Science.gov

Sample records for age ca controls

  1. Altered Ca2+ sparks in aging skeletal and cardiac muscle

    PubMed Central

    Weisleder, Noah; Ma, Jianjie

    2008-01-01

    Ca2+ sparks are the fundamental units that comprise Ca2+-induced Ca2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca2+ spark activity in aged cardiomyocytes. Ca2+ spark responses reflect the integrated function of the intracellular Ca2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca2+ spark signaling during aging of striated muscles. PMID:18272434

  2. Role of Ca2+, membrane excitability, and Ca2+ stores in failing muscle contraction with aging.

    PubMed

    Payne, Anthony Michael; Jimenez-Moreno, Ramón; Wang, Zhong-Ming; Messi, María Laura; Delbono, Osvaldo

    2009-04-01

    Excitation-contraction (EC) coupling in a population of skeletal muscle fibers of aged mice becomes dependent on the presence of external Ca(2+) ions (Payne, A.M., Zheng, Z., Gonzalez, E., Wang, Z.M., Messi, M.L., Delbono, O., 2004b. External Ca(2+)-dependent excitation - contraction coupling in a population of aging mouse skeletal muscle fibers. J. Physiol. 560, 137-155.). However, the mechanism(s) underlying this process remain unknown. In this work, we examined the role of (1) extracellular Ca(2+); (2) voltage-induced influx of external Ca(2+) ions; (3) sarcoplasmic reticulum (SR) Ca(2+) depletion during repeated contractions; (4) store-operated Ca(2+) entry (SOCE); (5) SR ultrastructure; (6) SR subdomain localization of the ryanodine receptor; and (7) sarcolemmal excitability in muscle force decline with aging. These experiments show that external Ca(2+), but not Ca(2+) influx, is needed to maintain force upon repetitive fiber electrical stimulation. Decline in fiber force is associated with depressed SR Ca(2+) release. SR Ca(2+) depletion, SOCE, and the putative segregated Ca(2+) release store do not play a significant role in external Ca(2+)-dependent contraction. More importantly, a significant number of action potentials fail in senescent mouse muscle fibers subjected to a stimulation frequency. These results indicate that failure to generate action potentials accounts for decreased intracellular Ca(2+) mobilization and tetanic force in aging muscle exposed to a Ca(2+)-free medium.

  3. Ca2+ dynamics in oocytes from naturally-aged mice

    PubMed Central

    Haverfield, Jenna; Nakagawa, Shoma; Love, Daniel; Tsichlaki, Elina; Nomikos, Michail; Lai, F. Anthony; Swann, Karl; FitzHarris, Greg

    2016-01-01

    The ability of human metaphase-II arrested eggs to activate following fertilisation declines with advancing maternal age. Egg activation is triggered by repetitive increases in intracellular Ca2+ concentration ([Ca2+]i) in the ooplasm as a result of sperm-egg fusion. We therefore hypothesised that eggs from older females feature a reduced ability to mount appropriate Ca2+ responses at fertilisation. To test this hypothesis we performed the first examination of Ca2+ dynamics in eggs from young and naturally-aged mice. Strikingly, we find that Ca2+ stores and resting [Ca2+]i are unchanged with age. Although eggs from aged mice feature a reduced ability to replenish intracellular Ca2+ stores following depletion, this difference had no effect on the duration, number, or amplitude of Ca2+ oscillations following intracytoplasmic sperm injection or expression of phospholipase C zeta. In contrast, we describe a substantial reduction in the frequency and duration of oscillations in aged eggs upon parthenogenetic activation with SrCl2. We conclude that the ability to mount and respond to an appropriate Ca2+ signal at fertilisation is largely unchanged by advancing maternal age, but subtle changes in Ca2+ handling occur that may have more substantial impacts upon commonly used means of parthenogenetic activation. PMID:26785810

  4. IP3 Receptors, Mitochondria, and Ca2+ Signaling: Implications for Aging

    PubMed Central

    Decuypere, Jean-Paul; Monaco, Giovanni; Missiaen, Ludwig; De Smedt, Humbert; Parys, Jan B.; Bultynck, Geert

    2011-01-01

    The tight interplay between endoplasmic-reticulum-(ER-) and mitochondria-mediated Ca2+ signaling is a key determinant of cellular health and cellular fate through the control of apoptosis and autophagy. Proteins that prevent or promote apoptosis and autophagy can affect intracellular Ca2+ dynamics and homeostasis through binding and modulation of the intracellular Ca2+-release and Ca2+-uptake mechanisms. During aging, oxidative stress becomes an additional factor that affects ER and mitochondrial function and thus their role in Ca2+ signaling. Importantly, mitochondrial dysfunction and sustained mitochondrial damage are likely to underlie part of the aging process. In this paper, we will discuss the different mechanisms that control intracellular Ca2+ signaling with respect to apoptosis and autophagy and review how these processes are affected during aging through accumulation of reactive oxygen species. PMID:21423550

  5. Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster

    PubMed Central

    Santalla, Manuela; Valverde, Carlos A.; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

    2014-01-01

    Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility. PMID:25003749

  6. Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster.

    PubMed

    Santalla, Manuela; Valverde, Carlos A; Harnichar, Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

    2014-01-01

    Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.

  7. Increased CaVbeta1A expression with aging contributes to skeletal muscle weakness.

    PubMed

    Taylor, Jackson R; Zheng, Zhenlin; Wang, Zhong-Min; Payne, Anthony M; Messi, María L; Delbono, Osvaldo

    2009-09-01

    Ca2+ release from the sarcoplasmic reticulum (SR) into the cytosol is a crucial part of excitation-contraction (E-C) coupling. Excitation-contraction uncoupling, a deficit in Ca2+ release from the SR, is thought to be responsible for at least some of the loss in specific force observed in aging skeletal muscle. Excitation-contraction uncoupling may be caused by alterations in expression of the voltage-dependent calcium channel alpha1s (CaV1.1) and beta1a (CaVbeta1a) subunits, both of which are necessary for E-C coupling to occur. While previous studies have found CaV1.1 expression declines in old rodents, CaVbeta1a expression has not been previously examined in aging models. Western blot analysis shows a substantial increase of CaVbeta1a expression over the full lifespan of Friend Virus B (FVB) mice. To examine the specific effects of CaVbeta1a overexpression, a CaVbeta1a-YFP plasmid was electroporated in vivo into young animals. The resulting increase in expression of CaVbeta1a corresponded to decline of CaV1.1 over the same time period. YFP fluorescence, used as a measure of CaVbeta1a-YFP expression in individual fibers, also showed an inverse relationship with charge movement, measured using the whole-cell patch-clamp technique. Specific force was significantly reduced in young CaVbeta1a-YFP electroporated muscle fibers compared with sham-electroporated, age-matched controls. siRNA interference of CaVbeta1a in young muscles reduced charge movement, while charge movement in old was restored to young control levels. These studies imply CaVbeta1a serves as both a positive and negative regulator CaV1.1 expression, and that endogenous overexpression of CaVbeta1a during old age may play a role in the loss of specific force.

  8. Epigenetic Control of Aging

    PubMed Central

    Sedivy, John M.

    2011-01-01

    Abstract Organismal aging and longevity are influenced by many complex interacting factors. Epigenetics has recently emerged as another possible determinant of aging. Here, we review some of the epigenetic pathways that contribute to cellular senescence and age-associated phenotypes. Strategies aimed to reverse age-linked epigenetic alterations may lead to the development of new therapeutic interventions to delay or alleviate some of the most debilitating age-associated diseases. Antioxid. Redox Signal. 14, 241–259. PMID:20518699

  9. Aging impairs Ca2+ sensitization pathways in gallbladder smooth muscle.

    PubMed

    Macias, Beatriz; Gomez-Pinilla, Pedro J; Camello-Almaraz, Cristina; Pascua, Patricia; Tresguerres, Jesus Af; Camello, Pedro J; Pozo, Maria J

    2012-08-01

    Calcium sensitization is an important physiological process in agonist-induced contraction of smooth muscle. In brief, calcium sensitization is a pathway that leads to smooth muscle contraction independently of changes in [Ca(2+)](i) by mean of inhibition of myosin light chain phosphatase. Aging has negative impacts on gallbladder contractile response due to partial impairment in calcium signaling and alterations in the contractile machinery. However, information regarding aging-induced alterations in calcium sensitization is scanty. We hypothesized that the calcium sensitization system is negatively affected by age. To investigate this, gallbladders were collected from adult (4 months old) and aged (22-24 months old) guinea pigs. To evaluate the contribution of calcium sensitization pathways we assayed the effect of the specific inhibitors Y-27632 and GF109203X on the "in vitro" isometric gallbladder contractions induced by agonist challenges. In addition, expression and phosphorylation (as activation index) of proteins participating in the calcium sensitization pathways were quantified by Western blotting. Aging reduced bethanechol- and cholecystokinin-evoked contractions, an effect associated with a reduction in MLC20 phosphorylation and in the effects of both Y-27632 and GF109203X. In addition, there was a drop in ROCK I, ROCK II, MYPT-1 and PKC expression and in the activation/phosphorylation of MYPT-1, PKC and CPI-17 in response to agonists. Interestingly, melatonin treatment for 4 weeks restored gallbladder contractile responses due to re-establishment of calcium sensitization pathways. These results demonstrate that age-related gallbladder hypocontractility is associated to alterations of calcium sensitization pathways and that melatonin treatment exerts beneficial effects in the recovery of gallbladder contractility.

  10. CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

    PubMed Central

    Yu, Xiao-Wen; Curlik, Daniel M; Oh, M Matthew; Yin, Jerry CP; Disterhoft, John F

    2017-01-01

    The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline. DOI: http://dx.doi.org/10.7554/eLife.19358.001 PMID:28051768

  11. Age-dependent uncoupling of mitochondria from Ca2+ release units in skeletal muscle

    PubMed Central

    Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T.; Boncompagni, Simona; Protasi, Feliciano

    2015-01-01

    Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling. Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8±0.4 vs. 5.5±0.3 tethers/100μm2) and CRU-mitochondrial pair density (37.4±0.8 vs. 27.0±0.7 pairs/100μm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68±0.08 vs 1.37±0.03) and mitochondrial Ca2+ uptake (9.6±0.050 vs 6.58±0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance. PMID:26485763

  12. Na+/Ca2+ exchangers: three mammalian gene families control Ca2+ transport.

    PubMed

    Lytton, Jonathan

    2007-09-15

    Mammalian Na+/Ca2+ exchangers are members of three branches of a much larger family of transport proteins [the CaCA (Ca2+/cation antiporter) superfamily] whose main role is to provide control of Ca2+ flux across the plasma membranes or intracellular compartments. Since cytosolic levels of Ca2+ are much lower than those found extracellularly or in sequestered stores, the major function of Na+/Ca2+ exchangers is to extrude Ca2+ from the cytoplasm. The exchangers are, however, fully reversible and thus, under special conditions of subcellular localization and compartmentalized ion gradients, Na+/Ca2+ exchangers may allow Ca2+ entry and may play more specialized roles in Ca2+ movement between compartments. The NCX (Na+/Ca2+ exchanger) [SLC (solute carrier) 8] branch of Na+/Ca2+ exchangers comprises three members: NCX1 has been most extensively studied, and is broadly expressed with particular abundance in heart, brain and kidney, NCX2 is expressed in brain, and NCX3 is expressed in brain and skeletal muscle. The NCX proteins subserve a variety of roles, depending upon the site of expression. These include cardiac excitation-contraction coupling, neuronal signalling and Ca2+ reabsorption in the kidney. The NCKX (Na2+/Ca2+-K+ exchanger) (SLC24) branch of Na+/Ca2+ exchangers transport K+ and Ca2+ in exchange for Na+, and comprises five members: NCKX1 is expressed in retinal rod photoreceptors, NCKX2 is expressed in cone photoreceptors and in neurons throughout the brain, NCKX3 and NCKX4 are abundant in brain, but have a broader tissue distribution, and NCKX5 is expressed in skin, retinal epithelium and brain. The NCKX proteins probably play a particularly prominent role in regulating Ca2+ flux in environments which experience wide and frequent fluctuations in Na+ concentration. Until recently, the range of functions that NCKX proteins play was generally underappreciated. This situation is now changing rapidly as evidence emerges for roles including photoreceptor

  13. Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat.

    PubMed

    Hosseini-sharifabad, Mohammad; Esfandiari, Ebrahim

    2015-01-01

    Experimental evidence indicates that administration of Boswellia resin, known as olibanum or Frankincense, increases memory power. It is reported that beta boswellic acid, the major component of Boswellia serrata gum resin, could enhance neurite outgrowth and branching in hippocampal neurons. We therefore studied whether Boswellia treatment produces morphological changes in the superior region of cornu ammonis (CA1) in aged rats. Sixteen male Wistar rats, 24 months of age, were randomly divided in experimental and control groups. The experimental group was orally administered Boswellia serrata gum resin (100 mg/kg per day for 8 weeks) and the control group received a similar volume of water. The Cavalieri principle was employed to estimate the volumes of CA1 hippocampal field, and a quantitative Golgi study was used to analysis of dendritic arborizations of CA1 pyramidal cells. Comparisons revealed that Boswellia-treated aged rats had greater volumes than control animals in stratum pyramidale and stratum radiatum lacunosum-moleculare. The neurons of CA1 in experimental rats had more dendritic segments (40.25 ± 4.20) than controls (30.9 ± 4.55), P = 0.001. The total dendritic length of CA1 neurons was approximately 20 % larger in the experimental group compared to control. Results also indicated that the aged rats treated with Boswellia resin had more numerical branching density in the apical dendrites of CA1 pyramidal neurons. The results of the present study show that long-term administration of Boswellia resin can attenuate age-related dendritic regression in CA1 pyramidal cells in rat hippocampus.

  14. Surface L-type Ca2+ channel expression levels are increased in aged hippocampus

    PubMed Central

    Núñez-Santana, Félix Luis; Oh, Myongsoo Matthew; Antion, Marcia Diana; Lee, Amy; Hell, Johannes Wilhelm; Disterhoft, John Francis

    2014-01-01

    Age-related increase in L-type Ca2+ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca2+ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav1.2 and Cav1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav1.2 and Cav1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav1.2 in the CA1 and CA3 regions and of Cav1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca2+ channel activity in CA1 pyramidal neurons. PMID:24033980

  15. Ca-41 in iron falls, Grant and Estherville - Production rates and related exposure age calculations

    NASA Technical Reports Server (NTRS)

    Fink, D.; Klein, J.; Middleton, R.; Vogt, S.; Herzog, G. F.

    1991-01-01

    Results are presented of the first phase of a Ca-41 cosmogenic studies program aimed at establishing baseline concentrations and trends in selected meteorites and the use of Ca-41 in estimating exposure ages and preatmospheric meteorite radii. The average Ca-41 saturation activity recorded in four small iron falls is 24 +/-1 dpm/kg. This finding, together with measurements at the center and surface of the large iron Grant, indicates that production of Ca-41 from spallation on iron is weakly dependent on shielding to depths as large as 250 g/sq cm. The (K-41)-Ca-41 exposure age of Grant is estimated at 330 +/-50 My, and an upper limit to its terrestrial age of 43 +/-15 ky. A comparison of the Ca-41 contents of stony and metallic material separated from the mesosiderite Estherville identifies low-energy neutron capture on native Ca as a second important channel of production. It is found that the Ca-41 signal in the stone phase from three meteorites correlates with their size, and that the inferred low-energy neutron fluxes vary by a factor of at least 20.

  16. Roles of three Fusarium oxysporum calcium ion (Ca(2+)) channels in generating Ca(2+) signatures and controlling growth.

    PubMed

    Kim, Hye-Seon; Kim, Jung-Eun; Frailey, Daniel; Nohe, Anja; Duncan, Randall; Czymmek, Kirk J; Kang, Seogchan

    2015-09-01

    Spatial and temporal changes of cytoplasmic calcium ions ([Ca(2+)]c), caused by external stimuli, are known as the Ca(2+) signature and presumably control cellular and developmental responses. Multiple types of ion channels, pumps, and transporters on plasma and organellar membranes modulate influx and efflux of Ca(2+) to and from the extracellular environment and internal Ca(2+) stores to form Ca(2+) signatures. Expression of a fluorescent protein-based Ca(2+) probe, Cameleon YC3.60, in Fusarium oxysporum enabled us to study how disruption of three Ca(2+) channel genes, including FoCCH1, FoMID1 and FoYVC1, affects Ca(2+) signature formation at polarized hyphal tips and whether specific changes in the Ca(2+) signature caused by these mutations are related to growth-related phenotypes. Resulting mutants displayed altered amplitude, interval, and duration of Ca(2+) pulses under various external Ca(2+) concentrations as well as changes in sporulation and growth. Loss of FoMID1 and FoCCH1, genes encoding putative plasma membrane channel proteins, had a major impact on Ca(2+) signatures and growth, while disruption of FoYVC1, which encodes a vacuolar channel, only subtly affected both traits. Results from our study provide new insights into the underpinning of Ca(2+) signaling in fungi and its role in controlling growth and also raise several new questions.

  17. The mitochondrial Na+/Ca2+ exchanger plays a key role in the control of cytosolic Ca2+ oscillations.

    PubMed

    Hernández-SanMiguel, Esther; Vay, Laura; Santo-Domingo, Jaime; Lobatón, Carmen D; Moreno, Alfredo; Montero, Mayte; Alvarez, Javier

    2006-07-01

    There is increasing evidence that mitochondria play an important role in the control of cytosolic Ca2+ signaling. We show here that the main mitochondrial Ca2+-exit pathway, the mitochondrial Na+/Ca2+ exchanger, controls the pattern of cytosolic Ca2+ oscillations in non-excitable cells. In HeLa cells, the inhibitor of the mitochondrial Na+/Ca2+ exchanger CGP37157 changed the pattern of the oscillations induced by histamine from a high-frequency irregular one to a lower frequency baseline spike type, surprisingly with little changes in the average Ca2+ values of a large cell population. In human fibroblasts, CGP37157 increased the frequency of the baseline oscillations in cells having spontaneous activity and induced the generation of oscillations in cells without spontaneous activity. This effect was dose-dependent, disappeared when the inhibitor was washed out and was not mimicked by mitochondrial depolarization. CGP37157 increased mitochondrial [Ca2+] and ATP production in histamine-stimulated HeLa cells, but the effect on ATP production was only transient. CGP37157 also activated histamine-induced Ca2+ release from the endoplasmic reticulum and increased the size of the cytosolic Ca2+ peak induced by histamine in HeLa cells. Our results suggest that the mitochondrial Na+/Ca2+ exchanger directly modulates inositol 1,4,5-trisphosphate-induced Ca2+ release and in that way controls cytosolic Ca2+ oscillations.

