chromosome walking. In this sequence, we found several types of promoter-related elements including TATA-box, CAAT-box and Skn1-motif. In order to further examine its function, three different 5'-deletion fragments were inserted into pBI101.3, a plant expression vector harboring the LPAAT upstream sequence, leading to pBI101.3-L1, pBI101.3-L2 and pBI101.3-L3, respectively. We obtained transgenic plants of rice by Agrobacterium-mediated callus transformation and plant regeneration and detected the expression of gus gene by histochemical staining and fluorometric determination. We found that gus gene driven by the three deletion fragments was specifically expressed in the endosperm of rice seeds, but not in the empty vector of pBI101.3 and other tissues. The highest expression level of GUS was at 15 DAF in pBI101.3-L3 and pBI101.3-L2 transgenic lines, while the same level was detected at 10 DAF in pBI101.3-L1. The expression driven by the whole fragment was up to 1.76- and 2.8-fold higher than those driven by the -817 bp and -453 bp upstream fragments, and 10.7-fold higher than that driven by the vector without the promoter. Taken together, our results strongly suggest that these promoter fragments from coconut have a significant potential in genetically improving endosperm in main crops.

Regulation of Isoflavone Biosynthesis by miRNAs in Two Contrasting Soybean Genotypes at Different Seed Developmental Stages.

PubMed

Gupta, Om P; Nigam, Deepti; Dahuja, Anil; Kumar, Sanjeev; Vinutha, T; Sachdev, Archana; Praveen, Shelly

2017-01-01

Owing to the presence of nutritionally important, health-promoting bioactive compounds, especially isoflavones, soybean has acquired the status of a functional food. miRNAs are tiny riboregulator of gene expression by either decreasing and/or increasing the expression of their corresponding target genes. Despite several works on identification and functional characterization of plant miRNAs, the role of miRNAs in the regulation of isoflavones metabolism is still a virgin field. In the present study, we identified a total of 31 new miRNAs along with their 245 putative target genes from soybean seed-specific ESTs using computational approach. The Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that miRNA putatively regulates metabolism and genetic information processing. Out of that, a total of 5 miRNAs ( Gma -miRNA12, Gma -miRNA24, Gma -miRNA26, Gma -miRNA28, and Gma -miRNA29) were predicted and validated for their probable role during isoflavone biosynthesis. We also validated their five target genes using RA-PCR, which is as good as 5'RLM-RACE. Temporal regulation [35 days after flowering, 45, 55, and 65 DAF] of miRNAs and their targets showed differential expression schema. Differential expression of Gma -miR26 and Gma -miRNA28 along with their corresponding target genes ( Glyma.10G197900 and Glyma.09G127200 ) showed a direct relationship with the total isoflavone content. Therefore, understanding the miRNA-based genetic regulation of isoflavone pathway would assist in selection and manipulation to get high-performing soybean genotypes with better isoflavone yield.

Prediction of dimethyl disulfide levels from biosolids using statistical modeling.

PubMed

Gabriel, Steven A; Vilalai, Sirapong; Arispe, Susanna; Kim, Hyunook; McConnell, Laura L; Torrents, Alba; Peot, Christopher; Ramirez, Mark

2005-01-01

Two statistical models were used to predict the concentration of dimethyl disulfide (DMDS) released from biosolids produced by an advanced wastewater treatment plant (WWTP) located in Washington, DC, USA. The plant concentrates sludge from primary sedimentation basins in gravity thickeners (GT) and sludge from secondary sedimentation basins in dissolved air flotation (DAF) thickeners. The thickened sludge is pumped into blending tanks and then fed into centrifuges for dewatering. The dewatered sludge is then conditioned with lime before trucking out from the plant. DMDS, along with other volatile sulfur and nitrogen-containing chemicals, is known to contribute to biosolids odors. These models identified oxidation/reduction potential (ORP) values of a GT and DAF, the amount of sludge dewatered by centrifuges, and the blend ratio between GT thickened sludge and DAF thickened sludge in blending tanks as control variables. The accuracy of the developed regression models was evaluated by checking the adjusted R2 of the regression as well as the signs of coefficients associated with each variable. In general, both models explained observed DMDS levels in sludge headspace samples. The adjusted R2 value of the regression models 1 and 2 were 0.79 and 0.77, respectively. Coefficients for each regression model also had the correct sign. Using the developed models, plant operators can adjust the controllable variables to proactively decrease this odorant. Therefore, these models are a useful tool in biosolids management at WWTPs.

Design, performance and economics of the DAF Indal 50 kW and 375 kW vertical axis wind turbine

NASA Astrophysics Data System (ADS)

Schienbein, L. A.; Malcolm, D. J.

1982-03-01

A review of the development and performance of the DAF Indal 50 kW vertical axis Darrieus wind turbines shows that a high level of technical development and reliability has been achieved. Features of the drive train, braking and control systems are discussed and performance details are presented. A description is given of a wind-diesel hybrid presently being tested. Details are also presented of a 375 kW VAWT planned for production in late 1982. A discussion of the economics of both the 50 kW and 375 kW VAWTs is included, showing the effects of charge rate, installed cost, operating cost, performance and efficiency. The energy outputs are translated into diesel fuel cost savings for remote communities.

Real-time electrochemical detection of extracellular nitric oxide in tobacco cells exposed to cryptogein, an elicitor of defence responses

PubMed Central

Besson-Bard, Angélique; Griveau, Sophie; Bedioui, Fethi; Wendehenne, David

2008-01-01

It was previously reported that cryptogein, an elicitor of defence responses, induces an intracellular production of nitric oxide (NO) in tobacco. Here, the possibility was explored that cryptogein might also trigger an increase of NO extracellular content through two distinct approaches, an indirect method using the NO probe 4,5-diaminofluorescein (DAF-2) and an electrochemical method involving a chemically modified microelectrode probing free NO in biological media. While the chemical nature of DAF-2-reactive compound(s) is still uncertain, the electrochemical modified microelectrodes provide real-time evidence that cryptogein induces an increase of extracellular NO. Direct measurement of free extracellular NO might offer important new insights into its role in plants challenged by biotic stresses. PMID:18653691

Late Noachian and early Hesperian ridge systems in the south circumpolar Dorsa Argentea Formation, Mars: Evidence for two stages of melting of an extensive late Noachian ice sheet

NASA Astrophysics Data System (ADS)

Kress, Ailish M.; Head, James W.

2015-05-01

The Dorsa Argentea Formation (DAF), extending from 270°-100° E and 70°-90° S, is a huge circumpolar deposit surrounding and underlying the Late Amazonian South Polar Layered Deposits (SPLD) of Mars. Currently mapped as Early-Late Hesperian in age, the Dorsa Argentea Formation has been interpreted as volatile-rich, possibly representing the remnants of an ancient polar ice cap. Uncertain are its age (due to the possibility of poor crater retention in ice-related deposits), its mode of origin, the origin of the distinctive sinuous ridges and cavi that characterize the unit, and its significance in the climate history of Mars. In order to assess the age of activity associated with the DAF, we examined the ridge populations within the Dorsa Argentea Formation, mapping and characterizing seven different ridge systems (composed of nearly 4,000 ridges covering a total area of ~300,000 km2, with a cumulative length of ridges of ~51,000 km) and performing crater counts on them using the method of buffered crater counting to determine crater retention ages of the ridge populations. We examined the major characteristics of the ridge systems and found that the majority of them were consistent with an origin as eskers, sediment-filled subglacial drainage channels. Ridge morphologies reflect both distributed and channelized esker systems, and evidence is also seen that some ridges form looping moraine-like termini distal to some distributed systems. The ridge populations fall into two age groups: ridge systems between 270° and 0° E date to the Early Hesperian, but to the east, the Promethei Planum and the Chasmata ridge systems date to the Late Noachian. Thus, these ages, and esker and moraine-like morphologies, support the interpretation that the DAF is a remnant ice sheet deposit, and that the esker systems represent evidence of significant melting and drainage of meltwater from portions of this ice sheet, thus indicating at least some regions and/or periods of wet-based glaciation. The Late Noachian and Early Hesperian ages of the ridge systems closely correspond to the ages of valley network/open basin lake systems, representing runoff, drainage and storage of liquid water in non-polar regions of the surface of Mars. Potential causes of such wet-based conditions in the DAF include: 1) top-down melting due to atmospheric warming, 2) enhanced snow and ice accumulation and raising of the melting isotherm to the base of the ice sheet, or 3) basal melting associated with intrusive volcanism (volcano-ice interactions). The early phase of melting is closely correlated in time with valley network formation and thus may be due to global atmospheric warming, while the later phase of melting may be linked to Early Hesperian global volcanism and specific volcano-ice interactions (table mountains) in the DAF. Crater ages indicate that these wet-based conditions ceased by the Late Hesperian, and that further retreat of the DAF to its present configuration occurred largely through sublimation, not melting, thus preserving the extensive ridge systems. MARSIS radar data suggest that significant areas of layered, potentially ice-rich parts of the Dorsa Argentea Formation remain today.

Transcriptomic analysis revealed the mechanism of oil dynamic accumulation during developing Siberian apricot (Prunus sibirica L.) seed kernels for the development of woody biodiesel.

PubMed

Niu, Jun; An, Jiyong; Wang, Libing; Fang, Chengliang; Ha, Denglong; Fu, Chengyu; Qiu, Lin; Yu, Haiyan; Zhao, Haiyan; Hou, Xinyu; Xiang, Zheng; Zhou, Sufan; Zhang, Zhixiang; Feng, Xinyi; Lin, Shanzhi

2015-01-01

Siberian apricot (Prunus sibirica L.) has emerged as a novel potential source of biodiesel in China, but the molecular regulatory mechanism of oil accumulation in Siberian apricot seed kernels (SASK) is still unknown at present. To better develop SASK oil as woody biodiesel, it is essential to profile transcriptome and to identify the full repertoire of potential unigenes involved in the formation and accumulation of oil SASK during the different developing stages. We firstly detected the temporal patterns for oil content and fatty acid (FA) compositions of SASK in 7 different developing stages. The best time for obtaining the high quality and quantity of SASK oil was characterized at 60 days after flowering (DAF), and the representative periods (10, 30, 50, 60, and 70 DAF) were selected for transcriptomic analysis. By Illumina/Solexa sequencings, approximately 65 million short reads (average length = 96 bp) were obtained, and then assembled into 124,070 unigenes by Trinity strategy (mean size = 829.62 bp). A total of 3,000, 2,781, 2,620, and 2,675 differentially expressed unigenes were identified at 30, 50, 60, and 70 DAF (10 DAF as the control) by DESeq method, respectively. The relationship between the unigene transcriptional profiles and the oil dynamic patterns in developing SASK was comparatively analyzed, and the specific unigenes encoding some known enzymes and transcription factors involved in acetyl-coenzyme A (acetyl-CoA) formation and oil accumulation were determined. Additionally, 5 key metabolic genes implicated in SASK oil accumulation were experimentally validated by quantitative real-time PCR (qRT-PCR). Our findings could help to construction of oil accumulated pathway and to elucidate the molecular regulatory mechanism of increased oil production in developing SASK. This is the first study of oil temporal patterns, transcriptome sequencings, and differential profiles in developing SASK. All our results will serve as the important foundation to further deeply explore the regulatory mechanism of SASK high-quality oil accumulation, and may also provide some reference for researching the woody biodiesel plants.

10 Steps to Building an Architecture for Space Surveillance Projects

NASA Astrophysics Data System (ADS)

Gyorko, E.; Barnhart, E.; Gans, H.

Space surveillance is an increasingly complex task, requiring the coordination of a multitude of organizations and systems, while dealing with competing capabilities, proprietary processes, differing standards, and compliance issues. In order to fully understand space surveillance operations, analysts and engineers need to analyze and break down their operations and systems using what are essentially enterprise architecture processes and techniques. These techniques can be daunting to the first- time architect. This paper provides a summary of simplified steps to analyze a space surveillance system at the enterprise level in order to determine capabilities, services, and systems. These steps form the core of an initial Model-Based Architecting process. For new systems, a well defined, or well architected, space surveillance enterprise leads to an easier transition from model-based architecture to model-based design and provides a greater likelihood that requirements are fulfilled the first time. Both new and existing systems benefit from being easier to manage, and can be sustained more easily using portfolio management techniques, based around capabilities documented in the model repository. The resulting enterprise model helps an architect avoid 1) costly, faulty portfolio decisions; 2) wasteful technology refresh efforts; 3) upgrade and transition nightmares; and 4) non-compliance with DoDAF directives. The Model-Based Architecting steps are based on a process that Harris Corporation has developed from practical experience architecting space surveillance systems and ground systems. Examples are drawn from current work on documenting space situational awareness enterprises. The process is centered on DoDAF 2 and its corresponding meta-model so that terminology is standardized and communicable across any disciplines that know DoDAF architecting, including acquisition, engineering and sustainment disciplines. Each step provides a guideline for the type of data to collect, and also the appropriate views to generate. The steps include 1) determining the context of the enterprise, including active elements and high level capabilities or goals; 2) determining the desired effects of the capabilities and mapping capabilities against the project plan; 3) determining operational performers and their inter-relationships; 4) building information and data dictionaries; 5) defining resources associated with capabilities; 6) determining the operational behavior necessary to achieve each capability; 7) analyzing existing or planned implementations to determine systems, services and software; 8) cross-referencing system behavior to operational behavioral; 9) documenting system threads and functional implementations; and 10) creating any required textual documentation from the model.

Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway

PubMed Central

Donato, Verónica; Ayala, Facundo Rodríguez; Cogliati, Sebastián; Bauman, Carlos; Costa, Juan Gabriel; Leñini, Cecilia; Grau, Roberto

2017-01-01

Beneficial bacteria have been shown to affect host longevity, but the molecular mechanisms mediating such effects remain largely unclear. Here we show that formation of Bacillus subtilis biofilms increases Caenorhabditis elegans lifespan. Biofilm-proficient B. subtilis colonizes the C. elegans gut and extends worm lifespan more than biofilm-deficient isogenic strains. Two molecules produced by B. subtilis — the quorum-sensing pentapeptide CSF and nitric oxide (NO) — are sufficient to extend C. elegans longevity. When B. subtilis is cultured under biofilm-supporting conditions, the synthesis of NO and CSF is increased in comparison with their production under planktonic growth conditions. We further show that the prolongevity effect of B. subtilis biofilms depends on the DAF-2/DAF-16/HSF-1 signalling axis and the downregulation of the insulin-like signalling (ILS) pathway. PMID:28134244

Long-Range Regulatory Polymorphisms Affecting a GABA Receptor Constitute a Quantitative Trait Locus (QTL) for Social Behavior in Caenorhabditis elegans

PubMed Central

Bendesky, Andres; Pitts, Jason; Rockman, Matthew V.; Chen, William C.; Tan, Man-Wah; Kruglyak, Leonid; Bargmann, Cornelia I.

2012-01-01

Aggregation is a social behavior that varies between and within species, providing a model to study the genetic basis of behavioral diversity. In the nematode Caenorhabditis elegans, aggregation is regulated by environmental context and by two neuromodulatory pathways, one dependent on the neuropeptide receptor NPR-1 and one dependent on the TGF-β family protein DAF-7. To gain further insight into the genetic regulation of aggregation, we characterize natural variation underlying behavioral differences between two wild-type C. elegans strains, N2 and CB4856. Using quantitative genetic techniques, including a survey of chromosome substitution strains and QTL analysis of recombinant inbred lines, we identify three new QTLs affecting aggregation in addition to the two known N2 mutations in npr-1 and glb-5. Fine-mapping with near-isogenic lines localized one QTL, accounting for 5%–8% of the behavioral variance between N2 and CB4856, 3′ to the transcript of the GABA neurotransmitter receptor gene exp-1. Quantitative complementation tests demonstrated that this QTL affects exp-1, identifying exp-1 and GABA signaling as new regulators of aggregation. exp-1 interacts genetically with the daf-7 TGF-β pathway, which integrates food availability and population density, and exp-1 mutations affect the level of daf-7 expression. Our results add to growing evidence that genetic variation affecting neurotransmitter receptor genes is a source of natural behavioral variation. PMID:23284308

Treatment of drinking water residuals: comparing sedimentation and dissolved air flotation performance with optimal cation ratios.

PubMed

Bourgeois, J C; Walsh, M E; Gagnon, G A

2004-03-01

Spent filter backwash water (SFBW) and clarifier sludge generally comprise the majority of the waste residual volume generated and in relative terms, these can be collectively referred to as combined filter backwash water (CFBW). CFBW is essentially a low-solids wastewater with metal hydroxide flocs that are typically light and slow to settle. This study evaluates the impact of adding calcium and magnesium carbonates to CFBW in terms of assessing the impacts on the sedimentation and DAF separation processes. Representative CFBW samples were collected from two surface water treatment plants (WTP): Lake Major WTP (Dartmouth, Nova Scotia, Canada) and Victoria Park WTP (Truro, Nova Scotia, Canada). Bench-scale results indicated that improvements in the CFBW settled water quality could be achieved through the addition of the divalent cations, thereby adjusting the monovalent to divalent (M:D) ratios of the wastewater. In general, the DAF process required slightly higher M:D ratios than the sedimentation process. The optimum M:D ratios for DAF and sedimentation were determined to be 1:1 and 0.33:1, respectively. It was concluded that the optimisation of the cation balance between monovalent cations (e.g., Na(+), K(+)) and added divalent cations (i.e., Ca(2+), Mg(2+)) aided in the settling mechanism through charge neutralisation-precipitation. The increase in divalent cation concentrations within the waste residual stream promoted destabilisation of the negatively charged colour molecules within the CFBW, thereby causing the colloidal content to become more hydrophobic.

Spontaneous Age-Related Neurite Branching in C. elegans

PubMed Central

Tank, Elizabeth M. H.; Rodgers, Kasey E.; Kenyon, Cynthia

2011-01-01

The analysis of morphological changes that occur in the nervous system during normal aging could provide insight into cognitive decline and neurodegenerative disease. Previous studies have suggested that the nervous system of C. elegans maintains its structural integrity with age despite the deterioration of surrounding tissues. Unexpectedly, we observed that neurons in aging animals frequently displayed ectopic branches, and that the prevalence of these branches increased with time. Within age-matched populations, the branching of mechnosensory neurons correlated with decreased response to light touch and decreased mobility. The incidence of branching was influenced by two pathways that can affect the rate of aging, the Jun kinase pathway and the insulin/IGF-1 pathway. Loss of Jun kinase signaling, which slightly shortens lifespan, dramatically increased and accelerated the frequency of neurite branching. Conversely, inhibition of the daf-2 insulin/IGF-1-like signaling pathway, which extends lifespan, delayed and suppressed branching, and this delay required DAF-16/FOXO activity. Both JNK-1 and DAF-16 appeared to act within neurons in a cell-autonomous manner to influence branching, and, through their tissue-specific expression, it was possible to disconnect the rate at which branching occurred from the overall rate of aging of the animal. Old age has generally been associated with the decline and deterioration of different tissues, except in the case of tumor cell growth. To our knowledge, this is the first indication that aging can potentiate another form of growth, the growth of neurite branches, in normal animals. PMID:21697377

ARCHITECT: The architecture-based technology evaluation and capability tradeoff method

NASA Astrophysics Data System (ADS)

Griendling, Kelly A.

The use of architectures for the design, development, and documentation of system-of-systems engineering has become a common practice in recent years. This practice became mandatory in the defense industry in 2004 when the Department of Defense Architecture Framework (DoDAF) Promulgation Memo mandated that all Department of Defense (DoD) architectures must be DoDAF compliant. Despite this mandate, there has been significant confusion and a lack of consistency in the creation and the use of the architecture products. Products are typically created as static documents used for communication and documentation purposes that are difficult to change and do not support engineering design activities and acquisition decision making. At the same time, acquisition guidance has been recently reformed to move from the bottom-up approach of the Requirements Generation System (RGS) to the top-down approach mandated by the Joint Capabilities Integration and Devel- opment System (JCIDS), which requires the use of DoDAF to support acquisition. Defense agencies have had difficulty adjusting to this new policy, and are struggling to determine how to meet new acquisition requirements. This research has developed the Architecture-based Technology Evaluation and Capability Tradeoff (ARCHITECT) Methodology to respond to these challenges and address concerns raised about the defense acquisition process, particularly the time required to implement parts of the process, the need to evaluate solutions across capability and mission areas, and the need to use a rigorous, traceable, repeatable method that utilizes modeling and simulation to better substantiate early-phase acquisition decisions. The objective is to create a capability-based systems engineering methodology for the early phases of design and acquisition (specifically Pre-Milestone A activities) which improves agility in defense acquisition by (1) streamlining the development of key elements of JCIDS and DoDAF, (2) moving the creation of DoDAF products forward in the defense acquisition process, and (3) using DoDAF products for more than documentation by integrating them into the problem definition and analysis of alternatives phases and applying executable architecting. This research proposes and demonstrates the plausibility of a prescriptive methodology for developing executable DoDAF products which will explicitly support decision-making in the early phases of JCIDS. A set of criteria by which CBAs should be judged is proposed, and the methodology is developed with these criteria in mind. The methodology integrates existing tools and techniques for systems engineering and system of systems engineering with several new modeling and simulation tools and techniques developed as part of this research to fill gaps noted in prior CBAs. A suppression of enemy air defenses (SEAD) mission is used to demonstrate the ap- plication of ARCHITECT and to show the plausibility of the approach. For the SEAD study, metrics are derived and a gap analysis is performed. The study then identifies and quantitatively compares system and operational architecture alternatives for performing SEAD. A series of down-selections is performed to identify promising architectures, and these promising solutions are subject to further analysis where the impacts of force structure and network structure are examined. While the numerical results of the SEAD study are notional and could not be applied to an actual SEAD CBA, the example served to highlight many of the salient features of the methodology. The SEAD study presented enabled pre-Milestone A tradeoffs to be performed quantitatively across a large number of architectural alternatives in a traceable and repeatable manner. The alternatives considered included variations on operations, systems, organizational responsibilities (through the assignment of systems to tasks), network (or collaboration) structure, interoperability level, and force structure. All of the information used in the study is preserved in the environment, which is dynamic and allows for on-the-fly analysis. The assumptions used were consistent, which was assured through the use of single file documenting all inputs, which was shared across all models. Furthermore, a model was made of the ARCHITECT methodology itself, and was used to demonstrate that even if the steps took twice as long to perform as they did in the case of the SEAD example, the methodology still provides the ability to conduct CBA analyses in less time than prior CBAs to date. Overall, it is shown that the ARCHITECT methodology results in an improvement over current CBAs in the criteria developed here.

Regulation of Isoflavone Biosynthesis by miRNAs in Two Contrasting Soybean Genotypes at Different Seed Developmental Stages

PubMed Central

Gupta, Om P.; Nigam, Deepti; Dahuja, Anil; Kumar, Sanjeev; Vinutha, T.; Sachdev, Archana; Praveen, Shelly

2017-01-01

Owing to the presence of nutritionally important, health-promoting bioactive compounds, especially isoflavones, soybean has acquired the status of a functional food. miRNAs are tiny riboregulator of gene expression by either decreasing and/or increasing the expression of their corresponding target genes. Despite several works on identification and functional characterization of plant miRNAs, the role of miRNAs in the regulation of isoflavones metabolism is still a virgin field. In the present study, we identified a total of 31 new miRNAs along with their 245 putative target genes from soybean seed-specific ESTs using computational approach. The Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that miRNA putatively regulates metabolism and genetic information processing. Out of that, a total of 5 miRNAs (Gma-miRNA12, Gma-miRNA24, Gma-miRNA26, Gma-miRNA28, and Gma-miRNA29) were predicted and validated for their probable role during isoflavone biosynthesis. We also validated their five target genes using RA-PCR, which is as good as 5'RLM-RACE. Temporal regulation [35 days after flowering, 45, 55, and 65 DAF] of miRNAs and their targets showed differential expression schema. Differential expression of Gma-miR26 and Gma-miRNA28 along with their corresponding target genes (Glyma.10G197900 and Glyma.09G127200) showed a direct relationship with the total isoflavone content. Therefore, understanding the miRNA-based genetic regulation of isoflavone pathway would assist in selection and manipulation to get high-performing soybean genotypes with better isoflavone yield. PMID:28450878

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

PubMed Central

Wollam, Joshua; Magner, Daniel B.; Magomedova, Lilia; Rass, Elisabeth; Shen, Yidong; Rottiers, Veerle; Habermann, Bianca; Cummins, Carolyn L.; Antebi, Adam

2012-01-01

Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span. In C. elegans, bile acid-like steroids called the dafachronic acids (DAs) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12, a homolog of mammalian sterol-regulated receptors LXR and FXR. Using metabolic genetics, mass spectrometry, and biochemical approaches, we identify new activities in DA biosynthesis and characterize an evolutionarily conserved short chain dehydrogenase, DHS-16, as a novel 3-hydroxysteroid dehydrogenase. Through regulation of DA production, DHS-16 controls DAF-12 activity governing longevity in response to signals from the gonad. Our elucidation of C. elegans bile acid biosynthetic pathways reveals the possibility of novel ligands as well as striking biochemical conservation to other animals, which could illuminate new targets for manipulating longevity in metazoans. PMID:22505847

Analysis of the signal for attachment of a glycophospholipid membrane anchor

PubMed Central

1989-01-01

The COOH terminus of decay accelerating factor (DAF) contains a signal that directs attachment of a glycophospholipid (GPI) membrane anchor. To define this signal we deleted portions of the DAF COOH terminus and expressed the mutant cDNAs it CV1 origin-deficient SV-40 cells. Our results show that the COOH-terminal hydrophobic domain (17 residues) is absolutely required for GPI anchor attachment. However, when fused to the COOH terminus of a secreted protein this hydrophobic domain is insufficient to direct attachment of a GPI anchor. Additional specific information located within the adjacent 20 residues appears to be necessary. We speculate that by analogy with signal sequences for membrane translocation, GPI anchor attachment requires both a COOH- terminal hydrophobic domain (the GPI signal) as well as a suitable cleavage/attachment site located NH2 terminal to the signal. PMID:2466848

Evaluation of flow hydrodynamics in a pilot-scale dissolved air flotation tank: a comparison between CFD and experimental measurements.

PubMed

Lakghomi, B; Lawryshyn, Y; Hofmann, R

2015-01-01

Computational fluid dynamics (CFD) models of dissolved air flotation (DAF) have shown formation of stratified flow (back and forth horizontal flow layers at the top of the separation zone) and its impact on improved DAF efficiency. However, there has been a lack of experimental validation of CFD predictions, especially in the presence of solid particles. In this work, for the first time, both two-phase (air-water) and three-phase (air-water-solid particles) CFD models were evaluated at pilot scale using measurements of residence time distribution, bubble layer position and bubble-particle contact efficiency. The pilot-scale results confirmed the accuracy of the CFD model for both two-phase and three-phase flows, but showed that the accuracy of the three-phase CFD model would partly depend on the estimation of bubble-particle attachment efficiency.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.« less

Chemosensation of Bacterial Secondary Metabolites Modulates Neuroendocrine Signaling and Behavior of C. elegans

PubMed Central

Meisel, Joshua D.; Panda, Oishika; Mahanti, Parag; Schroeder, Frank C.; Kim, Dennis H.

2014-01-01

Summary Discrimination among pathogenic and beneficial microbes is essential for host organism immunity and homeostasis. Here, we show that chemosensory detection of two secondary metabolites produced by Pseudomonas aeruginosa modulates a neuroendocrine signaling pathway that promotes avoidance behavior in the simple animal host Caenorhabditis elegans. Secondary metabolites phenazine-1-carboxamide and pyochelin activate a G protein-signaling pathway in the ASJ chemosensory neuron pair that induces expression of the neuromodulator DAF-7/TGF-β. DAF-7, in turn, activates a canonical TGF-β signaling pathway in adjacent interneurons to modulate aerotaxis behavior and promote avoidance of pathogenic P. aeruginosa. Our data provide a chemical, genetic, and neuronal basis for how the behavior and physiology of a simple animal host can be modified by the microbial environment, and suggest that secondary metabolites produced by microbes may provide environmental cues that contribute to pathogen recognition and host survival. PMID:25303524

Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

PubMed Central

Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

2016-01-01

Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabdtitis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new therapeutic strategies for addressing age-related degenerative changes. PMID:26918946

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PubMed

Buzinari, Tereza Cristina; Oishi, Jorge Camargo; De Moraes, Thiago Francisco; Vatanabe, Izabela Pereira; Selistre-de-Araújo, Heloisa Sobreiro; Pestana, Cezar Rangel; Rodrigues, Gerson Jhonatan

2017-07-15

Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O 2 •- ) was obtained by using DHE probe. Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O 2 •- in HUVEC cells. The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Copyright © 2017 Elsevier B.V. All rights reserved.

A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans

PubMed Central

Bretscher, Andrew Jonathan; Busch, Karl Emanuel; de Bono, Mario

2008-01-01

Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies. PMID:18524954

Effect of adsorbent addition on floc formation and clarification.

PubMed

Younker, Jessica M; Walsh, Margaret E

2016-07-01

Adding adsorbent into the coagulation process is an emerging treatment solution for targeting hard-to-remove dissolved organic compounds from both drinking water and industrial wastewater. The impact of adding powdered activated carbon (PAC) or organoclay (OC) adsorbents with ferric chloride (FeCl3) coagulant was investigated in terms of potential changes to the coagulated flocs formed with respect to size, structure, and breakage and regrowth properties. The ability of dissolved air flotation (DAF) and sedimentation (SED) clarification processes to remove hybrid adsorbent-coagulant flocs was also evaluated through clarified water quality analysis of samples collected in bench-scale jar test experiments. The jar tests were conducted using both a synthetic fresh water and oily wastewater test water spiked with dissolved aromatic compounds phenol and naphthalene. Results of the study demonstrated that addition of adsorbent reduced the median coagulated floc size by up to 50% but did not affect floc strength or regrowth potential after application of high shear. Experimental results in fresh water demonstrated that sedimentation was more effective than DAF for clarification of both FeCl3-PAC and FeCl3-OC floc aggregates. However, experimental tests performed on the synthetic oily wastewater showed that coagulant-adsorbent floc aggregates were effectively removed with both DAF and sedimentation treatment, with lower residual turbidity achieved in clarified water samples than with coagulation treatment alone. Addition of OC or PAC into the coagulation process resulted in removals of over half, or nearly all of the dissolved aromatics, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans.

PubMed

Bretscher, Andrew Jonathan; Busch, Karl Emanuel; de Bono, Mario

2008-06-10

Homeostasis of internal carbon dioxide (CO2) and oxygen (O2) levels is fundamental to all animals. Here we examine the CO2 response of the nematode Caenorhabditis elegans. This species inhabits rotting material, which typically has a broad CO2 concentration range. We show that well fed C. elegans avoid CO2 levels above 0.5%. Animals can respond to both absolute CO2 concentrations and changes in CO2 levels within seconds. Responses to CO2 do not reflect avoidance of acid pH but appear to define a new sensory response. Sensation of CO2 is promoted by the cGMP-gated ion channel subunits TAX-2 and TAX-4, but other pathways are also important. Robust CO2 avoidance in well fed animals requires inhibition of the DAF-16 forkhead transcription factor by the insulin-like receptor DAF-2. Starvation, which activates DAF-16, strongly suppresses CO2 avoidance. Exposure to hypoxia (<1% O2) also suppresses CO2 avoidance via activation of the hypoxia-inducible transcription factor HIF-1. The npr-1 215V allele of the naturally polymorphic neuropeptide receptor npr-1, besides inhibiting avoidance of high ambient O2 in feeding C. elegans, also promotes avoidance of high CO2. C. elegans integrates competing O2 and CO2 sensory inputs so that one response dominates. Food and allelic variation at NPR-1 regulate which response prevails. Our results suggest that multiple sensory inputs are coordinated by C. elegans to generate different coherent foraging strategies.

Agrometeorological parameters for prediction of the maturation period of Arabica coffee cultivars

NASA Astrophysics Data System (ADS)

Pezzopane, José Ricardo Macedo; Salva, Terezinha de Jesus Garcia; de Lima, Valéria Bittencourt; Fazuoli, Luiz Carlos

2012-09-01

The objective of this study was to determine the harvest period of coffee fruits based on the relationship between agrometeorological parameters and sucrose accumulation in the seeds. Over the crop years 2004/2005 and 2006/2007, from 150 days after flowering (DAF) onwards, samples of 50 fruits of cultivars Mundo Novo IAC 376-4, Obatã IAC 1669-20 and Catuaí Vermelho IAC 144 were collected from coffee trees located in Campinas, Brazil. The endosperm of the fruits was freeze-dried, ground and analyzed for sucrose content by high-performance liquid chromatography. A weather station provided data to calculate the accumulated growing degree-day (GDD) units, and the reference (ETo) and actual (ETr) evapotranspiration rates. The results showed that the highest rates of sucrose accumulation occurred at the transition from the cane-green to the cherry phenological stage. Models for the estimation of sucrose content during maturation based on meteorological variables exhibited similar or better performance than the DAF variable, with better results for the variables GDD and ETo. The Mundo Novo cultivar reached the highest sucrose level in the endosperm after 2,790 GDD, while cultivar Catuaí attained its maximum sucrose concentration after the accumulated evapotranspiration rate has reached a value of 870 mm. As for cultivar Obatã, the maximum sucrose concentration was predicted with the same degree of accuracy using any of the parameters investigated. For the Obatã cultivar, the values of the variables calculated for the maximum sucrose concentration to be reached were 249 DAF, 3,090 GDD, 1,020 ETo and 900 ETr.

Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans.

PubMed

Su, Shan; Wink, Michael

2015-09-01

Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100 μM significantly extended the mean life span of C. elegans. The strongest effect was observed with matairesinol, which at a concentration of 100 μM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1, indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

iTRAQ-Based Quantitative Proteomics Analysis of Black Rice Grain Development Reveals Metabolic Pathways Associated with Anthocyanin Biosynthesis.