  18. Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae

    PubMed Central

    Dahl, Ashley R.; Gagnon, Patricia M.

    2010-01-01

    Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as ‘good hearing’ standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70–83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (∼18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or ‘root’ cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis. PMID:20706857

  19. Age-dependent changes in diastolic Ca(2+) and Na(+) concentrations in dystrophic cardiomyopathy: Role of Ca(2+) entry and IP3.

    PubMed

    Mijares, Alfredo; Altamirano, Francisco; Kolster, Juan; Adams, José A; López, José R

    2014-10-03

    Duchenne muscular dystrophy (DMD) is a lethal X-inherited disease caused by dystrophin deficiency. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with a dilated cardiomyopathy that leads to progressive heart failure at the end of the second decade. The aim of the present study was to characterize the diastolic Ca(2+) concentration ([Ca(2+)]d) and diastolic Na(+) concentration ([Na(+)]d) abnormalities in cardiomyocytes isolated from 3-, 6-, 9-, and 12-month old mdx mice using ion-selective microelectrodes. In addition, the contributions of gadolinium (Gd(3+))-sensitive Ca(2+) entry and inositol triphosphate (IP3) signaling pathways in abnormal [Ca(2+)]d and [Na(+)]d were investigated. Our results showed an age-dependent increase in both [Ca(2+)]d and [Na(+)]d in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd(3+) treatment significantly reduced both [Ca(2+)]d and [Na(+)]d at all ages. In addition, blockade of the IP3-pathway with either U-73122 or xestospongin C significantly reduced ion concentrations in dystrophic cardiomyocytes. Co-treatment with U-73122 and Gd(3+) normalized both [Ca(2+)]d and [Na(+)]d at all ages in dystrophic cardiomyocytes. These data showed that loss of dystrophin in mdx cardiomyocytes produced an age-dependent intracellular Ca(2+) and Na(+) overload mediated at least in part by enhanced Ca(2+) entry through Gd(3+) sensitive transient receptor potential channels (TRPC), and by IP3 receptors.

  20. Optochemokine Tandem for Light-Control of Intracellular Ca2+

    PubMed Central

    Weissbecker, Juliane; Sauer, Frank; Wood, Phillip G.; Bamberg, Ernst

    2016-01-01

    An optochemokine tandem was developed to control the release of calcium from endosomes into the cytosol by light and to analyze the internalization kinetics of G-protein coupled receptors (GPCRs) by electrophysiology. A previously constructed rhodopsin tandem was re-engineered to combine the light-gated Ca2+-permeable cation channel Channelrhodopsin-2(L132C), CatCh, with the chemokine receptor CXCR4 in a functional tandem protein tCXCR4/CatCh. The GPCR was used as a shuttle protein to displace CatCh from the plasma membrane into intracellular areas. As shown by patch-clamp measurements and confocal laser scanning microscopy, heterologously expressed tCXCR4/CatCh was internalized via the endocytic SDF1/CXCR4 signaling pathway. The kinetics of internalization could be followed electrophysiologically via the amplitude of the CatCh signal. The light-induced release of Ca2+ by tandem endosomes into the cytosol via CatCh was visualized using the Ca2+-sensitive dyes rhod2 and rhod2-AM showing an increase of intracellular Ca2+ in response to light. PMID:27768773

  1. A mathematical model of cardiocyte Ca(2+) dynamics with a novel representation of sarcoplasmic reticular Ca(2+) control.

    PubMed Central

    Snyder, S M; Palmer, B M; Moore, R L

    2000-01-01

    Cardiac contraction and relaxation dynamics result from a set of simultaneously interacting Ca(2+) regulatory mechanisms. In this study, cardiocyte Ca(2+) dynamics were modeled using a set of six differential equations that were based on theories, equations, and parameters described in previous studies. Among the unique features of the model was the inclusion of bidirectional modulatory interplay between the sarcoplasmic reticular Ca(2+) release channel (SRRC) and calsequestrin (CSQ) in the SR lumen, where CSQ acted as a dynamic rather than simple Ca(2+) buffer, and acted as a Ca(2+) sensor in the SR lumen as well. The inclusion of this control mechanism was central in overcoming a number of assumptions that would otherwise have to be made about SRRC kinetics, SR Ca(2+) release rates, and SR Ca(2+) release termination when the SR lumen is assumed to act as a simple, buffered Ca(2+) sink. The model was sufficient to reproduce a graded Ca(2+)-induced Ca(2+) release (CICR) response, CICR with high gain, and a system with reasonable stability. As constructed, the model successfully replicated the results of several previously published experiments that dealt with the Ca(2+) dependence of the SRRC (, J. Gen. Physiol. 85:247-289), the refractoriness of the SRRC (, Am. J. Physiol. 270:C148-C159), the SR Ca(2+) load dependence of SR Ca(2+) release (, Am. J. Physiol. 268:C1313-C1329;, J. Biol. Chem. 267:20850-20856), SR Ca(2+) leak (, J. Physiol. (Lond.). 474:463-471;, Biophys. J. 68:2015-2022), SR Ca(2+) load regulation by leak and uptake (, J. Gen. Physiol. 111:491-504), the effect of Ca(2+) trigger duration on SR Ca(2+) release (, Am. J. Physiol. 258:C944-C954), the apparent relationship that exists between sarcoplasmic and sarcoplasmic reticular calcium concentrations (, Biophys. J. 73:1524-1531), and a variety of contraction frequency-dependent alterations in sarcoplasmic [Ca(2+)] dynamics that are normally observed in the laboratory, including rest potentiation, a

  2. Mitochondria and plasma membrane Ca2+-ATPase control presynaptic Ca2+ clearance in capsaicin-sensitive rat sensory neurons

    PubMed Central

    Shutov, Leonid P; Kim, Man-Su; Houlihan, Patrick R; Medvedeva, Yuliya V; Usachev, Yuriy M

    2013-01-01

    The central processes of primary nociceptors form synaptic connections with the second-order nociceptive neurons located in the dorsal horn of the spinal cord. These synapses gate the flow of nociceptive information from the periphery to the CNS, and plasticity at these synapses contributes to centrally mediated hyperalgesia and allodynia. Although exocytosis and synaptic plasticity are controlled by Ca2+ at the release sites, the mechanisms underlying presynaptic Ca2+ signalling at the nociceptive synapses are not well characterized. We examined the presynaptic mechanisms regulating Ca2+ clearance following electrical stimulation in capsaicin-sensitive nociceptors using a dorsal root ganglion (DRG)/spinal cord neuron co-culture system. Cytosolic Ca2+ concentration ([Ca2+]i) recovery following electrical stimulation was well approximated by a monoexponential function with a τ∼2 s. Inhibition of sarco-endoplasmic reticulum Ca2+-ATPase did not affect presynaptic [Ca2+]i recovery, and blocking plasmalemmal Na+/Ca2+ exchange produced only a small reduction in the rate of [Ca2+]i recovery (∼12%) that was independent of intracellular K+. However, [Ca2+]i recovery in presynaptic boutons strongly depended on the plasma membrane Ca2+-ATPase (PMCA) and mitochondria that accounted for ∼47 and 40%, respectively, of presynaptic Ca2+ clearance. Measurements using a mitochondria-targeted Ca2+ indicator, mtPericam, demonstrated that presynaptic mitochondria accumulated Ca2+ in response to electrical stimulation. Quantitative analysis revealed that the mitochondrial Ca2+ uptake is highly sensitive to presynaptic [Ca2+]i elevations, and occurs at [Ca2+]i levels as low as ∼200–300 nm. Using RT-PCR, we detected expression of several putative mitochondrial Ca2+ transporters in DRG, such as MCU, Letm1 and NCLX. Collectively, this work identifies PMCA and mitochondria as the major regulators of presynaptic Ca2+ signalling at the first sensory synapse, and underlines the high

  3. Intracellular activities related to in vitro hippocampal sharp waves are altered in CA3 pyramidal neurons of aged mice.

    PubMed

    Moradi-Chameh, H; Peng, J; Wu, C; Zhang, L

    2014-09-26

    Pyramidal neurons in the hippocampal CA3 area interconnect intensively via recurrent axonal collaterals, and such CA3-to-CA3 recurrent circuitry plays important roles in the generation of hippocampal network activities. In particular, the CA3 circuitry is able to generate spontaneous sharp waves (SPWs) when examined in vitro. These in vitro SPWs are thought to result from the network activity of GABAergic inhibitory interneurons as SPW-correlating intracellular activities are featured with strong IPSPs in pyramidal neurons and EPSPs or spikes in GABAergic interneurons. In view of accumulating evidence indicating a decrease in subgroups of hippocampal GABAergic interneurons in aged animals, we test the hypothesis that the intracellular activities related to in vitro SPWs are altered in CA3 pyramidal neurons of aged mice. Hippocampal slices were prepared from adult and aged C57 black mice (ages 3-6 and 24-28months respectively). Population and single-cell activities were examined via extracellular and whole-cell patch-clamp recordings. CA3 SPW frequencies were not significantly different between the slices of adult and aged mice but SPW-correlating intracellular activities featured weaker IPSC components in aged CA3 pyramidal neurons compared to adult neurons. It was unlikely that this latter phenomenon was due to general impairments of GABAergic synapses in the aged CA3 circuitry as evoked IPSC responses and pharmacologically isolated IPSCs were observed in aged CA3 pyramidal neurons. In addition, aged CA3 pyramidal neurons displayed more positive resting potentials and had a higher propensity of burst firing than adult neurons. We postulate that alterations of GABAergic network activity may explain the reduced IPCS contributions to in vitro SPWs in aged CA3 pyramidal neurons. Overall, our present observations are supportive of the notion that excitability of hippocampal CA3 circuitry is increased in aged mice.

  4. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  5. Aging in Sweden: local variation, local control.

    PubMed

    Davey, Adam; Malmberg, Bo; Sundström, Gerdt

    2014-08-01

    Aging in Sweden has been uniquely shaped by its history-most notably the long tradition of locally controlled services for older adults. We considered how local variations and local control shape the experience of aging in Sweden and organized the paper into 3 sections. First, we examine aging in Sweden along demography, economy, and housing. Next, we trace the origins and development of the Swedish welfare state to consider formal supports (service provision) and informal supports (caregiving and receipt of care). Finally, we direct researchers to additional data resources for understanding aging in Sweden in greater depth. Sweden was one of the first countries to experience rapid population aging. Quality of life for a majority of older Swedes is high. Local control permits a flexible and adaptive set of services and programs, where emphasis is placed on improving the quality and targeting of services that have already reached a plateau as a function of population and expenditures.

  6. Age-Related Synapse Loss In Hippocampal CA3 Is Not Reversed By Caloric Restriction

    PubMed Central

    Adams, Michelle M.; Donohue, Howard S.; Linville, M. Constance; Iversen, Elizabeth A.; Newton, Isabel G.; Brunso-Bechtold, Judy K.

    2010-01-01

    Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported age-related decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-moleculare (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 mos.) and old (29 mos) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated age-related decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss. PMID:20854882

  7. Quality Control Systems in Cardiac Aging

    PubMed Central

    Quarles, Ellen K; Dai, Dao-Fu; Tocchi, Autumn; Basisty, Nathan; Gitari, Lemuel; Rabinovitch, Peter S

    2015-01-01

    Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. These degenerative changes are intimately associated with quality control mechanisms. This review provides a general overview of the clinical and cellular changes which manifest in cardiac aging, and the quality control mechanisms involved in maintaining homeostasis and retarding aging. These mechanisms include autophagy, ubiquitin-mediated turnover, apoptosis, mitochondrial quality control and cardiac matrix homeostasis. Finally, we discuss aging interventions that have been observed to impact cardiac health outcomes. These include caloric restriction, rapamycin, resveratrol, GDF11, mitochondrial antioxidants and cardiolipin-targeted therapeutics. A greater understanding of the quality control mechanisms that promote cardiac homeostasis will help to understand the benefits of these interventions, and hopefully lead to further improved therapeutic modalities. PMID:25702865

  8. Inhibition of CaMKK2 Reverses Age-Associated Decline in Bone Mass

    PubMed Central

    Pritchard, Zachary J.; Cary, Rachel L.; Yang, Chang; Novack, Deborah V.; Voor, Michael J.; Sankar, Uma

    2016-01-01

    Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2−/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral midshaft geometry, the

  9. BK potassium channels control transmitter release at CA3-CA3 synapses in the rat hippocampus.

    PubMed

    Raffaelli, Giacomo; Saviane, Chiara; Mohajerani, Majid H; Pedarzani, Paola; Cherubini, Enrico

    2004-05-15

    Large conductance calcium- and voltage-activated potassium channels (BK channels) activate in response to calcium influx during action potentials and contribute to the spike repolarization and fast afterhyperpolarization. BK channels targeted to active zones in presynaptic nerve terminals have been shown to limit calcium entry and transmitter release by reducing the duration of the presynaptic spike at neurosecretory nerve terminals and at the frog neuromuscular junction. However, their functional role in central synapses is still uncertain. In the hippocampus, BK channels have been proposed to act as an 'emergency brake' that would control transmitter release only under conditions of excessive depolarization and accumulation of intracellular calcium. Here we demonstrate that in the CA3 region of hippocampal slice cultures, under basal experimental conditions, the selective BK channel blockers paxilline (10 microM) and iberiotoxin (100 nM) increase the frequency, but not the amplitude, of spontaneously occurring action potential-dependent EPSCs. These drugs did not affect miniature currents recorded in the presence of tetrodotoxin, suggesting that their action was dependent on action potential firing. Moreover, in double patch-clamp recordings from monosynaptically interconnected CA3 pyramidal neurones, blockade of BK channels enhanced the probability of transmitter release, as revealed by the increase in success rate, EPSC amplitude and the concomitant decrease in paired-pulse ratio in response to pairs of presynaptic action potentials delivered at a frequency of 0.05 Hz. BK channel blockers also enhanced the appearance of delayed responses, particularly following the second action potential in the paired-pulse protocol. These results are consistent with the hypothesis that BK channels are powerful modulators of transmitter release and synaptic efficacy in central neurones.

  10. Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent.

    PubMed

    Lu, Cheng B; Hamilton, James B; Powell, Andrew D; Toescu, Emil C; Vreugdenhil, Martin

    2011-05-01

    Normal ageing-associated spatial memory impairment has been linked to subtle changes in the hippocampal network. Here we test whether the age-dependent reduction in gamma oscillations can be explained by the changes in intrinsic properties of hippocampal interneurons. Kainate-induced gamma oscillations, but not spontaneous gamma oscillations, were reduced in slices from aged mice. CA3 interneurons were recorded in slices from young and aged mice using Fura-2-filled pipettes. Passive membrane properties, firing properties, medium- and slow-afterhyperpolarisation amplitudes, basal [Ca(2+)](i) and firing-induced [Ca(2+)](i) transients were not different with ageing. Kainate caused a larger depolarisation and increase in [Ca(2+)](i) signal in aged interneurons than in young ones. In contrast to young interneurons, kainate increased the medium- and slow-afterhyperpolarisation and underlying [Ca(2+)](i) transient in aged interneurons. Modulating the slow-afterhyperpolarisation by modulating L-type calcium channels with BAY K 8644 and nimodipine suppressed and potentiated, respectively, kainate-induced gamma oscillations in young slices. The age-dependent and stimulation-dependent increase in basal [Ca(2+)](i), firing-induced [Ca(2+)](i) transient and associated afterhyperpolarisation may reduce interneuron excitability and contribute to an age-dependent impairment of hippocampal gamma oscillations.

  11. [Information conception of the control at aging].

    PubMed

    Ban'kov, V I; Miakotnykh, V S; Talankina, N Z; Lespukh, N I; Borovkova, T A

    2004-01-01

    The exchange of energy between organism and environment perhaps may be to describe with help "entropia"--notion of thermodynamics. Point of view information technologies authors suggest to use "factor of controls", which work with help principle of reverse biological connection. This principle may be to use for control aging, when complicated modulated electromagnetic (information) field has regulationing negative entropic component. There are three principles of information control. All principles have on the basis of utilization by quantitative exponents of functional asymmetry.

  12. Interactions of hearing loss and Diabetes Mellitus in the middle age CBA/CaJ mouse model of presbycusis

    PubMed Central

    Vasilyeva, Olga N.; Frisina, Susan T.; Zhu, Xiaoxia; Walton, Joseph P.; Frisina, Robert D.

    2009-01-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broadband noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (~32g), but there was a significant (~5g) decline in the T1DM, while T2DM exhibited ~10g weight gain. Blood glucose levels significantly increased: 3 fold for T1DM, 1.3 fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus. PMID:19271313

  13. Control theory-based regulation of hippocampal CA1 nonlinear dynamics.

    PubMed

    Hsiao, Min-Chi; Song, Dong; Berger, Theodore W

    2008-01-01

    We are developing a biomimetic electronic neural prosthesis to replace regions of the hippocampal brain area that have been damaged by disease or insult. Our previous study has shown that the VLSI implementation of a CA3 nonlinear dynamic model can functionally replace the CA3 subregion of the hippocampal slice. As a result, the propagation of temporal patterns of activity from DG-->VLSI-->CA1 reproduces the activity observed experimentally in the biological DG-->CA3-->CA1 circuit. In this project, we incorporate an open-loop controller to optimize the output (CA1) response. Specifically, we seek to optimize the stimulation signal to CA1 using a predictive dentate gyrus (DG)-CA1 nonlinear model (i.e., DG-CA1 trajectory model) and a CA1 input-output model (i.e., CA1 plant model), such that the ultimate CA1 response (i.e., desired output) can be first predicted by the DG-CA1 trajectory model and then transformed to the desired stimulation through the inversed CA1 plant model. Lastly, the desired CA1 output is evoked by the estimated optimal stimulation. This study will be the first stage of formulating an integrated modeling-control strategy for the hippocampal neural prosthetic system.

  14. Social inappropriateness, executive control, and aging.

    PubMed

    Henry, Julie D; von Hippel, William; Baynes, Kate

    2009-03-01

    Age-related deficits in executive control might lead to socially inappropriate behavior if they compromise the ability to withhold inappropriate responses. Consistent with this possibility, older adults in the current study showed greater social inappropriateness than younger adults--as rated by their peers--and this effect was mediated by deficits in executive control as well as deficits in general cognitive ability. Older adults also responded with greater social inappropriateness to a provocative event in the laboratory, but this effect was unrelated to executive functioning or general cognitive ability. These findings suggest that changes in both social and cognitive factors are important in understanding age-related changes in social behavior.

  15. CALCINEURIN ENHANCES L-TYPE Ca2+ CHANNEL ACTIVITY IN HIPPOCAMPAL NEURONS: INCREASED EFFECT WITH AGE IN CULTURE

    PubMed Central

    NORRIS, C. M.; BLALOCK, E. M.; CHEN, K.-C.; PORTER, N. M.; LANDFIELD, P. W.

    2006-01-01

    The Ca2+/calmodulin-dependent protein phosphatase, calcineurin, modulates a number of key Ca2+ signaling pathways in neurons, and has been implicated in Ca2+-dependent negative feedback inactivation of N-methyl-d-aspartate receptors and voltage-sensitive Ca2+ channels. In contrast, we report here that three mechanistically disparate calcineurin inhibitors, FK-506, cyclosporin A, and the calcineurin autoinhibitory peptide, inhibited high-voltage-activated Ca2+ channel currents by up to 40% in cultured hippocampal neurons, suggesting that calcineurin acts to enhance Ca2+ currents. This effect occurred with Ba2+ or Ca2+ as charge carrier, and with or without intracellular Ca2+ buffered by EGTA. Ca2+-dependent inactivation of Ca2+ channels was not affected by FK-506. The immunosuppressant, rapamycin, and the protein phosphatase 1/2A inhibitor, okadaic acid, did not decrease Ca2+ channel current, showing specificity for effects on calcineurin. Blockade of L-type Ca2+ channels with nimodipine fully negated the effect of FK-506 on Ca2+ channel current, while blockade of N-, and P-/Q-type Ca2+ channels enhanced FK-506-mediated inhibition of the remaining L-type-enriched current. FK-506 also inhibited substantially more Ca2+ channel current in 4-week-old vs. 2-week-old cultures, an effect paralleled by an increase in calcineurin A mRNA levels. These studies provide the first evidence that calcineurin selectively enhances L-type Ca2+ channel activity in neurons. Moreover, this action appears to be increased concomitantly with the well-characterized increase in L-type Ca2+ channel availability in hippocampal neurons with age-in-culture. PMID:11958864

  16. Controls on shell Mg/Ca and Sr/Ca in cultured planktonic foraminiferan, Globigerinoides ruber (white)

    NASA Astrophysics Data System (ADS)

    Kısakürek, B.; Eisenhauer, A.; Böhm, F.; Garbe-Schönberg, D.; Erez, J.

    2008-09-01

    Mg/Ca and Sr/Ca ratios were determined on a single species of planktonic foraminiferan, Globigerinoides ruber (white), collected from the Gulf of Eilat and cultured in seawater at five different salinities (32 to 44), five temperatures (18 to 30 °C) and four pH values (7.9 to 8.4). The Mg/Ca-temperature calibration of cultured G. ruber (with an exponential slope of 8 ± 3%/°C) agrees well with previously published calibrations from core-tops and sediment traps. However, the dependence of Mg/Ca on salinity (with an exponential slope of 5 ± 3%/psu) is also significant and should be included in the calibration equation. With this purpose, we calculated a calibration equation for G. ruber dependent on both temperature and salinity within the 95% confidence limits: Mg/Ca(mmol/mol)=exp[0.06(±0.02)∗S(psu)+0.08(±0.02)∗T(°C)-2.8(±1.0)],R=0.95 The influence of pH on Mg/Ca ratios is negligible at ambient seawater pH (8.1 to 8.3). However, we observe a dominating pH control on shell Mg/Ca when the pH of seawater is lower than 8.0. Sr/Ca in G. ruber shows a significant positive correlation with average growth rate. Presumably, part of the variability in shell Sr/Ca in the geological record is linked to changes in growth rates of foraminifera as a response to changing environmental conditions.

  17. L-type Ca2+ currents at CA1 synapses, but not CA3 or dentate granule neuron synapses, are increased in 3xTgAD mice in an age-dependent manner

    PubMed Central

    Wang, Yue; Mattson, Mark P.

    2013-01-01

    Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimer’s disease (AD). To elucidate potential biophysical alterations underlying aberrant neuronal network activity in AD, we performed whole-cell patch clamp analyses of L-type (nifedipine-sensitive) Ca2+ currents (L-VGCC), 4–aminopyridine-sensitive K+ currents, and AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid) and NMDA (N-methyl-D-aspartate) currents in CA1, CA3, and dentate granule neurons in hippocampal slices from young, middle-age, and old 3xTgAD mice and age-matched wild type mice. 3xTgAD mice develop progressive widespread accumulation of amyloid b-peptide, and selective hyperphosphorylated tau pathology in hippocampal CA1 neurons, which are associated with cognitive deficits, but independent of overt neuronal degeneration. An age-related elevation of L-type Ca2+ channel current density occurred in CA1 neurons in 3xTgAD mice, but not in wild type mice, with the magnitude being significantly greater in older 3xTgAD mice. The NMDA current was also significantly elevated in CA1 neurons of old 3xTgAD mice compared with in old wild type mice. There were no differences in the amplitude of K+ or AMPA currents in CA1 neurons of 3xTgAD mice compared with wild type mice at any age. There were no significant differences in Ca2+, K+, AMPA, or NMDA currents in CA3 and dentate neurons from 3xTgAD mice compared with wild type mice at any age. Our results reveal an age-related increase of L-VGCC density in CA1 neurons, but not in CA3 or dentate granule neurons, of 3xTgAD mice. These findings suggest a potential contribution of altered L-VGCC to the selective vulnerability of CA1 neurons to tau pathology in the 3xTgAD mice and to their degeneration in AD patients. PMID:23932880

  18. Controlling factors of Ca isotope fractionation in scleractinian corals evaluated by temperature, pH and light controlled culture experiments

    NASA Astrophysics Data System (ADS)

    Inoue, Mayuri; Gussone, Nikolaus; Koga, Yasuko; Iwase, Akihiro; Suzuki, Atsushi; Sakai, Kazuhiko; Kawahata, Hodaka

    2015-10-01

    In this study, the 44Ca/40Ca ratios of Porites australiensis grown under three different culture experiments composed of temperature, pH and light controlled culture experiments are measured. The temperature dependent isotope fractionation of 0.02‰/°C deduced from this study is similar to inorganic aragonite, but the degree of isotope fractionation is about +0.4‰ offset in corals. These observations agree with earlier results on different coral species, suggesting Ca isotope fractionation during Ca transmembrane transport in corals. While in cultured corals a significant temperature dependence of δ44Ca is observed, the relationships between calcium isotope fractionation and pH as well as light intensity are negligible. Therefore variation of δ44Ca in Porites corals is mainly controlled by temperature. A combination of δ44Ca and Sr/Ca of corals in temperature controlled experiments cannot be explained by Rayleigh type fractionation directly from a fluid, which is seawater-like in terms of δ44Ca and Sr/Ca. Through coral-specific biomineralization processes, overall mean δ44Ca of scleractinian corals including previous studies are different from biogenic aragonites secreted by sclerosponges and pteropods, but are comparable with those of bivalves as well as calcitic coccolithophores and foraminifers. These findings are important for better understanding biomineralization in corals and in order to constrain the Ca isotopic composition of oceanic Ca sinks in response to climate changes and associated with shifts of calcite and aragonite seas.

  19. The quality control theory of aging.

    PubMed

    Ladiges, Warren

    2014-01-01

    The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society.

  20. Ca2+/Calmodulin-dependent Protein Kinase IIα (αCaMKII) Controls the Activity of the Dopamine Transporter

    PubMed Central

    Steinkellner, Thomas; Yang, Jae-Won; Montgomery, Therese R.; Chen, Wei-Qiang; Winkler, Marie-Therese; Sucic, Sonja; Lubec, Gert; Freissmuth, Michael; Elgersma, Ype; Sitte, Harald H.; Kudlacek, Oliver

    2012-01-01

    The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action of amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase αCaMKII attenuates amphetamine-triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP+) efflux. More importantly, αCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that αCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice, which lack αCaMKII or which express a permanently self-inhibited αCaMKII (αCaMKIIT305D), exhibit significantly reduced amphetamine-triggered DAT-mediated MPP+ efflux. Additionally, we investigated mice that mimic a neurogenetic disease known as Angelman syndrome. These mice possess reduced αCaMKII activity. Angelman syndrome mice demonstrated an impaired DAT efflux function, which was comparable with that of the αCaMKII mutant mice, indicating that DAT-mediated dopaminergic signaling is affected in Angelman syndrome. PMID:22778257

  1. Theta-frequency synaptic potentiation in CA1 in vitro distinguishes cognitively impaired from unimpaired aged Fischer 344 rats.

    PubMed

    Tombaugh, Geoffrey C; Rowe, Wayne B; Chow, Ana R; Michael, Timothy H; Rose, Gregory M

    2002-11-15

    Hippocampal-dependent learning and memory deficits have been well documented in aging rodents. The results of several recent studies have suggested that these deficits arise from weakened synaptic plasticity within the hippocampus. In the present study, we examined the relationship between hippocampal long-term potentiation (LTP) in vitro and spatial learning in aged (24-26 months) Fischer 344 rats. We found that LTP induced in the CA1 region using theta-frequency stimulation (5 Hz) is selectively impaired in slices from a subpopulation of aged rats that had shown poor spatial learning in the Morris water maze. LTP at 5 Hz in aged rats that did not show learning deficits was similar to that seen in young (4-6 months) controls. We also found that 5 Hz LTP amplitude strongly correlated with individual learning performance among aged rats. The difference in 5 Hz LTP magnitude among aged rats was not attributable to an altered response to 5 Hz stimulation or to differences in the NMDA receptor-mediated field EPSP. In addition, no performance-related differences in LTP were seen when LTP was induced with 30 or 70 Hz stimulation protocols. Finally, both 5 Hz LTP and spatial learning in learning-impaired rats were enhanced with the selective muscarinic M2 antagonist BIBN-99 (5,11-dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1-oxopentyl)ethylamino]propyl]-1-piperidinyl]acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one). These findings reinforce the idea that distinct types of hippocampal LTP offer mechanistic insight into age-associated cognitive decline.

  2. Motor neuron targeting of IGF-1 attenuates age-related external Ca2+-dependent skeletal muscle contraction in senescent mice.

    PubMed

    Payne, Anthony M; Messi, María Laura; Zheng, Zhenlin; Delbono, Osvaldo

    2007-04-01

    A population of fast muscle fibers from aging mice is dependent on external Ca(2+) to maintain tetanic force during repeated contractions. We hypothesized that age-related denervation in muscle fibers plays a role in initiating this contractile deficit, and that prevention of denervation by IGF-1 overexpression would prevent external Ca(2+)-dependent contraction in aging mice. IGF-1 overexpression in skeletal muscle prevents age-related denervation, and prevented external Ca(2+)-dependent contraction in this work. To determine if the effects of IGF-1 overexpression are on muscle or nerve, aging mice were injected with a tetanus toxin fragment-C (TTC) fusion protein that targets IGF-1 to spinal cord motor neurons. This treatment prevented external Ca(2+)-dependent contraction. We also show evidence that injections of the IGF-1-TTC fusion protein prevent age-related alterations to the nerve terminals at the neuromuscular junctions. We conclude that the slow age-related denervation of fast muscle fibers underlies dependence on external Ca(2+) to maintain tetanic force in a population of muscle fibers from senescent mice.

  3. CaMKII Controls Whether Touch Is Painful

    PubMed Central

    Yu, Hongwei; Pan, Bin; Weyer, Andy; Wu, Hsiang-En; Meng, Jingwei; Fischer, Gregory; Vilceanu, Daniel; Light, Alan R.; Stucky, Cheryl; Rice, Frank L.; Hudmon, Andy

    2015-01-01

    The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (Aβ-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history. Here we show that sensory neuron CaMKII autophosphorylation encodes the level of Aβ-LTMR activity in rat models of sensory deprivation (whisker clipping, tail suspension, casting). Blockade of CaMKII signaling limits normal adaptation of action potential generation in Aβ-LTMRs in excised skin. CaMKII activity is also required for natural filtering of impulse trains as they travel through the sensory neuron T-junction in the DRG. Blockade of CaMKII selectively in presynaptic Aβ-LTMRs removes dorsal horn inhibition that otherwise prevents Aβ-LTMR input from activating nociceptive lamina I neurons. Together, these consequences of reduced CaMKII function in Aβ-LTMRs cause low-intensity mechanical stimulation to produce pain behavior. We conclude that, without normal sensory activity to maintain adequate levels of CaMKII function, the touch pathway shifts into a pain system. In the clinical setting, sensory disuse may be a critical factor that enhances and prolongs chronic pain initiated by other conditions. SIGNIFICANCE STATEMENT The sensation of touch is served by specialized sensory neurons termed low-threshold mechanoreceptors (LTMRs). We examined the role of CaMKII in regulating the function of these neurons. Loss of CaMKII function, such as occurred in rats during sensory deprivation, elevated the generation and propagation of impulses by LTMRs, and altered the spinal cord circuitry in such a way that low-threshold mechanical stimuli produced pain behavior. Because limbs

  4. STRUCTURAL TRANSFORMATIONS IN CA-BASED SORBENTS USED FOR SO2 EMISSION CONTROL

    EPA Science Inventory

    The paper discusses structural transformations in Ca-based sorbents used for SO2 emission control. conomizer temperature injection of Ca-based sorbents is an option for dry control of SO2 emissions from coal-fired boilers. heir reactivity with SO2 was found to be a function of th...

  5. Electric Field Control of the Ferromagnetic CaRuO3 /CaMnO3 Interface

    NASA Astrophysics Data System (ADS)

    Grutter, Alexander; Kirby, Brian; Gray, Matthew; Flint, Charles; Suzuki, Yuri; Borchers, Julie

    2015-03-01

    Electric field control of magnetism has been recognized as one of the most important goals in nanoscale magnetics research. The most popular routes towards achieving magnetoelectric (ME) coupling have focused on heterostructures incorporating multiferroics or ferroelectrics. Such studies often rely on voltage induced distortion to induce strain in the magnetic film and alter the magnetic properties. However, successful attempts to induce ME coupling without multiferroicity or magnetoelasticity remain relatively rare. The ferromagnetic interface between the antiferromagnetic insulator CaMnO3 and the paramagnetic metal CaRuO3 is a promising candidate for direct magnetization control. This interfacial ferroagnetism is stabilized through the competition between interfacial double exchange and antiferromagnetic superexchange between adjacent Mn4+ so that the system is expected to be very sensitive to small changes in interfacial carrier density. Using polarized neutron reflectometry, we have probed the electric field dependence of the interfacial magnetization of CaRuO3/CaMnO3 bilayers deposited on SrTiO3. We find that electric fields of +/-8 kV/m are sufficient to switch the interfaces from largely ferromagnetic to completely antiferromagnetic.

  6. Age- and education-adjusted normative data for the Montreal Cognitive Assessment (MoCA) in older adults age 70-99.

    PubMed

    Malek-Ahmadi, Michael; Powell, Jessica J; Belden, Christine M; O'Connor, Kathy; Evans, Linda; Coon, David W; Nieri, Walter

    2015-01-01

    The original validation study for the Montreal Cognitive Assessment (MoCA) suggests a cutoff score of 26; however, this may be too stringent for older adults, particularly for those with less education. Given the rapidly increasing number of older adults and associated risk of dementia, this study aims to provide appropriate age- and education-adjusted norms for the MoCA. Data from 205 participants in an ongoing longevity study were used to derive normative data. Individuals were grouped based on age (70-79, 80-89, 90-99) and education level (≤12 Years, 13-15, ≥16 Years). There were significant differences between age and education groups with younger and more educated participants outperforming their counterparts. Forty-six percent of our sample scored below the suggested cutoff of 26. These normative data may provide a more accurate representation of MoCA performance in older adults for specific age and education stratifications.

  7. The Influence of CaCO3 Dissolution on Core Top Radiocarbon Ages for Deep-Sea Sediments

    NASA Astrophysics Data System (ADS)

    Broecker, Wallace S.; Klas, Mieczyslawa; Clark, Elizabeth; Bonani, Georges; Ivy, Susan; Wolfli, Willy

    1991-10-01

    Radiocarbon ages on CaCO3 from deep-sea cores offer constraints on the nature of the CaCO3 dissolution process. The idea is that the toll taken by dissolution on grains within the core top bioturbation zone should be in proportion to their time of residence in this zone. If so, dissolution would shift the mass distribution in favor of younger grains, thereby reducing the mean radiocarbon age for the grain ensemble. We have searched in vain for evidence supporting the existence of such an age reduction. Instead, we find that for water depths of more than 4 km in the tropical Pacific the radiocarbon age increases with the extent of dissolution. We can find no satisfactory steady state explanation and are forced to conclude that this increase must be the result of chemical erosion. The idea is that during the Holocene the rate of dissolution of CaCO3 has exceeded the rain rate of CaCO3. In this circumstance, bioturbation exhumes CaCO3 from the underlying glacial sediment and mixes it with CaCO3 raining from the sea surface.

  8. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    SciTech Connect

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-15

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  9. Altering sphingolipid composition with aging induces contractile dysfunction of gastric smooth muscle via K(Ca) 1.1 upregulation.