PubMed

Chen, Linghua; Huang, Yining; Xu, Ming; Cheng, Zuxin; Zhang, Dasheng; Zheng, Jingui

2016-01-01

Black rice (Oryza sativa L.), whose pericarp is rich in anthocyanins (ACNs), is considered as a healthier alternative to white rice. Molecular species of ACNs in black rice have been well documented in previous studies; however, information about the metabolic mechanisms underlying ACN biosynthesis during black rice grain development is unclear. The aim of the present study was to determine changes in the metabolic pathways that are involved in the dynamic grain proteome during the development of black rice indica cultivar, (Oryza sativa L. indica var. SSP). Isobaric tags for relative and absolute quantification (iTRAQ) MS/MS were employed to identify statistically significant alterations in the grain proteome. Approximately 928 proteins were detected, of which 230 were differentially expressed throughout 5 successive developmental stages, starting from 3 to 20 days after flowering (DAF). The greatest number of differentially expressed proteins was observed on 7 and 10 DAF, including 76 proteins that were upregulated and 39 that were downregulated. The biological process analysis of gene ontology revealed that the 230 differentially expressed proteins could be sorted into 14 functional groups. Proteins in the largest group were related to metabolic process, which could be integrated into multiple biochemical pathways. Specifically, proteins with a role in ACN biosynthesis, sugar synthesis, and the regulation of gene expression were upregulated, particularly from the onset of black rice grain development and during development. In contrast, the expression of proteins related to signal transduction, redox homeostasis, photosynthesis and N-metabolism decreased during grain maturation. Finally, 8 representative genes encoding different metabolic proteins were verified via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, these genes had differed in transcriptional and translational expression during grain development. Expression analyses of metabolism-related protein groups belonging to different functional categories and subcategories indicated that significantly upregulated proteins were related to flavonoid and starch synthesis. On the other hand, the downregulated proteins were determined to be related to nitrogen metabolism, as well as other functional categories and subcategories, including photosynthesis, redox homeostasis, tocopherol biosynthetic, and signal transduction. The results provide valuable new insights into the characterization and understanding of ACN pigment production in black rice.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging.

PubMed

Cornils, Astrid; Maurya, Ashish K; Tereshko, Lauren; Kennedy, Julie; Brear, Andrea G; Prahlad, Veena; Blacque, Oliver E; Sengupta, Piali

2016-12-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

Structural and Functional Recovery of Sensory Cilia in C. elegans IFT Mutants upon Aging

PubMed Central

Kennedy, Julie; Brear, Andrea G.; Prahlad, Veena; Blacque, Oliver E.; Sengupta, Piali

2016-01-01

The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies. PMID:27906968

75 FR 76444 - Environmental Impact Statement (EIS) for Construction and Operation of a Panoramic Survey...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

..., 3550 Aberdeen Ave., SE., Kirtland AFB, NM 87117- 5776 (Phone: 505-846-4321; e-mail [email protected]kirtland.af.mil ). Bao-Anh Trinh, GS-14, DAF, Air Force Federal Register Liaison Officer. [FR Doc. 2010...

75 FR 57686 - Hazardous Waste Management System; Identification and Listing of Hazardous Waste Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... amending the exclusion for the American Steel Cord facility in Scottsburg, Indiana to reflect changes in...- calculated from the delisting health-based levels and a DAF of 68: arsenic-3.4; barium- 100; cadmium-0.34...

Human Spaceflight Architecture Model (HSFAM) Data Dictionary

NASA Technical Reports Server (NTRS)

Shishko, Robert

2016-01-01

HSFAM is a data model based on the DoDAF 2.02 data model with some for purpose extensions. These extensions are designed to permit quantitative analyses regarding stakeholder concerns about technical feasibility, configuration and interface issues, and budgetary and/or economic viability.

Integration of M&S (Modeling and Simulation), Software Design and DoDAF (Department of Defense Architecture Framework (RT 24)

DTIC Science & Technology

2012-04-09

between BPMN , SysML, and Arena ........................................... 16 Capabilities, Activities, Resources, Performers...Proof of Concept ................................................................ 22 BPMN 2.0 XML to Arena Converter...21 Figure 5: BPMN 2.0 XML StartEvent (Excerpt

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.

PubMed

Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

2012-01-01

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 μm from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity.

Transcriptome Analysis of Genes Involved in Lipid Biosynthesis in the Developing Embryo of Pecan (Carya illinoinensis).

PubMed

Huang, Ruimin; Huang, Youjun; Sun, Zhichao; Huang, Jianqin; Wang, Zhengjia

2017-05-24

Pecan (Carya illinoinensis) is an important woody tree species because of the high content of healthy oil in its nut. Thus far, the pathways and key genes related to oil biosynthesis in developing pecan seeds remain largely unclear. Our analyses revealed that mature pecan embryo accumulated more than 80% oil, in which 90% was unsaturated fatty acids with abundant oleic acid. RNA sequencing generated 84,643 unigenes in three cDNA libraries prepared from pecan embryos collected at 105, 120, and 165 days after flowering (DAF). We identified 153 unigenes associated with lipid biosynthesis, including 107 unigenes for fatty acid biosynthesis, 34 for triacylglycerol biosynthesis, 7 for oil bodies, and 5 for transcription factors involved in oil synthesis. The genes associated with fatty acid synthesis were the most abundantly expressed genes at 120 DAF. Additionally, the biosynthesis of oil began to increase while crude fat contents increased from 16.61 to 74.45% (165 DAF). We identified four SAD, two FAD2, one FAD6, two FAD7, and two FAD8 unigenes responsible for unsaturated fatty acid biosynthesis. However, FAD3 homologues were not detected. Consequently, we inferred that the linolenic acid in developing pecan embryos is generated by FAD7 and FAD8 in plastids rather than FAD3 in endoplasmic reticula. During pecan embryo development, different unigenes are expressed for plastidial and cytosolic glycolysis. Plastidial glycolysis is more relevant to lipid synthesis than cytosolic glycolysis. The 18 most important genes associated with lipid biosynthesis were evaluated in five stages of developing embryos using quantitative PCR (qPCR). The qPCR data were well consistent with their expression in transcriptomic analyses. Our data would be important for the metabolic engineering of pecans to increase oil contents and modify fatty acid composition.

Diterpenes biochemical profile and transcriptional analysis of cytochrome P450s genes in leaves, roots, flowers, and during Coffea arabica L. fruit development.

PubMed

Ivamoto, Suzana T; Sakuray, Leonardo M; Ferreira, Lucia P; Kitzberger, Cíntia S G; Scholz, Maria B S; Pot, David; Leroy, Thierry; Vieira, Luiz G E; Domingues, Douglas S; Pereira, Luiz F P

2017-02-01

Lipids are among the major chemical compounds present in coffee beans, and they affect the flavor and aroma of the coffee beverage. Coffee oil is rich in kaurene diterpene compounds, mainly cafestol (CAF) and kahweol (KAH), which are related to plant defense mechanisms and to nutraceutical and sensorial beverage characteristics. Despite their importance, the final steps of coffee diterpenes biosynthesis remain unknown. To understand the molecular basis of coffee diterpenes biosynthesis, we report the content dynamics of CAF and KAH in several Coffea arabica tissues and the transcriptional analysis of cytochrome P450 genes (P450). We measured CAF and KAH concentrations in leaves, roots, flower buds, flowers and fruit tissues at seven developmental stages (30-240 days after flowering - DAF) using HPLC. Higher CAF levels were detected in flower buds and flowers when compared to fruits. In contrast, KAH concentration increased along fruit development, peaking at 120 DAF. We did not detect CAF or KAH in leaves, and higher amounts of KAH than CAF were detected in roots. Using P450 candidate genes from a coffee EST database, we performed RT-qPCR transcriptional analysis of leaves, flowers and fruits at three developmental stages (90, 120 and 150 DAF). Three P450 genes (CaCYP76C4, CaCYP82C2 and CaCYP74A1) had transcriptional patterns similar to CAF concentration and two P450 genes (CaCYP71A25 and CaCYP701A3) have transcript accumulation similar to KAH concentration. These data warrant further investigation of these P450s as potential candidate genes involved in the final stages of the CAF and KAH biosynthetic pathways. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Mechanism of Helium-Induced Preconditioning: A Direct Role for Nitric Oxide in Rabbits

PubMed Central

Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

2008-01-01

BACKGROUND Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium–30% oxygen administered for 5 min interspersed with 5 min of an air–oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS Helium reduced (P < 0.05) infarct size (24% ± 4% of the left ventricular area at risk; mean ± sd) compared with control (46% ± 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 ± 8 vs 15 ± 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo. PMID:18713880

The Effects of Fluency Enhancing Conditions on Sensorimotor Control of Speech in Typically Fluent Speakers: An EEG Mu Rhythm Study

PubMed Central

Kittilstved, Tiffani; Reilly, Kevin J.; Harkrider, Ashley W.; Casenhiser, Devin; Thornton, David; Jenson, David E.; Hedinger, Tricia; Bowers, Andrew L.; Saltuklaroglu, Tim

2018-01-01

Objective: To determine whether changes in sensorimotor control resulting from speaking conditions that induce fluency in people who stutter (PWS) can be measured using electroencephalographic (EEG) mu rhythms in neurotypical speakers. Methods: Non-stuttering (NS) adults spoke in one control condition (solo speaking) and four experimental conditions (choral speech, delayed auditory feedback (DAF), prolonged speech and pseudostuttering). Independent component analysis (ICA) was used to identify sensorimotor μ components from EEG recordings. Time-frequency analyses measured μ-alpha (8–13 Hz) and μ-beta (15–25 Hz) event-related synchronization (ERS) and desynchronization (ERD) during each speech condition. Results: 19/24 participants contributed μ components. Relative to the control condition, the choral and DAF conditions elicited increases in μ-alpha ERD in the right hemisphere. In the pseudostuttering condition, increases in μ-beta ERD were observed in the left hemisphere. No differences were present between the prolonged speech and control conditions. Conclusions: Differences observed in the experimental conditions are thought to reflect sensorimotor control changes. Increases in right hemisphere μ-alpha ERD likely reflect increased reliance on auditory information, including auditory feedback, during the choral and DAF conditions. In the left hemisphere, increases in μ-beta ERD during pseudostuttering may have resulted from the different movement characteristics of this task compared with the solo speaking task. Relationships to findings in stuttering are discussed. Significance: Changes in sensorimotor control related feedforward and feedback control in fluency-enhancing speech manipulations can be measured using time-frequency decompositions of EEG μ rhythms in neurotypical speakers. This quiet, non-invasive, and temporally sensitive technique may be applied to learn more about normal sensorimotor control and fluency enhancement in PWS. PMID:29670516

Evaluation of the Fluids Mixing Enclosure System for Life Science Experiments During a Commercial Caenorhabditis elegans Spaceflight Experiment.

PubMed

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J

2013-06-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments.

Evaluation of the fluids mixing enclosure system for life science experiments during a commercial Caenorhabditis elegans spaceflight experiment

NASA Astrophysics Data System (ADS)

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J.

2013-06-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments.

Evaluation of the Fluids Mixing Enclosure System for Life Science Experiments During a Commercial Caenorhabditis elegans Spaceflight Experiment

PubMed Central

Warren, Paul; Golden, Andy; Hanover, John; Love, Dona; Shephard, Freya; Szewczyk, Nathaniel J.

2013-01-01

The Student Spaceflight Experiments Program (SSEP) is a United States national science, technology, engineering, and mathematics initiative that aims to increase student interest in science by offering opportunities to perform spaceflight experiments. The experiment detailed here was selected and flown aboard the third SSEP mission and the first SSEP mission to the International Space Station (ISS). Caenorhabditis elegans is a small, transparent, self-fertilizing hermaphroditic roundworm that is commonly used in biological experiments both on Earth and in Low Earth Orbit. Past experiments have found decreased expression of mRNA for several genes whose expression can be controlled by the FOXO transcription factor DAF-16. We flew a daf-16 mutant and control worms to determine if the effects of spaceflight on C. elegans are mediated by DAF-16. The experiment used a Type Two Fluids Mixing Enclosure (FME), developed by Nanoracks LLC, and was delivered to the ISS aboard the SpaceX Dragon and returned aboard the Russian Soyuz. The short time interval between experiment selection and the flight rendered preflight experiment verification tests impossible. In addition, published research regarding the viability of the FME in life science experiments was not available. The experiment was therefore structured in such a way as to gather the needed data. Here we report that C. elegans can survive relatively short storage and activation in the FME but cannot produce viable populations for post-flight analysis on extended missions. The FME appears to support short-duration life science experiments, potentially on supply or crew exchange missions, but not on longer ISS expeditions. Additionally, the flown FME was not properly activated, reportedly due to a flaw in training procedures. We suggest that a modified transparent FME could prevent similar failures in future flight experiments. PMID:23794777

Analog-Digital-Wandler

NASA Astrophysics Data System (ADS)

Döring, Peter

Analogsignale in digital codierter Form haben Vorteile (z. B. Speicherung, Übertragung). Ein Beispiel dafür ist die Musik-Film-CD/DVD. In diesem Kapitel werden entsprechende Verfahren vorgestellt. Themen: Grundlagen; Spannungs-Frequenz-Umsetzer: Sägezahn-Verfahren; Dual-Slope-Verfahren; Flash-Umsetzer; Umsetzer nach dem Wägeverfahren. Integrierte Umsetzer.

Anaerobic Treatment of Palm Oil Mill Effluent in Pilot-Scale Anaerobic EGSB Reactor

PubMed Central

Mahmood, Qaisar; Qiu, Jiang-Ping; Li, Yin-Sheng; Chang, Yoon-Seong; Li, Xu-Dong

2015-01-01

Large volumes of untreated palm oil mill effluent (POME) pose threat to aquatic environment due to the presence of very high organic content. The present investigation involved two pilot-scale anaerobic expanded granular sludge bed (EGSB) reactors, continuously operated for 1 year to treat POME. Setting HRT at 9.8 d, the anaerobic EGSB reactors reduced COD from 71179 mg/L to 12341 mg/L and recycled half of sludge by a dissolved air flotation (DAF). The average effluent COD was 3587 mg/L with the consistent COD removal efficiency of 94.89%. Adding cationic polymer (PAM) dose of 30 mg/L to DAF unit and recycling its half of sludge caused granulation of anaerobic sludge. Bacilli and small coccid bacteria were the dominant microbial species of the reactor. The reactor produced 27.65 m3 of biogas per m3 of POME which was utilized for electricity generation. PMID:26167485

Exposure to the metabolic inhibitor sodium azide induces stress protein expression and thermotolerance in the nematode Caenorhabditis elegans

PubMed Central

Massie, Michelle R.; Lapoczka, Elizabeth M.; Boggs, Kristy D.; Stine, Karen E.; White, Glenn E.

2003-01-01

Historically, sodium azide has been used to anesthetize the nematode Caenorhabditis elegans; however, the mechanism by which it survives this exposure is not understood. In this study, we report that exposure of wild-type C elegans to 10 mM sodium azide for up to 90 minutes confers thermotolerance (defined as significantly increased survival probability [SP] at 37°C) on the animal. In addition, sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed enhanced Hsp70 expression, whereas Western blot analysis revealed the induction of Hsp16. We also tested the only known C elegans Hsp mutant daf-21 (codes for Hsp90), which constitutively enters the stress-resistant state known as the dauer larvae. Daf-21 mutants also acquire sodium azide–induced thermotolerance, whereas 3 non-Hsp, constitutive dauer-forming mutants exhibited a variable response to azide exposure. We conclude that the ability of C elegans to survive exposure to azide is associated with the induction of at least 2 stress proteins. PMID:12820649

Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity.

PubMed Central

Muñoz, Manuel J; Riddle, Donald L

2003-01-01

We developed selective conditions for long-lived mutants of the nematode Caenorhabditis elegans by subjecting the first larval stage (L1) to thermal stress at 30 degrees for 7 days. The surviving larvae developed to fertile adults after the temperature was shifted to 15 degrees. A total of one million F(2) progeny and a half million F(3) progeny of ethyl-methanesulfonate-mutagenized animals were treated in three separate experiments. Among the 81 putative mutants that recovered and matured to the reproductive adult, 63 retested as thermotolerant and 49 (80%) exhibited a >15% increase in mean life span. All the known classes of dauer formation (Daf) mutant that affect longevity were found, including six new alleles of daf-2, and a unique temperature-sensitive, dauer-constitutive allele of age-1. Alleles of dyf-2 and unc-13 were isolated, and mutants of unc-18, a gene that interacts with unc-13, were also found to be long lived. Thirteen additional mutations define at least four new genes. PMID:12586705

Poultry slaughterhouse wastewater treatment plant for high quality effluent.

PubMed

Del Nery, V; Damianovic, M H Z; Moura, R B; Pozzi, E; Pires, E C; Foresti, E

2016-01-01

This paper assesses a wastewater treatment plant (WWTP) regarding the technology used, as well as organic matter and nutrient removal efficiencies aiming to optimize the treatment processes involved and wastewater reclamation. The WWTP consists of a dissolved air flotation (DAF) system, an upflow anaerobic sludge blanket (UASB) reactor, an aerated-facultative pond (AFP) and a chemical-DAF system. The removal efficiencies of chemical oxygen demand (COD) (97.9 ± 1.0%), biochemical oxygen demand (BOD) (98.6 ± 1.0%) and oil and grease (O&G) (91.1 ± 5.2%) at the WWTP, the nitrogen concentration of 17 ± 11 mg N-NH3 and phosphorus concentration of 1.34 ± 0.93 mg PO4(-3)/L in the final effluent indicate that the processes used are suitable to comply with discharge standards in water bodies. Nitrification and denitrification tests conducted using biomass collected at three AFP points indicated that nitrification and denitrification could take place in the pond.

Differentiation-dependent expression of hypothetical proteins in the neuroblastoma cell line N1E-115.

PubMed

Oh, Ji-eun; Karlmark, Karlin Raja; Shin, Jooho; Hengstschläger, Markus; Lubec, Gert

2006-05-15

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND. (c) 2006 Wiley-Liss, Inc.

Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect

PubMed Central

Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul Ariel; De Giusti, Verónica Celeste; Aiello, Ernesto Alejandro; Hare, Joshua Michael; Vila Petroff, Martin

2014-01-01

Aims Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor l-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either l-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. PMID:25344365

Signal Processing in Cold Atom Interferometry-Based INS

DTIC Science & Technology

2014-03-27

INTERFEROMETRY-BASED INS Kara M. Willis, BS Civilian, DAF Approved: //signed// Meir Pachter, PhD (Chairman) //signed// Maj Marshall Haker , PhD (Member) //signed...matter mentors, Maj Marshall Haker and Dr Kyle Kauffman, for their insights and unwavering encouragement. Kara M. Willis v Table of Contents Page

Integrated Strategic Planning and Analysis Network Increment 4 (ISPAN Inc 4)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...Inc 4 will achieve FDD completion criteria when: 1) the system meets all the KPP thresholds as verified through an Initial Operational Test and

Integrated Strategic Planning and Analysis Network Increment 5 (ISPAN Inc 5)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision...achieve FDD in August 2018. ISPAN Inc 5 is envisioned as a follow-on to ISPAN Inc 4 in order to respond to USSTRATCOM requirements for improved

KiloPower Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClure, Patrick Ray

2016-08-04

These are the slides for a phone interview with Aerospace America magazine of the AIAA. It goes over the KiloPower Program at Los Alamos National Laboratory (LANL), and covers the following: 1 kWe Kilopower, 10 kWe Kilopower, Kilopower Reactor Using Stirling Technology (KRUSTY) Integration Test (DAF), Reactor Configuration, and Platen Positions.

Net-centric ACT-R-Based Cognitive Architecture with DEVS Unified Process

DTIC Science & Technology

2011-04-01

effort has been spent in analyzing various forms of requirement specifications, viz, state-based, Natural Language based, UML-based, Rule- based, BPMN ...requirement specifications in one of the chosen formats such as BPMN , DoDAF, Natural Language Processing (NLP) based, UML- based, DSL or simply

The xenoantibody response and immunoglobulin gene expression profile of cynomolgus monkeys transplanted with hDAF-transgenic porcine hearts.

PubMed

Zahorsky-Reeves, Joanne L; Kearns-Jonker, Mary K; Lam, Tuan T; Jackson, Jeremy R; Morris, Randall E; Starnes, Vaughn A; Cramer, Donald V

2007-03-01

Recent work has indicated a role for anti-Gal alpha 1-3Gal (Gal) and anti-non-Gal xenoantibodies in the primate humoral rejection response against human-decay accelerating factor (hDAF) transgenic pig organs. Our laboratory has shown that anti-porcine xenograft antibodies in humans and non-human primates are encoded by a small number of germline IgV(H) progenitors. In this study, we extended our analysis to identify the IgV(H) genes encoding xenoantibodies in immunosuppressed cynomolgus monkeys (Macaca fascicularis) transplanted with hDAF-transgenic pig organs. Three immunosuppressed monkeys underwent heterotopic heart transplantation with hDAF porcine heart xenografts. Two of three animals were given GAS914, a poly-L-lysine derivative shown to bind to anti-Gal xenoantibodies and neutralize them. One animal rejected its heart at post-operative day (POD) 39; a second animal rejected the transplanted heart at POD 78. The third monkey was euthanized on POD 36 but the heart was not rejected. Peripheral blood leukocytes (PBL) and serum were obtained from each animal before and at multiple time points after transplantation. We analyzed the immune response by enzyme-linked immunosorbent assay (ELISA) to confirm whether anti-Gal or anti-non-Gal xenoantibodies were induced after graft placement. Immunoglobulin heavy-chain gene (V(H)) cDNA libraries were then produced and screened. We generated soluble single-chain antibodies (scFv) to establish the binding specificity of the cloned immunoglobulin genes. Despite immunosuppression, which included the use of the polymer GAS914, the two animals that rejected their hearts showed elevated levels of cytotoxic anti-pig red blood cell (RBC) antibodies and anti-pig aortic endothelial cell (PAEC) antibodies. The monkey that did not reject its graft showed a decline in serum anti-RBC, anti-PAEC, and anti-Gal xenoantibodies when compared with pre-transplant levels. A V(H)3 family gene with a high level of sequence similarity to an allele of V(H)3-11, designated V(H)3-11(cyno), was expressed at elevated levels in the monkey that was not given GAS914 and whose graft was not rejected until POD 78. IgM but not IgG xenoantibodies directed at N-acetyl lactosamine (a precursor of the Gal epitope) were also induced in this animal. We produced soluble scFv from this new gene to determine whether this antibody could bind to the Gal carbohydrate, and demonstrated that this protein was capable of blocking the binding of human serum xenoantibody to Gal oligosaccharide, as had previously been shown with human V(H)3-11 scFv. DAF-transgenic organs transplanted into cynomolgus monkeys induce anti-Gal and anti-non-Gal xenoantibody responses mediated by both IgM and IgG xenoantibodies. Anti-non-Gal xenoantibodies are induced at high levels in animals treated with GAS914. Antibodies that bind to the Gal carbohydrate and to N-acetyl lactosamine are induced in the absence of GAS914 treatment. The animal whose heart remained beating for 78 days demonstrated increased usage of an antibody encoded by a germline progenitor that is structurally related, but distinct from IGHV311. This antibody binds to the Gal carbohydrate but does not induce the rapid rejection of the xenograft when expressed at high levels as early as day 8 post-transplantation.

Two Membrane-Associated Tyrosine Phosphatase Homologs Potentiate C. elegans AKT-1/PKB Signaling

PubMed Central

Hu, Patrick J; Xu, Jinling; Ruvkun, Gary

2006-01-01

Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues. PMID:16839187

iTRAQ-Based Quantitative Proteomics Analysis of Black Rice Grain Development Reveals Metabolic Pathways Associated with Anthocyanin Biosynthesis

PubMed Central

Chen, Linghua; Huang, Yining; Xu, Ming; Cheng, Zuxin; Zhang, Dasheng; Zheng, Jingui

2016-01-01

Background Black rice (Oryza sativa L.), whose pericarp is rich in anthocyanins (ACNs), is considered as a healthier alternative to white rice. Molecular species of ACNs in black rice have been well documented in previous studies; however, information about the metabolic mechanisms underlying ACN biosynthesis during black rice grain development is unclear. Results The aim of the present study was to determine changes in the metabolic pathways that are involved in the dynamic grain proteome during the development of black rice indica cultivar, (Oryza sativa L. indica var. SSP). Isobaric tags for relative and absolute quantification (iTRAQ) MS/MS were employed to identify statistically significant alterations in the grain proteome. Approximately 928 proteins were detected, of which 230 were differentially expressed throughout 5 successive developmental stages, starting from 3 to 20 days after flowering (DAF). The greatest number of differentially expressed proteins was observed on 7 and 10 DAF, including 76 proteins that were upregulated and 39 that were downregulated. The biological process analysis of gene ontology revealed that the 230 differentially expressed proteins could be sorted into 14 functional groups. Proteins in the largest group were related to metabolic process, which could be integrated into multiple biochemical pathways. Specifically, proteins with a role in ACN biosynthesis, sugar synthesis, and the regulation of gene expression were upregulated, particularly from the onset of black rice grain development and during development. In contrast, the expression of proteins related to signal transduction, redox homeostasis, photosynthesis and N-metabolism decreased during grain maturation. Finally, 8 representative genes encoding different metabolic proteins were verified via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, these genes had differed in transcriptional and translational expression during grain development. Conclusions Expression analyses of metabolism-related protein groups belonging to different functional categories and subcategories indicated that significantly upregulated proteins were related to flavonoid and starch synthesis. On the other hand, the downregulated proteins were determined to be related to nitrogen metabolism, as well as other functional categories and subcategories, including photosynthesis, redox homeostasis, tocopherol biosynthetic, and signal transduction. The results provide valuable new insights into the characterization and understanding of ACN pigment production in black rice. PMID:27415428

Towards Greater Individualization and Process-Oriented Learning through Electronic Self-Access: Project "e-daf"

ERIC Educational Resources Information Center

Chan, Wai Meng; Kim, Dong-Ha

2004-01-01

Research in cognitive psychology and second language learning has underlined the significance of learners' cognitive processes and individual preferences in language learning. Helping learners to be aware of these processes and preferences has in fact become an important methodological principle of language teaching. Advances in information and…

Consolidated Afloat Networks and Enterprise Services (CANES)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Deployment Decision Jun 2015 Oct 2015 Full Deployment1 Sep 2024 Sep 2023 Memo 1/ Per the FDD ADM approved by USD(AT&L) on October 13, 2015, the FD date was

Deliberate and Crisis Action Planning and Execution Segments Increment 2A (DCAPES Inc 2A)

DTIC Science & Technology

2016-03-01

Document DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full...Jun 2009 DT/OT Completion Jan 2015 Jan 2015 FDD Aug 2015 Oct 2015 FD TBD Oct 2015 Memo DCAPES is a National Security System. Acronyms and

Historical Lessons of Air Force Communications

DTIC Science & Technology

2010-12-01

AU/ACSC/ CUSTINE /AY10 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY HISTORICAL LESSONS OF AIR FORCE COMMUNICATIONS...by Jay D. Custine , Civ, DAF A Research Report Submitted to the Faculty In Partial Fulfillment of the Graduation...Requirements Advisor: Lt Col Paul E. Griffith Maxwell Air Force Base, Alabama December 2010 AU/ACSC/ CUSTINE /AY10 ii

The Role of Nanobubbles in the Precipitation and Recovery of Organic-Phosphine-Containing Beneficiation Wastewater.

PubMed

Xiao, Wei; Ke, Shuo; Quan, Nannan; Zhou, Limin; Wang, Jun; Zhang, Lijuan; Dong, Yaming; Qin, Wenqing; Qiu, Guanzhou; Hu, Jun

2018-05-29

Dissolved air flotation (DAF) is broadly applied in wastewater treatment, especially for the recovery of organic pollution with low concentration. However, the mechanism of interaction between nanoscale gas bubbles and nanoparticles in the process of DAF remains unclear. Here, we investigated the role of nanobubbles in the precipitation of styryl phosphoric acid (SPA)-Pb particles and recovering organic phosphine containined in beneficiation wastewater by UV-vis (ultraviolet-visible) spectra, microflotation tests, nanoparticle tracking analysis, dynamic light scattering, and atomic force microscopy measurements. As suggested from the results, nanobubbles can inhibit the crystallization of SPA-Pb precipitation, which makes the sediment flotation recovery below 20%. After the precipitation crystallization is completed, nanobubbles can flocculate precipitated particles, which can promote the flotation recovery of precipitated particles to 90%. On the basis of the results, we proposed a model to explain the different roles of nanobubbles in the process of precipitation and flotation of SPA-Pb particles. This study will be helpful to understand the interaction between nanobubbles and nanoparticles in the application of flotation.

Risk Assessment Update: Russian Segment

NASA Technical Reports Server (NTRS)

Christiansen, Eric; Lear, Dana; Hyde, James; Bjorkman, Michael; Hoffman, Kevin

2012-01-01

BUMPER-II version 1.95j source code was provided to RSC-E- and Khrunichev at January 2012 MMOD TIM in Moscow. MEMCxP and ORDEM 3.0 environments implemented as external data files. NASA provided a sample ORDEM 3.0 g."key" & "daf" environment file set for demonstration and benchmarking BUMPER -II v1.95j installation at the Jan-12 TIM. ORDEM 3.0 has been completed and is currently in beta testing. NASA will provide a preliminary set of ORDEM 3.0 ".key" & ".daf" environment files for the years 2012 through 2028. Bumper output files produced using the new ORDEM 3.0 data files are intended for internal use only, not for requirements verification. Output files will contain these words ORDEM FILE DESCRIPTION = PRELIMINARY VERSION: not for production. The projectile density term in many BUMPER-II ballistic limit equations will need to be updated. Cube demo scripts and output files delivered at the Jan-12 TIM have been updated for the new ORDEM 3.0 data files. Risk assessment results based on ORDEM 3.0 and MEM will be presented for the Russian Segment (RS) of ISS.

Criticality Safety Evaluation for the TACS at DAF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Percher, C. M.; Heinrichs, D. P.

2011-06-10

Hands-on experimental training in the physical behavior of multiplying systems is one of ten key areas of training required for practitioners to become qualified in the discipline of criticality safety as identified in DOE-STD-1135-99, Guidance for Nuclear Criticality Safety Engineer Training and Qualification. This document is a criticality safety evaluation of the training activities and operations associated with HS-3201-P, Nuclear Criticality 4-Day Training Course (Practical). This course was designed to also address the training needs of nuclear criticality safety professionals under the auspices of the NNSA Nuclear Criticality Safety Program1. The hands-on, or laboratory, portion of the course will utilizemore » the Training Assembly for Criticality Safety (TACS) and will be conducted in the Device Assembly Facility (DAF) at the Nevada Nuclear Security Site (NNSS). The training activities will be conducted by Lawrence Livermore National Laboratory following the requirements of an Integrated Work Sheet (IWS) and associated Safety Plan. Students will be allowed to handle the fissile material under the supervision of an LLNL Certified Fissile Material Handler.« less

Role of superoxide–nitric oxide interactions in the accelerated age-related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase

PubMed Central

Sakellariou, Giorgos K; Pye, Deborah; Vasilaki, Aphrodite; Zibrik, Lea; Palomero, Jesus; Kabayo, Tabitha; McArdle, Francis; Van Remmen, Holly; Richardson, Arlan; Tidball, James G; McArdle, Anne; Jackson, Malcolm J

2011-01-01

Summary Mice lacking Cu,Zn superoxide dismutase (SOD1) show accelerated, age-related loss of muscle mass. Lack of SOD1 may lead to increased superoxide, reduced nitric oxide (NO), and increased peroxynitrite, each of which could initiate muscle fiber loss. Single muscle fibers from flexor digitorum brevis of wild-type (WT) and Sod1−/− mice were loaded with NO-sensitive (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, DAF-FM) and superoxide-sensitive (dihydroethidium, DHE) probes. Gastrocnemius muscles were analyzed for SOD enzymes, nitric oxide synthases (NOS), and 3-nitrotyrosine (3-NT) content. A lack of SOD1 did not increase superoxide availability at rest because no increase in ethidium or 2-hydroxyethidium (2-HE) formation from DHE was seen in fibers from Sod1−/− mice compared with those from WT mice. Fibers from Sod1−/− mice had decreased NO availability (decreased DAF-FM fluorescence), increased 3-NT in muscle proteins indicating increased peroxynitrite formation and increased content of peroxiredoxin V (a peroxynitrite reductase), compared with WT mice. Muscle fibers from Sod1−/− mice showed substantially reduced generation of superoxide in response to contractions compared with fibers from WT mice. Inhibition of NOS did not affect DHE oxidation in fibers from WT or Sod1−/− mice at rest or during contractions, but transgenic mice overexpressing nNOS showed increased DAF-FM fluorescence and reduced DHE oxidation in resting muscle fibers. It is concluded that formation of peroxynitrite in muscle fibers is a major effect of lack of SOD1 in Sod1−/− mice and may contribute to fiber loss in this model, and that NO regulates superoxide availability and peroxynitrite formation in muscle. PMID:21443684

The Impact of Body Mass Index on Heterotopic Ossification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourad, Waleed Fouad, E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2012-04-01

Purpose: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). Methods and Materials: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT {+-} indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT {+-} indomethacinmore » in preventing HO in patients with different BMI. Results: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0 Multiplication-Sign (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). Conclusions: Despite similar surgical treatment and prophylactic measures (RT {+-} indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.« less

RNA-Sequencing Reveals Biological Networks during Table Grapevine (‘Fujiminori’) Fruit Development

PubMed Central

Shangguan, Lingfei; Mu, Qian; Fang, Xiang; Zhang, Kekun; Jia, Haifeng; Li, Xiaoying; Bao, Yiqun; Fang, Jinggui

2017-01-01

Grapevine berry development is a complex and genetically controlled process, with many morphological, biochemical and physiological changes occurring during the maturation process. Research carried out on grapevine berry development has been mainly concerned with wine grape, while barely focusing on table grape. ‘Fujiminori’ is an important table grapevine cultivar, which is cultivated in most provinces of China. In order to uncover the dynamic networks involved in anthocyanin biosynthesis, cell wall development, lipid metabolism and starch-sugar metabolism in ‘Fujiminori’ fruit, we employed RNA-sequencing (RNA-seq) and analyzed the whole transcriptome of grape berry during development at the expanding period (40 days after full bloom, 40DAF), véraison period (65DAF), and mature period (90DAF). The sequencing depth in each sample was greater than 12×, and the expression level of nearly half of the expressed genes were greater than 1. Moreover, greater than 64% of the clean reads were aligned to the Vitis vinifera reference genome, and 5,620, 3,381, and 5,196 differentially expressed genes (DEGs) were identified between different fruit stages, respectively. Results of the analysis of DEGs showed that the most significant changes in various processes occurred from the expanding stage to the véraison stage. The expression patterns of F3’H and F3’5’H were crucial in determining red or blue color of the fruit skin. The dynamic networks of cell wall development, lipid metabolism and starch-sugar metabolism were also constructed. A total of 4,934 SSR loci were also identified from 4,337 grapevine genes, which may be helpful for the development of phylogenetic analysis in grapevine and other fruit trees. Our work provides the foundation for developmental research of grapevine fruit as well as other non-climacteric fruits. PMID:28118385

Performance evaluation of a granular activated carbon-sequencing batch biofilm reactor pilot plant system used in treating real wastewater from recycled paper industry.