    PubMed

    Choi, Shinkyu; Kim, Ji Aee; Kim, Tae Hun; Li, Hai-Yan; Shin, Kyong-Oh; Lee, Yong-Moon; Oh, Seikwan; Pewzner-Jung, Yael; Futerman, Anthony H; Suh, Suk Hyo

    2015-12-01

    K(Ca) 1.1 regulates smooth muscle contractility by modulating membrane potential, and age-associated changes in K(Ca) 1.1 expression may contribute to the development of motility disorders of the gastrointestinal tract. Sphingolipids (SLs) are important structural components of cellular membranes whose altered composition may affect K(Ca) 1.1 expression. Thus, in this study, we examined whether altered SL composition due to aging may affect the contractility of gastric smooth muscle (GSM). We studied changes in ceramide synthases (CerS) and SL levels in the GSM of mice of varying ages and compared them with those in young CerS2-null mice. The levels of C16- and C18-ceramides, sphinganine, sphingosine, and sphingosine 1-phosphate were increased, and levels of C22, C24:1 and C24 ceramides were decreased in the GSM of both aged wild-type and young CerS2-null mice. The altered SL composition upregulated K(Ca) 1.1 and increased K(Ca) 1.1 currents, while no change was observed in K(Ca) 1.1 channel activity. The upregulation of KC a 1.1 impaired intracellular Ca²⁺mobilization and decreased phosphorylated myosin light chain levels, causing GSM contractile dysfunction. Additionally, phosphoinositide 3-kinase, protein kinase Cζ , c-Jun N-terminal kinases, and nuclear factor kappa-B were found to be involved in K(Ca) 1.1 upregulation. Our findings suggest that age-associated changes in SL composition or CerS2 ablation upregulate K(Ca) 1.1 via the phosphoinositide 3-kinase/protein kinase Cζ /c-Jun N-terminal kinases/nuclear factor kappa-B-mediated pathway and impair Ca²⁺ mobilization, which thereby induces the contractile dysfunction of GSM. CerS2-null mice exhibited similar effects to aged wild-type mice; therefore, CerS2-null mouse models may be utilized for investigating the pathogenesis of aging-associated motility disorders.

  10. Age and adaptation to Ca and P deficiencies: 2. Impacts on amino acid digestibility and phytase efficacy in broilers.

    PubMed

    Li, W; Angel, R; Kim, S-W; Jiménez-Moreno, E; Proszkowiec-Weglarz, M; Plumstead, P W

    2015-12-01

    A total of 1,152 straight-run hatchling Heritage 56M×fast feathering Cobb 500F broiler birds were used to determine Ca, age, and adaptation effects on apparent ileal digestibility of crude protein (AID of CP), amino acids (AID of AA) and phytase efficacy. Twelve treatments with 8 replicates, each were fed from 7 to 9 d (6 birds per replicate), 7 to 21 d (6 birds per replicate) and 19 to 21 d (3 birds per replicate) d of age. Diets were prepared with 3 Ca (0.65, 0.80, and 0.95%) and 2 non-phytate P, (0.20 and 0.40%) concentrations. A 6-phytase was added at 500 or 1,000 FTU/kg to the 0.20% nPP diet at each Ca concentration. The age and adaptation effects were determined by comparing the responses between birds fed from 7 to 9 and 19 to 21 d of age, 19 to 21, and 7 to 21 d of age, respectively. An age effect was observed regardless of Ca, nPP, or phytase concentration, with older birds (19 to 21 d) having greater apparent ileal digestibility (AID) of amino acids (AA) and CP than younger birds (7 to 9 d; P<0.05). Response to adaptation varied depending on Ca, nPP, and phytase concentrations. Constant lower AID of CP and AA was seen in adapted birds (7 to 21 d) compared to unadapted bird (19 to 21 d) when 0.20% nPP diets were fed at 0.95% Ca concentrations (P<0.05). At 0.40% nPP, there was no effect of adaptation on AID of CP and AA at any Ca concentration. Phytase efficacy was significantly lower in younger (7 to 9 d) compared to older birds (19 to 21 d; P<0.05), except at 0.65% Ca. Phytase inclusion increased AID of CP and AA regardless of Ca (P<0.05). In conclusion, the AID of CP and AA can be affected by diet, age, and adaptation.

  11. Epigenetic regulation of L-type voltage-gated Ca(2+) channels in mesenteric arteries of aging hypertensive rats.

    PubMed

    Liao, Jingwen; Zhang, Yanyan; Ye, Fang; Zhang, Lin; Chen, Yu; Zeng, Fanxing; Shi, Lijun

    2016-11-24

    Accumulating evidence has shown that epigenetic regulation is involved in hypertension and aging. L-type voltage-gated Ca(2+) channels (LTCCs), the dominant channels in vascular myocytes, greatly contribute to arteriole contraction and blood pressure (BP) control. We investigated the dynamic changes and epigenetic regulation of LTCC in the mesenteric arteries of aging hypertensive rats. LTCC function was evaluated by using microvascular rings and whole-cell patch-clamp in the mesenteric arteries of male Wistar-Kyoto rats and spontaneously hypertensive rats at established hypertension (3 month old) and an aging stage (16 month old), respectively. The expression of the LTCC α1C subunit was determined in the rat mesenteric microcirculation. The expression of miR-328, which targets α1C mRNA, and the DNA methylation status at the promoter region of the α1C gene (CACNA1C) were also determined. In vitro experiments were performed to assess α1C expression after transfection of the miR-328 mimic into cultured vascular smooth muscle cells (VSMCs). The results showed that hypertension superimposed with aging aggravated BP and vascular remodeling. Both LTCC function and expression were significantly increased in hypertensive arteries and downregulated with aging. miR-328 expression was inhibited in hypertension, but increased with aging. There was no significant difference in the mean DNA methylation of CACNA1C among groups, whereas methylation was enhanced in the hypertensive group at specific sites on a CpG island located upstream of the gene promoter. Overexpression of miR-328 inhibited the α1C level of cultured VSMCs within 48 h. The results of the present study indicate that the dysfunction of LTCCs may exert an epigenetic influence at both pre- and post-transcriptional levels during hypertension pathogenesis and aging progression. miR-328 negatively regulated LTCC expression in both aging and hypertension.Hypertension Research advance online publication, 24

  12. Impaired presynaptic cytosolic and mitochondrial calcium dynamics in aged compared to young adult hippocampal CA1 synapses ameliorated by calcium chelation.

    PubMed

    Tonkikh, A A; Carlen, P L

    2009-04-10

    Impaired regulation of presynaptic intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. We studied presynaptic cytosolic and mitochondrial calcium (Ca) dynamics using axonally loaded Calcium Green-AM and Rhod-2 AM fluorescence respectively in young (2-3 months) and aged (23-26 months) CA3 to CA1 Schaffer collateral excitatory synapses in hippocampal brain slices from Fisher 344 rats. After a tetanus (100 Hz, 200 ms), the presynaptic cytosolic Ca peaked at approximately 10 s in the young and approximately 12 s in the aged synapses. Administration of the membrane permeant Ca chelator, bis (O-aminophenoxy)-ethane-N,N,N,N-tetraacetic acid (BAPTA-AM), significantly attenuated the Ca response in the aged slices, but not in the young slices. The presynaptic mitochondrial Ca signal was much slower, peaking at approximately 90 s in both young and aged synapses, returning to baseline by 300 s. BAPTA-AM significantly attenuated the mitochondrial calcium signal only in the young synapses. Uncoupling mitochondrial respiration by carbonyl cyanide m-chlorophenylhydrazone (CCCP) application evoked a massive intracellular cytosolic Ca increase and a significant drop of mitochondrial Ca, especially in aged slices wherein the cytosolic Ca signal disappeared after approximately 150 s of washout and the mitochondrial Ca signal disappeared after 25 s of washout. These signals were preserved in aged slices by BAPTA-AM. Five minutes of oxygen glucose deprivation (OGD) was associated with a significant increase in cytosolic Ca in both young and aged synapses, which was irreversible in the aged synapses. These responses were significantly attenuated by BAPTA-AM in both the young and aged synapses. These results support the hypothesis that increasing intracellular calcium neuronal buffering in aged rats ameliorates age-related impaired presynaptic Ca regulation.

  13. Control and the Aged: Environmental or Personality Factors.

    ERIC Educational Resources Information Center

    Tiffany, Phyllis G.; Dey, Kay

    Control over self, lifestyle, and environment is a major factor in how one ages. To investigate how age acts as an environmental force in affecting perceptions of control, 45 adults, aged 60-80, from western Kansas were administered the Wechsler Adult Intelligence Scale (WAIS), the Tiffany Experienced Control Scales (ECS), the Minnesota…

  14. Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels.

    PubMed

    Norris, C M; Halpain, S; Foster, T C

    1998-05-01

    The role of L-type Ca2+ channels in the induction of synaptic plasticity in hippocampal slices of aged (22-24 months) and young adult (4-6 months) male Fischer 344 rats was investigated. Prolonged 1 Hz stimulation (900 pulses) of Schaffer collaterals, which normally depresses CA3/CA1 synaptic strength in aged rat slices, failed to induce long-term depression (LTD) during bath application of the L-channel antagonist nifedipine (10 microM). When 5 Hz stimulation (900 pulses) was used to modify synaptic strength, nifedipine facilitated synaptic enhancement in slices from aged, but not young, adult rats. This enhancement was pathway-specific, reversible, and impaired by the NMDA receptor (NMDAR) antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Induction of long-term potentiation (LTP) in aged rats, using 100 Hz stimulation, occluded subsequent synaptic enhancement by 5 Hz stimulation, suggesting that nifedipine-facilitated enhancement shares mechanisms in common with conventional LTP. Facilitation of synaptic enhancement by nifedipine likely was attributable to a reduction ( approximately 30%) in the Ca2+-dependent K+-mediated afterhyperpolarization (AHP), because the K+ channel blocker apamin (1 microM) similarly reduced the AHP and promoted synaptic enhancement by 5 Hz stimulation. In contrast, apamin did not block LTD induction using 1 Hz stimulation, suggesting that, in aged rats, the AHP does not influence LTD and LTP induction in a similar way. The results indicate that, during aging, L-channels can (1) facilitate LTD induction during low rates of synaptic activity and (2) impair LTP induction during higher levels of synaptic activation via an increase in the Ca2+-dependent AHP.

  15. Paleomagnetic secular variation and environmental magnetism of Holocene-age sediments from Tulare Lake, CA

    NASA Astrophysics Data System (ADS)

    Roza, Janine; Jackson, Brandon; Heaton, Eric; Negrini, Rob

    2016-05-01

    The lake-level record from Tulare Lake, CA has been shown to provide valuable constraints on late Pleistocene and Holocene runoff from the Sierra Nevada mountain range into the San Joaquin Valley of California, one of the world's most prolific agricultural centers. This project uses the magnetic properties of the Tulare Lake sediments in order to date the sediments and to constrain the relative lake level at the time of deposition. Shallowing lake conditions were identified leading up to a prominent unconformity; magnetic mineralogy and grain size indicators, primarily decreasing ARM/IRM and S-Ratio values suggest coarser grain sizes and more oxidizing conditions. Approximately half of the samples possessed well-behaved paleomagnetic directions suitable for paleomagnetic secular variation dating. The results indicate that the sediments below the unconformity were deposited approximately 7600-8500 cal yr BP, and the sediments above the unconformity were deposited approximately 2500-800 cal yr BP. The ages of the corresponding sediments are consistent with the time intervals during which previous studies indicate that lake level was above the elevation of this site, before and after a mid Holocene regression.

  16. Paleomagnetic Secular Variation and Environmental Magnetism of Holocene-aged Sediments from Tulare Lake, CA

    NASA Astrophysics Data System (ADS)

    Roza, J.; Jackson, B.; Heaton, E.; Negrini, R. M.

    2015-12-01

    The lake-level record from Tulare Lake, CA has been shown to provide valuable constraints on late Pleistocene and Holocene channelized runoff from the Sierra Nevada mountain range into the San Joaquin Valley of California, one of the world's most prolific agricultural centers. This project focuses on the use of magnetic properties of the Tulare Lake sediments in order to test previous results by dating the sediments and determining the relative lake level at the time of deposition. Shallowing lake conditions were identified leading up to a prominent unconformity from magnetic mineralogy and grain size indicators, primarily decreasing ARM/IRM and S-Ratio values suggesting coarser grain sizes and more oxidizing conditions. Approximately half of the samples possessed well-behaved paleomagnetic directions suitable for paleomagnetic secular variation dating. The results indicate that the sediments below the unconformity were deposited approximately 7600-6700 14C years ago (~7600 to 8500 cal yr B.P.), and the sediments above the unconformity were deposited approximately 2200-500 14C years ago. The ages of the corresponding sediments are consistent with the time intervals during which lake level was predicted to be above the elevation of the Poso Canal site before and after a mid-Holocene regression.

  17. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca2+

    PubMed Central

    Waldeck-Weiermair, Markus; Malli, Roland; Parichatikanond, Warisara; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T.; Klec, Christiane; Rost, Rene; Graier, Wolfgang F.

    2015-01-01

    Mitochondrial Ca2+ uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca2+ uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca2+ channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca2+ signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca2+ rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca2+ uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca2+ rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca2+ concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells. PMID:26489515

  18. Sarcolemmal Ca(2+)-entry through L-type Ca(2+) channels controls the profile of Ca(2+)-activated Cl(-) current in canine ventricular myocytes.

    PubMed

    Horváth, Balázs; Váczi, Krisztina; Hegyi, Bence; Gönczi, Mónika; Dienes, Beatrix; Kistamás, Kornél; Bányász, Tamás; Magyar, János; Baczkó, István; Varró, András; Seprényi, György; Csernoch, László; Nánási, Péter P; Szentandrássy, Norbert

    2016-08-01

    Ca(2+)-activated Cl(-) current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca(2+) cycling and AP voltage-clamp) as well as in conditions designed to change [Ca(2+)]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined. The possible spatial distribution of these proteins and their co-localization with Cav1.2 was also studied. The profile of ICl(Ca), identified as a 9-anthracene carboxylic acid-sensitive current under AP voltage-clamp conditions, contained an early fast outward and a late inward component, overlapping early and terminal repolarizations, respectively. Both components were moderately reduced by ryanodine, while fully abolished by BAPTA, but not EGTA. [Ca(2+)]i was monitored using Fura-2-AM. Setting [Ca(2+)]i to the systolic level measured in the bulk cytoplasm (1.1μM) decreased ICl(Ca), while application of Bay K8644, isoproterenol, and faster stimulation rates increased the amplitude of ICl(Ca). Ca(2+)-entry through L-type Ca(2+) channels was essential for activation of ICl(Ca). TMEM16A and Bestrophin-3 showed strong co-localization with one another and also with Cav1.2 channels, when assessed using immunolabeling and confocal microscopy in both canine myocytes and human ventricular myocardium. Activation of ICl(Ca) in canine ventricular cells requires Ca(2+)-entry through neighboring L-type Ca(2+) channels and is only augmented by SR Ca(2+)-release. Substantial activation of ICl(Ca) requires high Ca(2+) concentration in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA.

  19. The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca2+-Induced Inactivation

    PubMed Central

    Valiullina, Fliza; Zakharova, Yulia; Mukhtarov, Marat; Draguhn, Andreas; Burnashev, Nail; Rozov, Andrei

    2016-01-01

    NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca2+. At the same time, they are themselves inhibited by the elevation of intracellular Ca2+ concentration. It is unclear however, whether the Ca2+ entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca2+ buffers. Loading of pyramidal cells with exogenous Ca2+ buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca2+ influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg2+ concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca2+ buffer capacity of postsynaptic neurons. PMID:26858606

  20. Age-related homeostatic mid-channel proteolysis of neuronal L-type voltage-gated Ca2+ channels

    PubMed Central

    Michailidis, Ioannis E.; Abele-Henckels, Kathryn; Zhang, Wei K.; Lin, Bochao; Yu, Yong; Geyman, Larry; Ehlers, Michael D.; Pnevmatikakis, Eftychios A.; Yang, Jian

    2014-01-01

    SUMMARY Neural circuitry and brain activity depend critically on proper function of voltage-gated calcium channels (VGCCs), whose activity must be tightly controlled. We show that the main body of the pore-forming α1 subunit of neuronal L-type VGCCs, Cav1.2, is proteolytically cleaved, resulting in Cav1.2 fragment-channels that separate but remain on the plasma membrane. This “gmid-channel” proteolysis is regulated by channel activity, involves the Ca2+-dependent protease calpain and the ubiquitin-proteasome system, and causes attenuation and biophysical alterations of VGCC currents. Recombinant Cav1.2 fragment-channels mimicking the products of mid-channel proteolysis do not form active channels on their own, but when properly paired, produce currents with distinct biophysical properties. Mid-channel proteolysis increases dramatically with age and can be attenuated with an L-type VGCC blocker in vivo. Mid-channel proteolysis represents a novel form of homeostatic negative-feedback processing of VGCCs that could profoundly affect neuronal excitability, neurotransmission, neuroprotection, and calcium signaling in physiological and disease states. PMID:24908485

  1. The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

    PubMed

    Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

    2005-10-18

    We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

  2. Ca2+ spikes in the flagellum control chemotactic behavior of sperm

    PubMed Central

    Böhmer, Martin; Van, Qui; Weyand, Ingo; Hagen, Volker; Beyermann, Michael; Matsumoto, Midori; Hoshi, Motonori; Hildebrand, Eilo; Kaupp, Ulrich Benjamin

    2005-01-01

    The events that occur during chemotaxis of sperm are only partly known. As an essential step toward determining the underlying mechanism, we have recorded Ca2+ dynamics in swimming sperm of marine invertebrates. Stimulation of the sea urchin Arbacia punctulata by the chemoattractant or by intracellular cGMP evokes Ca2+ spikes in the flagellum. A Ca2+ spike elicits a turn in the trajectory followed by a period of straight swimming (‘turn-and-run'). The train of Ca2+ spikes gives rise to repetitive loop-like movements. When sperm swim in a concentration gradient of the attractant, the Ca2+ spikes and the stimulus function are synchronized, suggesting that precise timing of Ca2+ spikes controls navigation. We identified the peptide asterosap as a chemotactic factor of the starfish Asterias amurensis. The Ca2+ spikes and swimming behavior of sperm from starfish and sea urchin are similar, implying that the signaling pathway of chemotaxis has been conserved for almost 500 million years. PMID:16001082

  3. Pyroclasts Key to Age and Use of Meter-Size Granite Basins, Sierra Nevada, CA (Invited)

    NASA Astrophysics Data System (ADS)

    Moore, J. G.; Gorden, M. A.; Sisson, T. W.