PubMed

Muhamad, Mohd Hafizuddin; Sheikh Abdullah, Siti Rozaimah; Mohamad, Abu Bakar; Rahman, Rakmi Abdul; Kadhum, Abdul Amir Hasan

2012-01-01

A pilot scale granular activated carbon-sequencing batch biofilm reactor with a capacity of 2.2 m3 was operated for over three months to evaluate its performance treating real recycled paper industry wastewater under different operational conditions. In this study, dissolved air floatation (DAF) and clarifier effluents were used as influent sources of the pilot plant. During the course of the study, the reactor was able to biodegrade the contaminants in the incoming recycled paper mill wastewater in terms of chemical oxygen demand (COD), adsorbable organic halides (AOX; specifically 2,4-dichlorophenol (2,4-DCP)) and ammoniacal nitrogen (NH3-N) removal efficiencies at varying hydraulic retention times (HRTs) of 1-3 days, aeration rates (ARs) of 2.1-3.4 m3/min and influent feed concentration of 40-950 mg COD/l. Percentages of COD, 2,4-DCP and NH3-N removals increased with increasing HRT, resulting in more than 90% COD, 2,4-DCP and NH3-N removals at HRT values above two days. Degradation of COD, 2,4-DCP and NH3-N were seriously affected by variation of ARs, which resulted in significant decrease of COD, 2,4-DCP and NH3-N removals by decreasing ARs from 3.4 m3/min to 2.1 m3/min, varying in the ranges of 24-80%, 6-96% and 5-42%, respectively. In comparison to the clarifier effluent, the treatment performance of DAF effluent, containing high COD concentration, resulted in a higher COD removal of 82%. The use of diluted DAF effluent did not improve significantly the COD removal. Higher NH3-N removal efficiency of almost 100% was observed during operation after maintenance shutdown compared to normal operation, even at the same HRT of one day due to the higher dissolved oxygen concentrations (1-7 mg/l), while no significant difference in COD removal efficiency was observed.

Application of flow cytometry with a fluorescent dye to measurement of intracellular nitric oxide in plant cells.

PubMed

Kępczyński, Jan; Cembrowska-Lech, Danuta

2018-04-27

A simple and rapid method involving flow cytometry and NO-specific probe (DAF-FM DA) proved useful for detection and determination of intracellular NO production in Medicago truncatula suspension cells and leaves as well as in cells of Avena fatua, Amaranthus retroflexus embryos and leaves. The measurement of nitric oxide (NO) in plant material is important for examining the regulatory roles of endogenous NO in various physiological processes. The possibility of detecting and determining intracellular NO production by flow cytometry (FCM) with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA), an NO-specific probe in Medicago truncatula cells in suspension and leaves as well as in cells of embryos and leaves of Avena fatua L. or Amaranthus retroflexus L. was explored. To detect and measure NO production by cell suspension or embryos and leaves, the recommended DAF-FM DA concentration is 5 or 10 µM, respectively, applied for 30 min. Exogenous NO increased the intensity of the fluorescent signal in embryos and leaves of both plants, while carboxy-PTIO (cPTIO), an NO scavenger, decreased it. Thus, these results demonstrate that NO can be detected and an increase and a decrease of its intracellular level can be estimated. Wounding was observed to increase the fluorescence signal, indicating an increase in the intracellular NO level. In addition, the levels of exogenous and endogenous ascorbic acid were demonstrated to have no effect on the NO-related fluorescence signal, indicating the signal's specificity only in relation with NO. The applicability of the proposed method for detection and determination of NO was confirmed (1) by in situ NO imaging in cell suspensions and (2) by determining the NO concentration in embryos and leaves using the Griess reagent. In view of the data obtained, FCM is recommended as a rapid and simple method with which to detect and determine intracellular NO production in plant cells.

Comparing the drawings of children with attention deficit hyperactivity disorder with normal children.

PubMed

Haghighi, Mahnaz; Khaterizadeh, Maedeh; Chalbianloo, Gholamreza; Toobaei, Sholeh; Ghanizadeh, Ahmad

2014-10-01

Attention deficit hyperactivity disorder (ADHD) is the most common behavioral problem during childhood and in school-aged children. Various projection drawings have been designed for assessing children's personality and psychological disorders including the tests of draw a person (DAP) and draw a family (DAF). We aimed to compare the differences between typically developing children and children with ADHD using these tests. In this case-control study, all the 9-10 year-old boy students studying at the third and fourth grades were enrolled from schools in the 2nd educational district of Shiraz, south of Iran. Eighty students were then selected and enrolled into the ADHD group and the control group. The Diagnostic and Statistical Manual of Mental Disorders, 4th edition- text Revised (DSM-IV-TR), and the Child Symptoms Inventory were used to diagnose the children with ADHD. We evaluated and analyzed impulsiveness, non-impulsiveness, emotional problems and incompatibility indices in the DAP and DAF tests in each group. A significant difference was found in the indices of incompatibility and emotional problems, impulsiveness, non-impulsiveness and DAF between typically developing children and those with ADHD. The mean (±SD) total scores of the above mentioned indices in the ADHD group were 19.79(±2.94), 12.31(±1.84), 5.26(±2.29) and 5.89(±2.13), respectively (P<0.001). The corresponding figures for these indices in the normal group were 12.11(±4.74), 5.63(±2), 10.36± (2.33) and 2.88(±2.13), respectively (P<0.001). Significant differences were obtained between the control group and children with ADHD using these two drawing tests. The rate of impulsivity and emotional problems indices in drawings of children with ADHD was markedly more common than those of the typically developing children. This suggests the need for further assessment to screen ADHD.

Pig kidney transplantation in baboons: anti-Gal(alpha)1-3Gal IgM alone is associated with acute humoral xenograft rejection and disseminated intravascular coagulation.

PubMed

Bühler, L; Yamada, K; Kitamura, H; Alwayn, I P; Basker, M; Appel, J Z; Colvin, R B; White-Scharf, M E; Sachs, D H; Robson, S C; Awwad, M; Cooper, D K

2001-12-15

Kidneys harvested from miniature swine or pigs transgenic for human decay-accelerating factor (hDAF) were transplanted into baboons receiving an anti-CD154 monoclonal antibody (mAb) and either a whole body irradiation (WBI)- or cyclophosphamide (CPP)-based immunosuppressive regimen. Group 1 baboons (n=3) underwent induction therapy with WBI and thymic irradiation, pretransplantation antithymocyte globulin, and immunoadsorption of anti-Gal(alpha)1-3Gal (Gal) antibody (Ab). After transplantation of a miniature swine kidney, maintenance therapy comprised cobra venom factor, mycophenolate mofetil, and an anti-CD154 mAb (for 14-28 days). In group 2 (n=2), WBI was replaced by CPP in the induction protocol. Group 3 (n=3) animals received the group 2 regimen, but underwent transplantation with hDAF pig kidneys. Group 1 and 2 animals developed features of disseminated intravascular coagulation (DIC), with reductions of fibrinogen and platelets and increases of prothrombin time, partial thromboplastin time, and fibrin split products. Graft survival was for 6-13 days. Histology showed mild acute humoral xenograft rejection (AHXR) of the kidneys, but severe rejection of the ureters. Group 3 animals developed features of DIC in two of three cases during the fourth week, with AHXR in the third case. Graft survival was for 28 (n=1) or 29 (n=2) days. Histology of day 15 biopsy specimens showed minimal focal mononuclear cellular infiltrates, with predominantly CD3+ cells. By days 28 and 29, kidneys showed mild-to-moderate features of AHXR. In all groups, the humoral response was manifest by reappearance of anti-Gal IgM below baseline level, with no or low return of anti-Gal IgG. All excised kidneys showed IgM deposition, but no complement and no or minimal IgG deposition. No baboon showed a rebound of anti-Gal Ab immediately after excision of the graft, and anti-Gal Ab increased over pretransplantation levels only when anti-CD154 mAb was discontinued. DIC was observed with WBI- or CPP-based therapy, and after miniature swine or hDAF kidney transplantation. AHXR+/-DIC was observed in all recipients even in the absence of complement and no or low levels of anti-Gal IgG, but was significantly delayed in the hDAF recipients. These results confirm our earlier observation that CD154 blockade prevents T cell-dependent sensitization in baboons to pig antigens, but that baseline natural anti-Gal Ab production is not inhibited. We suggest that IgM deposition, even in the absence of IgG and complement, leads to endothelial cell activation with the development of DIC, even when there are only minimal histologic changes of AHXR.

Performation Metrics Development Analysis for Information and Communications Technology Outsourcing: A Case Study

ERIC Educational Resources Information Center

Travis, James L., III

2014-01-01

This study investigated how and to what extent the development and use of the OV-5a operational architecture decomposition tree (OADT) from the Department of Defense (DoD) Architecture Framework (DoDAF) affects requirements analysis with respect to complete performance metrics for performance-based services acquisition of ICT under rigid…

An Experimental Investigation of the Effect of Altered Auditory Feedback on the Conversational Speech of Adults Who Stutter

ERIC Educational Resources Information Center

Lincoln, Michelle; Packman, Ann; Onslow, Mark; Jones, Mark

2010-01-01

Purpose: To investigate the impact on percentage of syllables stuttered of various durations of delayed auditory feedback (DAF), levels of frequency-altered feedback (FAF), and masking auditory feedback (MAF) during conversational speech. Method: Eleven adults who stuttered produced 10-min conversational speech samples during a control condition…

Development and Psychometric Evaluation of the Index of Dental Anxiety and Fear (IDAF-4C[superscript +])

ERIC Educational Resources Information Center

Armfield, Jason M.

2010-01-01

The measurement of dental fear is important due to its high prevalence and appreciable individual, clinical, and public health consequences. However, existing measures of dental anxiety and fear (DAF) have theoretical or practical limitations. This study describes the development and subsequent assessment of the reliability and validity of test…

Integrated Personnel and Pay System-Army Increment 1 (IPPS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...2013 Feb 2014 Increment I FDD Apr 2013 Apr 2014 Full Deployment1 Jan 2015 Jul 2015 Memo Per 10 U.S.C. Chapter 144A, the MS C Decision exceeded the

Global Combat Support System - Joint Increment 8 (GCSS-J Inc 8)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal...Estimate (Or Actual) Milestone B1 Mar 2014 Mar 2014 Milestone C1 Mar 2014 Mar 2014 Increment 8 FDD Dec 2018 Dec 2018 Increment 8 FD TBD TBD Memo 1

The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation

PubMed Central

Mayer, Melanie G.; Rödelsperger, Christian; Witte, Hanh; Riebesell, Metta; Sommer, Ralf J.

2015-01-01

Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains´ pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as major target for dauer regulation. We discuss the consequences of the novel vs. fast-evolving nature of orphans for the evolution of developmental networks and their role in natural variation and intraspecific competition. PMID:26087034

Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity.

PubMed

Ewald, Collin Y; Landis, Jess N; Porter Abate, Jess; Murphy, Coleen T; Blackwell, T Keith

2015-03-05

Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit.

The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation.

PubMed

Mayer, Melanie G; Rödelsperger, Christian; Witte, Hanh; Riebesell, Metta; Sommer, Ralf J

2015-06-01

Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains' pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as major target for dauer regulation. We discuss the consequences of the novel vs. fast-evolving nature of orphans for the evolution of developmental networks and their role in natural variation and intraspecific competition.

Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity.

PubMed

Panossian, Alexander; Wikman, Georg

2009-09-01

The aim of this review article is to assess the level of scientific evidence presented by clinical trials of adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong scientific evidence is available for Rhodiola rosea SHR-5 extract, which improved attention, cognitive function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus increased endurance and mental performance in patients with mild fatigue and weakness. Based on their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal preparations that increase tolerance to mental exhaustion and enhance attention and mental endurance in situations of decreased performance. The beneficial stress-protective effect of adaptogens is related to regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key mediators of stress response such as molecular chaperons (e.g. Hsp70), stress-activated c-Jun N-terminal protein kinase (JNK1), Forkhead Box O transcription factor DAF-16, cortisol and nitric oxide (NO). The key point of action of phytoadaptogens appears to be their up-regulating and stress-mimetic effects on the "stress-sensor" protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress-induced increase in NO, and the associated decrease in ATP production, results in increased performance and endurance. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical performance and, possibly, increased longevity.

Genome-Wide Analysis of Germline Signaling Genes Regulating Longevity and Innate Immunity in the Nematode Pristionchus pacificus

PubMed Central

Sommer, Ralf J.

2012-01-01

Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and longevity. This is the first study to show that the influence of the reproductive system on extending lifespan and innate immunity is conserved in evolution. PMID:22912581

Identification and functional analysis of endogenous nitric oxide in a filamentous fungus.

PubMed

Pengkit, Anchalee; Jeon, Seong Sil; Son, Soo Ji; Shin, Jae Ho; Baik, Ku Yeon; Choi, Eun Ha; Park, Gyungsoon

2016-07-18

In spite of its prevalence in animals and plants, endogenous nitric oxide (NO) has been rarely reported in fungi. We present here our observations on production of intracellular NO and its possible roles during development of Neurospora crassa, a model filamentous fungus. Intracellular NO was detected in hypha 8-16 hours after incubation in Vogel's minimal liquid media and conidiophores during conidiation using a fluorescent indicator (DAF-FM diacetate). Treatment with cPTIO, an NO scavenger, significantly reduced fluorescence levels and hindered hyphal growth in liquid media and conidiation, whereas exogenous NO enhanced hyphal extension on VM agar media and conidia formation. NO scavenging also dramatically diminished transcription of con-10 and con-13, genes preferentially expressed during conidiation. Our results suggest that intracellular NO is generated in young hypha growing in submerged culture and during conidia development and regulate mycelial development and conidia formation.

Identification and functional analysis of endogenous nitric oxide in a filamentous fungus

PubMed Central

Pengkit, Anchalee; Jeon, Seong Sil; Son, Soo Ji; Shin, Jae Ho; Baik, Ku Yeon; Choi, Eun Ha; Park, Gyungsoon

2016-01-01

In spite of its prevalence in animals and plants, endogenous nitric oxide (NO) has been rarely reported in fungi. We present here our observations on production of intracellular NO and its possible roles during development of Neurospora crassa, a model filamentous fungus. Intracellular NO was detected in hypha 8–16 hours after incubation in Vogel’s minimal liquid media and conidiophores during conidiation using a fluorescent indicator (DAF-FM diacetate). Treatment with cPTIO, an NO scavenger, significantly reduced fluorescence levels and hindered hyphal growth in liquid media and conidiation, whereas exogenous NO enhanced hyphal extension on VM agar media and conidia formation. NO scavenging also dramatically diminished transcription of con-10 and con-13, genes preferentially expressed during conidiation. Our results suggest that intracellular NO is generated in young hypha growing in submerged culture and during conidia development and regulate mycelial development and conidia formation. PMID:27425220

Açaí (Euterpe oleracea Mart.) Modulates Oxidative Stress Resistance in Caenorhabditis elegans by Direct and Indirect Mechanisms

PubMed Central

Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J.; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; de Paula Oliveira, Riva

2014-01-01

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. PMID:24594796

Açaí (Euterpe oleracea Mart.) modulates oxidative stress resistance in Caenorhabditis elegans by direct and indirect mechanisms.

PubMed

Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Oliveira, Riva de Paula

2014-01-01

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms.

Global Combat Support System-Marine Corps Logistics Chain Management Increment 1 (GCSS-MC LCM Inc 1)

DTIC Science & Technology

2016-03-01

Production Document DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD ...Jul 2004 Milestone B Jun 2007 Jun 2007 Milestone C May 2010 May 2010 FDD Sep 2014 Mar 2015 FD Dec 2015 Dec 2015 GCSS-MC LCM Inc 1 2016 MAR

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

PubMed

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Polishing Step Purification of High-Strength Wastewaters by Nanofiltration and Reverse Osmosis

PubMed Central

Zhou, Jinxiang; Baker, Brian O.; Grimsley, Charles T.; Husson, Scott M.

2016-01-01

This article reports findings on the use of nanofiltration (NF) and reverse osmosis (RO) for secondary treatment of high-strength rendering facility wastewaters following an ultrafiltration step. These wastewaters present significant challenges to classical treatment technologies. Constant-pressure, direct-flow membrane filtration experiments were done to screen for flux and effluent water permeate quality of ten commercial NF and RO membranes. All membranes tested were effective in reducing total dissolved salts (TDS) and chemical oxygen demand (COD); however, only two membranes (Koch MPF-34 and Toray 70UB) gave sufficiently stable flux values to warrant longer term cross-flow filtration studies. Cross-flow flux measurements, scanning electron microscopy (SEM), X-ray dispersive spectroscopy (EDS), and attenuated total reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR) indicated that both membranes were eventually fouled by organic and inorganic foulants; however, the Toray 70UB RO membrane yielded a capacity of 1600 L/m2 prior to cleaning. A preliminary economic analysis compared the estimated costs of energy and consumables for a dual-stage UF/RO membrane process and dissolved air floatation (DAF) and found membrane process costs could be less than about 40% of the current DAF process. PMID:26978407

Homologous species restriction of the complement-mediated killing of nucleated cells.

PubMed Central

Yamamoto, H; Blaas, P; Nicholson-Weller, A; Hänsch, G M

1990-01-01

The homologous restriction of complement (C) lysis is attributed to membrane proteins: decay-accelerating factor (DAF), C8 binding protein (C8bp) and P18/CD59. Since these proteins are also expressed on peripheral blood cells, species restriction was tested for in the complement-mediated killing of antibody-coated human leucocytes by human or rabbit complement. Killing was more efficient when rabbit complement was used. Preincubation of cells with an antibody to DAF abolished the difference. When C1-7 sites were first attached to the cells and either rabbit or human C8, C9 were added, the killing of monocytes and lymphocytes was equally efficient; only in polymorphonuclear neutrophils was a higher efficiency of rabbit C8, C9 seen. Thus, in contrast to haemolysis, restriction occurred predominantly at the C3 level and the action of the terminal complement components was not inhibited. Since C8bp isolated from peripheral blood cells showed essentially similar characteristics as the erythrocyte-derived C8bp, the failure of C8bp to inhibit the action of the terminal components on nucleated cells might reflect differences of the complement membrane interactions between erythrocytes or nucleated cells, respectively. Images Figure 5 PMID:1697561

A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans.

PubMed

Khanna, Amit; Kumar, Jitendra; Vargas, Misha A; Barrett, LaKisha; Katewa, Subhash; Li, Patrick; McCloskey, Tom; Sharma, Amit; Naudé, Nicole; Nelson, Christopher; Brem, Rachel; Killilea, David W; Mooney, Sean D; Gill, Matthew; Kapahi, Pankaj

2016-12-13

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.

Characterisation of agroindustrial solid residues as biofuels and potential application in thermochemical processes.

PubMed

Virmond, Elaine; De Sena, Rennio F; Albrecht, Waldir; Althoff, Christine A; Moreira, Regina F P M; José, Humberto J

2012-10-01

In the present work, selected agroindustrial solid residues from Brazil - biosolids from meat processing wastewater treatment and mixture of sawdust with these biosolids; residues from apple and orange juice industries; sugarcane bagasse; açaí kernels (Euterpe oleracea) and rice husk - were characterised as solid fuels and an evaluation of their properties, including proximate and ultimate composition, energy content, thermal behaviour, composition and fusibility of the ashes was performed. The lower heating value of the biomasses ranged from 14.31 MJkg(-1) to 29.14 MJkg(-1), on a dry and ash free basis (daf), all presenting high volatile matter content, varying between 70.57 wt.% and 85.36 wt.% (daf) what improves the thermochemical conversion of the solids. The fouling and slagging tendency of the ashes was predicted based on the fuel ash composition and on the ash fusibility correlations proposed in the literature, which is important to the project and operation of biomass conversion systems. The potential for application of the Brazilian agroindustrial solid residues studied as alternative energy sources in thermochemical processes has been identified, especially concerning direct combustion for steam generation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fructan:fructan 1-fructosyltransferase and inulin hydrolase activities relating to inulin and soluble sugars in Jerusalem artichoke (Helianthus tuberosus Linn.) tubers during storage.

PubMed

Maicaurkaew, Sukanya; Jogloy, Sanun; Hamaker, Bruce R; Ningsanond, Suwayd

2017-03-01

Influences of harvest time and storage conditions on activities of fructan:fructan1-fructosyltransferase (1-FFT) and inulin hydrolase (InH) in relation to inulin and soluble sugars of Jerusalem artichoke ( Helianthus tuberosus L.) tubers were investigated. Maturity affected 1-FFT-activity, inulin contents, and inulin profiles of the tubers harvested between 30 and 70 days after flowering (DAF). Decreases in 1-FFT activity, high molecular weight inulin, and inulin content were observed in late-harvested tubers. The tubers harvested at 50 DAF had the highest inulin content (734.9 ± 20.5 g kg -1 DW) with a high degree of polymerization (28% of DP >30). During storage of the tubers, increases in InH activity (reached its peak at 15 days of storage) and gradual decreases in 1-FFT activity took placed. These changes were associated with inulin depolymerization, causing decreases in inulin content and increases in soluble sugars. As well, decreasing storage temperatures would retain high inulin content and keep low soluble sugars; and freezing at -18 °C would best retard 1-FFT, InH, and inulin changes.

Using lipidomics to reveal details of lipid accumulation in developing seeds from oilseed rape (Brassica napus L.).

PubMed

Woodfield, Helen K; Cazenave-Gassiot, Amaury; Haslam, Richard P; Guschina, Irina A; Wenk, Markus R; Harwood, John L

2018-03-01

With dwindling available agricultural land, concurrent with increased demand for oil, there is much current interest in raising oil crop productivity. We have been addressing this issue by studying the regulation of oil accumulation in oilseed rape (Brassica napus L). As part of this research we have carried out a detailed lipidomic analysis of developing seeds. The molecular species distribution in individual lipid classes revealed quite distinct patterns and showed where metabolic connections were important. As the seeds developed, the molecular species distributions changed, especially in the period of early (20days after flowering, DAF) to mid phase (27DAF) of oil accumulation. The patterns of molecular species of diacylglycerol, phosphatidylcholine and acyl-CoAs were used to predict the possible relative contributions of diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase to triacylglycerol production. Our calculations suggest that DGAT may hold a more important role in influencing the molecular composition of TAG. Enzyme selectivity had an important influence on the final molecular species patterns. Our data contribute significantly to our understanding of lipid accumulation in the world's third most important oil crop. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of C. elegans

PubMed Central

Ratnappan, Ramesh; Amrit, Francis R. G.; Chen, Shaw-Wen; Gill, Hasreet; Holden, Kyle; Ward, Jordan; Yamamoto, Keith R.; Olsen, Carissa P.; Ghazi, Arjumand

2014-01-01

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity. PMID:25474470

A Patch Density Recommendation based on Convergence Studies for Vehicle Panel Vibration Response resulting from Excitation by a Diffuse Acoustic Field

NASA Technical Reports Server (NTRS)

Smith, Andrew; LaVerde, Bruce; Jones, Douglas; Towner, Robert; Hunt, Ron

2013-01-01

Fluid structural interaction problems that estimate panel vibration from an applied pressure field excitation are quite dependent on the spatial correlation of the pressure field. There is a danger of either over estimating a low frequency response or under predicting broad band panel response in the more modally dense bands if the pressure field spatial correlation is not accounted for adequately. Even when the analyst elects to use a fitted function for the spatial correlation an error may be introduced if the choice of patch density is not fine enough to represent the more continuous spatial correlation function throughout the intended frequency range of interest. Both qualitative and quantitative illustrations evaluating the adequacy of different patch density assumptions to approximate the fitted spatial correlation function are provided. The actual response of a typical vehicle panel system is then evaluated in a convergence study where the patch density assumptions are varied over the same finite element model. The convergence study results are presented illustrating the impact resulting from a poor choice of patch density. The fitted correlation function used in this study represents a Diffuse Acoustic Field (DAF) excitation of the panel to produce vibration response.

Hydrogen Sulfide Regulates Ca2+ Homeostasis Mediated by Concomitantly Produced Nitric Oxide via a Novel Synergistic Pathway in Exocrine Pancreas

PubMed Central

Moustafa, Amira

2014-01-01

Abstract Aim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca2+ homeostasis in rat pancreatic acini. Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The NaHS-induced [Ca2+]i elevation persisted with an EC50 of 73.3 μM in the absence of extracellular Ca2+ but was abolished by thapsigargin, indicating that both Ca2+ entry and Ca2+ release contributed to the increase. The [Ca2+]i increase was markedly inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein-2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an EC50 of 64.8 μM, indicating that NO was involved in the H2S effect. The H2S-induced [Ca2+]i increase was inhibited by pretreatment with U73122, xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A, indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein play roles as intermediate components in the H2S-triggered intracellular signaling. Innovation: To our knowledge, our study is the first one highlighting the effect of H2S on intracellular Ca2+ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H2S and NO. Conclusion: We conclude that H2S affects [Ca2+]i homeostasis that is mediated by H2S-evoked NO production via an endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate-PKG-Gq-protein-PLC-IP3 pathway to induce Ca2+ release, and this pathway is identical to the one we recently proposed for a sole effect of NO and the two gaseous molecules synergistically function to regulate Ca2+ homeostasis. Antioxid. Redox Signal. 20, 747–758. PMID:24138560

Measuring the iron spectral opacity in solar conditions using a double ablation front scheme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colaitis, A.; Ducret, J. E.; Turck-Chieze, S

We propose a new method to achieve hydrodynamic conditions relevant for the investigation of the radiation transport properties of the plasma at the base of the solar convection zone. The method is designed in the framework of opacity measurements with high-power lasers and exploits the temporal and spatial stability of hydrodynamic parameters in counter-propagating Double Ablation Front (DAF) structures.

Evaluation of Inventory Reduction Strategies: Balad Air Base Case Study

DTIC Science & Technology

2012-03-01

produced by conducting individual simulations using a unique random seed generated by the default Anylogic © random number generator. The...develops an agent-based simulation model of the sustainment supply chain supporting Balad AB during its closure using the software AnyLogic ®. The...research. The goal of USAF Stockage Policy is to maximize customer support while minimizing inventory costs (DAF, 2011:1). USAF stocking decisions

90-Day Inhalation Toxicity Study of Bio-Derived Gevo Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) in Rats with Neurotoxicity Testing and Genotoxicity Assay

DTIC Science & Technology

2015-05-31

body weights, food consumption , and reproductive indices (vaginal cytology, sperm cell parameters). Neurobehavioral effects , evaluated by motor...Human Performance Wing Human Effectiveness Directorate Bioeffects Division Molecular Bioeffects Branch Wright-Patterson AFB OH 45433-5707...IV, DAF Chief, Bioeffects Division Human Effectiveness Directorate 711 th Human Perfmmance Wing Air Force Research Laboratmy This repmi is

Public Key Infrastructure Increment 2 (PKI Inc 2)

DTIC Science & Technology

2016-03-01

DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...experienced due to a delay in achieving the FDD . The Critical Change Report was provided to Congress on July 11, 2014. Firm, Fixed-Price Feasibility...to a delay in achieving the FDD . To support the Critical Change Report, the NSA Cost Estimating organization prepared a cost estimate that was

Teleport Generation 3 (Teleport Gen 3)

DTIC Science & Technology

2016-03-01

Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA - Information...144A) reported since the previous MAIS Annual Report to Congress. The program recently achieved a FDD from the MDA on February 13, 2015. Teleport Gen 3...February 13, 2015 granting approval of the FDD . Acronyms and Abbreviations MLGC - MUOS to Legacy UHF SATCOM Gateway Component MOT&E - Multiservice

Base Information Transport Infrastructure Wired (BITI Wired)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Estimate has been accomplished this period leading to an approved Air Force Service Cost Position in support of the program’s December 2014 FDD milestone...validated to ensure alignment with the business case. This certification is based on my review of the December 2014 Service Cost Position and FDD

Leucine Modulation of the mTOR Pathway for Cognition Modulation: Kinetic and In Vitro Studies and Model Development

DTIC Science & Technology

2015-09-30

isoleucine non-polar L1 131 Aromatic side chain phenylalanine non-polar L1 165 tyrosine polar L1 181 tryptophan slightly...Human Performance Wing Human Effectiveness Directorate Bioeffects Division Molecular Bioeffects Branch Wright-Patterson AFB OH 45433-5707 NOTICE...IV, DAF Chief, Bioeffects Division Human Effectiveness Directorate 711th Human Performance Wing Air Force Research Laboratory This report is

Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans.

PubMed

Wan, Qin-Li; Shi, Xiaohuo; Liu, Jiangxin; Ding, Ai-Jun; Pu, Yuan-Zhu; Li, Zhigang; Wu, Gui-Sheng; Luo, Huai-Rong

2017-02-06

In Caenorhabditis elegans (C. elegans) , ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans . Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans .

Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans

PubMed Central

Wan, Qin-Li; Shi, Xiaohuo; Liu, Jiangxin; Ding, Ai-Jun; Pu, Yuan-Zhu; Li, Zhigang; Wu, Gui-Sheng; Luo, Huai-Rong

2017-01-01

In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-less glp-1 mutants, we discovered that glp-1 mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome of daf-16;glp-1 double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals in C. elegans PMID:28177875

Synthesis of nitric oxide in human osteoblasts in response to physiologic stimulation of electrotherapy.

PubMed

Hamed, Ayman; Kim, Paul; Cho, Michael

2006-12-01

Electrotherapy for bone healing, remodeling and wound healing may be mediated by modulation of nitric oxide (NO). Using NO-specific fluorophore (DAF-2), we report here that application of non-invasive, physiologic electrical stimulation induces NO synthesis in human osteoblasts, and that such NO generation is comparable to that induced by estrogen treatment. For example, application of a sinusoidal 1 Hz, 2 V/cm (peak to peak) electrical stimulation (ES) increases NO-bound DAF-2 fluorescence intensity by a 2-fold within 60 min exposure by activating nitric oxide synthase (NOS). Increase in the NO level is found to depend critically on the frequency and strength of ES. While the frequency of 1 Hz ES seems optimal, the ES strength >0.5 V/cm is required to induce significant NO increase, however. Nitric oxide synthesis in response to ES is completely prevented by blocking estrogen receptors using a competitive inhibitor, suggesting that NO generation is likely initiated by activation of estrogen receptors at the cell surface. Based on these findings, physiologic stimulation of electrotherapy appears to represent a potential non-invasive, non-genomic, and novel physical technique that could be used to regulate NO-mediated bone density and facilitate bone remodeling without adverse effects associated with hormone therapy.

Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7

PubMed Central

Yunger, Elad; Safra, Modi; Levi-Ferber, Mor; Haviv-Chesner, Anat

2017-01-01

In C. elegans, removal of the germline triggers molecular events in the neighboring intestine, which sends an anti-aging signal to the rest of the animal. In this study, we identified an innate immunity related gene, named irg-7, as a novel mediator of longevity in germlineless animals. We consider irg-7 to be an integral downstream component of the germline longevity pathway because its expression increases upon germ cell removal and its depletion interferes with the activation of the longevity-promoting transcription factors DAF-16 and DAF-12 in germlineless animals. Furthermore, irg-7 activation by itself sensitizes the animals' innate immune response and extends the lifespan of animals exposed to live bacteria. This lifespan-extending pathogen resistance relies on the somatic gonad as well as on many genes previously associated with the reproductive longevity pathway. This suggests that these genes are also relevant in animals with an intact gonad, and can affect their resistance to pathogens. Altogether, this study demonstrates the tight association between germline homeostasis and the immune response of animals, and raises the possibility that the reproductive system can act as a signaling center to divert resources towards defending against putative pathogen attacks. PMID:28196094

On Using SysML, DoDAF 2.0 and UPDM to Model the Architecture for the NOAA's Joint Polar Satellite System (JPSS) Ground System (GS)

NASA Technical Reports Server (NTRS)

Hayden, Jeffrey L.; Jeffries, Alan

2012-01-01

The JPSS Ground System is a lIexible system of systems responsible for telemetry, tracking & command (TT &C), data acquisition, routing and data processing services for a varied lIeet of satellites to support weather prediction, modeling and climate modeling. To assist in this engineering effort, architecture modeling tools are being employed to translate the former NPOESS baseline to the new JPSS baseline, The paper will focus on the methodology for the system engineering process and the use of these architecture modeling tools within that process, The Department of Defense Architecture Framework version 2,0 (DoDAF 2.0) viewpoints and views that are being used to describe the JPSS GS architecture are discussed. The Unified Profile for DoOAF and MODAF (UPDM) and Systems Modeling Language (SysML), as ' provided by extensions to the MagicDraw UML modeling tool, are used to develop the diagrams and tables that make up the architecture model. The model development process and structure are discussed, examples are shown, and details of handling the complexities of a large System of Systems (SoS), such as the JPSS GS, with an equally complex modeling tool, are described

Accumulation of Phosphorus-Containing Compounds in Developing Seeds of Low-Phytate Pea (Pisum sativum L.) Mutants

PubMed Central

Shunmugam, Arun S.K.; Bock, Cheryl; Arganosa, Gene C.; Georges, Fawzy; Gray, Gordon R.; Warkentin, Thomas D.

2014-01-01

Low phytic acid (lpa) crops are low in phytic acid and high in inorganic phosphorus (Pi). In this study, two lpa pea genotypes, 1-150-81, 1-2347-144, and their progenitor CDC Bronco were grown in field trials for two years. The lpa genotypes were lower in IP6 and higher in Pi when compared to CDC Bronco. The total P concentration was similar in lpa genotypes and CDC Bronco throughout the seed development. The action of myo-inositol phosphate synthase (MIPS) (EC 5.5.1.4) is the first and rate-limiting step in the phytic acid biosynthesis pathway. Aiming at understanding the genetic basis of the lpa mutation in the pea, a 1530 bp open reading frame of MIPS was amplified from CDC Bronco and the lpa genotypes. Sequencing results showed no difference in coding sequence in MIPS between CDC Bronco and lpa genotypes. Transcription levels of MIPS were relatively lower at 49 days after flowering (DAF) than at 14 DAF for CDC Bronco and lpa lines. This study elucidated the rate and accumulation of phosphorus compounds in lpa genotypes. The data also demonstrated that mutation in MIPS was not responsible for the lpa trait in these pea lines. PMID:27135314

Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans

PubMed Central

Berber, Slavica; Wood, Mallory; Llamosas, Estelle; Thaivalappil, Priya; Lee, Karen; Liao, Bing Mana; Chew, Yee Lian; Rhodes, Aaron; Yucel, Duygu; Crossley, Merlin; Nicholas, Hannah R

2016-01-01

Proteins of the Homeodomain-Interacting Protein Kinase (HIPK) family regulate an array of processes in mammalian systems, such as the DNA damage response, cellular proliferation and apoptosis. The nematode Caenorhabditis elegans has a single HIPK homologue called HPK-1. Previous studies have implicated HPK-1 in longevity control and suggested that this protein may be regulated in a stress-dependent manner. Here we set out to expand these observations by investigating the role of HPK-1 in longevity and in the response to heat and oxidative stress. We find that levels of HPK-1 are regulated by heat stress, and that HPK-1 contributes to survival following heat or oxidative stress. Additionally, we show that HPK-1 is required for normal longevity, with loss of HPK-1 function leading to a faster decline of physiological processes that reflect premature ageing. Through microarray analysis, we have found that HPK-1-regulated genes include those encoding proteins that serve important functions in stress responses such as Phase I and Phase II detoxification enzymes. Consistent with a role in longevity assurance, HPK-1 also regulates the expression of age-regulated genes. Lastly, we show that HPK-1 functions in the same pathway as DAF-16 to regulate longevity and reveal a new role for HPK-1 in development. PMID:26791749

Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans.

PubMed

Berber, Slavica; Wood, Mallory; Llamosas, Estelle; Thaivalappil, Priya; Lee, Karen; Liao, Bing Mana; Chew, Yee Lian; Rhodes, Aaron; Yucel, Duygu; Crossley, Merlin; Nicholas, Hannah R

2016-01-21

Proteins of the Homeodomain-Interacting Protein Kinase (HIPK) family regulate an array of processes in mammalian systems, such as the DNA damage response, cellular proliferation and apoptosis. The nematode Caenorhabditis elegans has a single HIPK homologue called HPK-1. Previous studies have implicated HPK-1 in longevity control and suggested that this protein may be regulated in a stress-dependent manner. Here we set out to expand these observations by investigating the role of HPK-1 in longevity and in the response to heat and oxidative stress. We find that levels of HPK-1 are regulated by heat stress, and that HPK-1 contributes to survival following heat or oxidative stress. Additionally, we show that HPK-1 is required for normal longevity, with loss of HPK-1 function leading to a faster decline of physiological processes that reflect premature ageing. Through microarray analysis, we have found that HPK-1-regulated genes include those encoding proteins that serve important functions in stress responses such as Phase I and Phase II detoxification enzymes. Consistent with a role in longevity assurance, HPK-1 also regulates the expression of age-regulated genes. Lastly, we show that HPK-1 functions in the same pathway as DAF-16 to regulate longevity and reveal a new role for HPK-1 in development.

Realgar bioleaching solution suppress ras excessive activation by increasing ROS in Caenorhabditis elegans.

PubMed

Zhi, De Juan; Feng, Na; Liu, Dong Ling; Hou, Rong Li; Wang, Mei Zu; Ding, Xiao Xia; Li, Hong Yu

2014-03-01

Although realgar bioleaching solution (RBS) has been proved to be a potential candidate for cancer therapy, the mechanisms of RBS anticancer are still far from being completely understood. Dosed with RBS in C. elegans, the multivulva phenotype resulting from oncogenic ras gain-of-function was inhibited in a dose dependent manner. It could be abrogated by concurrent treatment C. elegans with RBS and the radical scavenger DMSO. However, RBS could not induce DAF-16 nuclear translocation in TJ356 or the increase of HSP 16.2 expression in CL2070, which both could be aroused visible GFP fluorescent variation to represent for oxidative stress generation. Treatment C. elegans with superoxide anion generator paraquat, similar results were also obtained. Our results indicated that RBS suppress excessive activated ras by increasing reactive oxygen species (ROS) in C. elegans. Secondly, ROS induced by RBS significantly accumulated on a higher level in C. elegans with a mutational ras than that with wild ras, thus leading to oxidative stress on ras gain-of-function background rather than on normal ras context. Our results firstly demonstrated that using C. elegans as a model organism for evaluating prooxidant drug candidates for cancer therapy.

Bacteria-Phagocyte Interactions: Emerging Tactics in an Ancient Rivalry

DTIC Science & Technology

1990-01-01

afhitan. mechanisms by which microbes cvade the deposi- Mimicry of decay -accelerating factor aExample. T ’ruzi tion of immunogiobulin and complement on...their , Possible Isis of decay accelerating factor on host cell, surfaces have been well-studied (Table 2). For Example. Bacterial phospholipase example...activators of protein that mimics the action of decay accelerat- the alternate complement pathway 1171. ing factor (DAF) [261. This protein is part of a

U.S. Army Workshop on Exploring Enterprise, System of Systems, System, and Software Architectures

DTIC Science & Technology

2009-03-01

state of a net-centric intelligence /surveillance/reconnaissance (ISR) capability featuring DCGS by the middle of the next decade.5 In some situations...boundaries. The DoDAF has a relatively long history. It started as a Command, Control, Communications, Computers, Surveillance and Intelligence ...Army have needed to perform tasks such as: col- lect and analyze intelligence information; maneuver the force; target and provide fire support; conduct

Theater Medical Information Program Joint Increment 2 (TMIP J Inc 2)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...the Full Deployment Decision ( FDD ), the TMIP-J Increment 2 Economic Analysis was approved on December 6, 2013. The USD(AT&L) signed an Acquisition...Decision Memorandum (ADM) on December 23, 2013 approving FDD for TMIP-J Increment 2 and establishing the Full Deployment Objective and Threshold dates as

Logistics Modernization Program Increment 2 (LMP Inc 2)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Documentation within the LMP Increment 2 MS C ADM, the LMP Increment 2 Business Case was updated for the FDD using change pages to remove information...following approval of the Army Cost Position being developed for the FDD . The LMP Increment 2 Business Case Change Pages were approved and signed by the

Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

DTIC Science & Technology

2010-04-09

Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

DEVS Unified Process for Web-Centric Development and Testing of System of Systems

DTIC Science & Technology

2008-05-20

gathering from the user. Further, methodologies have been developed to generate DEVS models from BPMN /BPEL-based and message-based requirement specifications...27] 3. BPMN /BPEL based system specifications: Business Process Modeling Notation ( BPMN ) [bpm] or Business Process Execution Language (BPEL) provide a...information is stored in .wsdl and .bpel files for BPEL but in proprietary format for BPMN . 4. DoDAF-based requirement specifications: Department of

Tailored Systems Architecture for Design of Space Science and Technology Missions Using DoDAF V2.0

DTIC Science & Technology

2009-12-01

programs do exist. Given the focus on rapid development and transition, if a system architecture framework could be developed and used to increase ...and scope are still being developed and refined at all levels within the DoD. As organizations have attempted to develop system architectures that...to produce architecture descriptions during the early-stages of system development. (3 p. 19) conformance, organizations ultimately using the

Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty.

PubMed Central

Glenn, Charles F.; Chow, David K.; Gami, Minaxi S.; Iser, Wendy B.; Hanselman, Keaton B.; Wolkow, Catherine A.; David, Lawrence; Goldberg, Ilya G.; Cooke, Carol A.

2005-01-01

Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits upon behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well-maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration did not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments. PMID:15699524

Modeling Operations Costs for Human Exploration Architectures

NASA Technical Reports Server (NTRS)

Shishko, Robert

2013-01-01

Operations and support (O&S) costs for human spaceflight have not received the same attention in the cost estimating community as have development costs. This is unfortunate as O&S costs typically comprise a majority of life-cycle costs (LCC) in such programs as the International Space Station (ISS) and the now-cancelled Constellation Program. Recognizing this, the Constellation Program and NASA HQs supported the development of an O&S cost model specifically for human spaceflight. This model, known as the Exploration Architectures Operations Cost Model (ExAOCM), provided the operations cost estimates for a variety of alternative human missions to the moon, Mars, and Near-Earth Objects (NEOs) in architectural studies. ExAOCM is philosophically based on the DoD Architecture Framework (DoDAF) concepts of operational nodes, systems, operational functions, and milestones. This paper presents some of the historical background surrounding the development of the model, and discusses the underlying structure, its unusual user interface, and lastly, previous examples of its use in the aforementioned architectural studies.

Increased NO bioavailability in aging male rats by genistein and exercise training: using 4, 5-diaminofluorescein diacetate.

PubMed

Eksakulkla, Sukanya; Suksom, Daroonwan; Siriviriyakul, Prasong; Patumraj, Suthiluk

2009-09-07

Several kinds of anti-oxidants have drawn a lot of intention for their benefits on vascular protection. In addition, it has been demonstrated that exercise training could improve endothelial function by up-regulating endothelial nitric oxide synthase (eNOS) protein. Therefore, the present study aims to investigate the effects of genistein, a potent phyto-antioxidant, and exercise training on age-induced endothelial dysfunction in relation to NO bioavailability using in situ NO-sensitive fluorescent dye detection. Male Wistar rats (20-22-month old) were divided into four groups: aged rats treated with corn oil, (Aged+Veh, n = 5), aged rats treated with genistein (Aged+Gen, n = 5, (0.25 mg/kg BW/day, s.c.)), aged rats with and without exercise training (Aged+Ex, n = 5, swimming 40 min/day, 5 days/week for 8 weeks) (Aged+Without-Ex, n = 5). Cremaster arterioles (15-35 micrometer) were visualized by fluorescein isothiocyanate labeled dextran (5 microgram/ml). The vascular response to acetylcholine (Ach; 10(-5)M, 5 ml/5 min) was accessed after 1-min norepinephrine preconstriction (10 micro molar). To determine NO bioavailability, the Krebs-Ringer buffer with 4, 5-diaminofluorescein-diacetate (3 micro molar DAF-2DA), and 10 micro- molar Ach saturated with 95%N2 and 5%CO2 were used. Changes of DAF-2T-intensities along the cremaster arterioles were analyzed by the Image Pro-Plus Software (Media Cybernatics, Inc, USA). Liver malondialdehyde (MDA) level was measured by thiobarbituric acid reaction and used as an indicator for oxidative stress. The results showed that means arterial blood pressure for both Aged+Gen and Aged+Ex groups were significantly reduced when compared to the Aged groups, Aged+Veh and Aged+Without-Ex (P < 0.05). Among the treated groups, Ach-induced vasodilatation were significantly increased (P < 0.05) and was associated with increased NO-associated fluorescent intensities (P < 0.05). On the other hand, MDA levels were significantly reduced (P < 0.05) when Aged+Veh was compared to Aged+Without-Ex. These findings showed that genistein and exercise training could improve age-induced endothelial dysfunction and is related to the increased NO bioavailability.

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

PubMed

Honda, Yoko; Fujita, Yasunori; Maruyama, Hiroe; Araki, Yoko; Ichihara, Kenji; Sato, Akira; Kojima, Toshio; Tanaka, Masashi; Nozawa, Yoshinori; Ito, Masafumi; Honda, Shuji

2011-01-01

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 interventions in the aging process.

Positive Feedback between Transcriptional and Kinase Suppression in Nematodes with Extraordinary Longevity and Stress Resistance

PubMed Central

Bharill, Puneet; Shmookler Reis, Robert J.

2009-01-01

Insulin/IGF-1 signaling (IIS) regulates development and metabolism, and modulates aging, of Caenorhabditis elegans. In nematodes, as in mammals, IIS is understood to operate through a kinase-phosphorylation cascade that inactivates the DAF-16/FOXO transcription factor. Situated at the center of this pathway, phosphatidylinositol 3-kinase (PI3K) phosphorylates PIP2 to form PIP3, a phospholipid required for membrane tethering and activation of many signaling molecules. Nonsense mutants of age-1, the nematode gene encoding the class-I catalytic subunit of PI3K, produce only a truncated protein lacking the kinase domain, and yet confer 10-fold greater longevity on second-generation (F2) homozygotes, and comparable gains in stress resistance. Their F1 parents, like weaker age-1 mutants, are far less robust—implying that maternally contributed trace amounts of PI3K activity or of PIP3 block the extreme age-1 phenotypes. We find that F2-mutant adults have <10% of wild-type kinase activity in vitro and <60% of normal phosphoprotein levels in vivo. Inactivation of PI3K not only disrupts PIP3-dependent kinase signaling, but surprisingly also attenuates transcripts of numerous IIS components, even upstream of PI3K, and those of signaling molecules that cross-talk with IIS. The age-1(mg44) nonsense mutation results, in F2 adults, in changes to kinase profiles and to expression levels of multiple transcripts that distinguish this mutant from F1 age-1 homozygotes, a weaker age-1 mutant, or wild-type adults. Most but not all of those changes are reversed by a second mutation to daf-16, implicating both DAF-16/ FOXO–dependent and –independent mechanisms. RNAi, silencing genes that are downregulated in long-lived worms, improves oxidative-stress resistance of wild-type adults. It is therefore plausible that attenuation of those genes in age-1(mg44)-F2 adults contributes to their exceptional survival. IIS in nematodes (and presumably in other species) thus involves transcriptional as well as kinase regulation in a positive-feedback circuit, favoring either survival or reproduction. Hyperlongevity of strong age-1(mg44) mutants may result from their inability to reset this molecular switch to the reproductive mode. PMID:19360094

Identification of phenolic secondary metabolites from Schotia brachypetala Sond. (Fabaceae) and demonstration of their antioxidant activities in Caenorhabditis elegans

PubMed Central

Labib, Rola M.; Handoussa, Heba; Swilam, Noha; El-Khatib, Ahmed H.; Sharapov, Farukh; Mohamed, Tamer; Krstin, Sonja; Linscheid, Michael W.; Singab, Abdel Nasser; Wink, Michael

2016-01-01

Background Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern Africa whose phytochemistry and pharmacology were slightly studied. The present work aimed at profiling the major phenolics compounds present in the hydro-alcohol extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR and prove their antioxidant capabilities using novel methods. Methods In vitro assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C. elegans, Survival assay, GFP expression and Subcellular DAF-16 localization were employed to evaluate the antioxidant activity. Results More than forty polyphenols, including flavonoid glycosides, galloylated flavonoid glycosides, isoflavones, dihydrochalcones, procyanidins, anthocyanins, hydroxy benzoic acid derivatives, hydrolysable tannins, and traces of methylated and acetylated flavonoid derivatives were identified. Three compounds were isolated and identified from the genus Schotia for the first time, namely gallic acid, myricetin-3-O-α-L-1C4-rhamnoside and quercetin-3-O-L-1C4-rhamnoside. The total phenolics content of SBE was (376 mg CAE/g), followed by flavonoids (67.87 QE/g). In vitro antioxidant activity of SBE was evidenced by DPPH radical scavenging activity (IC50 of 9 µg/mL), FRAP ferric reducing activity (5,000 mol Fe2+ E/mg) and ABTS peroxide inhibiting activity (1,054 mM Trolox E/mg). The tested extract was able to protect the worms against juglone induced oxidative stress, an increased survival rate (up to 41%) was recorded, when compared with the control group (11%) and attenuate the reactive oxygen species (ROS) accumulation in dose-dependent and reached up to 72% for the highest tested concentration. SBE was also able to attenuate the levels of heat shock protein (HSP) expression in dose-dependent up to 60% in the 150 µg SBE/mL group. In DAF-16 Subcellular localization SBE treated worms showed nuclear localization pattern up to 78%, while it was only 5% in the untreated control group. Discussion A pronounced antioxidant activity in vivo, which can be attributed to its ability to promote the nuclear translocation of DAF-16/FOXO, the main transcription factor regulating the expression of stress response genes. The remarkable antioxidant activity in vitro and in vivo correlates to SBE rich phenolic profile. PMID:27896020

On the Use of Literary Texts in the Daf Lesson with the Example of Heinrich Boell's Short Story "Die Blasse Anna" with a Focus on Writing on a B2 Level

ERIC Educational Resources Information Center

Ghorabi, Yassamin Ostad A.; Haddadi, Mohammad Hossein

2017-01-01

For the promotion and optimization of teaching foreign languages, new methods and strategies are always considered that include literary texts. The aim of the present paper is to provide arguments for the use of literature in the classroom. Learning target areas and selection criteria for the use of literary texts in the classroom are presented. A…

Performance testing of a 50 kW VAWT in a built-up environment

NASA Technical Reports Server (NTRS)

Schienbein, L. A.

1981-01-01

The results of performance tests of a DAF Indal 50 kW vertical axis wind turbine are presented. Results of limited free stream turbulence and vertical wind shear measurements at the site are also presented. The close agreement between measured and predicted energy outputs, required to verify the wind turbine power output performance relationship, was not attained. A discussion is presented of factors that may have contributed to the lack of better agreement.

Joint Space Operations Center (JSpOC) Mission System Increment 2 (JMS Inc 2)

DTIC Science & Technology

2016-03-01

Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY...date has slipped from September 2016 to December 2016 and FDD has slipped from October 2016 to March 2017 since the last MAIS Annual Report...testing. This added test time, in combination with funding reductions and the US Government furlough and shutdown in FY13, caused a total FDD slip

Distributed Common Ground System Army Increment 1 (DCGS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal...updated prior to the FDD ITAB in December 2012 and provided additional COA analysis/validation referenced in the FDD ADM (December 14, 2012) and FDD ...required by 10 U.S.C. 2334(a)(6). The Army Cost Review Board developed the FDD Army Cost Position (ACP), dated October 19, 2012, through the update of

Mission Planning System Increment 5 (MPS Inc 5)

DTIC Science & Technology

2016-03-01

DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Alternative Selected (Funds First Obligated (FFO)) (O/T) : Mar 2013 / Mar 2013 • MS B (O/T) : Apr 2012 / Apr 2012 • MS C (O/T) : N/A / N/A • FDD (O/T...Deployed Software Intensive Program" as described in the DOD Instruction 5000.02, January 7, 2015. 4. FDD provides approval to field the

Air and Space Operations Center-Weapon System Increment 10.2 (AOC-WS Inc 10.2)

DTIC Science & Technology

2016-03-01

DAE - Defense Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment...the AOC 10.2 MAIS was approximately 11 months beyond the original schedule estimates for MS-C, July 31, 2015, and FDD , July 31, 2016. Accordingly...ADM effectively acknowledged selection of AOC-WS Inc 10.2 as the Preferred Alternative, thereby starting the 5-year development window to attain FDD

Strukturen und Geschäftsmodelle eines neuen Energiemarkts

NASA Astrophysics Data System (ADS)

Mildebrath, Bernhard

Die Energiewende fördert nicht nur technologische, sondern auch organisatorische und kommerzielle Innovationen. Die Strukturen und Geschäftsmodelle eines neuen Energiemarktes entwickeln sich bereits. Im Spagat zwischen Versuch und Irrtum werden sie völlig neue Lösungen für eine altbekannte Forderung schaffen: Strom soll preiswert, sicher und umweltverträglich sein. Der nachstehende Artikel präsentiert dafür - teils zugespitzte - Überlegungen zu den Strukturen und Geschäftsmodellen eines neuen Energiemarkts.

The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause.

PubMed

Kulalert, Warakorn; Kim, Dennis H

2013-12-16

In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer, which is characterized by adaptive changes in stress resistance and metabolism. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191), causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Survey of dissolved air flotation system efficiency for reduce of pollution of vegetable oil industry wastewater.

PubMed

Keramati, H; Alidadi, H; Parvaresh, A R; Movahedian, H; Mahvi, A H

2008-10-01

The aim of this research was to sudy the reduction of pollution of vegetable oil manufacturing wastewater with DAF system. At first phase of this examination, the optimum dosage of the coagulants was determined. The coagulants that used in this study were Alum and Ferric Chloride. The second phase was flotation in this series of examinations, oil, COD, total solid, volatile solid, fixed solid and suspended solid measured in raw wastewater and the effluent of the DAF pilot. Optimum value of pH for alum and ferric chloride obtained 7.5 and 5.5, respectively. Optimum dosage for these obtained 30 and 32 mg L(-1) in this research. Mean removal for the parameters ofoil, COD, total solid, volatile solid, fixed solid and suspended solid obtained 75.85, 78.27, 77.32, 82.47, 73.52 and 85.53%, respectively. With pressure rising from 3 to 4 and 5 atm removing rate of COD, total solid, volatile solid, fixed solid parameters reduced, but oil and suspended solid have increase. In addition, following increase of flotation time up to 120 sec all of the measured parameters have increase in removing rate. Optimum A/S for removal of COD, total solid, volatile solid, fixed solid parameters obtained 0.001 and for oil and suspended solid obtained 0.0015.

Hormone-mediated growth dynamics of the barley pericarp as revealed by magnetic resonance imaging and transcript profiling

PubMed Central

Pielot, Rainer; Kohl, Stefan; Manz, Bertram; Rutten, Twan; Weier, Diana; Tarkowská, Danuše; Rolčík, Jakub; Strnad, Miroslav; Volke, Frank; Weber, Hans

2015-01-01

The shape of the maternal pericarp affects cereal grain mass and yield. Pericarp growth was analysed by magnetic resonance imaging (MRI), revealing topological maps of mobile water in developing pericarp of barley (Hordeum vulgare) and displaying tissue regions actively elongating in specific temporal–spatial patterns. Correlation analysis of MRI signals and growth rates reveals that growth in length is mediated by dorsal and also lateral rather than ventral regions. Growth in thickness is related to ventral regions. Switching from dorsal to ventral growth is associated with differential expression of axial regulators of the HD-ZipIII and Kanadi/Ettin types, and NPH3 photoreceptors, suggesting light-mediated auxin re-distribution. Auxin increases with the highest levels in the basal pericarp at 6 days after fertilization (DAF), together with transcriptionally up-regulated auxin transport and signalling. Gibberellin biosynthesis is transcriptionally up-regulated only later, and levels of bioactive gibberellins increase from 7 to 13 DAF, with higher levels in ventral than dorsal regions. Differential gene expression related to cell expansion indicates genes related to apoplast acidification, wall relaxation, sugar cleavage, water transport, and cell wall biosynthesis. Candidate genes potentially involved in pericarp extension are distinguished by their temporal expression, representing potential isoforms responsible for dorsal-mediated early growth in length or ventral-mediated late growth in thickness. PMID:26276866

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans.

PubMed

Sangaletti, Rachele; D'Amico, Massimo; Grant, Jeff; Della-Morte, David; Bianchi, Laura

2017-08-01

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions.

Bottlenecks in erucic acid accumulation in genetically engineered ultrahigh erucic acid Crambe abyssinica

PubMed Central

Guan, Rui; Lager, Ida; Li, Xueyuan; Stymne, Sten; Zhu, Li-Hua

2014-01-01

Erucic acid is a valuable industrial fatty acid with many applications. The main producers of this acid are today high erucic rapeseed (Brassica napus) and mustard (Brassica juncea), which have 45%–50% of erucic acid in their seed oils. Crambe abyssinica is an alternative promising producer of this acid as it has 55%–60% of erucic acid in its oil. Through genetic modification (GM) of three genes, we have previously increased the level of erucic acid to 71% (68 mol%) in Crambe seed oil. In this study, we further investigated different aspects of oil biosynthesis in the developing GM Crambe seeds in comparison with wild-type (Wt) Crambe, rapeseed and safflower (Carthamus tinctorius). We show that Crambe seeds have very low phosphatidylcholine-diacylglycerol interconversion, suggesting it to be the main reason why erucic acid is limited in the membrane lipids during oil biosynthesis. We further show that GM Crambe seeds have slower seed development than Wt, accompanied by slower oil accumulation during the first 20 days after flowering (DAF). Despite low accumulation of erucic acid during early stages of GM seed development, nearly 86 mol% of all fatty acids accumulated between 27 and 50 DAF was erucic acid, when 40% of the total oil is laid down. Likely bottlenecks in the accumulation of erucic acid during early stages of GM Crambe seed development are discussed. PMID:24119222

Breast cancer detection using time reversal

NASA Astrophysics Data System (ADS)

Sheikh Sajjadieh, Mohammad Hossein

Breast cancer is the second leading cause of cancer death after lung cancer among women. Mammography and magnetic resonance imaging (MRI) have certain limitations in detecting breast cancer, especially during its early stage of development. A number of studies have shown that microwave breast cancer detection has potential to become a successful clinical complement to the conventional X-ray mammography. Microwave breast imaging is performed by illuminating the breast tissues with an electromagnetic waveform and recording its reflections (backscatters) emanating from variations in the normal breast tissues and tumour cells, if present, using an antenna array. These backscatters, referred to as the overall (tumour and clutter) response, are processed to estimate the tumour response, which is applied as input to array imaging algorithms used to estimate the location of the tumour. Due to changes in the breast profile over time, the commonly utilized background subtraction procedures used to estimate the target (tumour) response in array processing are impractical for breast cancer detection. The thesis proposes a new tumour estimation algorithm based on a combination of the data adaptive filter with the envelope detection filter (DAF/EDF), which collectively do not require a training step. After establishing the superiority of the DAF/EDF based approach, the thesis shows that the time reversal (TR) array imaging algorithms outperform their conventional conterparts in detecting and localizing tumour cells in breast tissues at SNRs ranging from 15 to 30dB.

A Distributed Chemosensory Circuit for Oxygen Preference in C. elegans

PubMed Central

Chang, Andy J; Chronis, Nikolas; Karow, David S; Marletta, Michael A; Bargmann, Cornelia I

2006-01-01

The nematode Caenorhabditis elegans has complex, naturally variable behavioral responses to environmental oxygen, food, and other animals. C. elegans detects oxygen through soluble guanylate cyclase homologs (sGCs) and responds to it differently depending on the activity of the neuropeptide receptor NPR-1: npr-1(lf) and naturally isolated npr-1(215F) animals avoid high oxygen and aggregate in the presence of food; npr-1(215V) animals do not. We show here that hyperoxia avoidance integrates food with npr-1 activity through neuromodulation of a distributed oxygen-sensing network. Hyperoxia avoidance is stimulated by sGC-expressing oxygen-sensing neurons, nociceptive neurons, and ADF sensory neurons. In npr-1(215V) animals, the switch from weak aerotaxis on food to strong aerotaxis in its absence requires close regulation of the neurotransmitter serotonin in the ADF neurons; high levels of ADF serotonin promote hyperoxia avoidance. In npr-1(lf) animals, food regulation is masked by increased activity of the oxygen-sensing neurons. Hyperoxia avoidance is also regulated by the neuronal TGF-β homolog DAF-7, a secreted mediator of crowding and stress responses. DAF-7 inhibits serotonin synthesis in ADF, suggesting that ADF serotonin is a convergence point for regulation of hyperoxia avoidance. Coalitions of neurons that promote and repress hyperoxia avoidance generate a subtle and flexible response to environmental oxygen. PMID:16903785

Final Report for Bio-Inspired Approaches to Moving-Target Defense Strategies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink, Glenn A.; Oehmen, Christopher S.

This report records the work and contributions of the NITRD-funded Bio-Inspired Approaches to Moving-Target Defense Strategies project performed by Pacific Northwest National Laboratory under the technical guidance of the National Security Agency’s R6 division. The project has incorporated a number of bio-inspired cyber defensive technologies within an elastic framework provided by the Digital Ants. This project has created the first scalable, real-world prototype of the Digital Ants Framework (DAF)[11] and integrated five technologies into this flexible, decentralized framework: (1) Ant-Based Cyber Defense (ABCD), (2) Behavioral Indicators, (3) Bioinformatic Clas- sification, (4) Moving-Target Reconfiguration, and (5) Ambient Collaboration. The DAF canmore » be used operationally to decentralize many such data intensive applications that normally rely on collection of large amounts of data in a central repository. In this work, we have shown how these component applications may be decentralized and may perform analysis at the edge. Operationally, this will enable analytics to scale far beyond current limitations while not suffering from the bandwidth or computational limitations of centralized analysis. This effort has advanced the R6 Cyber Security research program to secure digital infrastructures by developing a dynamic means to adaptively defend complex cyber systems. We hope that this work will benefit both our client’s efforts in system behavior modeling and cyber security to the overall benefit of the nation.« less

Effect of delayed auditory feedback on stuttering with and without central auditory processing disorders.

PubMed

Picoloto, Luana Altran; Cardoso, Ana Cláudia Vieira; Cerqueira, Amanda Venuti; Oliveira, Cristiane Moço Canhetti de

2017-12-07

To verify the effect of delayed auditory feedback on speech fluency of individuals who stutter with and without central auditory processing disorders. The participants were twenty individuals with stuttering from 7 to 17 years old and were divided into two groups: Stuttering Group with Auditory Processing Disorders (SGAPD): 10 individuals with central auditory processing disorders, and Stuttering Group (SG): 10 individuals without central auditory processing disorders. Procedures were: fluency assessment with non-altered auditory feedback (NAF) and delayed auditory feedback (DAF), assessment of the stuttering severity and central auditory processing (CAP). Phono Tools software was used to cause a delay of 100 milliseconds in the auditory feedback. The "Wilcoxon Signal Post" test was used in the intragroup analysis and "Mann-Whitney" test in the intergroup analysis. The DAF caused a statistically significant reduction in SG: in the frequency score of stuttering-like disfluencies in the analysis of the Stuttering Severity Instrument, in the amount of blocks and repetitions of monosyllabic words, and in the frequency of stuttering-like disfluencies of duration. Delayed auditory feedback did not cause statistically significant effects on SGAPD fluency, individuals with stuttering with auditory processing disorders. The effect of delayed auditory feedback in speech fluency of individuals who stutter was different in individuals of both groups, because there was an improvement in fluency only in individuals without auditory processing disorder.

A Patch Density Recommendation based on Convergence Studies for Vehicle Panel Vibration Response resulting from Excitation by a Diffuse Acoustic Field

NASA Technical Reports Server (NTRS)

Smith, Andrew; LaVerde, Bruce; Jones, Douglas; Towner, Robert; Waldon, James; Hunt, Ron

2013-01-01

Producing fluid structural interaction estimates of panel vibration from an applied pressure field excitation are quite dependent on the spatial correlation of the pressure field. There is a danger of either over estimating a low frequency response or under predicting broad band panel response in the more modally dense bands if the pressure field spatial correlation is not accounted for adequately. It is a useful practice to simulate the spatial correlation of the applied pressure field over a 2d surface using a matrix of small patch area regions on a finite element model (FEM). Use of a fitted function for the spatial correlation between patch centers can result in an error if the choice of patch density is not fine enough to represent the more continuous spatial correlation function throughout the intended frequency range of interest. Several patch density assumptions to approximate the fitted spatial correlation function are first evaluated using both qualitative and quantitative illustrations. The actual response of a typical vehicle panel system FEM is then examined in a convergence study where the patch density assumptions are varied over the same model. The convergence study results illustrate the impacts possible from a poor choice of patch density on the analytical response estimate. The fitted correlation function used in this study represents a diffuse acoustic field (DAF) excitation of the panel to produce vibration response.