    2010-12-01

    More than 1000 meter-size granite basins at more than 220 sites occur in a 240-km-long belt from Lake Isabella north to the San Joaquin River on the west slope of the southern Sierra Nevada. The circular basins are carved in granitic outcrops at an average elevation of 1950 m. They range in volume from 40 to 1400 liters, median 130 liters. The basins display features compatible with a man-made origin, but required enormous, sustained labor to excavate. Until now their apparent purpose was believed to be some aspect of food preparation (Moore, Gorden, Robinson, Moring, 2008). About 120 km north of this belt a separate cluster of more than 350 similar granite basins occurs near a rare salt spring. They were clearly made by Indians to contain saline water to produce salt by evaporation (Moore and Diggles, 2009). An early study identified rhyolitic volcanic ash in the bottom of many basins in Sequoia National Park at both Giant Forest and at Redwood Meadow 13 km ESE (Stewart, 1929). That ash is unavailable, having been removed in recent time. Subsequent study of meadowland soils identified two ash layers in the region from explosive eruptions in the Mono Lake area: Tephra 1 and Tephra 2 (Wood, 1977). Later work indicates that Tephra 1 was erupted from the Glass Creek vent of the Inyo Craters (Miller, 1985) and that its refined age by tree-ring techniques is AD 1350 (Millar, King, Westfall, Alden, Delany, 2006). A fossil forest killed by Tephra 1 differs from modern forests in that it grew in the warmer climate of the Medieval Warm Period (MWP)--a period when drought conditions prevailed at lower elevations (Stine, 1994; Millar et al, 2006). In July 2010 ash was discovered near the bottom of a pristine granite basin (TUL-496) in a remote area of Giant Sequoia National Monument 14.5 km NW of Giant Forest. High-beam-current electron microprobe analyses of pumice glasses give Zr 145-420 ppm, homogeneous within lapilli, and correlated with MgO and CaO concentrations. The

  4. Reduction in Sensorimotor Control with Age.

    ERIC Educational Resources Information Center

    Seidler, Rachael D.; Stelmach, George E.

    1995-01-01

    Reviews age-related declines in motor performance, examining the known types of sensorimotor deficits in the elderly. The article highlights recent data that show changes in kinematics of arm movements, prehension tasks, and handwriting that reveal why movement becomes slower and less accurate in older adults. (SM)

  5. The effect of glycemic control on CEA, CA 19-9, amylase and lipase levels

    PubMed Central

    Ata, Naim; Dal, Kürşat; Kucukazman, Metin; Karakaya, Serdar; Unsal, Oktay; Dagdeviren, Murat; Akın, Kadir O.; Baser, Salih; Beyan, Esin; Ertugrul, Derun T.

    2015-01-01

    Background Diabetes mellitus is closely related to pancreas cancer. In this study we aimed to investigate the effect of hyperglycemia on tumor and inflammation markers, as well as pancreatic exocrine functions. Methods A total of 98 consecutive diabetic patients with poor glycemic control, and 50 healthy controls were included in the study. We measured hsCRP, erythrocyte sedimentation rate (ESR), CA19-9, CEA, amylase and lipase in addition to routine biochemistry tests, before and after euglycemia was achieved. Results Fasting blood glucose, HbA1c, CA19-9, CEA, hsCRP, ESR, triglycerides, AST, ALT, GGT, ALP, total cholesterol and LDL-C levels decreased significantly with the regulation of glycemic control. Amylase and lipase levels increased with the regulation of glycemic control. After glycemic control, CA19-9 and CEA levels were still higher, whereas amylase and lipase levels were still lower in the diabetic group compared with the control group. Basal HbA1c showed significant correlation with CA19-9, CEA, amylase and lipase. Conclusions We propose to repeat observations of tumor markers after hyperglycemia is resolved, in order to avoid unnecessary invasive tests. Our data also suggest that pancreatic exocrine function was improved with lowering blood glucose in a short period of time. PMID:28352671

  6. NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis

    PubMed Central

    Favia, Annarita; Pafumi, Irene; Desideri, Marianna; Padula, Fabrizio; Montesano, Camilla; Passeri, Daniela; Nicoletti, Carmine; Orlandi, Augusto; Del Bufalo, Donatella; Sergi, Manuel; Ziparo, Elio; Palombi, Fioretta; Filippini, Antonio

    2016-01-01

    A novel transduction pathway for the powerful angiogenic factor VEGF has been recently shown in endothelial cells to operate through NAADP-controlled intracellular release of Ca2+. In the present report the possible involvement of NAADP-controlled Ca2+ signaling in tumor vascularization, growth and metastatic dissemination was investigated in a murine model of VEGF-secreting melanoma. Mice implanted with B16 melanoma cells were treated with NAADP inhibitor Ned-19 every second day for 4 weeks and tumor growth, vascularization and metastatization were evaluated. Control specimens developed well vascularized tumors and lung metastases, whereas in Ned-19-treated mice tumor growth and vascularization as well as lung metastases were strongly inhibited. In vitro experiments showed that Ned-19 treatment controls the growth of B16 cells in vitro, their migratory ability, adhesive properties and VEGFR2 expression, indicating NAADP involvement in intercellular autocrine signaling. To this regard, Ca2+ imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca2+ signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells. PMID:26733361

  7. BK potassium channels control transmitter release at CA3−CA3 synapses in the rat hippocampus

    PubMed Central

    Raffaelli, Giacomo; Saviane, Chiara; Mohajerani, Majid H; Pedarzani, Paola; Cherubini, Enrico

    2004-01-01

    Large conductance calcium- and voltage-activated potassium channels (BK channels) activate in response to calcium influx during action potentials and contribute to the spike repolarization and fast afterhyperpolarization. BK channels targeted to active zones in presynaptic nerve terminals have been shown to limit calcium entry and transmitter release by reducing the duration of the presynaptic spike at neurosecretory nerve terminals and at the frog neuromuscular junction. However, their functional role in central synapses is still uncertain. In the hippocampus, BK channels have been proposed to act as an ‘emergency brake’ that would control transmitter release only under conditions of excessive depolarization and accumulation of intracellular calcium. Here we demonstrate that in the CA3 region of hippocampal slice cultures, under basal experimental conditions, the selective BK channel blockers paxilline (10 μm) and iberiotoxin (100 nm) increase the frequency, but not the amplitude, of spontaneously occurring action potential-dependent EPSCs. These drugs did not affect miniature currents recorded in the presence of tetrodotoxin, suggesting that their action was dependent on action potential firing. Moreover, in double patch-clamp recordings from monosynaptically interconnected CA3 pyramidal neurones, blockade of BK channels enhanced the probability of transmitter release, as revealed by the increase in success rate, EPSC amplitude and the concomitant decrease in paired-pulse ratio in response to pairs of presynaptic action potentials delivered at a frequency of 0.05 Hz. BK channel blockers also enhanced the appearance of delayed responses, particularly following the second action potential in the paired-pulse protocol. These results are consistent with the hypothesis that BK channels are powerful modulators of transmitter release and synaptic efficacy in central neurones. PMID:15034127

  8. Developmental Level and Psychopathology: Comparing Children with Developmental Delays to Chronological and Mental Age Matched Controls

    PubMed Central

    Caplan, Barbara; Neece, Cameron L.; Baker, Bruce L.

    2015-01-01

    Children with developmental delays (DD) are at heightened risk for developing clinically significant behavioral and emotional difficulties as compared to children with typical development (TD). However, nearly all studies comparing psychopathology in youth with DD employ TD control groups of the same chronological age (CA). It is unclear, then, whether the heightened symptomology found in age-matched children with DD is beyond what would be expected given their developmental level. The present study assessed rates of behavior problems and mental disorder in 35 children with DD at age 9 years. These were compared with rates from 35 children with TD matched for CA at age 9 and also earlier rates for these same children at age 6, when matched for mental age (MA). Children with DD had significantly more behavior problems in 7 of the 17 scales of the CBCL when compared to TD children matched for CA, and 6 of 17 scales when compared to the MA-matched group. Rates of meeting DSM-IV criteria for a psychiatric disorder were significantly higher in the DD group than both the CA- and MA-matched TD groups for three and four, respectively, of the seven diagnoses examined. Descriptively, the mean ratings for all variables assessed were higher for the DD group than both TD comparison groups, with the exception of the Anxious/Depressed scale of the CBCL. These findings validate the heightened risk for clinically significant behavior problems and mental disorders in youth with DD above and beyond their developmental functioning. PMID:25498740

  9. Hypothalamic control of sleep in aging.

    PubMed

    Rolls, Asya

    2012-09-01

    The timing of sleep and its duration are affected by circadian and homeostatic factors. Physiological and behavioral attributes such as the duration of previous wake period, food availability, temperature, and stress all affect sleep and its quality. As many of these physiological inputs are integrated in the hypothalamus, it is not surprising that this brain structure plays a crucial role in the regulation of sleep. I will discuss this role also in the context of aging, which is associated with changes in both hypothalamic function and the composition of sleep.

  10. Ca(2+)/calmodulin-dependent protein kinase IIα (αCaMKII) controls the activity of the dopamine transporter: implications for Angelman syndrome.

    PubMed

    Steinkellner, Thomas; Yang, Jae-Won; Montgomery, Therese R; Chen, Wei-Qiang; Winkler, Marie-Therese; Sucic, Sonja; Lubec, Gert; Freissmuth, Michael; Elgersma, Ype; Sitte, Harald H; Kudlacek, Oliver

    2012-08-24

    The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action of amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase αCaMKII attenuates amphetamine-triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP(+)) efflux. More importantly, αCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that αCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice, which lack αCaMKII or which express a permanently self-inhibited αCaMKII (αCaMKII(T305D)), exhibit significantly reduced amphetamine-triggered DAT-mediated MPP(+) efflux. Additionally, we investigated mice that mimic a neurogenetic disease known as Angelman syndrome. These mice possess reduced αCaMKII activity. Angelman syndrome mice demonstrated an impaired DAT efflux function, which was comparable with that of the αCaMKII mutant mice, indicating that DAT-mediated dopaminergic signaling is affected in Angelman syndrome.

  11. Presynaptic size of associational/commissural CA3 synapses is controlled by fibroblast growth factor 22 in adult mice.

    PubMed

    Pasaoglu, Taliha; Schikorski, Thomas

    2016-02-01

    Associational/commissural CA3-CA3 synapses define the recurrent CA3 network that generates the input to CA1 pyramidal neurons. We quantified the fine structure of excitatory synapses in the stratum radiatum of the CA3d area in adult wild type (WT) and fibroblast growth factor 22 knock-out (FGF22KO) mice by using serial 3D electron microscopy. WT excitatory CA3 synapses are rather small yet range 10 fold in size. Spine size, however, was small and uniform and did not correlate with the size of the synaptic junction. To reveal mechanisms that regulate presynaptic structure, we investigated the role of FGF22, a target-derived signal specific for the distal part of area CA3 (CA3d). In adult FGF22KO mice, postsynaptic properties of associational CA3 synapses were unaltered. Presynaptically, the number of synaptic vesicles (SVs), the bouton volume, and the number of vesicles in axonal regions (the super pool) were reduced. This concurrent decrease suggests concerted control by FGF22 of presynaptic size. This hypothesis is supported by the finding that WT presynapses in the proximal part of area CA3 (CA3p) that do not receive FGF22 signaling in WT mice were smaller than presynapses in CA3d in WT but of comparable size in CA3d of FGF22KO mice. Docked SV density was decreased in CA1, CA3d, and CA3p in FGF22KO mice. Because CA1 and CA3p are not directly affected by the loss of FGF22, the smaller docked SV density may be an adaptation to activity changes in the CA3 network. Thus, docked SV density potentially is a long-term regulator for the synaptic release probability and/or the strength of short-term depression in vivo.

  12. Contribution of Ca²⁺-dependent Cl⁻ channels to norepinephrine-induced contraction of femoral artery is replaced by increasing EDCF contribution during ageing.

    PubMed

    Liskova, Silvia; Petrova, Miriam; Karen, Petr; Behuliak, Michal; Zicha, Josef

    2014-01-01

    The activation of Ca(2+)-dependent Cl(-) channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca(2+) entry. Hypertension and ageing are associated with altered Ca(2+) handling including possible activation of Ca(2+)-dependent Cl(-) channels. Our study was aimed to determine Ca(2+)-dependent Cl(-) channels contribution to norepinephrine-induced contraction during hypertension and ageing. Norepinephrine-induced concentration-response curves of femoral arteries from 6- and 12-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were recorded using wire myograph. Pretreatment with Ca(2+)-dependent Cl- channel inhibitor indanyloxyacetic acid 94 [R(+)-IAA-94](IAA) attenuated norepinephrine-induced contraction in all groups, but relatively more in WKY than SHR arteries. The attenuation of norepinephrine-induced contraction after Ca(2+)-dependent Cl(-) channels blockade was partially reduced in 12-month-old WKY rats, but substantially diminished in 12-month-old SHR. IAA effect was enhanced after NO synthase inhibition but decreased by ageing. In 20-month-old WKY rats norepinephrine-induced contraction was not affected by IAA but was almost abolished after cyclooxygenase inhibition by indomethacin or niflumic acid. In conclusion, contribution of Ca(2+)-dependent Cl(-) channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca(2+)-dependent Cl(-) channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism.

  13. Age Related Decline in Postural Control Mechanisms.

    ERIC Educational Resources Information Center

    Stelmach, George E.; And Others

    1989-01-01

    Studied voluntary and reflexive mechanisms of postural control of young (N=8) and elderly (N=8) adults through measurement of reflexive reactions to large-fast and small-slow ankle rotation postural disturbances. Found reflexive mechanisms relatively intact for both groups although elderly appeared more disadvantaged when posture was under the…

  14. Improvement of the mechanical properties and corrosion resistance of biodegradable β-Ca3(PO4)2/Mg-Zn composites prepared by powder metallurgy: the adding β-Ca3(PO4)2, hot extrusion and aging treatment.

    PubMed

    Yan, Yang; Kang, Yijun; Li, Ding; Yu, Kun; Xiao, Tao; Deng, Youwen; Dai, Han; Dai, Yilong; Xiong, Hanqing; Fang, Hongjie

    2017-05-01

    In this study, 10%β-Ca3(PO4)2/Mg-6%Zn (wt.%) composites with Mg-6%Zn alloy as control were prepared by powder metallurgy. After hot extrusion, the as-extruded composites were aged for 72h at 150°C. The effects of the adding β-Ca3(PO4)2, hot extrusion and aging treatment on their microstructure, mechanical properties and corrosion resistance were investigated. The XRD results identified α-Mg, MgZn phase and β-Ca3(PO4)2 phase in these composites. After hot extrusion, grains were significantly refined, and the larger-sized β-Ca3(PO4)2 particles and coarse MgZn phases were broken into linear-distributed β-Ca3(PO4)2 and MgZn phases along the extrusion direction. After aging treatment, the elements of Zn, Ca, P and O presented a more homogeneous distribution. The compressive strengths of the β-Ca3(PO4)2/Mg-Zn composites were approximately double those of natural bone, and their densities and elastic moduli matched those of natural bone. The immersion tests and electrochemical tests revealed that the adding β-Ca3(PO4)2, hot extrusion and aging treatment could promote the formation of protective corrosion product layer on the sample surface in Ringer's solution, which improved corrosion resistance of the β-Ca3(PO4)2/Mg-Zn composites. The XRD results indicated that the corrosion product layer contained Mg(OH)2, β-Ca3(PO4)2 and hydroxyapatite (HA). The cytotoxicity assessments showed the as-extruded β-Ca3(PO4)2/Mg-Zn composite aged for 72h was harmless to L-929 cells. These results suggested that the β-Ca3(PO4)2/Mg-Zn composites prepared by powder metallurgy were promising to be used for bone tissue engineering.

  15. Optically stimulated luminescence age controls on late Pleistocene and Holocene coastal lithosomes, North Carolina, USA

    USGS Publications Warehouse

    Mallinson, D.; Burdette, K.; Mahan, S.; Brook, G.

    2008-01-01

    Luminescence ages from a variety of coastal features on the North Carolina Coastal Plain provide age control for shoreline formation and relative sea-level position during the late Pleistocene. A series of paleoshoreline ridges, dating to Marine Isotope Stage (MIS) 5a and MIS 3 have been defined. The Kitty Hawk beach ridges, on the modern Outer Banks, yield ages of 3 to 2??ka. Oxygen-isotope data are used to place these deposits in the context of global climate and sea-level change. The occurrence of MIS 5a and MIS 3 shorelines suggests that glacio-isostatic adjustment (GIA) of the study area is large (ca. 22 to 26??m), as suggested and modeled by other workers, and/or MIS 3 sea level was briefly higher than suggested by some coral reef studies. Correcting the shoreline elevations for GIA brings their elevation in line with other sea-level indicators. The age of the Kitty Hawk beach ridges places the Holocene shoreline well west of its present location at ca. 3 to 2??ka. The age of shoreline progradation is consistent with the ages of other beach ridge complexes in the southeast USA, suggesting some regionally contemporaneous forcing mechanism. ?? 2007 University of Washington.

  16. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

    PubMed

    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents.

  17. Age-structured optimal control in population economics.

    PubMed

    Feichtinger, Gustav; Prskawetz, Alexia; Veliov, Vladimir M

    2004-06-01

    This paper brings both intertemporal and age-dependent features to a theory of population policy at the macro-level. A Lotka-type renewal model of population dynamics is combined with a Solow/Ramsey economy. We consider a social planner who maximizes an aggregate intertemporal utility function which depends on per capita consumption. As control policies we consider migration and saving rate (both age-dependent). By using a new maximum principle for age-structured control systems we derive meaningful results for the optimal migration and saving rate in an aging population. The model used in the numerical calculations is calibrated for Austria.

  18. α2-containing GABAA receptors expressed in hippocampal region CA3 control fast network oscillations.

    PubMed

    Heistek, Tim S; Ruiperez-Alonso, Marta; Timmerman, A Jaap; Brussaard, Arjen B; Mansvelder, Huibert D

    2013-02-15

    GABA(A) receptors are critically involved in hippocampal oscillations. GABA(A) receptor α1 and α2 subunits are differentially expressed throughout the hippocampal circuitry and thereby may have distinct contributions to oscillations. It is unknown which GABA(A) receptor α subunit controls hippocampal oscillations and where these receptors are expressed. To address these questions we used transgenic mice expressing GABA(A) receptor α1 and/or α2 subunits with point mutations (H101R) that render these receptors insensitive to allosteric modulation at the benzodiazepine binding site, and tested how increased or decreased function of α subunits affects hippocampal oscillations. Positive allosteric modulation by zolpidem prolonged decay kinetics of hippocampal GABAergic synaptic transmission and reduced the frequency of cholinergically induced oscillations. Allosteric modulation of GABAergic receptors in CA3 altered oscillation frequency in CA1, while modulation of GABA receptors in CA1 did not affect oscillations. In mice having a point mutation (H101R) at the GABA(A) receptor α2 subunit, zolpidem effects on cholinergically induced oscillations were strongly reduced compared to wild-type animals, while zolpidem modulation was still present in mice with the H101R mutation at the α1 subunit. Furthermore, genetic knockout of α2 subunits strongly reduced oscillations, whereas knockout of α1 subunits had no effect. Allosteric modulation of GABAergic receptors was strongly reduced in unitary connections between fast spiking interneurons and pyramidal neurons in CA3 of α2H101R mice, but not of α1H101R mice, suggesting that fast spiking interneuron to pyramidal neuron synapses in CA3 contain α2 subunits. These findings suggest that α2-containing GABA(A) receptors expressed in the CA3 region provide the inhibition that controls hippocampal rhythm during cholinergically induced oscillations.