Propagation of 3-D Beams Using a Finite-Difference Algorithm: Practical Considerations

DTIC Science & Technology

2011-05-22

electric-discharge laser ,” J. Appl. Phys. 49(3), 1012–1027 (1978). [6] Sziklas, E. A. and Siegman , A. E., “Mode calculations in unstable resonators with...flowing saturable gain .2. fast fourier-transform method,” Applied Optics 14(8), 1874–1889 (1975). [7] Siegman , A. E., [ Lasers ], University Science...Signed// ALAN H. PAXTON, DR-III Project Manager //Signed// MICHAEL F. SHEEHAN, DR-III, DAF Acting Chief, Laser Division This report is published in

The Differential Vector Phase-Locked Loop for Global Navigation Satellite System Signal Tracking

DTIC Science & Technology

2014-06-01

DAF Approved: //signed// John F. Raquet, PhD (Chairman) //signed// Mark E. Oxley, PhD (Member) //signed// Maj Marshall E. Haker , PhD (Member) 16 May...busy as you keep yourself. Dr. Mark Oxley and Dr. Marshall Haker for your sage guidance as members of my committee. Dr. Ken Fisher for making Kalman...Raquet, Dr. Marshall Haker , and Mr. Ben Downing at AFIT, following notes for Dr. Raquet’s Advanced GPS Receiver Design class. The second type was RINEX

integrated Electronic Health Record Increment 1 (iEHR Inc 1)

DTIC Science & Technology

2016-03-01

Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA...Acronyms and Abbreviations ADM - Acquisition Decision Memorandum FD - Full Deployment FDD - Full Deployment Decision iEHR Inc 1 2016 MAR UNCLASSIFIED...iEHR Increment 1 APB for FDD achieved in November 2014 was signed by the MDA March 2, 2015. Current estimate is consistent with the FDD APB. iEHR Inc 1 2016 MAR UNCLASSIFIED 11

Global Combat Support System Army Increment 1 (GCSS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year...another economic anaylsis was completed on November 14, 2012, in advance of a successful FDD . The program is now in the O&S Phase. GCSS-A Inc 1 2016...Increment I Feb 2011 Aug 2011 Full Deployment Decision ( FDD )1 Feb 2012 Dec 2012 Full Deployment (FD)2 Sep 2017 Mar 2018 Memo 1/ GCSS-A Increment 1

Tailored Systems Architecture for Design of Space Science and Technology Missions Using DoDAF V2.0

DTIC Science & Technology

2009-12-01

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...ADDRESS(ES) Air Force Institute of Technology,2950 Hobson Way,WPAFB,OH,45433-7765 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING...the focus on rapid development and transition, if a system architecture framework could be developed and used to increase visibility within the

Tailored Systems Architecture for Design of Space Science and Technology Missions using DoDAF V2.0

DTIC Science & Technology

2009-12-01

GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...ADDRESS(ES) Air Force Institute of Technology,2950 Hobson Way,WPAFB,OH,45433-7765 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING...the focus on rapid development and transition, if a system architecture framework could be developed and used to increase visibility within the

Synthesis, spectroscopic, coordination and biological activities of some organometallic complexes derived from thio-Schiff base ligands

NASA Astrophysics Data System (ADS)

Abou-Hussein, Azza A.; Linert, Wolfgang

2014-01-01

Two series of mono- and binuclear complexes cyclic or acyclic thio-ferocine Schiff base ligands, derived from the condensation of 2-aminobenzenthiol (L) with monoacetyl ferrocene in the molar ratio 1:1 or in the molar ratio 1:2 for diacetyl ferocine have been prepared. The condensation reactions yield the corresponding Schiff Base ligands, HLa-Maf and H2Lb-Daf. The chelation of the ligands to metal ions occurs through the sulfur of the thiol group as well as the nitrogen atoms of the azomethine group of the ligands. HLa-Maf acts as monobasic bidentate or dibasic tetradentate, while H2Lb-Daf behaves as twice negatively cargend tetradentate ligand. The structures of these ligands were elucidated by elemental analysis, infrared, ultraviolet-visible spectra, as well as 1H NMR spectra. Reactions of the Schiff bases ligands with ruthenium(III), oxovanadium(IV) and dioxouranium(VI) afforded the corresponding transition metal complexes. The properties of the newly prepared complexes were analyse by elemental analyses, infrared, electronic spectra, 1H NMR as well as the magnetic susceptibility and conductivity measurement. The metal complexes exhibits different geometrical arrangements such as octahedral and square pyramidal coordination. Schiff base ligands and their metal complexes were tested against two pathogenic bacteria as Gram-positive and Gram-negative bacteria as well as one kind of fungi to study their biological activity. All the complexes exhibit antibacterial and antifungal activities against these organisms.

Knock-out of a mitochondrial sirtuin protects neurons from degeneration in Caenorhabditis elegans

PubMed Central

Sangaletti, Rachele; Grant, Jeff; Della-Morte, David

2017-01-01

Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis. Furthermore, the protective effect of sir-2.3 knock-out is enhanced by block of glycolysis and eliminated by a null mutation in daf-16/FOXO transcription factor, supporting the involvement of the insulin/IGF pathway. However, data in Caenorhabditis elegans cell culture suggest that the effects of sir-2.3 knock-out act downstream of the DAF-2/IGF-1 receptor. Analysis of ROS in sir-2.3 knock-out reveals that ROS become elevated in this mutant under ischemic conditions in dietary deprivation (DD), but to a lesser extent than in wild type, suggesting more robust activation of a ROS scavenging system in this mutant in the absence of food. This work suggests a deleterious role of SIRT4 during ischemic processes in mammals that must be further investigated and reveals a novel pathway that can be targeted for the design of therapies aimed at protecting neurons from death in ischemic conditions. PMID:28820880

Pretreatment of bakery wastewater by coagulation-flocculation and dissolved air flotation.

PubMed

Liu, J C; Lien, C S

2001-01-01

The pretreatment of wastewater from a large-scale bakery was studied. In the coagulation-flocculation reaction, it was found that both alum and FeCl3 were effective in the jar tests. When at coagulant dosage of 90 to 100 mg/l, 55% of COD and 95 to 100% of SS could be removed. The optimum pH was at 6.0. In addition, the removal of SS was affected by pH more significantly, while the removal of COD was not affected in the pH range of 6.0 to 8.0. In the DAF experiments, 48.6% of COD and 69.8% of SS were removed in 10 min at a pressure of 4 kg/cm2, recycle ratio of 0.3 l/min, and pH of 6.0. Upon the addition of 100 mg/l of alum, the removal efficiency of COD did not increase while SS removal increased to 82.1%. It was found that 5-min flocculation time did improve the COD removal while it had little effect on SS removal. Flocculation for longer than 5 min did not enhance the flotation performance. Similar phenomena were observed when FeCl3 was used as the coagulant, except that flocculation had an insignificant effect on COD and SS removal. It was also found that FeCl3 was relatively more effective than alum. In summary, both coagulation-flocculation and DAF were efficient for the pretreatment. The advantages and disadvantages were discussed.

DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.

PubMed

Lans, H; Lindvall, J M; Thijssen, K; Karambelas, A E; Cupac, D; Fensgård, O; Jansen, G; Hoeijmakers, J H J; Nilsen, H; Vermeulen, W

2013-12-01

Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.

The cell non-autonomous function of ATG-18 is essential for neuroendocrine regulation of Caenorhabditis elegans lifespan

PubMed Central

Minnerly, Justin; Zhang, Jiuli; Parker, Thomas

2017-01-01

Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear. Here we show that the autophagy protein ATG-18 acts cell non-autonomously in neuronal and intestinal tissues to maintain C. elegans wildtype lifespan and to respond to DR and IGF-mediated longevity signaling. Moreover, ATG-18 activity in chemosensory neurons that are involved in food detection sufficiently mediates the effect of these longevity pathways. Additionally, ATG-18-mediated cell non-autonomous signaling depends on the release of neurotransmitters and neuropeptides. Interestingly, our data suggest that neuronal and intestinal ATG-18 acts in parallel and converges on unidentified neurons that secrete neuropeptides to regulate C. elegans lifespan through the transcription factor DAF-16/FOXO in response to reduced IGF signaling. PMID:28557996

Ciliopathy proteins establish a bipartite signaling compartment in a C. elegans thermosensory neuron

PubMed Central

Nguyen, Phuong Anh T.; Liou, Willisa; Hall, David H.; Leroux, Michel R.

2014-01-01

ABSTRACT How signaling domains form is an important, yet largely unexplored question. Here, we show that ciliary proteins help establish two contiguous, yet distinct cyclic GMP (cGMP) signaling compartments in Caenorhabditis elegans thermosensory AFD neurons. One compartment, a bona fide cilium, is delineated by proteins associated with Bardet–Biedl syndrome (BBS), Meckel syndrome and nephronophthisis at its base, and requires NPHP-2 (known as inversin in mammals) to anchor a cGMP-gated ion channel within the proximal ciliary region. The other, a subcompartment with profuse microvilli and a different lipid environment, is separated from the dendrite by a cellular junction and requires BBS-8 and DAF-25 (known as Ankmy2 in mammals) for correct localization of guanylyl cyclases needed for thermosensation. Consistent with a requirement for a membrane diffusion barrier at the subcompartment base, we reveal the unexpected presence of ciliary transition zone proteins where no canonical transition zone ultrastructure exists. We propose that differential compartmentalization of signal transduction components by ciliary proteins is important for the functions of ciliated sensory neurons. PMID:25335890

Geologic history of the polar regions of Mars based on Mars Global survey data. I. Noachian and Hesperian Periods

USGS Publications Warehouse

Tanaka, K.L.; Kolb, E.J.

2001-01-01

During the Noachian Period, the south polar region of Mars underwent intense cratering, construction of three groups of volcanoes, widespread contractional deformation, resurfacing of low areas, and local dissection of valley networks; no evidence for polar deposits, ice sheets, or glaciation is recognized. South polar Hesperian geology is broadly characterized by waning impacts, volcanism, and tectonism. Emplacement of the polar Dorsa Argentea Formation (DAF) occurred during the Hesperian Period. Mars Orbiter Laser Altimeter topographic data and Mars Orbiter Camera images elucidate stratigraphic, morphologic, and topographic relations, permitting the dividing of the DAF into eight members, which surround and underlie about half of the Amazonian south polar layered deposits. The lobate fronts and lack of typical volcanic-flow morphology of the six plains units indicate that they may be made up of debris flows. We think that these flows, tens of meters to 200 m thick, may have originated by the discharge of huge volumes of slurry fluidized by ground water or liquid CO2, perhaps triggered by local impacts, igneous activity, or basal melting beneath polar deposits. The cavi and rugged members include irregular depressions that penetrate the subsurface; some of the pits have raised rims. The depressions may have formed by collapse due to expulsion of subsurface material in which local explosive activity built up the raised rims. Further, smaller eruptions of volatile-rich material may have resulted in narrow, sinuous channel deposits within aggrading fine-grained unconsolidated material perhaps produced by gaseous discharge of subsurface volatiles; preferential erosion of the latter material could have produced the Dorsa Argentea-type ginuous ridges associated mainly with the DAF. Alternatively, the ridges may be eskers, but the lack of associated glacial and fluvial morphologies casts doubt on this interpretation. The knobby, degraded materials forming Scandia Colles may represent the only Noachian geologic record exposed in the north polar region. Most of the north polar region was buried by water- or debris-ocean sediments during the Hesperian Period, originating from uplands areas and perhaps knobby terrains in the northern plains. The sediments either mantle or were deformed by wrinkle ridges radial and concentric to Utopia basin and concentric to northern Tharsis. Sources of stress probably included sediment loading in the northern plains and regional magmatic and loading activity at Tharsis. Polar layered deposits began piling up during the Early Amazonian or later. ?? 2001 Elsevier Science.

Geologic History of the Polar Regions of Mars Based on Mars Global Surveyor Data. I. Noachian and Hesperian Periods

NASA Astrophysics Data System (ADS)

Tanaka, Kenneth L.; Kolb, Eric J.

2001-11-01

During the Noachian Period, the south polar region of Mars underwent intense cratering, construction of three groups of volcanoes, widespread contractional deformation, resurfacing of low areas, and local dissection of valley networks; no evidence for polar deposits, ice sheets, or glaciation is recognized. South polar Hesperian geology is broadly characterized by waning impacts, volcanism, and tectonism. Emplacement of the polar Dorsa Argentea Formation (DAF) occurred during the Hesperian Period. Mars Orbiter Laser Altimeter topographic data and Mars Orbiter Camera images elucidate stratigraphic, morphologic, and topographic relations, permitting the dividing of the DAF into eight members, which surround and underlie about half of the Amazonian south polar layered deposits. The lobate fronts and lack of typical volcanic-flow morphology of the six plains units indicate that they may be made up of debris flows. We think that these flows, tens of meters to 200 m thick, may have originated by the discharge of huge volumes of slurry fluidized by ground water or liquid CO 2, perhaps triggered by local impacts, igneous activity, or basal melting beneath polar deposits. The cavi and rugged members include irregular depressions that penetrate the subsurface; some of the pits have raised rims. The depressions may have formed by collapse due to expulsion of subsurface material in which local explosive activity built up the raised rims. Further, smaller eruptions of volatile-rich material may have resulted in narrow, sinuous channel deposits within aggrading fine-grained unconsolidated material perhaps produced by gaseous discharge of subsurface volatiles; preferential erosion of the latter material could have produced the Dorsa Argentea-type sinuous ridges associated mainly with the DAF. Alternatively, the ridges may be eskers, but the lack of associated glacial and fluvial morphologies casts doubt on this interpretation. The knobby, degraded materials forming Scandia Colles may represent the only Noachian geologic record exposed in the north polar region. Most of the north polar region was buried by water- or debris-ocean sediments during the Hesperian Period, originating from uplands areas and perhaps knobby terrains in the northern plains. The sediments either mantle or were deformed by wrinkle ridges radial and concentric to Utopia basin and concentric to northern Tharsis. Sources of stress probably included sediment loading in the northern plains and regional magmatic and loading activity at Tharsis. Polar layered deposits began piling up during the Early Amazonian or later.

Histologic Changes Caused by Application of Lewisite Analogs to Mouse Skin and Human Skin Xenografts

DTIC Science & Technology

1985-01-01

CLASSIICATION OF THIS PAGE (Nh..1 DO&a Eatat1d UNCLAS8inED S6CURmTV CLASSISCATION OP THIS PA•r(em Daf EMo* skin grafts : 1) epidermal cellular nuclear...microscopy. Under light microscopy, we observed the following changes In PDA-treated human skin grafts : I) epidermal cellular nuclear degeneration (apparent...needed. (Oe such model is ti-e human skin grafted athymic nude mouse (4,5). This animal model was recently established at LAIR. PhenyLdichLoroarsine (PDA

Highly Polluted Wastewaters Treatment by Improved Dissolved Air Flotation Technology

NASA Astrophysics Data System (ADS)

Moga, I. C.; Covaliu, C. I.; Matache, M. G.; Doroftei, B. I.

2017-06-01

Numerous investigations are oriented towards the development of new wastewater treatment technologies, having high efficiencies for removing even low concentrations of pollutants found in water. These efforts were determined by the destroyer impact of the pollutants to the environment and human’s health. For this reason this paper presents our study concerning an improved dissolved air flotation technology for wastewater treatment. There is described a dissolved air flotation (DAF) installation composed by two equipments: pressurized capsule and lamellar settling. Also, there are presented some advantages of using nanoparticles as flotation collectors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heinrichs, Dave; Beller, Tim; Burch, Jennifer

This document is the Final Design (CED-2) Report for IER-148, “International Inter-comparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV.” The report describes the structure of the exercise consisting of three irradiations; identifies the participating laboratories and their points of contact; provides the details of all dosimetry elements and their placement in proximity to Godiva-IV on support stands or phantoms ; and lists the counting and spectroscopy equipment each laboratory will utilize in the Mercury NAD Lab. The exercise is tentatively scheduled for one week in August 2015.

Augmentation of Antitumor T-Cell Responses by Increasing APC T-Cell C5a/C3a-C5aR/C3aR Interactions

DTIC Science & Technology

2013-03-01

the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. The Journal of experimental medicine . 1984;160(5...cell immunity. The Journal of experimental medicine . 2005;201(10):1523-30. PubMed PMID: 15883171. 3. Vogel CW, Wilkie SD, Morgan AC. In vivo studies...with covalent conjugates of cobra venom factor and monoclonal antibodies to human tumors. Haematology and blood transfusion. 1985;29:514- 7. Epub

d-Allulose, a stereoisomer of d-fructose, extends Caenorhabditis elegans lifespan through a dietary restriction mechanism: A new candidate dietary restriction mimetic.

PubMed

Shintani, Tomoya; Sakoguchi, Hirofumi; Yoshihara, Akihide; Izumori, Ken; Sato, Masashi

2017-12-02

Dietary restriction (DR) is an effective intervention known to increase lifespan in a wide variety of organisms. DR also delays the onset of aging-associated diseases. DR mimetics, compounds that can mimic the effects of DR, have been intensively explored. d-Allulose (d-Alu), the C3-epimer of d-fructose, is a rare sugar that has various health benefits, including anti-hyperglycemia and anti-obesity effects. Here, we report that d-Alu increased the lifespan of Caenorhabditis elegans both under monoxenic and axenic culture conditions. d-Alu did not further extend the lifespan of the long-lived DR model eat-2 mutant, strongly indicating that the effect is related to DR. However, d-Alu did not reduce the food intake of wild-type C. elegans. To explore the mechanisms of the d-Alu longevity effect, we examined the lifespan of d-Alu-treated mutants deficient for nutrient sensing pathway-related genes daf-16, sir-2.1, aak-2, and skn-1. As a result, d-Alu increased the lifespan of the daf-16, sir-2.1, and skn-1 mutants, but not the aak-2 mutant, indicating that the lifespan extension was dependent on the energy sensor, AMP-activated protein kinase (AMPK). d-Alu also enhanced the mRNA expression and enzyme activities of superoxide dismutase (SOD) and catalase. From these findings, we conclude that d-Alu extends lifespan by increasing oxidative stress resistance through a DR mechanism, making it a candidate DR mimetic. Copyright © 2017 Elsevier Inc. All rights reserved.

Diversity among Cynodon accessions and taxa based on DNA amplification fingerprinting.

PubMed

Assefa, S; Taliaferro, C M; Anderson, M P; de los Reyes, B G; Edwards, R M

1999-06-01

The genus Cynodon (Gramineae), comprised of 9 species, is geographically widely distributed and genetically diverse. Information on the amounts of molecular genetic variation among and within Cynodon taxa is needed to enhance understanding of phylogenetic relations and facilitate germplasm management and breeding improvement efforts. Genetic relatedness among 62 Cynodon accessions, representing eight species, was assessed using DNA amplification fingerprinting (DAF). Ten 8-mer oligonucleotides were used to amplify specific Cynodon genomic sequences. The DNA amplification products of individual accessions were scored for presence (1) or absence (0) of bands. Similarity matrices were developed and the accessions were grouped by cluster (UPGMA) and principal coordinate analysis. Analyses were conducted within ploidy level (2x = 18 and 4x = 36) and over ploidy levels. Each primer revealed polymorphic loci among accessions within species. Of 539 loci (bands) scored, 496 (92%) were polymorphic. Cynodon arcuatus was clearly separated from other species by numerous monomorphic bands. The strongest species similarities were between C. aethiopicus and C. arcuatus, C. transvaalensis and C. plectostachyus, and C. incompletus and C. nlemfuensis. Intraspecific variation was least for C. aethiopicus, C. arcuatus, and C. transvaalensis, and greatest for C. dactylon. Accessions of like taxonomic classification were generally clustered, except the cosmopolitan C. dactylon var. dactylon and C. dactylon var. afganicus. Within taxa, accessions differing in chromosome number clustered in all instances indicating the 2x and 4x forms to be closely related. Little, if any, relationship was found between relatedness as indicated by the DAF profiles and previous estimates of hybridization potential between the different taxa.

Integrated mRNA and miRNA transcriptome reveal a cross-talk between developing response and hormone signaling for the seed kernels of Siberian apricot

PubMed Central

Niu, Jun; Wang, Jia; An, Jiyong; Liu, Lili; Lin, Zixin; Wang, Rui; Wang, Libing; Ma, Chao; Shi, Lingling; Lin, Shanzhi

2016-01-01

Recently, our transcriptomic analysis has identified some functional genes responsible for oil biosynthesis in developing SASK, yet miRNA-mediated regulation for SASK development and oil accumulation is poorly understood. Here, 3 representative periods of 10, 30 and 60 DAF were selected for sRNA sequencing based on the dynamic patterns of growth tendency and oil content of developing SASK. By miRNA transcriptomic analysis, we characterized 296 known and 44 novel miRNAs in developing SASK, among which 36 known and 6 novel miRNAs respond specifically to developing SASK. Importantly, we performed an integrated analysis of mRNA and miRNA transcriptome as well as qRT-PCR detection to identify some key miRNAs and their targets (miR156-SPL, miR160-ARF18, miR164-NAC1, miR171h-SCL6, miR172-AP2, miR395-AUX22B, miR530-P2C37, miR393h-TIR1/AFB2 and psi-miRn5-SnRK2A) potentially involved in developing response and hormone signaling of SASK. Our results provide new insights into the important regulatory function of cross-talk between development response and hormone signaling for SASK oil accumulation. PMID:27762296

Integrated mRNA and miRNA transcriptome reveal a cross-talk between developing response and hormone signaling for the seed kernels of Siberian apricot.

PubMed

Niu, Jun; Wang, Jia; An, Jiyong; Liu, Lili; Lin, Zixin; Wang, Rui; Wang, Libing; Ma, Chao; Shi, Lingling; Lin, Shanzhi

2016-10-20

Recently, our transcriptomic analysis has identified some functional genes responsible for oil biosynthesis in developing SASK, yet miRNA-mediated regulation for SASK development and oil accumulation is poorly understood. Here, 3 representative periods of 10, 30 and 60 DAF were selected for sRNA sequencing based on the dynamic patterns of growth tendency and oil content of developing SASK. By miRNA transcriptomic analysis, we characterized 296 known and 44 novel miRNAs in developing SASK, among which 36 known and 6 novel miRNAs respond specifically to developing SASK. Importantly, we performed an integrated analysis of mRNA and miRNA transcriptome as well as qRT-PCR detection to identify some key miRNAs and their targets (miR156-SPL, miR160-ARF18, miR164-NAC1, miR171h-SCL6, miR172-AP2, miR395-AUX22B, miR530-P2C37, miR393h-TIR1/AFB2 and psi-miRn5-SnRK2A) potentially involved in developing response and hormone signaling of SASK. Our results provide new insights into the important regulatory function of cross-talk between development response and hormone signaling for SASK oil accumulation.

D-beta-hydroxybutyrate extends lifespan in C. elegans

PubMed Central

Edwards, Clare; Canfield, John; Copes, Neil; Rehan, Muhammad; Lipps, David; Bradshaw, Patrick C.

2014-01-01

The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan of C. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated βHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and βHB dehydrogenase activity induced by βHB addition, suggesting that F55E10.6 functions as an inducible βHB dehydrogenase. Furthermore, βHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-βHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways. PMID:25127866

S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans.

PubMed

Cascella, Roberta; Evangelisti, Elisa; Zampagni, Mariagioia; Becatti, Matteo; D'Adamio, Giampiero; Goti, Andrea; Liguri, Gianfranco; Fiorillo, Claudia; Cecchi, Cristina

2014-08-01

Oxidative stress has a prominent role in life-span regulation of living organisms. One of the endogenous free radical scavenger systems is associated with glutathione (GSH), the most abundant nonprotein thiol in mammalian cells, acting as a major reducing agent and in antioxidant defense by maintaining a tight control over redox status. We have recently designed a series of novel S-acyl-GSH derivatives capable of preventing amyloid oxidative stress and cholinergic dysfunction in Alzheimer disease models, upon an increase in GSH intake. In this study we show that the longevity of the wild-type N2 Caenorhabditis elegans strain was significantly enhanced by dietary supplementation with linolenoyl-SG (lin-SG) thioester with respect to the ethyl ester of GSH, linolenic acid, or vitamin E. RNA interference analysis and activity inhibition assay indicate that life-span extension was mediated by the upregulation of Sir-2.1, a NAD-dependent histone deacetylase ortholog of mammalian SIRT1. In particular, lin-SG-mediated overexpression of Sir-2.1 appears to be related to the Daf-16 (FoxO) pathway. Moreover, the lin-SG derivative protects N2 worms from the paralysis and oxidative stress induced by Aβ/H2O2 exposure. Overall, our findings put forward lin-SG thioester as an antioxidant supplement triggering sirtuin upregulation, thus opening new future perspectives for healthy aging or delayed onset of oxidative-related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Design, performance, and economics of 50-kW and 500-kW vertical axis wind turbines

NASA Astrophysics Data System (ADS)

Schienbein, L. A.; Malcolm, D. J.

1983-11-01

A review of the development and performance of the DAF Indal 50-kW vertical axis Darrieus wind turbine shows that a high level of technical development and reliability has been achieved. Features of the drive train, braking and control systems are discussed and performance details are presented. Details are also presented of a 500-kW VAWT that is currently in production. A discussion of the economics of both the 50-kW and 500-kW VAWTs is included, showing the effects of charge rate, installed cost, operating cost, performance, and efficiency.

DIVWAG Model Documentation. Volume II. Programmer/Analyst Manual. Part 5.

DTIC Science & Technology

1976-07-01

Words Number Mission type: I=DAFS; 2= CAS 1 8 Estimated X coordinate of target 1 9 Estimated Y coordinate of target 1 10 Reject code: 0-mission unit... CAS 1 8 Abort indicator: O-no abort; 1-abort 1 9 X coordinate of target 1 10 " :oordinate of target 1 11 Aircraft munitions item code 6 12-17 Aircraft...L300 CALL TRNSMT U. TO TRANSMIT FIRST BLOCK OF DATA L100 YES REQUEST FOR INPU? LIOI CA " TRAN21I TO TRANSMIT LAST BLOCK OF DATA Figure VII-3-B- 10

The R148.3 Gene Modulates Caenorhabditis elegans Lifespan and Fat Metabolism

PubMed Central

Roy-Bellavance, Catherine; Grants, Jennifer M.; Miard, Stéphanie; Lee, Kayoung; Rondeau, Évelyne; Guillemette, Chantal; Simard, Martin J.; Taubert, Stefan; Picard, Frédéric

2017-01-01

Despite many advances, the molecular links between energy metabolism and longevity are not well understood. Here, we have used the nematode model Caenorhabditis elegans to study the role of the yet-uncharacterized gene R148.3 in fat accumulation and lifespan. In wild-type worms, a R148.3p::GFP reporter showed enhanced expression throughout life in the pharynx, in neurons, and in muscles. Functionally, a protein fusing a predicted 22 amino acid N-terminal signal sequence (SS) of R148.3 to mCherry displayed robust accumulation in coelomyocytes, indicating that R148.3 is a secreted protein. Systematic depletion of R148.3 by RNA interference (RNAi) at L1 but not at young-adult stage enhanced triglyceride accumulation, which was associated with increased food uptake and lower expression of genes involved in lipid oxidation. However, RNAi of R148.3 at both L1 and young-adult stages robustly diminished mean and maximal lifespan of wild-type worms, and also abolished the long-lived phenotypes of eat-2 and daf-2/InsR mutants. Based on these data, we propose that R148.3 is an SS that modulates fat mass and longevity in an independent manner. PMID:28620088

Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Shen, En-Zhi; Song, Chun-Qing; Lin, Yuan; Zhang, Wen-Hong; Su, Pei-Fang; Liu, Wen-Yuan; Zhang, Pan; Xu, Jiejia; Lin, Na; Zhan, Cheng; Wang, Xianhua; Shyr, Yu; Cheng, Heping; Dong, Meng-Qiu

2014-04-01

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

Visualization and contractile activity of cochlear pericytes in the capillaries of the spiral ligament.

PubMed

Dai, Min; Nuttall, Alfred; Yang, Yue; Shi, Xiaorui

2009-08-01

Pericytes, mural cells located on microvessels, are considered to play an important role in the formation of the vasculature and the regulation of local blood flow in some organs. Little is known about the physiology of cochlear pericytes. In order to investigate the function of cochlear pericytes, we developed a method to visualize cochlear pericytes using diaminofluorescein-2 diacetate (DAF-2DA) and intravital fluorescence microscopy. This method can permit the study of the effect of vasoactive agents on pericytes under the in vivo and normal physiological condition. The specificity of the labeling method was verified by the immunofluorescence labeling of pericyte maker proteins such as desmin, neural proteoglycan (NG2), and thymocyte differentiation antigen 1 (Thy-1). Superfused K(+) and Ca(2+) to the cochlear lateral wall resulted in localized constriction of capillaries at pericyte locations both in vivo and in vitro, while there was no obvious change in cochlear capillary diameters with application of the adrenergic neurotransmitter noradrenaline. The method could be an effective way to visualize cochlear pericytes and microvessels and study lateral wall vascular physiology. Moreover, we demonstrate for the first time that cochlear pericytes have contractility, which may be important for regulation of cochlear blood flow.

Predictors of functional status at service entry and discharge among young people with first episode psychosis.

PubMed

Cotton, S M; Lambert, M; Schimmelmann, B G; Filia, K; Rayner, V; Hides, L; Foley, D L; Ratheesh, A; Watson, A; Rodger, P; McGorry, P D; Conus, P

2017-05-01

Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

The Molecular Chaperone HSP90 Promotes Notch Signaling in the Germline of Caenorhabditis elegans

PubMed Central

Lissemore, James L.; Connors, Elyse; Liu, Ying; Qiao, Li; Yang, Bing; Edgley, Mark L.; Flibotte, Stephane; Taylor, Jon; Au, Vinci; Moerman, Donald G.; Maine, Eleanor M.

2018-01-01

In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40, defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90, previously known as daf-21, which encodes the C. elegans ortholog of the cytosolic form of HSP90. This protein is a molecular chaperone with a central position in the protein homeostasis network, which is responsible for proper folding, structural maintenance, and degradation of proteins. In addition to its essential role in cellular function, HSP90 plays an important role in stem cell maintenance and renewal. Complementation analysis using a deletion allele of hsp-90 confirmed that ego-3 is the same gene. hsp-90(om40) is an I→N conservative missense mutation of a highly conserved residue in the middle domain of HSP-90. RNA interference-mediated knockdown of hsp-90 expression partially phenocopied hsp-90(om40), confirming the loss-of-function nature of hsp-90(om40). Furthermore, reduced HSP-90 activity enhanced the effect of reduced function of both the GLP-1 receptor and the downstream LAG-1 transcription factor. Taken together, our results provide the first experimental evidence of an essential role for HSP90 in Notch signaling in development. PMID:29507057

Effect of functionalized and non-functionalized nanodiamond on the morphology and activities of antioxidant enzymes of lung epithelial cells (A549).

PubMed

Solarska-Ściuk, Katarzyna; Gajewska, Agnieszka; Glińska, Sława; Michlewska, Sylwia; Balcerzak, Łucja; Jamrozik, Agnieszka; Skolimowski, Janusz; Burda, Květoslava; Bartosz, Grzegorz

2014-10-05

The development of nanotechnology opens up new ways for biomedical applications of unmodified and modified diamond nanoparticles which are one of the most popular nanomaterials used in biology, biotechnology, medicine, cosmetics and engineering. They have been applied as diagnostic and therapeutic agents because they can be targeted to and localized in cells causing apoptosis and necrosis. The problem of biocompatibility of nanodiamonds at higher concentrations is thus of primary importance. The first step in the modification of DNPs is usually the introduction of hydrogen groups, which can bind other functional groups. The basic method to introduce -OH groups onto nanoparticles is the Fenton reaction. The aim of this study was to compare the effect of unmodified nanodiamond particles and nanoparticles modified by introduction of -OH groups and etoposide onto their surface reaction on human non-small lung cancer cells. A549 cells were incubated with 2-100μg/ml nanopowders and at 0.6-24μg/ml etoposide in the DMEM medium. We observed a decrease of cells viability and generation of reactive oxygen/ nitrogen species in the cells after incubation, estimated by oxidation of H2DCF-DA and DAF-FM-DA. Modified detonation nanoparticles affected also the cellular content of glutathione and activities of main antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase and catalase). The results of TEM microscopy show changes in cell morphology. These data demonstrate that modified nanoparticles induce oxidative stress in the target cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Molecular Chaperone HSP90 Promotes Notch Signaling in the Germline of Caenorhabditis elegans.

PubMed

Lissemore, James L; Connors, Elyse; Liu, Ying; Qiao, Li; Yang, Bing; Edgley, Mark L; Flibotte, Stephane; Taylor, Jon; Au, Vinci; Moerman, Donald G; Maine, Eleanor M

2018-05-04

In a genetic screen to identify genes that promote GLP-1/Notch signaling in Caenorhabditis elegans germline stem cells, we found a single mutation, om40 , defining a gene called ego-3. ego-3(om40) causes several defects in the soma and the germline, including paralysis during larval development, sterility, delayed proliferation of germline stem cells, and ectopic germline stem cell proliferation. Whole genome sequencing identified om40 as an allele of hsp-90 , previously known as daf-21 , which encodes the C. elegans ortholog of the cytosolic form of HSP90. This protein is a molecular chaperone with a central position in the protein homeostasis network, which is responsible for proper folding, structural maintenance, and degradation of proteins. In addition to its essential role in cellular function, HSP90 plays an important role in stem cell maintenance and renewal. Complementation analysis using a deletion allele of hsp-90 confirmed that ego-3 is the same gene. hsp-90(om40) is an I→N conservative missense mutation of a highly conserved residue in the middle domain of HSP-90 RNA interference-mediated knockdown of hsp-90 expression partially phenocopied hsp-90(om40) , confirming the loss-of-function nature of hsp-90(om40) Furthermore, reduced HSP-90 activity enhanced the effect of reduced function of both the GLP-1 receptor and the downstream LAG-1 transcription factor. Taken together, our results provide the first experimental evidence of an essential role for HSP90 in Notch signaling in development. Copyright © 2018 Lissemore et al.

Health-Related Quality of Life, Functional Status, and Cardiac Event-Free Survival in Patients With Heart Failure.

PubMed

Wu, Jia-Rong; Lennie, Terry A; Frazier, Susan K; Moser, Debra K

2016-01-01

Health-related quality of life (HRQOL), functional status, and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure (HF). However, the nature of the relationships among HRQOL, functional status, and cardiac event-free survival remains unclear. The purpose of this study is to examine the nature of the relationships among HRQOL, functional status, and cardiac event-free survival in patients with HF. This was a prospective, observational study of 313 patients with HF that was a secondary analysis from a registry. At baseline, patient demographic and clinical data were collected. Health-related quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire and functional status was measured using the Duke Activity Status Index. Cardiac event-free survival data were obtained by patient interview, hospital database, and death certificate review. Multiple linear and Cox regressions were used to explore the relationships among HRQOL, functional status, and cardiac event-free survival while adjusting for demographic and clinical factors. Participants (n = 313) were men (69%), white (79%), and aged 62 ± 11 years. Mean left ventricular ejection fraction was 35% ± 14%. The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status. Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status. Patients who had better functional status had better HRQOL (P < .001). Health-related quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model (P = .54), demonstrating that it was a mediator of the relationship between HRQOL and outcome. Functional status was a mediator between HRQOL and cardiac event-free survival. These data suggest that intervention studies to improve functional status are needed.

Experimental SSM-CVB3 infection in macaques.

PubMed

Han, Tiesuo; He, Wenqi; Song, Deguang; Zhao, Kui; Wu, Chenchen; Gao, Feng; Lu, Huijun; Gai, Xianying; Wang, Xinrui; Li, Fei; Ji, Cuicui; Lin, Xijuan

2012-02-01

To evaluate the pathogenicity of SSM-CVB3 in a macaque model. The clinical symptoms of macaques were recorded; hematological, biochemical and histopathological evaluations were completed; viral titers and neutralization titers (NT-titers) in sera were tested; and the mRNA levels of SSM-CVB3, coxsackievirus and adenovirus receptor (CAR) and decay accelerating factor (DAF) were determined. After SSM-CVB3 infection, the macaques showed a lack of activity, a poor appetite, a higher body temperature, and severe diarrhea. The macaques also developed hematuria and albuminuria at 4 to 10 days post-inoculation. Virus titers (5.1-6.5 LogTCID(50)/mL) were higher at 6 to 10 days post-inoculation, and NT-titers (6.5-7.3 Log2) reached plateaus at 8 to 14 days post-inoculation. The infected macaques developed serious anemia with decreased RBC and WBC, but the percentages of LYM were increased. The levels of CK, CK-MB, AST and ALT in the sera were 84-169 U/L, 87.6-271.1 U/L, 43-87 U/L and 43-82 U/L, respectively, and all of those were higher than normal. Histological analysis showed obvious cardiac, hepatic and renal damages in the infected macaques and the mRNA contents of SSM-CVB3, CAR and DAF in the heart, liver and kidneys of infected macaques were higher (P<0.05). This was the first report on experimental SSM-CVB3 infections in macaques with serious hepatic and renal damage, except for myocarditis. The information obtained from this study suggests that the SSM-CVB3 strain and this macaque model could be used for studying CVB3-induced cardiac, hepatic or renal diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of High-Throughput Method for Measurement of Vascular Nitric Oxide Generation in Microplate Reader.

PubMed

Abd El-Hay, Soad S; Colyer, Christa L

2017-01-13

Despite the importance of nitric oxide (NO) in vascular physiology and pathology, a high-throughput method for the quantification of its vascular generation is lacking. By using the fluorescent probe 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM), we have optimized a simple method for the determination of the generation of endothelial nitric oxide in a microplate format. A nitric oxide donor was used (3-morpholinosydnonimine hydrochloride, SIN-1). Different factors affecting the method were studied, such as the effects of dye concentration, different buffers, time of reaction, gain, and number of flashes. Beer's law was linear over a nanomolar range (1-10 nM) of SIN-1 with wavelengths of maximum excitation and emission at 495 and 525 nm; the limit of detection reached 0.897 nM. Under the optimized conditions, the generation of rat aortic endothelial NO was measured by incubating DAF-FM with serial concentrations (10-1000 µM) of acetylcholine (ACh) for 3 min. To confirm specificity, N ω -Nitro-l-arginine methyl ester (l-NAME)-the standard inhibitor of endothelial NO synthase-was found to inhibit the ACh-stimulated generation of NO. In addition, vessels pre-exposed for 1 h to 400 µM of the endothelial damaging agent methyl glyoxal showed inhibited NO generation when compared to the control stimulated by ACh. The capability of the method to measure micro-volume samples makes it convenient for the simultaneous handling of a very large number of samples. Additionally, it allows samples to be run simultaneously with their replicates to ensure identical experimental conditions, thus minimizing the effect of biological variability.

Carlina acaulis Exhibits Antioxidant Activity and Counteracts Aβ Toxicity in Caenorhabditis elegans.

PubMed

Link, Pille; Roth, Kevin; Sporer, Frank; Wink, Michael

2016-07-02

Carlina acaulis is a medicinal plant that has shown antioxidant activity in in vitro studies, but to date no corresponding in vivo data is available. Therefore, in the present study the antioxidant activity and its impact in counteracting Aβ toxicity were studied in the Caenorhabditis elegans model. A dichloromethane extract of the roots of C. acaulis was prepared and characterised via gas-liquid-chromatography/mass-spectrometry (GLC-MS). The in vitro antioxidant activity was confirmed via 2,2-diphenyl-1-picrylhydracyl assay. The extract was further separated by thin layer chromatography into two fractions, one of which was a fraction of the dichloromethane extract of C. acaulis containing mostly Carlina oxide (CarOx). Different strains of C. elegans were employed to study the expression of hsp-16.2p::GFP as a marker for oxidative stress, delocalisation of the transcription factor DAF-16 as a possible mechanism of antioxidant activity, the effect of the drug under lethal oxidative stress, and the effect against beta-amyloid (Aβ) toxicity in a paralysis assay. The C. acaulis extract and CarOx showed high antioxidant activity (stress reduction by 47% and 64%, respectively) in C. elegans and could activate the transcription factor DAF-16 which directs the expression of anti-stress genes. In paralysis assay, only the total extract was significantly active, delaying paralysis by 1.6 h. In conclusion, in vivo antioxidant activity was shown for C. acaulis for the first time in the C. elegans model. The active antioxidant compound is Carlina oxide. This activity, however, is not sufficient to counteract Aβ toxicity. Other mechanisms and possibly other active compounds are involved in this effect.

The temporal scaling of Caenorhabditis elegans ageing.

PubMed

Stroustrup, Nicholas; Anthony, Winston E; Nash, Zachary M; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F; Apfeld, Javier; Fontana, Walter

2016-02-04

The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.

Phosphorus uptake, partitioning and redistribution during grain filling in rice

PubMed Central

Julia, Cécile; Wissuwa, Matthias; Kretzschmar, Tobias; Jeong, Kwanho; Rose, Terry

2016-01-01

Backgrounds and Aims In cultivated rice, phosphorus (P) in grains originates from two possible sources, namely exogenous (post-flowering root P uptake from soil) or endogenous (P remobilization from vegetative parts) sources. This study investigates P partitioning and remobilization in rice plants throughout grain filling to resolve contributions of P sources to grain P levels in rice. Methods Rice plants (Oryza sativa ‘IR64’) were grown under P-sufficient or P-deficient conditions in the field and in hydroponics. Post-flowering uptake, partitioning and re-partitioning of P was investigated by quantifying tissue P levels over the grain filling period in the field conditions, and by employing 33P isotope as a tracer in the hydroponic study. Key Results Post-flowering P uptake represented 40–70 % of the aerial plant P accumulation at maturity. The panicle was the main P sink in all studies, and the amount of P potentially remobilized from vegetative tissues to the panicle during grain filling was around 20 % of the total aerial P measured at flowering. In hydroponics, less than 20 % of the P tracer taken up at 9 d after flowering (DAF) was found in the above-ground tissues at 14 DAF and half of it was partitioned to the panicle in both P treatments. Conclusions The results demonstrate that P uptake from the soil during grain filling is a critical contributor to the P content in grains in irrigated rice. The P tracer study suggests that the mechanism of P loading into grains involves little direct transfer of post-flowering P uptake to the grain but rather substantial mobilization of P that was previously taken up and stored in vegetative tissues. PMID:27590335

The temporal scaling of Caenorhabditis elegans ageing

NASA Astrophysics Data System (ADS)

Stroustrup, Nicholas; Anthony, Winston E.; Nash, Zachary M.; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F.; Apfeld, Javier; Fontana, Walter

2016-02-01

The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating the manner and extent to which specific molecular processes contribute to the aspect of ageing that determines lifespan.

Effect of exogenous GA3 and its inhibitor paclobutrazol on floral formation, endogenous hormones, and flowering-associated genes in 'Fuji' apple (Malus domestica Borkh.).

PubMed

Zhang, Songwen; Zhang, Dong; Fan, Sheng; Du, Lisha; Shen, Yawen; Xing, Libo; Li, Youmei; Ma, Juanjuan; Han, Mingyu

2016-10-01

Gibberellins (GAs) reduce apple (Malus domestica) flowering rates; however, the mechanism of their action is not fully understood. To gain a better insight into gibberellin-regulated flowering, here, 5 year-old 'Fuji' apple trees were used to explore the responses of hormones [GA1+3, GA4+7, indole-3-acetic acid (IAA), zeatin-riboside (ZR), and abscisic acid (ABA)], and gibberellin- and flowering-associated genes, to applications of gibberellin acid (GA3) and paclobutrazol (PAC). Results showed that GA3 relatively stimulated vegetative growth and delayed floral induction. Moreover, GA3 spraying significantly affected contents of all endogenous hormones and all the genes tested in at least one time points: the content of endogenous GAs was increased instantly and that of ZR was reduced at 44 days after fullbloom (DAF), which might constitute an unfavorable factor for flower formation; MdKO (ent-kaurene oxidase gene) and MdGA20ox (GA20 oxidase gene) were significantly repressed by a high level of GAs through the negative feedback regulation of GA; additionally, the MdSPLs (SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE) in this study were all significantly repressed by GA3 but promoted by PAC; the expression of MdFT1/2 (FLOWERING LOCUS T), MdSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) and MdAP1 (APETALA1) in GA3-treated buds changed in the same way, and they were repressed at 44 DAF. We suppose that GA3 spraying disrupts the balance between ZR and GAs, and inhibits floral induction, probably by suppressing MdSPLs and the floral integrators in flower induction, which ultimately contributed to inhibiting flower formation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans.

PubMed

Harvey, Simon C; Barker, Gary L A; Shorto, Alison; Viney, Mark E

2009-07-18

The free-living nematode Caenorhabditis elegans makes a developmental decision based on environmental conditions: larvae either arrest as dauer larva, or continue development into reproductive adults. There is natural variation among C. elegans lines in the sensitivity of this decision to environmental conditions; that is, there is variation in the phenotypic plasticity of dauer larva development. We hypothesised that these differences may be transcriptionally controlled in early stage larvae. We investigated this by microarray analysis of different C. elegans lines under different environmental conditions, specifically the presence and absence of dauer larva-inducing pheromone. There were substantial transcriptional differences between four C. elegans lines under the same environmental conditions. The expression of approximately 2,000 genes differed between genetically different lines, with each line showing a largely line-specific transcriptional profile. The expression of genes that are markers of larval moulting suggested that the lines may be developing at different rates. The expression of a total of 89 genes was putatively affected by dauer larva or non-dauer larva-inducing conditions. Among the upstream regions of these genes there was an over-representation of DAF-16-binding motifs. Under the same environmental conditions genetically different lines of C. elegans had substantial transcriptional differences. This variation may be due to differences in the developmental rates of the lines. Different environmental conditions had a rather smaller effect on transcription. The preponderance of DAF-16-binding motifs upstream of these genes was consistent with these genes playing a key role in the decision between development into dauer or into non-dauer larvae. There was little overlap between the genes whose expression was affected by environmental conditions and previously identified loci involved in the plasticity of dauer larva development.

Effect of GA3 treatment on seed development and seed-related gene expression in grape.

PubMed

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars ('Kyoho' and 'Red Globe'), along with a seedless cultivar ('Thompson Seedless'), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both 'Kyoho' and 'Red Globe' seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development.

Effect of GA3 Treatment on Seed Development and Seed-Related Gene Expression in Grape

PubMed Central

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D.; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

Background The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. Methodology/Principal Findings In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars (‘Kyoho’ and ‘Red Globe’), along with a seedless cultivar (‘Thompson Seedless’), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both ‘Kyoho’ and ‘Red Globe’ seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Conclusion Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development. PMID:24224035

The temporal scaling of Caenorhabditis elegans ageing

PubMed Central

Stroustrup, Nicholas; Anthony, Winston E.; Nash, Zachary M.; Gowda, Vivek; Gomez, Adam; López-Moyado, Isaac F.; Apfeld, Javier; Fontana, Walter

2016-01-01

The process of ageing makes death increasingly likely, but involves a random aspect that produces a wide distribution of lifespan even in homogeneous populations1,2. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating how and how much specific molecular processes contribute to the aspect of ageing that determines lifespan. PMID:26814965

Analysis of gene expression profiles of two near-isogenic lines differing at a QTL region affecting oil content at high temperatures during seed maturation in oilseed rape (Brassica napus L.).

PubMed

Zhu, Yana; Cao, Zhengying; Xu, Fei; Huang, Yi; Chen, Mingxun; Guo, Wanli; Zhou, Weijun; Zhu, Jun; Meng, Jinling; Zou, Jitao; Jiang, Lixi

2012-02-01

Seed oil production in oilseed rape is greatly affected by the temperature during seed maturation. However, the molecular mechanism of the interaction between genotype and temperature in seed maturation remains largely unknown. We developed two near-isogenic lines (NIL-9 and NIL-1), differing mainly at a QTL region influencing oil content on Brassica napus chromosome C2 (qOC.C2.2) under high temperature during seed maturation. The NILs were treated under different temperatures in a growth chamber after flowering. RNA from developing seeds was extracted on the 25th day after flowering (DAF), and transcriptomes were determined by microarray analysis. Statistical analysis indicated that genotype, temperature, and the interaction between genotype and temperature (G × T) all significantly affected the expression of the genes in the 25 DAF seeds, resulting in 4,982, 19,111, and 839 differentially expressed unisequences, respectively. NIL-9 had higher seed oil content than NIL-1 under all of the temperatures in the experiments, especially at high temperatures. A total of 39 genes, among which six are located at qOC.C2.2, were differentially expressed among the NILs regardless of temperature, indicating the core genetic divergence that was unaffected by temperature. Increasing the temperature caused a reduction in seed oil content that was accompanied by the downregulation of a number of genes associated with red light response, photosynthesis, response to gibberellic acid stimulus, and translational elongation, as well as several genes of importance in the lipid metabolism pathway. These results contribute to our knowledge of the molecular nature of QTLs and the interaction between genotype and temperature.

Identification and transcript profiles of citrus growth-regulating factor genes involved in the regulation of leaf and fruit development.

PubMed

Liu, Xiao; Guo, Ling-Xia; Jin, Long-Fei; Liu, Yong-Zhong; Liu, Tao; Fan, Yu-Hua; Peng, Shu-Ang

2016-10-01

Growth-regulating factor (GRF) is an important protein in GA-mediated response, with key roles in plant growth and development. However, it is not known whether or how the GRF proteins in citrus to regulate organ size. In this study, nine citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL, Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and 9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all citrus GRF genes had significantly higher expression in young leaves than mature leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8 increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect the transcript levels of CsGRF5 and CsGRF6 but significantly increased the transcript levels of the other seven CsGRF genes in young leaves. These results suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6, and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in fruit cell enlargement, which may be through GA pathway or GA-independent pathway.

Ozone inactivation of infectious prions in rendering plant and municipal wastewaters.

PubMed

Ding, Ning; Neumann, Norman F; Price, Luke M; Braithwaite, Shannon L; Balachandran, Aru; Belosevic, Miodrag; Gamal El-Din, Mohamed

2014-02-01

Disposal of tissues and organs associated with prion accumulation and infectivity in infected animals (designated as Specified Risk Materials [SRM]) is strictly regulated by the Canadian Food Inspection Agency (CFIA); however, the contamination of wastewater from slaughterhouses that handle SRM still poses public concern. In this study, we examined for the first time the partitioning of infectious prions in rendering plant wastewater and found that a large proportion of infectious prions were partitioned into the scum layer formed at the top after gravity separation, while quite a few infectious prions still remained in the wastewater. Subsequently, we assessed the ozone inactivation of infectious prions in the raw, natural gravity-separated and dissolved air flotation (DAF)-treated (i.e., primary-treated) rendering plant wastewater, and in a municipal final effluent (i.e., secondary-treated municipal wastewater). At applied ozone doses of 43.4-44.6 mg/L, ozone was instantaneously depleted in the raw rendering plant wastewater, while a greater than 4-log10 inactivation was achieved at a 5 min exposure in the DAF-treated rendering plant wastewater. Prion inactivation in the municipal final effluent was conducted with two levels of applied ozone doses of 13.4 and 22.5mg/L, and a greater than 4-log10 inactivation was achieved at a 5 min exposure with the higher ozone dose. Efficiency factor Hom (EFH) models were used to model (i.e., fit) the experimental data. The CT (disinfectant concentration multiplied by contact time) values were determined for 2- and 3-log10 inactivation in the municipal final effluent treated with an ozone dose of 13.4 mg/L. Our results indicate that ozone could serve as a final barrier for prion inactivation in primary- and/or secondary-treated wastewaters. © 2013.

Quantification of GC-biased gene conversion in the human genome

PubMed Central

Glémin, Sylvain; Arndt, Peter F.; Messer, Philipp W.; Petrov, Dmitri; Galtier, Nicolas; Duret, Laurent

2015-01-01

Much evidence indicates that GC-biased gene conversion (gBGC) has a major impact on the evolution of mammalian genomes. However, a detailed quantification of the process is still lacking. The strength of gBGC can be measured from the analysis of derived allele frequency spectra (DAF), but this approach is sensitive to a number of confounding factors. In particular, we show by simulations that the inference is pervasively affected by polymorphism polarization errors and by spatial heterogeneity in gBGC strength. We propose a new general method to quantify gBGC from DAF spectra, incorporating polarization errors, taking spatial heterogeneity into account, and jointly estimating mutation bias. Applying it to human polymorphism data from the 1000 Genomes Project, we show that the strength of gBGC does not differ between hypermutable CpG sites and non-CpG sites, suggesting that in humans gBGC is not caused by the base-excision repair machinery. Genome-wide, the intensity of gBGC is in the nearly neutral area. However, given that recombination occurs primarily within recombination hotspots, 1%–2% of the human genome is subject to strong gBGC. On average, gBGC is stronger in African than in non-African populations, reflecting differences in effective population sizes. However, due to more heterogeneous recombination landscapes, the fraction of the genome affected by strong gBGC is larger in non-African than in African populations. Given that the location of recombination hotspots evolves very rapidly, our analysis predicts that, in the long term, a large fraction of the genome is affected by short episodes of strong gBGC. PMID:25995268

S6K links cell fate, cell cycle and nutrient response in C. elegans germline stem/progenitor cells

PubMed Central

Korta, Dorota Z.; Tuck, Simon; Hubbard, E. Jane Albert

2012-01-01

Coupling of stem/progenitor cell proliferation and differentiation to organismal physiological demands ensures the proper growth and homeostasis of tissues. However, in vivo mechanisms underlying this control are poorly characterized. We investigated the role of ribosomal protein S6 kinase (S6K) at the intersection of nutrition and the establishment of a stem/progenitor cell population using the C. elegans germ line as a model. We find that rsks-1 (which encodes the worm homolog of mammalian p70S6K) is required germline-autonomously for proper establishment of the germline progenitor pool. In the germ line, rsks-1 promotes cell cycle progression and inhibits larval progenitor differentiation, promotes growth of adult tumors and requires a conserved TOR phosphorylation site. Loss of rsks-1 and ife-1 (eIF4E) together reduces the germline progenitor pool more severely than either single mutant and similarly to reducing the activity of let-363 (TOR) or daf-15 (RAPTOR). Moreover, rsks-1 acts in parallel with the glp-1 (Notch) and daf-2 (insulin-IGF receptor) pathways, and does not share the same genetic dependencies with its role in lifespan control. We show that overall dietary restriction and amino acid deprivation cause germline defects similar to a subset of rsks-1 mutant phenotypes. Consistent with a link between diet and germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely insensitive to the effects of dietary restriction. Our studies establish the C. elegans germ line as an in vivo model to understand TOR-S6K signaling in proliferation and differentiation and suggest that this pathway is a key nutrient-responsive regulator of germline progenitors. PMID:22278922

Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood

PubMed Central

Schaedel, Oren N.; Gerisch, Birgit; Antebi, Adam; Sternberg, Paul W.

2012-01-01

Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals. PMID:22505848

Toxicity interactions between manganese (Mn) and lead (Pb) or cadmium (Cd) in a model organism the nematode C. elegans.

PubMed

Lu, Cailing; Svoboda, Kurt R; Lenz, Kade A; Pattison, Claire; Ma, Hongbo

2018-06-01

Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.

Crystal Structure of Swine Vesicular Disease Virus and Implications for Host Adaptation

PubMed Central

Fry, Elizabeth E.; Knowles, Nick J.; Newman, John W. I.; Wilsden, Ginette; Rao, Zihe; King, Andrew M. Q.; Stuart, David I.

2003-01-01

Swine vesicular disease virus (SVDV) is an Enterovirus of the family Picornaviridae that causes symptoms indistinguishable from those of foot-and-mouth disease virus. Phylogenetic studies suggest that it is a recently evolved genetic sublineage of the important human pathogen coxsackievirus B5 (CBV5), and in agreement with this, it has been shown to utilize the coxsackie and adenovirus receptor (CAR) for cell entry. The 3.0-Å crystal structure of strain UK/27/72 SVDV (highly virulent) reveals the expected similarity in core structure to those of other picornaviruses, showing most similarity to the closest available structure to CBV5, that of coxsackievirus B3 (CBV3). Features that help to cement together and rigidify the protein subunits are extended in this virus, perhaps explaining its extreme tolerance of environmental factors. Using the large number of capsid sequences available for both SVDV and CBV5, we have mapped the amino acid substitutions that may have occurred during the supposed adaptation of SVDV to a new host onto the structure of SVDV and a model of the SVDV/CAR complex generated by reference to the cryo-electron microscopy-visualized complex of CBV3 and CAR. The changes fall into three clusters as follows: one lines the fivefold pore, a second maps to the CAR-binding site and partially overlaps the site for decay accelerating factor (DAF) to bind to echovirus 7 (ECHO7), and the third lies close to the fivefold axis, where the low-density lipoprotein receptor binds to the minor group of rhinoviruses. Later changes in SVDV (post-1971) map to the first two clusters and may, by optimizing recognition of a pig CAR and/or DAF homologue, have improved the adaptation of the virus to pigs. PMID:12692248

Effect of Debagging Time on Pigment Patterns in the Peel and Sugar and Organic Acid Contents in the Pulp of ‘Golden Delicious’ and ‘Qinguan’ Apple Fruit at Mid and Late Stages of Development

PubMed Central

Jing, Chenjuan; Ma, Changqing; Zhang, Juan; Jing, Shujuan; Jiang, Xiaobing; Yang, Yazhou; Zhao, Zhengyang

2016-01-01

This study examined the effect of debagging time on color and flavor / taste compounds in the non-red apple cultivar ‘Golden Delicious’ and red cultivar ‘Qinguan’ at mid and late stages of fruit development. Debagging briefly improved the red color in both cultivars, the peel of ‘Golden Delicious’ presenting pale-pink hue. However, rapid anthocyanin accumulation occurred in apple peel at a specific time (after 179 days after flowering (DAF) in ‘Qinguan’) and was unaltered by debagging time in the red cultivar ‘Qinguan’. Furthermore, untimely debagging had a detrimental effect on the content of anthocyanin. All sugars increased and organic acids decreased in apple pulp at mid to late stages of development. Bagging treatment reduced the content of most sugars and organic acids, as well as, the overall total. However, glucose and citric acid contents were higher in bagged fruit than non-bagged fruit; the maximum occurred in T7 treatment that was no-debagging at DAF 159 / 196 (‘Golden delicious’ / ‘Qinguan’), i.e., 24.35 and 0.07 mg g-1 FW in ‘Golden delicious’, and 38.86 and 0.06 mg g-1 FW in ‘Qinguan’, respectively. In a word, bagging treatment can alter the pattern of peel color development in apple fruit; however, it remains difficult to alter the timing of rapid anthocyanin accumulation as it is regulated solely by development. Moreover, bagging treatment reduced the total accumulation of sugars and organic acids, and even the over total in pulp, but increased the glucose and citric acid contents in apple pulp. PMID:27788164

Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes.

PubMed

Kwon, Dae-Jin; Kim, Dong-Hwan; Hwang, In-Sul; Kim, Dong-Ern; Kim, Hyung-Joo; Kim, Jang-Seong; Lee, Kichoon; Im, Gi-Sun; Lee, Jeong-Woong; Hwang, Seongsoo

2017-02-01

Recent progress in genetic manipulation of pigs designated for xenotransplantation ha6s shown considerable promise on xenograft survival in primates. However, genetic modification of multiple genes in donor pigs by knock-out and knock-in technologies, aiming to enhance immunological tolerance against transplanted organs in the recipients, has not been evaluated for health issues of donor pigs. We produced transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in an expression cassette containing five different human genes including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20) [GT -(DAF/CD39/TFPI/C1-INH/TNFAIP3)/+ ] that are connected by 2A peptide cleavage sequences to release individual proteins from a single translational product. All five individual protein products were successfully produced as determined by western blotting of umbilical cords from the newborn transgenic pigs. Although gross observation and histological examination revealed no significant pathological abnormality in transgenic piglets, hematological examination found that the transgenic piglets had abnormally low numbers of platelets and WBCs, including neutrophils, eosinophils, basophils, and lymphocytes. However, transgenic piglets had similar numbers of RBC and values of parameters related to RBC compared to the control littermate piglets. These data suggest that transgenic expression of those human genes in pigs impaired hematopoiesis except for erythropoiesis. In conclusion, our data suggest that transgenic expression of up to five different genes can be efficiently achieved and provide the basis for determining optimal dosages of transgene expression and combinations of the transgenes to warrant production of transgenic donor pigs without health issues.

The Relationship between Functional Status and Judgment/Problem Solving Among Individuals with Dementia

PubMed Central

Mayo, Ann M.; Wallhagen, Margaret; Cooper, Bruce A.; Mehta, Kala; Ross, Leslie; Miller, Bruce

2012-01-01

Objective To determine the relationship between functional status (independent activities of daily living) and judgment/problem solving and the extent to which select demographic characteristics such as dementia subtype and cognitive measures may moderate that relationship in older adult individuals with dementia. Methods The National Alzheimer’s Coordinating Center Universal Data Set was accessed for a study sample of 3,855 individuals diagnosed with dementia. Primary variables included functional status, judgment/problem solving, and cognition. Results Functional status was related to judgment/problem solving (r= 0.66; p< .0005). Functional status and cognition jointly predicted 56% of the variance in judgment/problem solving (R-squared = .56, p <.0005). As cognition decreases, the prediction of poorer judgment/problem solving by functional status became stronger. Conclusions Among individuals with a diagnosis of dementia, declining functional status as well as declining cognition should raise concerns about judgment/problem solving. PMID:22786576

Functional Status in ICU Survivors and out of hospital outcomes: a cohort study

PubMed Central

Rydingsward, Jessica E.; Horkan, Clare M.; Mogensen, Kris M.; Quraishi, Sadeq A.; Amrein, Karin; Christopher, Kenneth B.

2016-01-01

Objective Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. Design Single center retrospective cohort study Setting Academic Medical Center Patients 10,343 adults who received critical care from 1997 to 2011 and survived hospitalization. Interventions None Measurements and Main Results The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day post-discharge mortality compared to patients with independent functional status [OR=7.63 (95%CI 3.83, 15.22; P<0.001)]. In patients who had at least seven days of physical therapy treatment prior to hospital discharge (N=2,293), the adjusted odds of 90-day post-discharge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status [OR 0.36 (95%CI 0.24–0.53); P<0.001]. Conclusions Lower functional status at hospital discharge in survivors of critical illness is associated with increased post-discharge mortality. Further, patients whose functional status improves before discharge have decreased odds of post-discharge mortality. PMID:26929191

Trends in der IT-Sicherheit

NASA Astrophysics Data System (ADS)

Eckert, Claudia

Ich möchte Ihnen einen Überblick geben über Trends, Challenges, offene Fragestellungen sowie Lösungsansätze aus dem Bereich der IT-Sicherheit. Meine Vorredner haben mir schon eine wunderbare Basis dafür geschaffen, indem sie wichtige Trends im Bereich IT bereits angesprochen haben. Deshalb werde ich auf diese Trends, nämlich das Internet of Things and Services nur noch einmal kurz eingehen, um daran dann die IT-Sicherheitsthemen, die sich aus diesen IT-Trends ergeben, zu skizzieren und anschließend Lösungen vorstellen, die insbesondere im Forschungsumfeld entwickelt werden, aber schon reif sind, auch in die unternehmerische Praxis übernommen zu werden.

Alternative Antriebe für Automobile: Hybridsysteme, Brennstoffzellen, alternative Energieträger

NASA Astrophysics Data System (ADS)

Stan, Cornel

Über die Realisierungsmöglichkeiten zukünftiger Antriebskonzepte - von Hybridsystemen Elektro-/Verbrennungsmotor über Brennstoffzellen bis zu alternativen Energieträgern wie Wasserstoff oder Alkohol - werden fundierte Kriterien der Qualität eines Antriebs entscheiden. Leistungsdichte, Drehmomentverlauf, Beschleunigungscharakteristik, spezifischer Energieverbrauch sowie Emission chemischer Stoffe und Geräusche sind dafür wichtige Merkmale zur Qualitätsbeurteilung. Die Verfügbarkeit und die Speicherfähigkeit vorgesehener Energieträger, die technische Komplexität, Kosten, Sicherheit, Infrastruktur und Service werden die Randbedingungen für die Einführung realisierbarer Konzepte alternativer Antriebe für Automobile stellen.

Identification of the numerical model of FEM in reference to measurements in situ

NASA Astrophysics Data System (ADS)

Jukowski, Michał; Bec, Jarosław; Błazik-Borowa, Ewa

2018-01-01

The paper deals with the verification of various numerical models in relation to the pilot-phase measurements of a rail bridge subjected to dynamic loading. Three types of FEM models were elaborated for this purpose. Static, modal and dynamic analyses were performed. The study consisted of measuring the acceleration values of the structural components of the object at the moment of the train passing. Based on this, FFT analysis was performed, the main natural frequencies of the bridge were determined, the structural damping ratio and the dynamic amplification factor (DAF) were calculated and compared with the standard values. Calculations were made using Autodesk Simulation Multiphysics (Algor).

Direct and indirect effects of nutritional status, physical function and cognitive function on activities of daily living in Japanese older adults requiring long-term care.

PubMed

Kamo, Tomohiko; Nishida, Yuusuke

2014-10-01

To identify the direct and indirect effects of nutritional status, physical function, and cognitive function on activities of daily living in Japanese older adults requiring long-term care. In total, 179 participants aged ≥ 65 years who were eligible for long-term care insurance (mean age 85.5 ± 7.8 years) were recruited for this study. Nutritional status (Mini Nutritional Assessment, Short Form) and physical function (Short Physical Performance Battery) were examined. Activities of daily living, cognitive function and frailty were assessed using the Barthel Index, Mini-Mental State Examination and Clinical Frailty Scale, respectively. Path analysis was used to determine relationships between these factors and the activities of daily living. For Japanese older adults requiring long-term care, pathways were modeled for nutritional status, physical function and the activities of daily living. The total effect of nutritional status was 0.516 (P<0.001). The indirect effect of nutritional status through physical function on the activities of daily living was 0.458 (P<0.001). Finally, no significant direct effect of nutritional status on activities of daily living was observed (b=0.058, P=0.258). The present study identified the complex pathway from nutritional status to the activities of daily living through physical function in aged Japanese people requiring long-term care. These findings suggest that maintaining good nutritional status and nutritional support might delay physical function decline, and prolong the activities of daily living. © 2013 Japan Geriatrics Society.

Assessment of nutritional status in the elderly: a proposed function-driven model.

PubMed

Engelheart, Stina; Brummer, Robert

2018-01-01

There is no accepted or standardized definition of 'malnutrition'. Hence, there is also no definition of what constitutes an adequate nutritional status. In elderly people, assessment of nutritional status is complex and is complicated by multi-morbidity and disabilities combined with nutrition-related problems, such as dysphagia, decreased appetite, fatigue, and muscle weakness. We propose a nutritional status model that presents nutritional status from a comprehensive functional perspective. This model visualizes the complexity of the nutritional status in elderly people. The presented model could be interpreted as the nutritional status is conditional to a person's optimal function or situation. Another way of looking at it might be that a person's nutritional status affects his or her optimal situation. The proposed model includes four domains: (1) physical function and capacity; (2) health and somatic disorders; (3) food and nutrition; and (4) cognitive, affective, and sensory function. Each domain has a major impact on nutritional status, which in turn has a major impact on the outcome of each domain. Nutritional status is a multifaceted concept and there exist several knowledge gaps in the diagnosis, prevention, and optimization of treatment of inadequate nutritional status in elderly people. The nutritional status model may be useful in nutritional assessment research, as well as in the clinical setting.

Regression-Based Estimates of Observed Functional Status in Centenarians

PubMed Central

Mitchell, Meghan B.; Miller, L. Stephen; Woodard, John L.; Davey, Adam; Martin, Peter; Burgess, Molly; Poon, Leonard W.

2011-01-01

Purpose of the Study: There is lack of consensus on the best method of functional assessment, and there is a paucity of studies on daily functioning in centenarians. We sought to compare associations between performance-based, self-report, and proxy report of functional status in centenarians. We expected the strongest relationships between proxy reports and observed performance of basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs). We hypothesized that the discrepancy between self-report and observed daily functioning would be modified by cognitive status. We additionally sought to provide clinicians with estimates of centenarians’ observed daily functioning based on their mental status in combination with subjective measures of activities of daily living (ADLs). Design and Methods: Two hundred and forty-four centenarians from the Georgia Centenarian Study were included in this cross-sectional population-based study. Measures included the Direct Assessment of Functional Status, self-report and proxy report of functional status, and the Mini-Mental State Examination (MMSE). Results: Associations between observed and proxy reports were stronger than between observed and self-report across BADL and IADL measures. A significant MMSE by type of report interaction was found, indicating that lower MMSE performance is associated with a greater discrepancy between subjective and objective ADL measures. Implications: Results demonstrate associations between 3 methods of assessing functional status and suggest proxy reports are generally more accurate than self-report measures. Cognitive status accounted for some of the discrepancy between observed and self-reports, and we provide clinicians with tables to estimate centenarians’ performance on observed functional measures based on MMSE and subjective report of functional status. PMID:20974657

Cognitive function in older adults according to current socioeconomic status.