  19. Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen species contributes to aberrant Ca2+ handling in ageing rabbit hearts.

    PubMed

    Cooper, Leroy L; Li, Weiyan; Lu, Yichun; Centracchio, Jason; Terentyeva, Radmila; Koren, Gideon; Terentyev, Dmitry

    2013-12-01

    Ageing is associated with a blunted response to sympathetic stimulation and an increased risk of arrhythmia and sudden cardiac death. Aberrant calcium (Ca(2+)) handling is an important contributor to the electrical and contractile dysfunction associated with ageing. Yet, the specific molecular mechanisms underlying abnormal Ca(2+) handling in ageing heart remain poorly understood. In this study, we used ventricular myocytes isolated from young (5-9 months) and old (4-6 years) rabbit hearts to test the hypothesis that changes in Ca(2+) homeostasis are caused by post-translational modification of ryanodine receptors (RyRs) by mitochondria-derived reactive oxygen species (ROS) generated in the ageing heart. Changes in parameters of Ca(2+) handling were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) Ca(2+) dynamics in intact and permeabilized ventricular myocytes using confocal microscopy. We also measured age-related changes in ROS production and mitochondria membrane potential using a ROS-sensitive dye and a mitochondrial voltage-sensitive fluorescent indicator, respectively. In permeablized myocytes, ageing did not change SERCA activity and spark frequency but decreased spark amplitude and SR Ca(2+) load suggesting increased RyR activity. Treatment with the antioxidant dithiothreitol reduced RyR-mediated SR Ca(2+) leak in permeabilized myocytes from old rabbit hearts to the level comparable to young. Moreover, myocytes from old rabbits had more depolarized mitochondria membrane potential and increased rate of ROS production. Under β-adrenergic stimulation, Ca(2+) transient amplitude, SR Ca(2+) load, and latency of pro-arrhythmic spontaneous Ca(2+) waves (SCWs) were decreased while RyR-mediated SR Ca(2+) leak was increased in cardiomyocytes from old rabbits. Additionally, with β-adrenergic stimulation, scavenging of mitochondrial ROS in myocytes from old rabbit hearts restored redox status of RyRs, which reduced SR Ca(2+) leak, ablated most

  20. Synaptic Correlates Of Increased Cognitive Vulnerability With Aging: Peripheral Immune Challenge and Aging Interact to Disrupt Theta-Burst L-LTP in Hippocampal Area CA1

    PubMed Central

    Chapman, Timothy R.; Barrientos, Ruth M.; Ahrendsen, Jared T.; Maier, Steven F.; Patterson, Susan L.

    2010-01-01

    Variability in cognitive functioning increases markedly with age, as does cognitive vulnerability to physiological and psychological challenges. Exploring the basis of this vulnerability may provide important insights into the mechanisms underlying aging-associated cognitive decline. As we have previously reported, the cognitive abilities of aging (24-month-old) F344xBN rats are generally good, but are more vulnerable to the consequences of a peripheral immune challenge (an i.p. injection of live E. coli) than those of their younger (3-month-old) counterparts. Four days after the injection, the aging, but not the young rats show profound memory deficits, specific to the consolidation of hippocampus-dependent memory processes. Here, we have extended these observations, using hippocampal slices to examine for the first time the combined effects of aging and a recent infection on several forms of synaptic plasticity. We have found that the specific deficit in long-lasting memory observed in the aged animals following infection is mirrored by a specific deficit in a form of long-lasting synaptic plasticity. The late-phase long-term potentiation (L-LTP) induced in area CA1 using theta burst stimulation is particularly compromised by the combined effects of aging and infection – a deficit that can be ameliorated by intra-cisterna magna administration of the naturally occurring anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra). These data support the idea that the combination of aging and a negative life event such as an infection might produce selective, early-stage failures of synaptic plasticity in the hippocampus, with corresponding selective deficits in memory. PMID:20519534

  1. Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

    PubMed

    Potier, B; Krzywkowski, P; Lamour, Y; Dutar, P

    1994-10-24

    Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

  2. Store-operated Ca(2+) entry (SOCE) contributes to normal skeletal muscle contractility in young but not in aged skeletal muscle.

    PubMed

    Thornton, Angela M; Zhao, Xiaoli; Weisleder, Noah; Brotto, Leticia S; Bougoin, Sylvain; Nosek, Thomas M; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome; Brotto, Marco

    2011-06-01

    Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca(2+) to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca(2+) entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca(2+) to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca(2+) release channel-mediated Ca(2+) release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca(2+) entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

  3. Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

    PubMed Central

    Brotto, Leticia S.; Bougoin, Sylvain; Nosek, Thomas M.; Reid, Michael; Hardin, Brian; Pan, Zui; Ma, Jianjie; Parness, Jerome

    2011-01-01

    Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle. PMID:21666285

  4. Age-dependent changes in diastolic Ca{sup 2+} and Na{sup +} concentrations in dystrophic cardiomyopathy: Role of Ca{sup 2+} entry and IP{sub 3}

    SciTech Connect

    Mijares, Alfredo; Altamirano, Francisco; Kolster, Juan; Adams, José A.; López, José R.

    2014-10-03

    Highlights: • Age-dependent increase in [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} in mdx cardiomyocytes. • Gadolinium significantly reduced both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages. • IP{sub 3}-pathway inhibition reduced cations concentrations in dystrophic cardiomyocytes. - Abstract: Duchenne muscular dystrophy (DMD) is a lethal X-inherited disease caused by dystrophin deficiency. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with a dilated cardiomyopathy that leads to progressive heart failure at the end of the second decade. The aim of the present study was to characterize the diastolic Ca{sup 2+} concentration ([Ca{sup 2+}]{sub d}) and diastolic Na{sup +} concentration ([Na{sup +}]{sub d}) abnormalities in cardiomyocytes isolated from 3-, 6-, 9-, and 12-month old mdx mice using ion-selective microelectrodes. In addition, the contributions of gadolinium (Gd{sup 3+})-sensitive Ca{sup 2+} entry and inositol triphosphate (IP{sub 3}) signaling pathways in abnormal [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} were investigated. Our results showed an age-dependent increase in both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd{sup 3+} treatment significantly reduced both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages. In addition, blockade of the IP{sub 3}-pathway with either U-73122 or xestospongin C significantly reduced ion concentrations in dystrophic cardiomyocytes. Co-treatment with U-73122 and Gd{sup 3+} normalized both [Ca{sup 2+}]{sub d} and [Na{sup +}]{sub d} at all ages in dystrophic cardiomyocytes. These data showed that loss of dystrophin in mdx cardiomyocytes produced an age-dependent intracellular Ca{sup 2+} and Na{sup +} overload mediated at least in part by enhanced Ca{sup 2+} entry through Gd{sup 3+} sensitive transient receptor potential channels (TRPC), and by IP{sub 3} receptors.

  5. Age-related changes of NGF, BDNF, parvalbumin and neuronal nitric oxide synthase immunoreactivity in the mouse hippocampal CA1 sector.

    PubMed

    Hayakawa, Natsumi; Abe, Manami; Eto, Risa; Kato, Hiroyuki; Araki, Tsutomu

    2008-06-01

    We investigated the age-related alterations in nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), parvalbumin and neuronal nitric oxide synthase (nNOS) immunoreactivity of the mouse hippocampal CA1 sector. NGF and BDNF immunoreactivity was unchanged in the hippocampal CA1 pyramidal neurons from 2 to 50-59 weeks of birth. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector from 40-42 to 50-59 weeks of birth. On the other hand, the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. Our results indicate that NGF and BDNF immunoreactivity was unaltered in the hippocampal CA1 pyramidal neurons during aging processes. In contrast, a significant increase in the NGF and BDNF immunoreactivity was observed in glial cells of the hippocampal CA1 sector during aging processes. The present study also shows that the number of parvalbumin- and nNOS-positive interneurons was unchanged in the hippocampal CA1 sector during aging processes, except for a significant decrease of nNOS-positive interneurons 2 weeks of birth. These results demonstrate that the expression of glial NGF and BDNF may play a key role for helping survival and maintenance of pyramidal neurons and neuronal functions in the hippocampal CA1 sector during aging processes. Furthermore, our findings suggest that parvalbumin- and nNOS-positive interneurons in the hippocampal CA1 sector are resistant to aging processes. Moreover, our findings suggest that nitric oxide synthesized by the nNOS may play some role for neuronal growth during postnatal development.

  6. Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation

    PubMed Central

    He, Lian; Zhang, Yuanwei; Ma, Guolin; Tan, Peng; Li, Zhanjun; Zang, Shengbing; Wu, Xiang; Jing, Ji; Fang, Shaohai; Zhou, Lijuan; Wang, Youjun; Huang, Yun; Hogan, Patrick G; Han, Gang; Zhou, Yubin

    2015-01-01

    The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed 'Opto-CRAC') that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a mouse model of melanoma by using ovalbumin as surrogate tumor antigen, Opto-CRAC has been shown to act as a genetically-encoded 'photoactivatable adjuvant' to improve antigen-specific immune responses to specifically destruct tumor cells. Our study represents a solid step forward towards the goal of achieving remote and wireless control of Ca2+-modulated activities with tailored function. DOI: http://dx.doi.org/10.7554/eLife.10024.001 PMID:26646180

  7. p53 controls neuronal death in the CA3 region of the newborn mouse hippocampus.

    PubMed

    Murase, Sachiko; Poser, Steve W; Joseph, Joby; McKay, Ronald D

    2011-08-01

    It is important to determine the mechanisms controlling the number of neurons in the nervous system. Previously, we reported that neuronal activity plays a central role in controlling neuron number in the neonatal hippocampus of rodents. Neuronal survival requires sustained activation of the serine-threonine kinase Akt, which is initiated by neurotrophins and continued for several hours by neuronal activity and integrin signaling. Here, we focus on the CA3 region to show that neuronal apoptosis requires p53. As in wild-type animals, neuronal death occurs in the first postnatal week and ends by postnatal day (P)10 in p53(-/-) mice. During this period, the CA3 region of p53(-/-) mice contains significantly lower numbers of apoptotic cells, and at the end of the death period, it contains more neurons than the wild type. At P10, the p53(-/-) CA3 region contains a novel subpopulation of neurons with small soma size. These neurons show normal levels of tropomyosin receptor kinase receptor activation, but lower levels of activated Akt than the neurons with somata of normal size. These results suggest that p53 is the key downstream regulator of the novel survival-signaling pathway that regulates the number of CA3 neurons in the first 10 days of postnatal life.

  8. Effect of Aging on ERP Components of Cognitive Control

    PubMed Central

    Kropotov, Juri; Ponomarev, Valery; Tereshchenko, Ekaterina P.; Müller, Andreas; Jäncke, Lutz

    2016-01-01

    As people age, their performance on tasks requiring cognitive control often declines. Such a decline is frequently explained as either a general or specific decline in cognitive functioning with age. In the context of hypotheses suggesting a general decline, it is often proposed that processing speed generally declines with age. A further hypothesis is that an age-related compensation mechanism is associated with a specific cognitive decline. One prominent theory is the compensation hypothesis, which proposes that deteriorated functions are compensated for by higher performing functions. In this study, we used event-related potentials (ERPs) in the context of a GO/NOGO task to examine the age-related changes observed during cognitive control in a large group of healthy subjects aged between 18 and 84 years. The main question we attempted to answer was whether we could find neurophysiological support for either a general decline in processing speed or a compensation strategy. The subjects performed a relatively demanding cued GO/NOGO task with similar omissions and reaction times across the five age groups. The ERP waves of cognitive control, such as N2, P3cue and CNV, were decomposed into latent components by means of a blind source separation method. Based on this decomposition, it was possible to more precisely delineate the different neurophysiological and psychological processes involved in cognitive control. These data support the processing speed hypothesis because the latencies of all cognitive control ERP components increased with age, by 8 ms per decade for the early components (<200 ms) and by 20 ms per decade for the late components. At the same time, the compensatory hypothesis of aging was also supported, as the amplitudes of the components localized in posterior brain areas decreased with age, while those localized in the prefrontal cortical areas increased with age in order to maintain performance on this simple task at a relatively stable level

  9. Unique Relations of Age and Delinquency with Cognitive Control

    ERIC Educational Resources Information Center

    Iselin, Anne-Marie R.; DeCoster, Jamie

    2012-01-01

    Context processing has significant empirical support as an explanation of age- and psychopathology-related deficiencies in cognitive control. We examined whether context processing generalizes to younger individuals who are in trouble with the law. We tested whether age and delinquency might have unique relations to context processing skills in…

  10. Cholinergic control of firing pattern and neurotransmission in rat neostriatal projection neurons: role of CaV2.1 and CaV2.2 Ca2+ channels.

    PubMed

    Perez-Rosello, Tamara; Figueroa, Alejandra; Salgado, Humberto; Vilchis, Carmen; Tecuapetla, Fatuel; Guzman, Jaime N; Galarraga, Elvira; Bargas, Jose

    2005-05-01

    Besides a reduction of L-type Ca2+-currents (Ca(V)1), muscarine and the peptidic M1-selective agonist, MT-1, reduced currents through Ca(V)2.1 (P/Q) and Ca(V)2.2 (N) Ca2+ channel types. This modulation was strongly blocked by the peptide MT-7, a specific muscarinic M1-type receptor antagonist but not significantly reduced by the peptide MT-3, a specific muscarinic M4-type receptor antagonist. Accordingly, MT-7, but not MT-3, blocked a muscarinic reduction of the afterhyperpolarizing potential (AHP) and decreased the GABAergic inhibitory postsynaptic currents (IPSCs) produced by axon collaterals that interconnect spiny neurons. Both these functions are known to be dependent on P/Q and N types Ca2+ channels. The action on the AHP had an important effect in increasing firing frequency. The action on the IPSCs was shown to be caused presynaptically as it coursed with an increase in the paired-pulse ratio. These results show: first, that muscarinic M1-type receptor activation is the main cholinergic mechanism that modulates Ca2+ entry through voltage-dependent Ca2+ channels in spiny neurons. Second, this muscarinic modulation produces a postsynaptic facilitation of discharge together with a presynaptic inhibition of the GABAergic control mediated by axon collaterals. Together, both effects would tend to recruit more spiny neurons for the same task.

  11. Managing Threats against Control in Old Age: A Narrative Inquiry

    PubMed Central

    Black, Helen K.; Santanello, Holly R.; Caruso, Christa J.

    2014-01-01

    Background The desire to retain personal control over self and life circumstances continues into old age; it exists in tension with late-life vulnerabilities. Objectives This article investigates how elders respond to threats against control in light of changes surrounding health and identity. Methods Community-dwelling African-American (n = 10) and European-American elders (n = 10), aged 70 years and older, with varied self-reported health statuses were qualitatively interviewed. Open-ended interviews explored elders’ perceptions of control and threats to control in older age. Results Three themes linked elders’ responses to threats to control. Elders: (a) proactively monitored physical and mental health; (b) maintained roles that shaped important aspects of identity, and (c) fostered personal growth and development by generative practices. Responses of participants who had difficulty countering threats to control are also offered. Discussion This study shows that the construct of control is not abstract; it is interpreted and applied by elders in the contexts of everyday life. Respondents used personal resources honed throughout the life course to respond to threats to control. Elders viewed control as a cultural construct with nuanced meanings that recalled past roles and current changes that occur with age. Suggestions are offered for how health professionals can assist elders with the cognitive and emotional tasks required to deal with threats to personal control surrounding health and identity. PMID:24165219

  12. In vivo aging of rat skeletal muscle sarcoplasmic reticulum Ca-ATPase. Chemical analysis and quantitative simulation by exposure to low levels of peroxyl radicals.

    PubMed

    Viner, R I; Ferrington, D A; Aced, G I; Miller-Schlyer, M; Bigelow, D J; Schöneich, C

    1997-10-23

    Sarcoplasmic reticulum (SR) Ca-ATPase of young adult (5 months) and aged (28 months) Fischer 344 male rat skeletal muscle was analyzed for posttranslational modifications as a result of biological aging and their potential functional consequences. The significant differences in the amino acid composition were a 6.8% lower content of sulfhydryl groups and a ca. 4% lower content of Arg residues of the Ca-ATPase from old as compared to young rats. Based on a total of 24 Cys residues the difference in protein thiols corresponds to a loss of 1.5 mol Cys/mol Ca-ATPase as a result of in vivo aging. The loss of Cys residues was not accompanied by a loss of enzyme activity though the 'aged' Ca-ATPase was more sensitive to heat inactivation, aggregation, and tryptic digestion. A comparison of the total sulfhydryl content of all SR proteins present revealed a 13% lower amount for SR vesicles isolated from aged rats. Compared to the alterations of Cys and Arg, there was only a slight and probably physiologically insignificant increase of protein carbonyls with aging, i.e. from 0.32 to 0.46 mol carbonyl groups per mol of Ca-ATPase. When SR vesicles from young rats were exposed to AAPH-derived peroxyl radicals, there was a loss of ca. 1.38 x 10(-4) M total SR sulfhydryl groups per 4 mg SR protein/ml (corresponding to ca. 25%) and a loss of 9.6 x 10(-5) M Ca-ATPase sulfhydryl groups (corresponding to ca. 31%) per 1.6 x 10(-5) M initiating peroxyl radicals, indicating that the stoichiometry of sulfhydryl oxidation was > or = 6 oxidized thiols per initiating AAPH-derived peroxyl radical. Besides Cys, the exposure to AAPH-derived radicals caused a slight loss of Ca-ATPase Arg, Met, and Ser residues. Most importantly, the SR Ca-ATPase exposed to this low concentration of peroxyl radicals displayed physical and functional properties quantitatively comparable to those of SR Ca-ATPase isolated from aged rats, i.e. no immediate loss of activity, increased susceptibility to heat

  13. The prion protein constitutively controls neuronal store-operated Ca(2+) entry through Fyn kinase.

    PubMed

    De Mario, Agnese; Castellani, Angela; Peggion, Caterina; Massimino, Maria Lina; Lim, Dmitry; Hill, Andrew F; Sorgato, M Catia; Bertoli, Alessandro

    2015-01-01

    The prion protein (PrP(C)) is a cell surface glycoprotein mainly expressed in neurons, whose misfolded isoforms generate the prion responsible for incurable neurodegenerative disorders. Whereas PrP(C) involvement in prion propagation is well established, PrP(C) physiological function is still enigmatic despite suggestions that it could act in cell signal transduction by modulating phosphorylation cascades and Ca(2+) homeostasis. Because PrP(C) binds neurotoxic protein aggregates with high-affinity, it has also been proposed that PrP(C) acts as receptor for amyloid-β (Aβ) oligomers associated with Alzheimer's disease (AD), and that PrP(C)-Aβ binding mediates AD-related synaptic dysfunctions following activation of the tyrosine kinase Fyn. Here, use of gene-encoded Ca(2+) probes targeting different cell domains in primary cerebellar granule neurons (CGN) expressing, or not, PrP(C), allowed us to investigate whether PrP(C) regulates store-operated Ca(2+) entry (SOCE) and the implication of Fyn in this control. Our findings show that PrP(C) attenuates SOCE, and Ca(2+) accumulation in the cytosol and mitochondria, by constitutively restraining Fyn activation and tyrosine phosphorylation of STIM1, a key molecular component of SOCE. This data establishes the existence of a PrP(C)-Fyn-SOCE triad in neurons. We also demonstrate that treating cerebellar granule and cortical neurons with soluble Aβ(1-42) oligomers abrogates the control of PrP(C) over Fyn and SOCE, suggesting a PrP(C)-dependent mechanizm for Aβ-induced neuronal Ca(2+) dyshomeostasis.

  14. Serum CA19-9 Level Associated with Metabolic Control and Pancreatic Beta Cell Function in Diabetic Patients

    PubMed Central

    Yu, Haoyong; Li, Ruixia; Zhang, Lei; Chen, Haibing; Bao, Yuqian; Jia, Weiping

    2012-01-01

    CA19-9 is a tumor-associated antigen. It is also a marker of pancreatic tissue damage that might be caused by diabetes. Long-term poor glycemic control may lead to pancreatic beta cell dysfunction which is reflected by elevated serum CA19-9 level. Intracellular cholesterol accumulation leads to islet dysfunction and impaired insulin secretion which provide a new lipotoxic model. This study firstly found total cholesterol was one of the independent contributors to CA19-9. Elevated serum CA19-9 level in diabetic patients may indicate further investigations of glycemic control, pancreatic beta cell function, and total cholesterol level. PMID:22778715

  15. Mitochondrial proteases and protein quality control in ageing and longevity.

    PubMed

    Hamon, Marie-Paule; Bulteau, Anne-Laure; Friguet, Bertrand

    2015-09-01

    Mitochondria have been implicated in the ageing process and the lifespan modulation of model organisms. Mitochondria are the main providers of energy in eukaryotic cells but also represent both a major source of reactive oxygen species and targets for protein oxidative damage. Since protein damage can impair mitochondrial function, mitochondrial proteases are critically important for protein maintenance and elimination of oxidized protein. In the mitochondrial matrix, protein quality control is mainly achieved by the Lon and Clp proteases which are also key players in damaged mitochondrial proteins degradation. Accumulation of damaged macromolecules resulting from oxidative stress and failure of protein maintenance constitutes a hallmark of cellular and organismal ageing and is believed to participate to the age-related decline of cellular function. Hence, age-related impairment of mitochondrial protein quality control may therefore contribute to the age-associated build-up of oxidized protein and alterations of mitochondrial redox and protein homeostasis.

  16. Relationship between surface roughness and age of deposits in debris flow fans, Eastern Owens Valley, CA

    NASA Astrophysics Data System (ADS)

    Mihir, Monika; Wasklewicz, Thad; Liu, Tanzhuo

    2015-04-01

    The episodic nature of debris flows result in deposits of variable ages on the debris flow fan surface. This study maps the variable ages of fan deposits (called geomorphic units here) of four debris flow fans of south-eastern Owens Valley, California, USA from aerial photographs and field surveys. It then assesses the relationships between the age of the deposits, and their surface roughness and particle sizes. The deposits of different ages have different characteristics and are distinguished on the basis of different soil development, varnish accumulation, desert pavement development and surficial topography. The four fans typically have 4 geomorphic units on their surface. Numerical dates of the geomorphic units were obtained with the aid of varnish microlamination dating techniques. High resolution digital elevation data (5 cm planimetric resolution), were generated from a terrestrial laser scanner for each geomorphic unit (16 geomorphic units in total). The elevation data was then used in quantifying surface roughness. Particle sizes were also measured at each geomorphic unit where 50 particles were measured within a rectangular box (1.24 m by 1.00 m). We find that (i) the age of the oldest deposits range from 11,100 to 12,350 years BP (before present), second oldest deposits are around 7300-9500 years BP, third oldest deposits are around 4000 to 6000 years BP and the active deposits are essentially modern to several hundred years old, (ii) the oldest deposits have maximum surface roughness while the youngest deposits have comparatively less surface roughness, (iii) the average particle sizes of the deposits range from 3.15 cm to 22.04 cm with high variability (standard deviation ranging from 2.75 to 10.50) observed in all geomorphic units. Study of relationships between the variables brings out (i) an insignificant relationship between the surface roughness and age of deposits, (ii) an insignificant relationship between particle size variability and age of

  17. Bilingualism, aging, and cognitive control: evidence from the Simon task.

    PubMed

    Bialystok, Ellen; Craik, Fergus I M; Klein, Raymond; Viswanathan, Mythili

    2004-06-01

    Previous work has shown that bilingualism is associated with more effective controlled processing in children; the assumption is that the constant management of 2 competing languages enhances executive functions (E. Bialystok, 2001). The present research attempted to determine whether this bilingual advantage persists for adults and whether bilingualism attenuates the negative effects of aging on cognitive control in older adults. Three studies are reported that compared the performance of monolingual and bilingual middle-aged and older adults on the Simon task. Bilingualism was associated with smaller Simon effect costs for both age groups; bilingual participants also responded more rapidly to conditions that placed greater demands on working memory. In all cases the bilingual advantage was greater for older participants. It appears, therefore, that controlled processing is carried out more effectively by bilinguals and that bilingualism helps to offset age-related losses in certain executive processes.

  18. Aging-Related Hyperexcitability in CA3 Pyramidal Neurons Is Mediated by Enhanced A-Type K+ Channel Function and Expression

    PubMed Central

    Simkin, Dina; Hattori, Shoai; Ybarra, Natividad; Musial, Timothy F.; Buss, Eric W.; Richter, Hannah; Oh, M. Matthew

    2015-01-01

    Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29–32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K+ channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K+ channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state. SIGNIFICANCE STATEMENT Age-related learning deficits have been attributed, in part, to altered hippocampal pyramidal neuronal function with normal aging. Much evidence has come from work on CA1 neurons, with CA3 neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing. Hence, we conducted a series of experiments to identify the cellular mechanisms that underlie the hyperexcitability reported in the CA3 region. Contrary to CA1 neurons, we demonstrate that postburst afterhyperpolarization is not altered with aging and that aged CA3 pyramidal neurons are able to fire significantly more action potentials and that this is associated with

  19. Uniquely Human Self-Control Begins at School Age

    ERIC Educational Resources Information Center

    Herrmann, Esther; Misch, Antonia; Hernandez-Lloreda, Victoria; Tomasello, Michael

    2015-01-01

    Human beings have remarkable skills of self-control, but the evolutionary origins of these skills are unknown. Here we compare children at 3 and 6 years of age with one of humans' two nearest relatives, chimpanzees, on a battery of reactivity and self-control tasks. Three-year-old children and chimpanzees were very similar in their abilities to…

  20. Self-Control in School-Age Children

    ERIC Educational Resources Information Center

    Duckworth, Angela L.; Gendler, Tamar Szabó; Gross, James J.

    2014-01-01

    Conflicts between immediately rewarding activities and more enduringly valued goals abound in the lives of school-age children. Such conflicts call upon children to exercise self-control, a competence that depends in part on the mastery of metacognitive, prospective strategies. The "process model of self-control" organizes these…

  1. Optimal birth control of age-dependent competitive species

    NASA Astrophysics Data System (ADS)

    He, Ze-Rong

    2005-05-01

    We study optimal birth policies for two age-dependent populations in a competing system, which is controlled by fertilities. New results on problems with free final time and integral phase constraints are presented, and the approximate controllability of system is discussed.

  2. Role of small conductance Ca²⁺-activated K⁺ channels in controlling CA1 pyramidal cell excitability.

    PubMed

    Chen, Shmuel; Benninger, Felix; Yaari, Yoel

    2014-06-11

    Small-conductance Ca(2+)-activated K(+) (SK or K(Ca)2) channels are widely expressed in the CNS. In several types of neurons, these channels were shown to become activated during repetitive firing, causing early spike frequency adaptation. In CA1 pyramidal cells, SK channels in dendritic spines were shown to regulate synaptic transmission. However, the presence of functional SK channels in the somata and their role in controlling the intrinsic firing of these neurons has been controversial. Using whole-cell voltage-clamp and current-clamp recordings in acute hippocampal slices and focal applications of irreversible and reversible SK channel blockers, we provide evidence that functional SK channels are expressed in the somata and proximal dendrites of adult rat CA1 pyramidal cells. Although these channels can generate a medium duration afterhyperpolarizing current, they play only an auxiliary role in controlling the intrinsic excitability of these neurons, secondary to the low voltage-activating, noninactivating K(V)7/M channels. As long as K(V)7/M channels are operative, activation of SK channels during repetitive firing does not notably affect the spike output of CA1 pyramidal cells. However, when K(V)7/M channel activity is compromised, SK channel activation significantly and uniquely reduces spike output of these neurons. Therefore, proximal SK channels provide a "second line of defense" against intrinsic hyperexcitability, which may play a role in multiple conditions in which K(V)7/M channels activity is compromised, such as hyposmolarity.

  3. Combined Administration of Levetiracetam and Valproic Acid Attenuates Age Related Hyperactivity of CA3 Place Cells, Reduces Place Field Area, and Increases Spatial Information Content in Aged Rat Hippocampus

    PubMed Central

    Robitsek, RJ; Ratner, MH; Stewart, TM; Eichenbaum, H; Farb, DH

    2015-01-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA. PMID:25941121

  4. Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

    PubMed

    Robitsek, Jonathan; Ratner, Marcia H; Stewart, Tara; Eichenbaum, Howard; Farb, David H

    2015-12-01

    Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

  5. /sup 45/Ca uptake from water by snails (Lymnaea vulgaris) in control and detergent-polluted samples

    SciTech Connect

    Misra, V.; Lal, H.; Viswanathan, P.N.; Murti, C.R.

    1984-02-01

    A biostatic assay method involving /sup 45/Ca uptake into shells and tissues of snails (Lymnaea vulgaris) in 72 hr was developed to follow the effect of detergent-polluted water on ecosystems. There was a marked decrease in the /sup 45/Ca uptake by shells and tissues of linear alkyl benzene sulfonate-exposed animals as compared to controls. No change in /sup 45/Ca uptake was observed in dead shells, thereby excluding the possibility of passive exchange.

  6. Age differences in the motor control of speech: An fMRI study of healthy aging.

    PubMed

    Tremblay, Pascale; Sato, Marc; Deschamps, Isabelle

    2017-03-06

    Healthy aging is associated with a decline in cognitive, executive, and motor processes that are concomitant with changes in brain activation patterns, particularly at high complexity levels. While speech production relies on all these processes, and is known to decline with age, the mechanisms that underlie these changes remain poorly understood, despite the importance of communication on everyday life. In this cross-sectional group study, we investigated age differences in the neuromotor control of speech production by combining behavioral and functional magnetic resonance imaging (fMRI) data. Twenty-seven healthy adults underwent fMRI while performing a speech production task consisting in the articulation of nonwords of different sequential and motor complexity. Results demonstrate strong age differences in movement time (MT), with longer and more variable MT in older adults. The fMRI results revealed extensive age differences in the relationship between BOLD signal and MT, within and outside the sensorimotor system. Moreover, age differences were also found in relation to sequential complexity within the motor and attentional systems, reflecting both compensatory and de-differentiation mechanisms. At very high complexity level (high motor complexity and high sequence complexity), age differences were found in both MT data and BOLD response, which increased in several sensorimotor and executive control areas. Together, these results suggest that aging of motor and executive control mechanisms may contribute to age differences in speech production. These findings highlight the importance of studying functionally relevant behavior such as speech to understand the mechanisms of human brain aging. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  7. Brain-derived neurotrophic factor, phosphorylated cyclic AMP response element binding protein and neuropeptide Y decline as early as middle age in the dentate gyrus and CA1 and CA3 subfields of the hippocampus.

    PubMed

    Hattiangady, Bharathi; Rao, Muddanna S; Shetty, Geetha A; Shetty, Ashok K

    2005-10-01

    The hippocampus is very susceptible to aging. Severely diminished dentate neurogenesis at middle age is one of the most conspicuous early changes in the aging hippocampus, which is likely linked to an early decline in the concentration of neurotrophic factors and signaling proteins that influence neurogenesis. We analyzed three proteins that are well-known to promote dentate neurogenesis and learning and memory function in the dentate gyrus and the hippocampal CA1 and CA3 subfields of young, middle-aged and aged F344 rats. These include the brain-derived neurotrophic factor (BDNF), the transcription factor phosphorylated cyclic AMP response element binding protein (p-CREB) and the neuropeptide neuropeptide Y (NPY). The BDNF was analyzed via ELISA and BDNF immunohistochemistry, the p-CREB through densitometric analysis of p-CREB immunopositive cells, and the NPY via stereological counting of NPY-immunopositive interneurons. We provide new evidence that the BDNF concentration, the p-CREB immunoreactivity and the number of NPY immunopositive interneurons decline considerably by middle age in both dentate gyrus and CA1 and CA3 subfields of the hippocampus. However, both BDNF concentration and NPY immunopositive interneuron numbers exhibit no significant decrease between middle age and old age. In contrast, the p-CREB immunoreactivity diminishes further during this period, which is also associated with reduced BDNF immunoreaction within the soma of dentate granule cells and hippocampal pyramidal neurons. Collectively, these results suggest that severely dampened dentate neurogenesis observed at middle age is linked at least partially to reduced concentrations of BDNF, p-CREB and NPY, as each of these proteins is a positive regulator of dentate neurogenesis. Dramatically diminished CREB phosphorylation (and persistently reduced levels of BDNF and NPY) at old age may underlie the learning and memory impairments observed during senescence.

  8. Synthesis of CaTiO3 Nanofibers with Controllable Drug-Release Kinetics

    PubMed Central

    Zhang, Qiuhong; Ren, Zhaohui

    2016-01-01

    Calcium titanate (CaTiO3) nanofibers with controlled microstructure were fabricated by a combination of sol–gel and electrospinning approaches. The fiber morphology has been found to rely significantly on the precursor composition. Altering the volume ratio of ethanol to acetic acid from 3.5 to 1.25 enables the morphology of the CaTiO3 nanofibers to be transformed from fibers with a circular cross section to curved ribbon-like structures. Ibuprofen (IBU) was used as a model drug to investigate the drug-loading capacity and drug-release profile of the nanofibers. It was found that the BET surface area and the pore volume decrease markedly with the utilization of F127 surfactant. The nanofibers synthesized without F127 surfactant present the highest drug-loading capacity and the most sustained release kinetics. This study suggests that calcium titanate nanofibers can offer a promising platform for localized drug delivery. PMID:27818612

  9. Parallel circuits control temperature preference in Drosophila during ageing.

    PubMed

    Shih, Hsiang-Wen; Wu, Chia-Lin; Chang, Sue-Wei; Liu, Tsung-Ho; Lai, Jason Sih-Yu; Fu, Tsai-Feng; Fu, Chien-Chung; Chiang, Ann-Shyn

    2015-07-16

    The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β'- and β-systems. The β'-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the β-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in β'-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence.

  10. Protein synthesis as an integral quality control mechanism during ageing.

    PubMed

    Charmpilas, Nikolaos; Daskalaki, Ioanna; Papandreou, Margarita Elena; Tavernarakis, Nektarios

    2015-09-01

    Ageing is manifested as functional and structural deterioration that affects cell and tissue physiology. mRNA translation is a central cellular process, supplying cells with newly synthesized proteins. Accumulating evidence suggests that alterations in protein synthesis are not merely a corollary but rather a critical factor for the progression of ageing. Here, we survey protein synthesis regulatory mechanisms and focus on the pre-translational regulation of the process exerted by non-coding RNA species, RNA binding proteins and alterations of intrinsic RNA properties. In addition, we discuss the tight relationship between mRNA translation and two central pathways that modulate ageing, namely the insulin/IGF-1 and TOR signalling cascades. A thorough understanding of the complex interplay between protein synthesis regulation and ageing will provide critical insights into the pathogenesis of age-related disorders, associated with impaired proteostasis and protein quality control.