PubMed

Zhang, Michael; Gale, Shawn D; Erickson, Lance D; Brown, Bruce L; Woody, Parker; Hedges, Dawson W

2015-01-01

Cognitive function may be influenced by education, socioeconomic status, sex, and health status. Furthermore, aging interacts with these factors to influence cognition and dementia risk in late life. Factors that may increase or decrease successful cognitive aging are of critical importance, particularly if they are modifiable. The purpose of this study was to determine if economic status in late life is associated with cognition independent of socioeconomic status in early life. Cross-sectional demographic, socioeconomic, and cognitive function data were obtained in 2592 older adults (average age 71.6 years) from the Center for Disease Control's National Health and Nutrition Examination Survey (NHANES) and analyzed with linear regression modeling. Cognitive function, as measured with a test of processing speed, was significantly associated with poverty index scores after adjusting for educational attainment as an estimate of childhood socioeconomic status, ethnic background, age, health status, and sex (P < 0.001). Our findings suggest that current economic status is independently associated with cognitive function in adults over age 60 years.

Functional Status of Long-Term Breast Cancer Survivors: Demonstrating Chronicity.

ERIC Educational Resources Information Center

Polinsky, Margaret L.

1994-01-01

Surveyed 223 breast cancer survivors 16 months to 32 years from original surgery to assess their current physical, psychological, and social functional status. Although general measures of functioning indicated high physical, psychological, and social functional status, measures specific to breast cancer diagnosis and treatment indicated problems…

Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

PubMed

Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

2014-01-01

Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

An ancient role for nitric oxide in regulating the animal pelagobenthic life cycle: evidence from a marine sponge

PubMed Central

Ueda, Nobuo; Richards, Gemma S.; Degnan, Bernard M.; Kranz, Alexandrea; Adamska, Maja; Croll, Roger P.; Degnan, Sandie M.

2016-01-01

In many marine invertebrates, larval metamorphosis is induced by environmental cues that activate sensory receptors and signalling pathways. Nitric oxide (NO) is a gaseous signalling molecule that regulates metamorphosis in diverse bilaterians. In most cases NO inhibits or represses this process, although it functions as an activator in some species. Here we demonstrate that NO positively regulates metamorphosis in the poriferan Amphimedon queenslandica. High rates of A. queenslandica metamorphosis normally induced by a coralline alga are inhibited by an inhibitor of nitric oxide synthase (NOS) and by a NO scavenger. Consistent with this, an artificial donor of NO induces metamorphosis even in the absence of the alga. Inhibition of the ERK signalling pathway prevents metamorphosis in concert with, or downstream of, NO signalling; a NO donor cannot override the ERK inhibitor. NOS gene expression is activated late in embryogenesis and in larvae, and is enriched in specific epithelial and subepithelial cell types, including a putative sensory cell, the globular cell; DAF-FM staining supports these cells being primary sources of NO. Together, these results are consistent with NO playing an activating role in induction of A. queenslandica metamorphosis, evidence of its highly conserved regulatory role in metamorphosis throughout the Metazoa. PMID:27874071

Fatigue, pain, and functional status during outpatient chemotherapy.

PubMed

Siefert, Mary Lou

2010-03-01

To examine the relationship of fatigue and pain with functional status and the pattern of the two symptoms' occurrence over time in individuals with cancer who were receiving outpatient chemotherapy. The aims were to describe the levels of fatigue and pain with functional status and the inter-relationships with each other and with demographic and clinical variables over time. Descriptive, correlational. Outpatient chemotherapy clinic in the New England region of the United States. Total available population of 70 consecutive adult patients with breast cancer (n = 9), colorectal cancer (n = 21), lung cancer (n = 21), or lymphoma (n = 19). Retrospective data were extracted from the medical records; descriptive, correlational, and mixed-modeling methods were used to describe the sample and to examine the relationships of the symptoms and functional status. Fatigue, pain, functional status, and demographic and clinical factors. Fatigue was the most frequently reported symptom; pain was rarely and almost exclusively reported by patients with lung cancer or lymphoma during their early treatments. Fatigue and functional status impairment were highly associated with each other and had similar relationships with the other variables. The patterns and relationships of fatigue and functional status reported by this fairly healthy sample provide useful information to help guide early assessments and nursing interventions for people receiving outpatient chemotherapy. The patterns and severity of symptoms and functional status impairment in people with colorectal cancer or lymphoma warrant further investigation. Targeted exercise interventions for specific outpatient populations should be developed and tested to address specific patterns of symptoms and functional status impairment in individuals with cancer.

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at www.controlled-trials.com as ISRCTN54195799. © 2016 American Society for Nutrition.

The relationship between patient functional status and environmental contamination by Clostridium difficile: a pilot study

PubMed Central

Blakney, Rebekah; Gudnadottir, Unnur; Warrack, Simone; O'Horo, John C.; Anderson, Michael; Sethi, Ajay; Schmitz, Michelle; Wang, Jennifer; Duster, Megan; Ide, Emma; Safdar, Nasia

2016-01-01

Introduction Limited data exist on patient factors related to environmental contamination with Clostridium difficile. Methods We evaluated the association between the functional status of patients with C. difficile infection (CDI) and environmental contamination with C. difficile. Results Contamination of patient rooms was frequent and higher functional status was associated with contaminated surfaces remote from the bed. All but one environmental isolates matched the corresponding patient's stool isolate for the seven patients tested. Conclusion Functional status is a factor that influences environmental contamination with C. difficile. Future studies should evaluate strategies to reduce contamination in CDI patient rooms, taking into account the patient's functional status. PMID:25869819

Influence of educational status on executive function and functional balance in individuals with Parkinson disease.

PubMed

Souza, Carolina de Oliveira; Voos, Mariana Callil; Francato, Débora Valente; Chien, Hsin Fen; Barbosa, Egberto Reis

2013-03-01

This study investigated whether educational status influenced how people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the Trail Making Test (TMT) and on the Berg Balance Scale (BBS). Recent studies have shown that educational status may influence cognitive and motor test performance. We gave the TMT and the BBS to assess executive function and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and 3) and 30 healthy elderly people. Participants reported their number of years of formal education. We divided each group of participants by educational status: low (4 to 10 years of education) or high (≥11 years). In both the PD (P=0.018) and control (P=0.003) groups, participants with low educational status performed worse on the TMT Part B than did those with high educational status. Within the PD group, the less-educated participants scored worse on the BBS than did the more educated (P<0.001); this difference was not significant between the more- and less-educated controls (P=0.976). Whether or not they had PD, less-educated people performed worse than more-educated people on the TMT Part B. Educational status affected executive function, but PD status did not. Among individuals with PD, educational status influenced functional balance.

Assessment of nutritional status in the elderly: a proposed function-driven model

PubMed Central

Engelheart, Stina; Brummer, Robert

2018-01-01

Background There is no accepted or standardized definition of ‘malnutrition’. Hence, there is also no definition of what constitutes an adequate nutritional status. In elderly people, assessment of nutritional status is complex and is complicated by multi-morbidity and disabilities combined with nutrition-related problems, such as dysphagia, decreased appetite, fatigue, and muscle weakness. Objective We propose a nutritional status model that presents nutritional status from a comprehensive functional perspective. This model visualizes the complexity of the nutritional status in elderly people. Design and results The presented model could be interpreted as the nutritional status is conditional to a person’s optimal function or situation. Another way of looking at it might be that a person’s nutritional status affects his or her optimal situation. The proposed model includes four domains: (1) physical function and capacity; (2) health and somatic disorders; (3) food and nutrition; and (4) cognitive, affective, and sensory function. Each domain has a major impact on nutritional status, which in turn has a major impact on the outcome of each domain. Conclusions Nutritional status is a multifaceted concept and there exist several knowledge gaps in the diagnosis, prevention, and optimization of treatment of inadequate nutritional status in elderly people. The nutritional status model may be useful in nutritional assessment research, as well as in the clinical setting. PMID:29720931

FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan

2016-09-01

Cellular protein quality can be maintained by proteolytic elimination of damaged proteins and replacing them with newly synthesized copies, a process called protein turnover (Ward, 2000). Protein turnover rates have been estimated using SILAC (stable isotope labeling by amino acids in cell culture) in prokaryotes and eukaryotes. The last decade has witnessed a growing interest in the analysis of whole-organism proteome dynamics in metazoans using the same approach (Claydon and Beynon, 2012). In recent work, SILAC was applied to monitor protein synthesis throughout life in adult Caenorhabditis elegans (Vukoti et al., 2015) and to investigate food intake (Gomez-Amaro et al.,more » 2015« less

Vermittlungstechnik

NASA Astrophysics Data System (ADS)

Plaßmann, Wilfried

In einem vorhandenen Nachrichtennetz sorgt die Vermittlungstechnik dafür, dass Informationen zu jeder Zeit von einem beliebigen Zugangspunkt zu einem beliebigen anderen Zugangspunkt übertragen werden können. Der gesamte Vorgang wird mit Vermittlung bezeichnet. Das größte weltweit vorhandene Nachrichtennetz ist das kombinierte Internet-Telefonnetz. Die Zugangspunkte sind die Anschlusspunkte (ortsfeste Anschlussdosen) für die Endgeräte, wie z. B. Rechner, Telefonapparate, Faxgeräte oder Modems, oder aber ortsveränderliche Endgeräte wie Laptops, schnurlose Telefone oder Funktelefone ("Handys"). Die Vermittlungsstelle klassischer Art mit hierarchischem Aufbau ist nahezu vollständig durch komplexe rechnergesteuerte national arbeitende Anlagen ersetzt worden. In diesem Kapitel werden deshalb grundlegende Eigenschaften dargestellt. Stichworte: Grundbegriffe; Vermittlung; Verkehrstheorie; Endgeräte.

Open architecture design and approach for the Integrated Sensor Architecture (ISA)

NASA Astrophysics Data System (ADS)

Moulton, Christine L.; Krzywicki, Alan T.; Hepp, Jared J.; Harrell, John; Kogut, Michael

2015-05-01

Integrated Sensor Architecture (ISA) is designed in response to stovepiped integration approaches. The design, based on the principles of Service Oriented Architectures (SOA) and Open Architectures, addresses the problem of integration, and is not designed for specific sensors or systems. The use of SOA and Open Architecture approaches has led to a flexible, extensible architecture. Using these approaches, and supported with common data formats, open protocol specifications, and Department of Defense Architecture Framework (DoDAF) system architecture documents, an integration-focused architecture has been developed. ISA can help move the Department of Defense (DoD) from costly stovepipe solutions to a more cost-effective plug-and-play design to support interoperability.

Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway

PubMed Central

Williams, David S.; Cash, Alan; Hamadani, Lara; Diemer, Tanja

2010-01-01

Summary Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction. PMID:19793063

Nutritional status according to Mini Nutritional Assessment is related to functional status in geriatric patients--independent of health status.

PubMed

Schrader, E; Baumgärtel, C; Gueldenzoph, H; Stehle, P; Uter, W; Sieber, C C; Volkert, D

2014-03-01

The aim of this study was to investigate the relationship between nutritional and functional status in acute geriatric patients including mobility and considering health status. Cross-sectional study. Hospital. 205 geriatric patients (median age 82.0 (IQR: 80-86) years, 69.3% women). Nutritional status was determined by Mini Nutritional Assessment (MNA) and patients were categorized as well-nourished (≥ 24 points), at risk of malnutrition (17-23.5 points) or as malnourished (< 17 points). Functional status was determined by Barthel Index (BI) and Timed 'Up and Go' Test (TUG) and related to MNA categories. Using binary multiple logistic regression the impact of nutritional status on functional status was examined, adjusted for health status. 60.3% of the patients were at risk of malnutrition and 29.8% were malnourished. Ability to perform basic activities of daily living (ADL) decreased with declining nutritional status. The proportion of patients unable to perform the TUG increased with worsening of nutritional status (45.0% vs. 50.4% vs. 77.0%, p<0.01). After adjusting for age, gender, number of diagnoses, disease severity and cognitive function, a higher MNA score significantly lowered the risk of being dependent in ADL (OR 0.85, 95 % CI 0.77-0.94) and inability to perform the TUG (OR 0.90, 95 % CI 0.82-0.99). Nutritional status according to MNA was related to ADL as well as to mobility in acute geriatric patients. This association remained after adjusting for health status.

Physicochemical, pasting, and functional properties of amaranth seed flours: effects of lipids removal.

PubMed

Shevkani, Khetan; Singh, Narpinder; Kaur, Amritpal; Rana, Jai Chand

2014-07-01

The present work was carried out to evaluate physicochemical (composition, hunter color, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]), pasting, and functional properties (foaming, emulsification, water, and fat absorption capacity) of amaranth full-fat flours from 6 lines/cultivars (AFs), and to see the effects of lipid removal/defatting on these properties. Protein, ash, and lipid content of AFs ranged between 12.5% to 15.2%, 3.0% to 3.5%, and 7.1% to 8.0%, respectively. The flours showed a number of bands between 97 and 7 kDa, with main subunits of approximately 58, 37, 33, 31, 23, and 16 kDa in the SDS-PAGE profiles. The protein content and L* value increased, while b* values decreased following defatting for most of the lines/cultivars. The defatted flours (DAFs) had higher final viscosity and stability (lower breakdown viscosity) as compared to counterpart AFs. The protein profiling of the flours was not affected with the lipid removal/defatting. However, water absorption capacity and foam stability of the flours improved upon defatting. Principal component analysis revealed that pasting temperature was positively related to lipid content, while breakdown viscosity was negatively related to protein content. Foaming properties (capacity and stability) showed negative relationship with lipid content, and positive with protein content, ash content, water, and fat absorption capacity. Amaranth grains are known to have higher amount of proteins and lipids than cereals. Amaranth lipids are rich in unsaturated fatty acids, which are prone to oxidative rancidity. Removal of lipids or defatting of flours may be carried out to enhance product shelf life by preventing undesirable oxidative chain reactions. Therefore, this research was undertaken to see the effects of defatting on the functional properties of amaranth flours. The defatting was a value addition process as it improved the functional properties of the flours. © 2014 Institute of Food Technologists®

Methane in the Upper Silesian Coal Basin (Poland) - problem of reserves and exploitation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wojcik, A.J.

1995-08-01

The Upper Silesian Coal Basin (USCB) is the best recognized and the most productive coal basin in Poland. The USCB is primarily defined by the extent of Carboniferous coal-bearing formations. The sedimentary fill displays the stratigraphic record of major progressive inversion phases of the entire Moravo-Silesian basin during the late and post-geosynclinal period of the Variscan orogeny. According to the last estimates the coal reserves occurring above the depth limit of 1500 in are as follows: documented reserves - 58 billion tons, prognostic reserves - 46 billion tons, total - 104 billion tons. The coal type is predominantly vitrinitic, andmore » ash content is reported to be in the range of 11-17% and average sulphur content is 1.13%. The rank of USCB coal is largely controlled by complex coalification processes. It ranges from high volatile bituminous B, through medium volatile bituminous to high rank special coal semi anthracite and anthracite. The methane content of coal seams in USCB varies in a very broad range of 0-22 m{sup 3}/t coal (dry, ash free basis). The average gas content increases considerably within the depth range 600-1000 in from 0.99 to 4.68 m{sup 3}/t coal (daf). In deeper horizons it is more or less stable varying within the range of 4.7-7.0 m{sup 3}/t coal (daf). By this estimate, on average, the methane content is about 12,5 m{sup 3}/ton. There are several estimates of coal-bed methane resources in the USCB based on different methods. The resources are as follows: documented deposits in active mines to 1000 m: 370 BCM, undeveloped deposits to 1000 in: 340 BCM, deposit between 1000 and 1500 m: 590 BCM, total: 1300 BCM. The coalbed gas from this basin is primarily composed of saturated hydrocarbons and Nitrogen which amount to 97 volume percent. The rest is dominant by Carbon dioxide and Hydrogen.« less

The role of algal organic matter in the separation of algae and cyanobacteria using the novel "Posi" - Dissolved air flotation process.

PubMed

Hanumanth Rao, Narasinga Rao; Yap, Russell; Whittaker, Michael; Stuetz, Richard M; Jefferson, Bruce; Peirson, William L; Granville, Anthony M; Henderson, Rita K

2018-03-01

Algae and cyanobacteria frequently require separation from liquid media in both water treatment and algae culturing for biotechnology applications. The effectiveness of cell separation using a novel dissolved air flotation process that incorporates positively charged bubbles (PosiDAF) has recently been of interest but has been shown to be dependent on the algae or cyanobacteria species tested. Previously, it was hypothesised that algal organic matter (AOM) could be impacting the separation efficiency. Hence, this study investigates the influence of AOM on cell separation using PosiDAF, in which bubbles are modified using a commercially available cationic polyelectrolyte poly(N, N-diallyl-N,N-dimethylammonium chloride) (PDADMAC). The separation of Chlorella vulgaris CS-42/7, Mychonastes homosphaera CS-556/01 and two strains of Microcystis aeruginosa (CS-564/01 and CS-555/1), all of which have similar cell morphology but different AOM character, was investigated. By testing the cell separation in the presence and absence of AOM, it was determined that AOM enhanced cell separation for all the strains but to different extents depending on the quantity and composition of carbohydrates and proteins in the AOM. By extracting AOM from the strain for which optimal separation was observed and adding it to the others, cell separation improved from <55% to >90%. This was attributed to elevated levels of acidic carbohydrates as well as glycoprotein-carbohydrate conjugations, which in turn were related to the nature and quantity of proteins and carbohydrates present in the AOM. Therefore, it was concluded that process optimisation requires an in-depth understanding of the AOM and its components. If culturing algae for biotechnology applications, this indicates that strain selection is not only important with respect to high value product content, but also for cell separation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Marshall Application Realignment System (MARS) Architecture

NASA Technical Reports Server (NTRS)

Belshe, Andrea; Sutton, Mandy

2010-01-01

The Marshall Application Realignment System (MARS) Architecture project was established to meet the certification requirements of the Department of Defense Architecture Framework (DoDAF) V2.0 Federal Enterprise Architecture Certification (FEAC) Institute program and to provide added value to the Marshall Space Flight Center (MSFC) Application Portfolio Management process. The MARS Architecture aims to: (1) address the NASA MSFC Chief Information Officer (CIO) strategic initiative to improve Application Portfolio Management (APM) by optimizing investments and improving portfolio performance, and (2) develop a decision-aiding capability by which applications registered within the MSFC application portfolio can be analyzed and considered for retirement or decommission. The MARS Architecture describes a to-be target capability that supports application portfolio analysis against scoring measures (based on value) and overall portfolio performance objectives (based on enterprise needs and policies). This scoring and decision-aiding capability supports the process by which MSFC application investments are realigned or retired from the application portfolio. The MARS Architecture is a multi-phase effort to: (1) conduct strategic architecture planning and knowledge development based on the DoDAF V2.0 six-step methodology, (2) describe one architecture through multiple viewpoints, (3) conduct portfolio analyses based on a defined operational concept, and (4) enable a new capability to support the MSFC enterprise IT management mission, vision, and goals. This report documents Phase 1 (Strategy and Design), which includes discovery, planning, and development of initial architecture viewpoints. Phase 2 will move forward the process of building the architecture, widening the scope to include application realignment (in addition to application retirement), and validating the underlying architecture logic before moving into Phase 3. The MARS Architecture key stakeholders are most interested in Phase 3 because this is where the data analysis, scoring, and recommendation capability is realized. Stakeholders want to see the benefits derived from reducing the steady-state application base and identify opportunities for portfolio performance improvement and application realignment.

Gene Cloning, Expression and Enzyme Activity of Vitis vinifera Vacuolar Processing Enzymes (VvVPEs)

PubMed Central

Gong, Peijie; Li, Shuxiu; Wang, Yuejin; Zhang, Chaohong

2016-01-01

Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvβVPE, VvγVPE, and VvδVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the ‘Vitis vinifera cv. Pinot Noir’ and ‘Vitis vinifera cv. Thompson Seedless’ varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvγVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvδVPE is only expressed in flowers, buds and ovules, that VvγVPE is expressed in various tissues, and that VvβVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvβVPE in seeded grapes increased significantly at 30 days after full-bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvβVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs. PMID:27551866

Phosphorus uptake, partitioning and redistribution during grain filling in rice.

PubMed

Julia, Cécile; Wissuwa, Matthias; Kretzschmar, Tobias; Jeong, Kwanho; Rose, Terry

2016-11-01

In cultivated rice, phosphorus (P) in grains originates from two possible sources, namely exogenous (post-flowering root P uptake from soil) or endogenous (P remobilization from vegetative parts) sources. This study investigates P partitioning and remobilization in rice plants throughout grain filling to resolve contributions of P sources to grain P levels in rice. Rice plants (Oryza sativa 'IR64') were grown under P-sufficient or P-deficient conditions in the field and in hydroponics. Post-flowering uptake, partitioning and re-partitioning of P was investigated by quantifying tissue P levels over the grain filling period in the field conditions, and by employing 33 P isotope as a tracer in the hydroponic study. Post-flowering P uptake represented 40-70 % of the aerial plant P accumulation at maturity. The panicle was the main P sink in all studies, and the amount of P potentially remobilized from vegetative tissues to the panicle during grain filling was around 20 % of the total aerial P measured at flowering. In hydroponics, less than 20 % of the P tracer taken up at 9 d after flowering (DAF) was found in the above-ground tissues at 14 DAF and half of it was partitioned to the panicle in both P treatments. The results demonstrate that P uptake from the soil during grain filling is a critical contributor to the P content in grains in irrigated rice. The P tracer study suggests that the mechanism of P loading into grains involves little direct transfer of post-flowering P uptake to the grain but rather substantial mobilization of P that was previously taken up and stored in vegetative tissues. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A De novo Transcriptomic Approach to Identify Flavonoids and Anthocyanins “Switch-Off” in Olive (Olea europaea L.) Drupes at Different Stages of Maturation

PubMed Central

Iaria, Domenico L.; Chiappetta, Adriana; Muzzalupo, Innocenzo

2016-01-01

Highlights A de novo transcriptome reconstruction of olive drupes was performed in two genotypesGene expression was monitored during drupe development in two olive cultivarsTranscripts involved in flavonoid and anthocyanin pathways were analyzed in Cassanese and Leucocarpa cultivarsBoth cultivar and developmental stage impact gene expression in Olea europaea fruits. During ripening, the fruits of the olive tree (Olea europaea L.) undergo a progressive chromatic change characterized by the formation of a red-brown “spot” which gradually extends on the epidermis and in the innermost part of the mesocarp. This event finds an exception in the Leucocarpa cultivar, in which we observe a destabilized equilibrium between the metabolisms of chlorophyll and other pigments, particularly the anthocyanins whose switch-off during maturation promotes the white coloration of fruits. Despite its importance, genomic information on the olive tree is still lacking. Different RNA-seq libraries were generated from drupes of “Leucocarpa” and “Cassanese” olive genotypes, sampled at 100 and 130 days after flowering (DAF), and were used in order to identify transcripts involved in the main phenotypic changes of fruits during maturation and their corresponding expression patterns. A total of 103,359 transcripts were obtained and 3792 and 3064 were differentially expressed in “Leucocarpa” and “Cassanese” genotypes, respectively, during 100–130 DAF transition. Among them flavonoid and anthocyanin related transcripts such as phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavonol 3′-hydrogenase (F3′H), flavonol 3′5 ′-hydrogenase (F3′5′H), flavonol synthase (FLS), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), UDP-glucose:anthocianidin: flavonoid glucosyltransferase (UFGT) were identified. These results contribute to reducing the current gap in information regarding metabolic processes, including those linked to fruit pigmentation in the olive. PMID:26834761

Complement in Lupus Nephritis: New Perspectives.

PubMed

Bao, Lihua; Cunningham, Patrick N; Quigg, Richard J

2015-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

Analysis of cDNA libraries from developing seeds of guar (Cyamopsis tetragonoloba (L.) Taub)

PubMed Central

Naoumkina, Marina; Torres-Jerez, Ivone; Allen, Stacy; He, Ji; Zhao, Patrick X; Dixon, Richard A; May, Gregory D

2007-01-01

Background Guar, Cyamopsis tetragonoloba (L.) Taub, is a member of the Leguminosae (Fabaceae) family and is economically the most important of the four species in the genus. The endosperm of guar seed is a rich source of mucilage or gum, which forms a viscous gel in cold water, and is used as an emulsifier, thickener and stabilizer in a wide range of foods and industrial applications. Guar gum is a galactomannan, consisting of a linear (1→4)-β-linked D-mannan backbone with single-unit, (1→6)-linked, α-D-galactopyranosyl side chains. To better understand regulation of guar seed development and galactomannan metabolism we created cDNA libraries and a resulting EST dataset from different developmental stages of guar seeds. Results A database of 16,476 guar seed ESTs was constructed, with 8,163 and 8,313 ESTs derived from cDNA libraries I and II, respectively. Library I was constructed from seeds at an early developmental stage (15–25 days after flowering, DAF), and library II from seeds at 30–40 DAF. Quite different sets of genes were represented in these two libraries. Approximately 27% of the clones were not similar to known sequences, suggesting that these ESTs represent novel genes or may represent non-coding RNA. The high flux of energy into carbohydrate and storage protein synthesis in guar seeds was reflected by a high representation of genes annotated as involved in signal transduction, carbohydrate metabolism, chaperone and proteolytic processes, and translation and ribosome structure. Guar unigenes involved in galactomannan metabolism were identified. Among the seed storage proteins, the most abundant contig represented a conglutin accounting for 3.7% of the total ESTs from both libraries. Conclusion The present EST collection and its annotation provide a resource for understanding guar seed biology and galactomannan metabolism. PMID:18034910

Gene Cloning, Expression and Enzyme Activity of Vitis vinifera Vacuolar Processing Enzymes (VvVPEs).

PubMed

Tang, Yujin; Wang, Ruipu; Gong, Peijie; Li, Shuxiu; Wang, Yuejin; Zhang, Chaohong

2016-01-01

Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvβVPE, VvγVPE, and VvδVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the 'Vitis vinifera cv. Pinot Noir' and 'Vitis vinifera cv. Thompson Seedless' varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvγVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvδVPE is only expressed in flowers, buds and ovules, that VvγVPE is expressed in various tissues, and that VvβVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvβVPE in seeded grapes increased significantly at 30 days after full-bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvβVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs.

Pre-fracture nutritional status is predictive of functional status at discharge during the acute phase with hip fracture patients: A multicenter prospective cohort study.

PubMed

Inoue, Tatsuro; Misu, Syogo; Tanaka, Toshiaki; Sakamoto, Hiroki; Iwata, Kentaro; Chuman, Yuki; Ono, Rei

2017-10-01

Malnutrition is common in patients with hip fractures, and elderly patients with hip fractures lose functional independence and often fail to recover previous functional status. The aim of this study was to determine whether pre-fracture nutritional status predicts functional status of patients with hip fracture at discharge from acute hospitals. In the present multicenter prospective cohort study, pre-fracture nutritional status was assessed using the Mini Nutritional Assessment Short-Form (MNA-SF). At discharge from acute hospitals, functional status was evaluated using a functional independent measurement instrument (FIM). Subsequently, multiple regression analyses were performed using FIM as the dependent variable and MNA-SF as the independent variable. Among the 204 patients analyzed in the present study, the mean length of hospital stay was 26.2 ± 12.6 days, and according to MNA-SF assessments, 51 (25.0%) patients were malnourished, 98 (48.0%) were at risk of malnutrition, and 55 (27.0%) were well-nourished before fracture. At discharge, FIM scores were higher in patients who were well-nourished than in those who were malnourished or were at risk of malnutrition (p < 0.01). After adjustment for confounding factors, multiple regression analyses showed that MNA-SF was a significant independent predictor for FIM at discharge (well-nourished vs. malnourished, β = -0.86, p < 0.01). Pre-fracture nutritional status was a significant independent predictor for functional status at discharge during the acute phase, warranting early assessment of nutritional status and early intervention for successful postoperative rehabilitation. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Spirituality and sexual orientation: relationship to mental well-being and functional health status.

PubMed

Coleman, Christopher L

2003-09-01

Research has shown that spirituality has a positive effect on physical and mental health; however, few studies have explored the influence of spirituality and sexuality on mental well-being and functional health status in people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). This descriptive cross-sectional study was designed to examine the relationships among spirituality, sexual orientation, mental well-being and aspects of functional health status (physical, role, social and cognitive functioning) in a sample of 117 African-American men and women living with HIV/AIDS. Spirituality was measured using the Spiritual Well-Being Scale. A demographic questionnaire gathered data on sexual orientation, age and gender. The Medical Outcomes Study Questionnaire-30 assessed aspects of functional health status and mental well-being. The HIV Symptom Checklist for Persons With HIV disease was used to collect data on HIV symptoms. The data were collected in 1996. The findings indicate that spirituality had a direct relationship with cognitive and social functioning and was inversely related to HIV symptoms. Sexual orientation had direct relationships with mental well-being, cognitive, physical, social and role functioning. t-Tests showed that heterosexual participants reported poorer mental well-being and functional health status compared with homosexual participants. Regression analysis showed that spirituality, sexual orientation, age and HIV symptoms contributed significantly to mental well-being and functional health status. The regression analysis showed that spirituality, sexual orientation, age and HIV symptoms contributed significantly to mental well-being and functional health status. Further research is needed to explore the various ways that sexual orientation influences health status findings in those with HIV disease in certain segments of the population. The findings support the inclusion of spirituality as a variable when examining mental well-being and physical health. Finally, given the limitations of the design, more rigorous methods should be employed to understand further the contribution of spirituality to the health status of African-Americans living with HIV, because of its social importance to this particular community.

Role of endothelial dysfunction in modulating the plasma redox homeostasis in visceral leishmaniasis.

PubMed

Chowdhury, Kaustav Dutta; Sen, Gargi; Sarkar, Avik; Biswas, Tuli

2011-07-01

Evidence in the literature suggests that down-regulation of nitric oxide (NO) is associated with the pathophysiological conditions during visceral leishmaniasis (VL). Here we have investigated the mechanism that leads to the down regulation of systemic NO in the infected condition. Moreover, we have determined whether down regulation of NO is associated with increased generation of reactive oxygen species (ROS) during this disease. Therapeutic strategy targeting signaling molecules of these events was evaluated. Plasma protein-nitrotyrosine was examined by ELISA kit. Generation of superoxides and peroxynitrites was investigated by flow cytometry. NO bioavailability in endothelial cells was evaluated using DAF-2DA fluorescence. Ceramide contents were evaluated using FACS analysis, HPTLC and HPLC. L. donovani infected reticulo-endothelial cells regulated the activity of eNOS and NAD(P)H oxidase in the endothelial cells through the generation of intercellular messenger, ceramide. Activation of SMases played an important role in the generation of ceramide in animals during chronic infection. These events led to generation of ROS within endothelial cells. Modulation of redox status of plasma and accumulation of ROS in endothelial cells were critically involved in the regulation of NO bioavailability in plasma of the infected animal. Endothelial dysfunction and decline of NO were resulted from an increased production of superoxide where upregulation of eNOS expression appeared as an ineffective compensatory event. Inhibition of ceramide generation increased NO bioavailability, prevented endothelial dysfunction and concomitant oxidative stress. Decreased NO bioavailability and endothelial dysfunction were the downstream of ceramide signaling cascade. ROS accumulation promoted peroxynitrite generation and reduced NO bioavailability. Inhibition of ceramide generation may be a potential therapeutic option in preventing the co-morbidity associated with VL. 2011 Elsevier B.V. All rights reserved.

The relation of education and cognitive activity to mini-mental state in old age: the role of functional fitness status.

PubMed

Ihle, Andreas; Gouveia, Élvio R; Gouveia, Bruna R; Freitas, Duarte L; Jurema, Jefferson; Ornelas, Rui T; Antunes, António M; Muniz, Bárbara R; Kliegel, Matthias

2018-06-01

It remains unclear so far whether the role of cognitive reserve for cognitive functioning in old age may differ between individuals with low, compared to those with high functional fitness status. Therefore, the present study set out to investigate the relation of education and cognitive leisure activity as key markers of cognitive reserve to mini-mental state in old age (as an indicator of the extent of cognitive impairment) and its interplay with functional fitness status in a large sample of older adults. We assessed MMSE in 701 older adults ( M  = 70.4 years, SD = 6.9, range: 60-91). We measured functional fitness status using the Senior Fitness Test battery and interviewed individuals on their education and cognitive leisure activity. Results showed that better functional fitness status, longer education, and greater engagement in cognitive leisure activity were significantly related to higher MMSE scores. Moderation analyses showed that the relations of education and cognitive leisure activity to MMSE scores were significantly larger in individuals with low, compared to those with high functional fitness status. In conclusion, cognitive functioning in old age may more strongly depend on cognitive reserve accumulated during the life course in older adults with low, compared to those with high functional fitness status. These findings may be explained by cross-domain compensation effects in vulnerable individuals and may (at least partly) account for the large variability in cognitive reserve-cognition relations debated in the literature.

Obstructive Sleep Apnea is Related to Impaired Cognitive and Functional Status after Stroke.

PubMed

Aaronson, Justine A; van Bennekom, Coen A M; Hofman, Winni F; van Bezeij, Tijs; van den Aardweg, Joost G; Groet, Erny; Kylstra, Wytske A; Schmand, Ben

2015-09-01

Obstructive sleep apnea (OSA) is a common sleep disorder in stroke patients and is associated with prolonged hospitalization, decreased functional outcome, and recurrent stroke. Research on the effect of OSA on cognitive functioning following stroke is scarce. The primary objective of this study was to compare stroke patients with and without OSA on cognitive and functional status upon admission to inpatient rehabilitation. Case-control study. 147 stroke patients admitted to a neurorehabilitation unit. N/A. All patients underwent sleep examination for diagnosis of OSA. We assessed cognitive status by neuropsychological examination and functional status by two neurological scales and a measure of functional independence. We included 80 stroke patients with OSA and 67 stroke patients without OSA. OSA patients were older and had a higher body mass index than patients without OSA. OSA patients performed worse on tests of attention, executive functioning, visuoperception, psychomotor ability, and intelligence than those without OSA. No differences were found for vigilance, memory, and language. OSA patients had a worse neurological status, lower functional independence scores, and a longer period of hospitalization in the neurorehabilitation unit than the patients without OSA. OSA status was not associated with stroke type or classification. Obstructive sleep apnea (OSA) is associated with a lower cognitive and functional status in patients admitted for stroke rehabilitation. This underlines the importance of OSA as a probable prognostic factor, and calls for well-designed randomized controlled trials to study its treatability. © 2015 Associated Professional Sleep Societies, LLC.

Functional health status of adolescents after the Fontan procedure -- comparison with their siblings.

PubMed

Manlhiot, Cedric; Knezevich, Stevan; Radojewski, Elizabeth; Cullen-Dean, Geraldine; Williams, William G; McCrindle, Brian W

2009-09-01

Studies have suggested that patients who have undergone the Fontan procedure experience lower functional health status and diminished exercise capacity compared with other children. To compare the functional health status of Fontan patients with and without siblings, assess whether there are any differences between Fontan patients and their siblings, and determine associated factors. A cross-sectional, single-centre, observational study was performed on Fontan patients 10 to 20 years of age, and their sibling closest in age, followed in a tertiary pediatric hospital. Functional health status was measured by the Child Health Questionnaire Child Form and the Pediatric Quality of Life Inventory. A total of 68 patients and 38 siblings were enrolled. Patients with siblings scored significantly lower on numerous domains of physical functional status than those without siblings. Compared with their matched siblings, Fontan patients reported significantly lower scores in all domains of the Pediatric Quality of Life Inventory and on physical (but not psychosocial) domains of the Child Health Questionnaire Child Form. Factors associated with increased patient-sibling differences included younger patient age, female sex, intracardiac lateral tunnel Fontan connection and lower ejection fraction at the time of study enrollment. Adolescents with Fontan physiology reported a lower functional health status in physical domains than their siblings, but had similar status in psychosocial domains. Having a sibling was associated with lower reported functional health status, suggesting an important effect of self-perceived physical limitations over true limitations.

Functional health status of adolescents after the Fontan procedure – comparison with their siblings

PubMed Central

Manlhiot, Cedric; Knezevich, Stevan; Radojewski, Elizabeth; Cullen-Dean, Geraldine; Williams, William G; McCrindle, Brian W

2009-01-01

BACKGROUND: Studies have suggested that patients who have undergone the Fontan procedure experience lower functional health status and diminished exercise capacity compared with other children. OBJECTIVES: To compare the functional health status of Fontan patients with and without siblings, assess whether there are any differences between Fontan patients and their siblings, and determine associated factors. METHODS: A cross-sectional, single-centre, observational study was performed on Fontan patients 10 to 20 years of age, and their sibling closest in age, followed in a tertiary pediatric hospital. Functional health status was measured by the Child Health Questionnaire Child Form and the Pediatric Quality of Life Inventory. RESULTS: A total of 68 patients and 38 siblings were enrolled. Patients with siblings scored significantly lower on numerous domains of physical functional status than those without siblings. Compared with their matched siblings, Fontan patients reported significantly lower scores in all domains of the Pediatric Quality of Life Inventory and on physical (but not psychosocial) domains of the Child Health Questionnaire Child Form. Factors associated with increased patient-sibling differences included younger patient age, female sex, intracardiac lateral tunnel Fontan connection and lower ejection fraction at the time of study enrollment. CONCLUSIONS: Adolescents with Fontan physiology reported a lower functional health status in physical domains than their siblings, but had similar status in psychosocial domains. Having a sibling was associated with lower reported functional health status, suggesting an important effect of self-perceived physical limitations over true limitations. PMID:19746247

Employment as a Social Determinant of Health: Exploring the Relationship between Neurocognitive Function and Employment Status

ERIC Educational Resources Information Center

Hergenrather, Kenneth C.; Emmanuel, Diona; McGuire-Kuletz, Maureen; Rhodes, Scott D.

2018-01-01

Purpose: To explore employment as a social determinant of health through examining the relationship between neurocognitive function and employment status. Method: The authors explored the causal relationship between employment status and neurocognitive function by conducting a systematic review of 15 longitudinal studies. The identified studies…

[Cognitive impairment, nutritional status and clinical profile in chronic obstructive pulmonary disease].

PubMed

López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen

2014-11-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (p<0.05). Cognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

PubMed

Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

2016-05-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

Mutation of C. elegans demethylase spr-5 extends transgenerational longevity

PubMed Central

Greer, Eric Lieberman; Becker, Ben; Latza, Christian; Antebi, Adam; Shi, Yang

2016-01-01

Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension. PMID:26691751

UPDM - Unified Profile for DoDAF/MODAF

DTIC Science & Technology

2012-04-01

Expected target DoDAF 2.03 – MODAF MODEM – DNDAF 1.7 may also be required by the Canadians – UML for  BPMN  profile • Allows the seamless integration of... BPMN  artefacts into a DoDAF  Architecture along with an exchange environment – Others? – Priorities will be based on demand and participation • UPDM 2...19         ,  ,  ,  . • Provides flow‐down, traceability, integration across sectors • BPMN  integration is under development UPDM – Unified Profile

Nutritional Status and Energy Intake as Predictors of Functional Status After Cardiac Rehabilitation in Elderly Inpatients With Heart Failure　- A Retrospective Cohort Study.

PubMed

Katano, Satoshi; Hashimoto, Akiyoshi; Ohori, Katsuhiko; Watanabe, Ayako; Honma, Remi; Yanase, Rimi; Ishigo, Tomoyuki; Fujito, Takefumi; Ohnishi, Hirofumi; Tsuchihashi, Kazufumi; Ishiai, Sumio; Miura, Tetsuji

2018-05-25

Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

The Palliative Function of Hostile Sexism among High and Low-Status Chilean Students

PubMed Central

Vargas-Salfate, Salvador

2017-01-01

Previous studies have demonstrated that justifying the social, economic, and political systems is associated with psychological well-being, which has been termed as the palliative function of ideology. However, little research has been conducted on gender stereotypes among children, comparing by socioeconomic status. This study aimed to fill this gap in the system justification literature. We present data from the Chilean version of the International Survey of Children Well-Being (ISCWeB), which was conducted in 2012. We found that the palliative function of gender stereotypes is present among this sample, being qualified by a socioeconomic status by hostile gender stereotype interaction. In other words, the effect on the psychological well-being was observed in low-status, but not in high-status students. These results extend the previous knowledge about the palliative function of the ideology, suggesting why the low-status members of a society actively engage in system justification. PMID:29046657

Functional Status Change Among Children With Extracorporeal Membrane Oxygenation to Support Cardiopulmonary Resuscitation in a Pediatric Cardiac ICU: A Single Institution Report.

PubMed

Beshish, Asaad G; Baginski, Mathew R; Johnson, Thomas J; Deatrick, Barry K; Barbaro, Ryan P; Owens, Gabe E

2018-04-13

The purpose of this study is to describe the functional status of survivors from extracorporeal cardiopulmonary resuscitation instituted during in-hospital cardiac arrest using the Functional Status Scale. We aimed to determine risk factors leading to the development of new morbidity and unfavorable functional outcomes. This was a single-center retrospective chart review abstracting patient characteristics/demographic data, duration of cardiopulmonary resuscitation, duration of extracorporeal membrane oxygenation support, as well as maximum lactate levels within 2 hours before and after extracorporeal cardiopulmonary resuscitation. Cardiac arrest was defined as the administration of chest compressions for a nonperfusing cardiac rhythm. Extracorporeal cardiopulmonary resuscitation was defined by instituting extracorporeal membrane oxygenation during active chest compressions. Functional Status Scale scores were calculated at admission and on hospital discharge for patients who survived. Patients admitted in the pediatric cardiac ICU at C.S. Mott Children's Hospital from January 1, 2005, to December 31, 2015. Children less than 18 years who underwent extracorporeal cardiopulmonary resuscitation. Not applicable. Of 608 extracorporeal membrane oxygenation events during the study period, 80 were extracorporeal cardiopulmonary resuscitation (14%). There were 40 female patients (50%). Median age was 40 days (interquartile range, 9-342 d). Survival to hospital discharge was 48% (38/80). Median Functional Status Scale score at admission was 6 (interquartile range, 6-6) and at hospital discharge 9 (interquartile range, 8-11). Out of 38 survivors, 19 (50%) had a change of Functional Status Scale score greater than or equal to 3, that is consistent with new morbidity, and 26 (68%) had favorable functional outcomes with a change in Functional Status Scale score of less than 5. This is the first extracorporeal cardiopulmonary resuscitation report to examine changes in Functional Status Scale from admission (baseline) to discharge as a measure of overall functional outcome. Half of surviving patients (19/38) had new morbidity, while 68% (26/38) had favorable outcomes. Lactate levels, duration of cardiopulmonary resuscitation, and duration of extracorporeal membrane oxygenation were not found to be risk factors for the development of new morbidity and poor functional outcomes. Functional Status Scale may be used as a metric to monitor improvement of extracorporeal cardiopulmonary resuscitation outcomes and help guide research initiatives to decrease morbidity in this patient population.

Relationship between periodontal status and intellectual function among community-dwelling elderly persons.

PubMed

Moriya, Shingo; Tei, Kanchu; Toyoshita, Yoshifumi; Koshino, Hisashi; Inoue, Nobuo; Miura, Hiroko

2012-06-01

The aim of this study was to indicate the relationship between periodontal status and intellectual function in the elderly. Periodontal status has been shown to be related to demographic, socioeconomic, and psychological status. Intellectual function is a significant indicator of health status. Nevertheless, the relationship between periodontal status and intellectual function has not been elucidated in detail among the elderly. A total of 152 community-dwelling elderly persons, aged 70-74 years, were enrolled in the study. Periodontal status was evaluated using the WHO Community Periodontal Index of Treatment Needs (CPITN). Intellectual function was assessed by four neuropsychological tests: Raven's Coloured Progressive Matrices (RCPM) test, the Verbal Paired Associates 1 (VerPA) task and the Visual Paired Associates 1 (VirPA) task, extracted from the Wechsler Memory Scale Revised Edition, and the Block Design subtest, extracted from the Wechsler Adult Intelligence Scales, Third Edition. Correlations between CPITN and each test were examined using Spearman rank correlation coefficients. The ordinal regression model was constructed with CPITN as the dependent variable and neuropsychological test as the principal independent variable to adjust for demographic factors, general health, lifestyle and oral health behaviour. Significant correlations were found between the RCPM test, the VerPA task, the Visual Paired Associates 1 and CPITN. In the ordinal regression model, CPITN was significantly related to measures of RCPM after adjusting for demographic factors, general health status, lifestyle and oral health behaviour. Intellectual function is considered a significant indicator of periodontal status among community-dwelling elderly persons. © 2011 The Gerodontology Society and John Wiley & Sons A/S.

Shoulder Pain, Functional Status, and Health-Related Quality of Life after Head and Neck Cancer Surgery

PubMed Central

Wang, Hsiao-Lan; Keck, Juanita F.; Weaver, Michael T.; Mikesky, Alan; Bunnell, Karen; Buelow, Janice M.; Rawl, Susan M.

2013-01-01

Head and neck cancer (HNC) patients experience treatment-related complications that may interfere with health-related quality of life (HRQOL). The purpose of this study was to describe the symptom experience (shoulder pain) and functional status factors that are related to global and domain-specific HRQOL at one month after HNC surgery. In this exploratory study, we examined 29 patients. The outcome variables included global HRQOL as well as physical, functional, emotional, and social well-being. Symptom experience and functional status factors were the independent variables. In the symptom experience variables, shoulder pain distress was negatively associated with physical well-being (R 2 = 0.24). Among the functional status variables, eating impairment was negatively related to global HRQOL (R 2 = 0.18) and physical well-being (R 2 = 0.21). Speaking impairment and impaired body image explained a large amount of the variance in functional well-being (R 2 = 0.45). This study provided initial results regarding symptom experience and functional status factors related to poor HRQOL in the early postoperative period for HNC patients. PMID:24455274

Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia.

PubMed

Schmaling, Karen B; Betterton, Karran L

2016-05-01

The purpose of this study was to conduct a longitudinal examination of cognitive complaints and functional status in patients with chronic fatigue syndrome (CFS) alone and those who also had fibromyalgia (CFS/FM). A total of 93 patients from a tertiary care fatigue clinic were evaluated on four occasions, each 6 months apart. Each evaluation included a tender point assessment, and self-reported functional status and cognitive complaints. Patients with CFS/FM reported significantly worse physical functioning, more bodily pain, and more cognitive difficulties (visuo-perceptual ability and verbal memory) than patients with CFS alone. Over time, bodily pain decreased only for participants with CFS alone. Verbal memory problems were associated with more bodily pain for both patient groups, whereas visuo-perceptual problems were associated with worse functional status for patients with CFS alone. This study adds to the literature on functional status, longitudinal course, and cognitive difficulties among patients with CFS and those with CFS and FM. The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells.

PubMed

Samuel, Sherin; Zhang, Kuo; Tang, Yi-Da; Gerdes, A Martin; Carrillo-Sepulveda, Maria Alicia

2017-01-01

Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation. © 2017 The Author(s)Published by S. Karger AG, Basel.

Cranberry Extract Standardized for Proanthocyanidins Alleviates β-Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis elegans Model of Alzheimer's Disease.

PubMed

Guo, Hong; Cao, Min; Zou, Sige; Ye, Boping; Dong, Yuqing

2016-12-01

A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans In this article, we report that supplementation of this cranberry extract delayed Aβ toxicity-triggered body paralysis in the C elegans AD model. Genetic analyses indicated that the cranberry-mediated Aβ toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C elegans against Aβ toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated Aβ toxicity in C elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Chen, He; Li, Huirong; Wang, Dayong

2017-01-01

Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.

Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation

PubMed Central

Kong, Cin; Tan, Man-Wah; Nathan, Sheila

2014-01-01

ABSTRACT Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans–S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host. PMID:24972867

The dynamic relationships between economic status and health measures among working-age adults in the United States.

PubMed

Meraya, Abdulkarim M; Dwibedi, Nilanjana; Tan, Xi; Innes, Kim; Mitra, Sophie; Sambamoorthi, Usha

2018-04-18

We examine the dynamic relationships between economic status and health measures using data from 8 waves of the Panel Study of Income Dynamics from 1999 to 2013. Health measures are self-rated health (SRH) and functional limitations; economic status measures are labor income (earnings), family income, and net wealth. We use 3 different types of models: (a) ordinary least squares regression, (b) first-difference, and (c) system-generalized method of moment (GMM). Using ordinary least squares regression and first difference models, we find that higher levels of economic status are associated with better SRH and functional status among both men and women, although declines in income and wealth are associated with a decline in health for men only. Using system-GMM estimators, we find evidence of a causal link from labor income to SRH and functional status for both genders. Among men only, system-GMM results indicate that there is a causal link from net wealth to SRH and functional status. Results overall highlight the need for integrated economic and health policies, and for policies that mitigate the potential adverse health effects of short-term changes in economic status. Copyright © 2018 John Wiley & Sons, Ltd.

Effectiveness of the second-stage rehabilitation in stroke patients with cognitive impairment.

PubMed

Milinavičienė, Eglė; Rastenytė, Daiva; Kriščiūnas, Aleksandras

2011-01-01

The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of rehabilitation, Hospital of Lithuanian University of Health Sciences. Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status was significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001), while moderate and mild cognitive impairment was not associated with the recovery of functional status. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment.

Risk factors for poor work functioning of persons with schizophrenia in rural China.

PubMed

Ran, Mao-Sheng; Chen, Sheying; Chen, Elaina Y; Ran, Bo-Yu; Tang, Cui-Ping; Lin, Fu-Rong; Li, Li; Li, Si-Gan; Mao, Wen-Jun; Hu, Shi-Hui

2011-11-01

The long-term work performance of persons with schizophrenia in the community is unclear. This study examined the status of long-term work functioning and the predictors of poor work status among patients with schizophrenia in a Chinese rural area. A 10-year follow-up investigation (1994-2004) of a cohort (n = 510) of persons with schizophrenia was conducted in Xinjin County, Chengdu, China. Compared with baseline data, work functioning of patients with schizophrenia deteriorated after 10 years. The rates of not working increased significantly from 12.0% in 1994 to 23.0% in 2004. Bivariate analyses showed that the poor work functioning in 2004 was significantly associated with male gender, older age, older age of first onset, higher level of education, longer duration of illness, lower family economic status, lack of caregivers, poor work status in 1994, living in shabby or unstable house, marked symptoms, and higher score on the Social Disability Screening Schedule (SDSS). In multiple logistic regression analyses, higher score of SDSS and poor work status in 1994 were identified as unique predictors of poor work status in 2004. The status of work functioning of persons with schizophrenia decreased over the course of the illness. The risk factors for poor work functioning and specific socio-cultural environment should be considered in planning community mental health services and rehabilitation for these patients.

Physicians' impression on the elders' functionality influences decision making for emergency care.

PubMed

Rodríguez-Molinero, Alejandro; López-Diéguez, María; Tabuenca, Ana I; de la Cruz, Juan J; Banegas, José R

2010-09-01

This study analyzes the elements that compose the emergency physicians' criterion for selecting elderly patients for intensive care treatment. This issue has not been studied in-depth. A cross-sectional study was conducted at 4 university teaching hospitals, covering 101 randomly selected elderly patients admitted to emergency department and their respective physicians. Physicians were asked to forecast their plans for treatment or therapeutic abstention, in the event that patients might require aggressive measures (cardiopulmonary resuscitation or admission to critical care units). Data were collected on physicians' reasons for taking such decisions and their patients' functional capacity and cognitive status (Katz index and Informant Questionnaire on Cognitive Decline in the Elderly). A logistic regression model was constructed taking physicians' decisions as the dependent variables and adjusting for patient factors and physician impressions. The functional status reported by reliable informants and the mental status measured by validated instruments were not coincident with the physicians' perception (functional status κ, 0.47; mental status κ, 0.26). A multivariate analysis showed that the age and the functional and mental status of patients, as perceived by the physicians, were the variables that better explained the physicians' decisions. Physicians' impressions on the functional and mental status of their patients significantly influenced their selection of patients for high-intensity treatments despite the fact that some of these impressions were not correct. Copyright © 2010 Elsevier Inc. All rights reserved.

[Relationships between nutritional status and the effects of exercise training in frail elderly people].

PubMed

Arai, Takeshi; Obuchi, Shuichi

2011-01-01

The objectives of this study were to examine the relationship between nutritional status indicators such as body mass index (BMI) and serum albumin, and the effects of exercise intervention in community-dwelling frail elderly people. We enrolled 44 subjects aged 65 years and older (average age 73.9±5.1 years) in this study. The subjects participated in exercise intervention, including muscle strength training twice a week for 3 months. We evaluated various functional performance measures at the start and end of the intervention, and calculated the measurement differences. We then evaluated any relationships between nutritional status and the amount of changes. Some physical functions improved after exercise intervention, even in participants with under-nutritional status. There were no significant differences or relationships found between nutritional status and improvements in physical function. These results suggest that the physical functions of frail elderly people can improve regardless of their nutritional status. Further study is necessary to evaluate the influence of nutritional status on exercise effects, and the optimal method of applying exercise interventions, primarily for community-dwelling frail older people.

Sufficient vitamin K status combined with sufficient vitamin D status is associated with better lower extremity function: a prospective analysis of two knee osteoarthritis cohorts

USDA-ARS?s Scientific Manuscript database

Objective: Vitamins K and D are important for the function of vitamin K-dependent proteins in joint tissues. It is unclear if these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). This study aimed to evaluate the association of vitamin K and D status with...

Multiple Types of Memory and Everyday Functional Assessment in Older Adults

PubMed Central

Beaver, Jenna

2017-01-01

Abstract Objective Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. Method A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. Results After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. Conclusion The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability. PMID:28334170

The relationship between oral health status and biological and psychosocial function in the bedridden elderly.

PubMed

Hanada, N; Tada, A

2001-01-01

The present study was conducted in order to determine what item of biological and psychosocial function is related to oral health status in the bedridden elderly. The subjects were 94 elderly individuals (30 males, 64 females) who had been admitted to a nursing home in Chiba city, Japan. We assessed the number of remaining teeth and the number of functional teeth as oral health status variables. Biological and psychosocial function levels were determined using the functional independence measure method developed by the State University of New York at Buffalo. More than 70% of subjects had less than ten remaining teeth. Almost all subjects needed prosthesis treatment. More than 50% of subjects had 27 or less functional teeth. Mann-Whitney U-test and logistic regression models showed that 'expression' was concerned with the number of remaining teeth and 'bladder management', 'locomotion', 'transfers' were related to the number of functional teeth. These data suggest close relation between oral health status and biological and psychosocial function levels in the bedridden elderly.

Antioxidant and neuroprotective effects of Dictyophora indusiata polysaccharide in Caenorhabditis elegans.

PubMed

Zhang, Ju; Shi, Ruona; Li, Haifeng; Xiang, Yanxia; Xiao, Lingyun; Hu, Minghua; Ma, Fangli; Ma, Chung Wah; Huang, Zebo

2016-11-04

Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively. DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-β protein. These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Di(2-ethylhexyl) phthalate and diethyl phthalate disrupt lipid metabolism, reduce fecundity and shortens lifespan of Caenorhabditis elegans.

PubMed

Pradhan, Ajay; Olsson, Per-Erik; Jass, Jana

2018-01-01

The widespread use of phthalates is of major concern as they have adverse effects on many different physiological functions, including reproduction, metabolism and cell differentiation. The aim of this study was to compare the toxicity of the widely-used di (2-ethydlhexyl) phthalate (DEHP) with its substitute, diethyl phthalate (DEP). We analyzed the toxicity of these two phthalates using Caenorhabditis elegans as a model system. Gene expression analysis following exposure during the L1 to young adult stage showed that DEHP and DEP alter the expression of genes involved in lipid metabolism and stress response. Genes associated with lipid metabolism, including fasn-1, pod-2, fat-5, acs-6 and sbp-1, and vitellogenin were upregulated. Among the stress response genes, ced-1 wah-1, daf-21 and gst-4 were upregulated, while ctl-1, cdf-2 and the heat shock proteins (hsp-16.1, hsp-16.48 and sip-1) were downregulated. Lipid staining revealed that DEHP significantly increased lipid content following 1 μM exposure, however, DEP required 10 μM exposure to elicit an effect. Both DEHP and DEP reduced the fecundity at 1 μM concentration. Lifespan analysis indicated that DEHP and DEP reduced the average lifespan from 14 days in unexposed worms to 13 and 12 days, respectively. Expression of lifespan associated genes showed a correlation to shortened lifespan in the exposed groups. As reported previously, our data also indicates that the banned DEHP is toxic to C. elegans, however its substitute DEP has not been previously tested in this model organism and our data revealed that DEP is equally potent as DEHP in regulating C. elegans physiological functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health and functional status and utilization of health care services among holocaust survivors and their counterparts in Israel.

PubMed

Iecovich, Esther; Carmel, Sara

2010-01-01

To examine differences in health and functional status and in utilization of health services between holocaust survivors and their counterparts; and (b) to investigate if holocaust survivor status is a significant predictor of health status, functional status, and utilization of health services. The study included 1255 respondents of whom 272 were holocaust survivors. Interviews were conducted face-to-face at the respondents' homes. Participants were asked about their health (self-rated health and comorbidity) and functional (ADL and IADL) status, utilization of inpatient and outpatient health care services, age, gender, education, marital status, length of residence in Israel, and if they were holocaust survivors. Holocaust survivors, who were frailer and more chronically ill compared to their counterparts, visited their family physician and the nurse at the health care clinic more often than their counterparts did, and received more homecare services. Yet, there were no differences between them in the utilization of other health care services such as visits to specialists, emergency department, and hospitalizations. Holocaust survivors are more homebound due to more morbidity and functional limitations and therefore receive more health home care services that offset the utilization of other health services. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Cross-Sectional Study of Nutrient Intake and Health Status among Older Adults in Yogyakarta Indonesia

PubMed Central

Arjuna, Tony; Soenen, Stijn; Hasnawati, Rasita Amelia; Lange, Kylie; Chapman, Ian; Luscombe-Marsh, Natalie D.

2017-01-01

Many communities around the world, particularly developing countries including Indonesia, are experiencing population ageing. There is little knowledge regarding the impact of malnutrition, or its prevalence within rural compared to urban areas, on the nutritional, functional and mental status of community-living older residents in these countries. Hence, a cross-sectional study was conducted to determine socio-demographic and anthropometric characteristics, nutritional, mental and functional status, and energy and nutrient intake of community-dwelling Indonesians from both rural and urban areas of Yogyakarta. Older individuals were included in the study if they had been living in Yogyakarta for the last year and were aged ≥65 years (n = 527; mean ± SD age of 74 ± 7 years). Rural compared with urban participants had a lower level of education and income, more hospital admissions, less dietary protein intake, lower cognitive function, poorer nutritional status and grip strength, but faster gait speed while being more dependent on assistance to perform daily activities (all p < 0.05). Cognitive function was more strongly associated than nutritional status with physical function. Rural older Indonesians living in Yogyakarta were more likely than urban older people to be malnourished and cognitively impaired, and to have associated reductions in functional capacity and independence. Strategies to improve cognitive function and nutritional status are therefore important for the wellbeing of Indonesian citizens. PMID:29137185

Physical function and independence 1 year after myocardial infarction: observations from the Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction: Patients' Health status registry.

PubMed

Dodson, John A; Arnold, Suzanne V; Reid, Kimberly J; Gill, Thomas M; Rich, Michael W; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Alexander, Karen P

2012-05-01

Acute myocardial infarction (AMI) may contribute to health status declines including "independence loss" and "physical function decline." Despite the importance of these outcomes for prognosis and quality of life, their incidence and predictors have not been well described. We studied 2,002 patients with AMI enrolled across 24 sites in the TRIUMPH registry who completed assessments of independence and physical function at the time of AMI and 1 year later. Independence was evaluated by the EuroQol-5D (mobility, self-care, and usual activities), and physical function was assessed with the Short Form-12 physical component score. Declines in ≥1 level on EuroQol-5D and >5 points in PCS were considered clinically significant changes. Hierarchical, multivariable, modified Poisson regression models accounting for within-site variability were used to identify predictors of independence loss and physical function decline. One-year post AMI, 43.0% of patients experienced health status declines: 12.8% independence loss alone, 15.2% physical function decline alone, and 15.0% both. After adjustment, variables that predicted independence loss included female sex, nonwhite race, unmarried status, uninsured status, end-stage renal disease, and depression. Variables that predicted physical function decline were uninsured status, lack of cardiac rehabilitation referral, and absence of pre-AMI angina. Age was not predictive of either outcome after adjustment. >40% of patients experience independence loss or physical function decline 1 year after AMI. These changes are distinct but can occur simultaneously. Although some risk factors are not modifiable, others suggest potential targets for strategies to preserve patients' health status. Copyright © 2012 Mosby, Inc. All rights reserved.

Patient-Reported Outcome Measures (PROM) as A Preoperative Assessment Tool.

PubMed

Kim, Sunghye; Duncan, Pamela W; Groban, Leanne; Segal, Hannah; Abbott, Rica Moonyeen; Williamson, Jeff D

2017-11-28

Patient-reported outcomes (PRO) on functional, social, and behavioral factors might be important preoperative predictors of postoperative outcomes. We conducted a literature review to explore associations of preoperative depression, socioeconomic status, social support, functional status/frailty, cognitive status, self-management skills, health literacy, and nutritional status with surgical outcomes. Two electronic data bases, including PubMed and Google Scholar, were searched linking either depression, socioeconomic status, social support, functional status/frailty, cognitive status, self-management skills, health literacy, or nutritional status with surgery, postoperative complications, or perioperative period within the past 2 decades. Preoperative depression has been linked to postoperative delirium, complications, persistent pain, longer lengths of stay, and mortality. Socioeconomic status associates with overall and cancer-free survival. Low socioeconomic status has also been connected to medication non- compliance. Social support can predict overall and cancer- free survival, as well as physical, social and emotional quality of life. Poor functional status and frailty have been related to postoperative complications, longer lengths of stay, post-discharge institutionalization, and higher costs. Preoperative cognitive impairment also associates with self-medication management errors, postoperative cognitive impairment, delirium, complications and mortality. In addition, a greater tendency for reduced adherence to preoperative medication instructions has been linked to health illiteracy. Preoperative malnutrition is prevalent and associates with postoperative morbidity. Efficient and effective assessments of social and behavioral determinants of health, functional status, health literacy, patient's perception of health, and preferences for self-management may improve postoperative management and surgical outcomes, particularly among vulnerable patients undergoing elective surgery who might have subtle physical, social, or psychological deficits or challenges, otherwise missed upon routine evaluation. Patient Reported Outcome Measures (PROMs) can be used to effectively and efficiently collect these factors in the preoperative period, thereby identifying areas that can be intervened preemptively. (Partially Funded by the National Institute on Aging and the Wake Forest University Claude D. Pepper Older Americans Independence Center.).

Examining acute rehabilitation outcomes for children with total functional dependence after traumatic brain injury: a pilot study.

PubMed

Kramer, Megan E; Suskauer, Stacy J; Christensen, James R; DeMatt, Ellen J; Trovato, Melissa K; Salorio, Cynthia F; Slomine, Beth S

2013-01-01

To examine in a pilot cohort factors associated with functional outcome at discharge and 3-month follow-up after discharge from inpatient rehabilitation in children with severe traumatic brain injury (TBI) who entered rehabilitation with the lowest level of functional skills. Thirty-nine children and adolescents (3-18 years old) who sustained a severe TBI and had the lowest possible rating at rehabilitation admission on the Functional Independence Measure for Children (total score = 18). Retrospective review of data collected as part of routine clinical care. At discharge, 59% of the children were partially dependent for basic activities, while 41% remained dependent for basic activities. Initial Glasgow Coma Scale score, time to follow commands, and time from injury to rehabilitation admission were correlated with functional status at discharge. Time to follow commands and time from injury to rehabilitation admission were correlated with functional status at 3-month follow-up. Changes in functional status during the first few weeks of admission were associated with functional status at discharge and follow-up. Even children with the most severe brain injuries, who enter rehabilitation completely dependent for all daily activities, have the potential to make significant gains in functioning by discharge and in the following few months. Assessment of functional status early in the course of rehabilitation contributes to the ability to predict outcome from severe TBI.

Examining the Association Between Comorbidity Indexes and Functional Status in Hospitalized Medicare Fee-for-Service Beneficiaries

PubMed Central

Graham, James E.; Resnik, Linda; Karmarkar, Amol M.; Deutsch, Anne; Tan, Alai; Al Snih, Soham; Ottenbacher, Kenneth J.

2016-01-01

Background Medicare data from acute hospitals do not contain information on functional status. This lack of information limits the ability to conduct rehabilitation-related health services research. Objective The purpose of this study was to examine the associations between 5 comorbidity indexes derived from acute care claims data and functional status assessed at admission to an inpatient rehabilitation facility (IRF). Comorbidity indexes included tier comorbidity, Functional Comorbidity Index (FCI), Charlson Comorbidity Index, Elixhauser Comorbidity Index, and Hierarchical Condition Category (HCC). Design This was a retrospective cohort study. Methods Medicare beneficiaries with stroke, lower extremity joint replacement, and lower extremity fracture discharged to an IRF in 2011 were studied (N=105,441). Data from the beneficiary summary file, Medicare Provider Analysis and Review (MedPAR) file, and Inpatient Rehabilitation Facility–Patient Assessment Instrument (IRF-PAI) file were linked. Inpatient rehabilitation facility admission functional status was used as a proxy for acute hospital discharge functional status. Separate linear regression models for each impairment group were developed to assess the relationships between the comorbidity indexes and functional status. Base models included age, sex, race/ethnicity, disability, dual eligibility, and length of stay. Subsequent models included individual comorbidity indexes. Values of variance explained (R2) with each comorbidity index were compared. Results Base models explained 7.7% of the variance in motor function ratings for stroke, 3.8% for joint replacement, and 7.3% for fracture. The R2 increased marginally when comorbidity indexes were added to base models for stroke, joint replacement, and fracture: Charlson Comorbidity Index (0.4%, 0.5%, 0.3%), tier comorbidity (0.2%, 0.6%, 0.5%), FCI (0.4%, 1.2%, 1.6%), Elixhauser Comorbidity Index (1.2%, 1.9%, 3.5%), and HCC (2.2%, 2.1%, 2.8%). Limitation Patients from 3 impairment categories were included in the sample. Conclusions The 5 comorbidity indexes contributed little to predicting functional status. The indexes examined were not useful as proxies for functional status in the acute settings studied. PMID:26564253

Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets

PubMed Central

Stadler, Michael; Artiles, Karen; Pak, Julia; Fire, Andrew

2012-01-01

miRNAs are post-transcriptional regulators of gene activity that reduce protein accumulation from target mRNAs. Elucidating precise molecular effects that animal miRNAs have on target transcripts has proven complex, with varied evidence indicating that miRNA regulation may produce different molecular outcomes in different species, systems, and/or physiological conditions. Here we use high-throughput ribosome profiling to analyze detailed translational parameters for five well-studied targets of miRNAs that regulate C. elegans developmental timing. For two targets of the miRNA lin-4 (lin-14 and lin-28), functional down-regulation was associated with decreases in both overall mRNA abundance and ribosome loading; however, these changes were of substantially smaller magnitude than corresponding changes observed in protein abundance. For three functional targets of the let-7 miRNA family for which down-regulation is critical in temporal progression of the animal (daf-12, hbl-1, and lin-41), we observed only modest changes in mRNA abundance and ribosome loading. lin-41 provides a striking example in that populations of ribosome-protected fragments from this gene remained essentially unchanged during the L3–L4 time interval when lin-41 activity is substantially down-regulated by let-7. Spectra of ribosomal positions were also examined for the five lin-4 and let-7 target mRNAs as a function of developmental time, with no indication of miRNA-induced ribosomal drop-off or significant pauses in translation. These data are consistent with models in which physiological regulation by this set of C. elegans miRNAs derives from combinatorial effects including suppressed recruitment/activation of translational machinery, compromised stability of target messages, and post- or peri-translational effects on lifetimes of polypeptide products. PMID:22855835

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Badrasawi, M; Shahar, Suzana; Zahara, A M; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine ( P <0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

PubMed Central

Badrasawi, M; Shahar, Suzana; Zahara, AM; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults. PMID:27895474