  11. Spike and Neuropeptide-Dependent Mechanisms Control GnRH Neuron Nerve Terminal Ca(2+) over Diverse Time Scales.

    PubMed

    Iremonger, Karl J; Porteous, Robert; Herbison, Allan E

    2017-03-22

    Fast cell-to-cell communication in the brain is achieved by action potential-dependent synaptic release of neurotransmitters. The fast kinetics of transmitter release are determined by transient Ca(2+) elevations in presynaptic nerve terminals. Neuromodulators have previously been shown to regulate transmitter release by inhibiting presynaptic Ca(2+) influx. Few studies to date have demonstrated the opposite, that is, neuromodulators directly driving presynaptic Ca(2+) rises and increases in nerve terminal excitability. Here we use GCaMP Ca(2+) imaging in brain slices from mice to address how nerve terminal Ca(2+) is controlled in gonadotropin-releasing hormone (GnRH) neurons via action potentials and neuromodulators. Single spikes and bursts of action potentials evoked fast, voltage-gated Ca(2+) channel-dependent Ca(2+) elevations. In contrast, brief exposure to the neuropeptide kisspeptin-evoked long-lasting Ca(2+) plateaus that persisted for tens of minutes. Neuropeptide-mediated Ca(2+) elevations were independent of action potentials, requiring Ca(2+) entry via voltage-gated Ca(2+) channels and transient receptor potential channels in addition to release from intracellular store mechanisms. Together, these data reveal that neuromodulators can exert powerful and long-lasting regulation of nerve terminal Ca(2+) independently from actions at the soma. Thus, GnRH nerve terminal function is controlled over disparate timescales via both classical spike-dependent and nonclassical neuropeptide-dependent mechanisms.SIGNIFICANCE STATEMENT Nerve terminals are highly specialized regions of a neuron where neurotransmitters and neurohormones are released. Many neuroendocrine neurons release neurohormones in long-duration bursts of secretion. To understand how this is achieved, we have performed live Ca(2+) imaging in the nerve terminals of gonadotropin-releasing hormone neurons. We find that bursts of action potentials and local neuropeptide signals are both capable of

  12. Early age strength enhancement of blended cement systems by CaCl{sub 2} and diethanol-isopropanolamine

    SciTech Connect

    Riding, Kyle; Silva, Denise A.; Scrivener, Karen

    2010-06-15

    The enhancement of the 1 day strength of cementitious systems by a combination of calcium chloride (CaCl{sub 2}) and diethanol-isopropanolamine (DEIPA) was studied, particularly in blended cement systems. A combination of quantitative X-ray diffraction with Rietveld refinement (QXRD), scanning electron microscopy (SEM)/backscattered electron image analysis, thermogravimetric analysis (TGA), and isothermal calorimetry were used to investigate the mechanism of strength enhancement by the additives. The additives were found to increase the early age mortar strength by enhancing the cement hydration, with the DEIPA enhancing primarily the aluminate hydration. DEIPA also affected the morphology of portlandite which was formed as thin plates. In parallel, the calcium-to-silica ratio of the C-S-H was found to increase with the use of DEIPA, possibly because of the inclusion of microcrystalline portlandite. After 48 h DEIPA was found to directly enhance the rate of reaction of granulated blast-furnace slag and fly ash.

  13. Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling.

    PubMed

    Fernández-Ruiz, Antonio; Oliva, Azahara; Nagy, Gergő A; Maurer, Andrew P; Berényi, Antal; Buzsáki, György

    2017-03-08

    Theta-gamma phase coupling and spike timing within theta oscillations are prominent features of the hippocampus and are often related to navigation and memory. However, the mechanisms that give rise to these relationships are not well understood. Using high spatial resolution electrophysiology, we investigated the influence of CA3 and entorhinal inputs on the timing of CA1 neurons. The theta-phase preference and excitatory strength of the afferent CA3 and entorhinal inputs effectively timed the principal neuron activity, as well as regulated distinct CA1 interneuron populations in multiple tasks and behavioral states. Feedback potentiation of distal dendritic inhibition by CA1 place cells attenuated the excitatory entorhinal input at place field entry, coupled with feedback depression of proximal dendritic and perisomatic inhibition, allowing the CA3 input to gain control toward the exit. Thus, upstream inputs interact with local mechanisms to determine theta-phase timing of hippocampal neurons to support memory and spatial navigation.

  14. Human aging compromises attentional control of auditory perception.

    PubMed

    Passow, Susanne; Westerhausen, René; Wartenburger, Isabell; Hugdahl, Kenneth; Heekeren, Hauke R; Lindenberger, Ulman; Li, Shu-Chen

    2012-03-01

    Older adults often experience hearing difficulties in multitalker situations. Attentional control of auditory perception is crucial in situations where a plethora of auditory inputs compete for further processing. We combined an intensity-modulated dichotic listening paradigm with attentional manipulations to study adult age differences in the interplay between perceptual saliency and attentional control of auditory processing. When confronted with two competing sources of verbal auditory input, older adults modulated their attention less flexibly and were more driven by perceptual saliency than younger adults. These findings suggest that aging severely impairs the attentional regulation of auditory perception.

  15. Age model for a continuous, ca 250-ka Quaternary lacustrine record from Bear Lake, Utah-Idaho

    USGS Publications Warehouse

    Colman, Steven M.; Kaufman, D.S.; Bright, Jordon; Heil, C.; King, J.W.; Dean, W.E.; Rosenbaum, J.G.; Forester, R.M.; Bischoff, J.L.; Perkins, Marie; McGeehin, J.P.

    2006-01-01

    The Quaternary sediments sampled by continuous 120-m-long drill cores from Bear Lake (Utah-Idaho) comprise one of the longest lacustrine sequences recovered from an extant lake. The cores serve as a good case study for the construction of an age model for sequences that extend beyond the range of radiocarbon dating. From a variety of potential age indicators, we selected a combination of radiocarbon ages, one magnetic excursion (correlated to a standard sequence), and a single Uranium-series age to develop an initial data set. The reliability of the excursion and U-series data require consideration of their position with respect to sediments of inferred interglacial character, but not direct correlation with other paleoclimate records. Data omitted from the age model include amino acid age estimates, which have a large amount of scatter, and tephrochronology correlations, which have relatively large uncertainties. Because the initial data set was restricted to the upper half of the BL00-1 core, we inferred additional ages by direct correlation to the independently dated paleoclimate record from Devils Hole. We developed an age model for the entire core using statistical methods that consider both the uncertainties of the original data and that of the curve-fitting process, with a combination of our initial data set and the climate correlations as control points. This age model represents our best estimate of the chronology of deposition in Bear Lake. Because the age model contains assumptions about the correlation of Bear Lake to other climate records, the model cannot be used to address some paleoclimate questions, such as phase relationships with other areas.

  16. Scanning Ultrasound (SUS) Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice

    PubMed Central

    Hatch, Robert John; Leinenga, Gerhard

    2016-01-01

    Scanning ultrasound (SUS) is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability. PMID:27727310

  17. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

  18. Dystrobrevin controls neurotransmitter release and muscle Ca2+ transients by localizing BK channels in C. elegans

    PubMed Central

    Chen, Bojun; Liu, Ping; Zhan, Haiying; Wang, Zhao-Wen

    2011-01-01

    Dystrobrevin is a major component of a dystrophin-associated protein complex (DAPC). It is widely expressed in mammalian tissues including the nervous system, where it is localized to the presynaptic nerve terminal with unknown function. In a genetic screen for suppressors of a lethargic phenotype caused by a gain-of-function (gf) isoform of SLO-1 in C. elegans, we isolated multiple loss-of-function (lf) mutants of the dystrobrevin gene dyb-1. dyb-1(lf) phenocopied slo-1(lf), causing increased neurotransmitter release at the neuromuscular junction, increased frequency of Ca2+ transients in body-wall muscle, and abnormal locomotion behavior. Neuron- and muscle-specific rescue experiments suggest that DYB-1 is required for SLO-1 function in both neurons and muscle cells. DYB-1 colocalized with SLO-1 at presynaptic sites in neurons and dense body regions in muscle cells, and dyb-1(lf) caused SLO-1 mislocalization in both types of cells without altering SLO-1 protein level. The neuronal phenotypes of dyb-1(lf) were partially rescued by mouse α-dystrobrevin-1 (αDB1). These observations revealed novel functions of the BK channel in regulating muscle Ca2+ transients, and of dystrobrevin in controlling neurotransmitter release and muscle Ca2+ transients by localizing the BK channel. PMID:22131396

  19. Adult Age Differences in Functional Connectivity during Executive Control

    PubMed Central

    Madden, David J.; Costello, Matthew C.; Dennis, Nancy A.; Davis, Simon W.; Shepler, Anne M.; Spaniol, Julia; Bucur, Barbara; Cabeza, Roberto

    2010-01-01

    Task switching requires executive control processes that undergo age-related decline. Previous neuroimaging studies have identified age-related differences in brain activation associated with global switching effects (dual-task blocks vs. single-task blocks), but age-related differences in activation during local switching effects (switch trials vs. repeat trials, within blocks) have not been investigated. This experiment used functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI), to examine adult age differences in task switching across adjacent trials (i.e., local task switching). During fMRI scanning, participants performed a cued, word categorization task. From interspersed cue-only trials, switch-related processing associated with the cue was estimated separately from the target. Activation associated with task switching, within a distributed frontoparietal network, differed for cue- and target-related processing. The magnitude of event-related activation for task switching was similar for younger adults (n = 20; 18-27 years) and older adults (n = 20; 60-85 years), although activation sustained throughout the on-tasks periods exhibited some age-related decline. Critically, the functional connectivity of switch-related regions, during cue processing, was higher for younger adults than for older adults, whereas functional connectivity during target processing was comparable across the age groups. Further, individual differences in cue-related functional connectivity shared a substantial portion of the age-related variability in the efficiency of target categorization response (drift rate). This age-related difference in functional connectivity, however, was independent of white matter integrity within task-relevant regions. These findings highlight the functional connectivity of frontoparietal activation as a potential source of age-related decline in executive control. PMID:20434565

  20. NWA 7034 Martian breccia: Ar/Ar ages of ca. 1.2 to 1.4 Ga

    NASA Astrophysics Data System (ADS)

    Cohen, B. E.; Mark, D. F.; Cassata, W.; Lee, M. R.; Smith, C. L.

    2015-12-01

    NWA 7034 and its paired stones are some of the oldest and most diverse of the Martian meteorites. They are complex polymict breccias of impact, igneous, and sedimentary clasts set in a dark grey matrix [1; 2]. The rock also contains angular mineral fragments, including K-feldspar, plagioclase feldspar, and pyroxene [1; 2]. Mineral fragments are often > 1 mm wide, and clasts can be > 1 cm. This diverse breccia assemblage indicates formation via repeated impact events, supported by Rb-Sr, Sm-Nd and U-Pb ages ranging from 1.3 to 4.4 Ga [1, 2, and references therein]. In this study we investigate the distribution of ages yielded by Ar/Ar, with nine aliquots analyzed to date, and additional analyses planned. In order to analyze only single phases, chips of matrix/clasts were restricted to visibly monomict fragments < 1 mm diameter, while mineral separates were analyzed as single crystals. Cosmogenic Ar corrections are from [3]. Analyses were undertaken at SUERC and Lawrence Livermore National Laboratory, and the results pooled. The bulk of aliquots (n = 8) yielded ages of ca. 1.2-1.4 Ga indicating a major thermal event occurred at around the same time as crystallization of the Nakhlite group of meteorites. Select step ages are considerably older (> 2 Ga), supporting results of other chronometers that much older material is present in this sample. These results also demonstrate that some older fragments retained Ar during breccia formation. [1] Wittmann A. et al. (2015) Meteoritics & Planet. Sci., 50, 326-352. [2] Santos A. R. et al. (2015) GCA, 157, 56-85. [3] Cassata W. S., and Borg L. E. (2015) 46th LPSC, Abstract #2742.

  1. Lifelong bilingualism maintains neural efficiency for cognitive control in aging.

    PubMed

    Gold, Brian T; Kim, Chobok; Johnson, Nathan F; Kryscio, Richard J; Smith, Charles D

    2013-01-09

    Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task-switching performance. In addition, the lower blood oxygenation level-dependent response in frontal regions accounted for 82% of the variance in the bilingual task-switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.

  2. Lifelong Bilingualism Maintains Neural Efficiency for Cognitive Control in Aging

    PubMed Central

    Gold, Brian T.; Kim, Chobok; Johnson, Nathan F.; Kryscio, Richard J.; Smith, Charles D.

    2013-01-01

    Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task switching paradigm, and including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task switching experiment while fMRI was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task switching performance. In addition, the lower BOLD response in frontal regions accounted for 82% of the variance in the bilingual task switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes. PMID:23303919

  3. Barley Seed Aging: Genetics behind the Dry Elevated Pressure of Oxygen Aging and Moist Controlled Deterioration

    PubMed Central

    Nagel, Manuela; Kodde, Jan; Pistrick, Sibylle; Mascher, Martin; Börner, Andreas; Groot, Steven P. C.

    2016-01-01

    Experimental seed aging approaches intend to mimic seed deterioration processes to achieve a storage interval reduction. Common methods apply higher seed moisture levels and temperatures. In contrast, the “elevated partial pressure of oxygen” (EPPO) approach treats dry seed stored at ambient temperatures with high oxygen pressure. To analyse the genetic background of seed longevity and the effects of seed aging under dry conditions, the EPPO approach was applied to the progeny of the Oregon Wolfe Barley (OWB) mapping population. In comparison to a non-treated control and a control high-pressure nitrogen treatment, EPPO stored seeds showed typical symptoms of aging with a significant reduction of normal seedlings, slower germination, and less total germination. Thereby, the parent Dom (“OWB-D”), carrying dominant alleles, is more sensitive to aging in comparison to the population mean and in most cases to the parent Rec (“OWB-R”), carrying recessive alleles. Quantitative trait locus (QTL) analyses using 2832 markers revealed 65 QTLs, including two major loci for seed vigor on 2H and 7H. QTLs for EPPO tolerance were detected on 3H, 4H, and 5H. An applied controlled deterioration (CD) treatment (aged at higher moisture level and temperature) revealed a tolerance QTL on 5H, indicating that the mechanism of seed deterioration differs in part between EPPO or CD conditions. PMID:27066038

  4. Barley Seed Aging: Genetics behind the Dry Elevated Pressure of Oxygen Aging and Moist Controlled Deterioration.

    PubMed

    Nagel, Manuela; Kodde, Jan; Pistrick, Sibylle; Mascher, Martin; Börner, Andreas; Groot, Steven P C

    2016-01-01

    Experimental seed aging approaches intend to mimic seed deterioration processes to achieve a storage interval reduction. Common methods apply higher seed moisture levels and temperatures. In contrast, the "elevated partial pressure of oxygen" (EPPO) approach treats dry seed stored at ambient temperatures with high oxygen pressure. To analyse the genetic background of seed longevity and the effects of seed aging under dry conditions, the EPPO approach was applied to the progeny of the Oregon Wolfe Barley (OWB) mapping population. In comparison to a non-treated control and a control high-pressure nitrogen treatment, EPPO stored seeds showed typical symptoms of aging with a significant reduction of normal seedlings, slower germination, and less total germination. Thereby, the parent Dom ("OWB-D"), carrying dominant alleles, is more sensitive to aging in comparison to the population mean and in most cases to the parent Rec ("OWB-R"), carrying recessive alleles. Quantitative trait locus (QTL) analyses using 2832 markers revealed 65 QTLs, including two major loci for seed vigor on 2H and 7H. QTLs for EPPO tolerance were detected on 3H, 4H, and 5H. An applied controlled deterioration (CD) treatment (aged at higher moisture level and temperature) revealed a tolerance QTL on 5H, indicating that the mechanism of seed deterioration differs in part between EPPO or CD conditions.

  5. An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

    PubMed Central

    Keller, Daniel; Babai, Norbert; Kochubey, Olexiy; Han, Yunyun; Markram, Henry; Schürmann, Felix; Schneggenburger, Ralf

    2015-01-01

    The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young animals. To study the geometrical constraints of Ca2+ channel placement in domain overlap control of release, we used stochastic MCell modelling, at active zones for which the position of docked vesicles was derived from electron microscopy (EM). We found that random placement of Ca2+ channels was unable to produce high slope values between release and presynaptic Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release probabilities. The simple assumption that Ca2+ channels can be located anywhere at active zones, except below a critical distance of ~ 30 nm away from docked vesicles ("exclusion zone"), rescued high slope values and low release probabilities. Alternatively, high slope values can also be obtained by placing all Ca2+ channels into a single supercluster, which however results in significantly higher heterogeneity of release probabilities. We also show experimentally that high slope values, and the sensitivity to the slow Ca2+ chelator EGTA-AM, are maintained with developmental maturation of the calyx synapse. Taken together, domain overlap control of release represents a highly organized active zone architecture in which Ca2+ channels must obey a certain distance to docked vesicles. Furthermore, domain overlap can be employed by near-mature, fast-releasing synapses. PMID:25951120

  6. Age and Sex Factors in the Control of Automobiles.

    ERIC Educational Resources Information Center

    Allen, John A., Jr.; Soliday, Stanley M.

    The study investigated age and sex in the control of an automobile under normal driving conditions. Its major purpose was to gather baseline data for a driver license, road testing program. Forty volunteer subjects (10 men and 10 women over 30, 10 men and 10 women under 30) drove a specially instrumented car over an interstate highway course and a…

  7. Assessing sedimentation issues within aging of flood-control reservoirs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flood control reservoirs designed and built by federal agencies have been extremely effective in reducing the ravages of floods nationwide. Yet some structures are being removed for a variety of reasons, while other structures are aging rapidly and require either rehabilitation or decommissioning. ...

  8. Age and sex differences in object control skills by children ages 5 to 14.

    PubMed

    Butterfield, Stephen A; Angell, Rose M; Mason, Craig A

    2012-02-01

    Object control skills provide children the tools to be physically active-a major societal priority. At the fundamental movement level, object control skills form the foundation of further sports skill development. The purpose of this study was to examine children's (ages 5 to 14 years, Grades K-8) development of four key object control skills: catching, throwing, kicking, and striking. 186 children were tested on selected items from the Object Control Subtest of the Test of Gross Motor Development-2, using a cross-sectional and correlational design. As anticipated, significant differences were found for age on all four skills. These improvements were characterized by early, rapid gains at ages 9 to 10, beyond which development occurred at a slower rate for catching, throwing, and kicking; striking development continued at a steady rate to age 14 years. Contrary to previous findings, no overall sex differences were found for catching or kicking. Overall sex differences favoring boys were observed for throwing and striking. Implications for evolutionary contributions to throwing and striking were discussed.

  9. Q- and L-type Ca2+ channels dominate the control of secretion in bovine chromaffin cells.

    PubMed

    López, M G; Villarroya, M; Lara, B; Martínez Sierra, R; Albillos, A; García, A G; Gandía, L

    1994-08-08

    Potassium-stimulated catecholamine release from superfused bovine adrenal chromaffin cells (70 mM K+ in the presence of 2 mM Ca2+ for 10 s, applied at 5-min intervals) was inhibited by the dihydropyridine furnidipine (3 microM) by 50%. omega-Conotoxin MVIIC (CTx-MVIIC, 3 microM) also reduced the secretory response by about half. Combined CTx-MVIIC plus furnidipine blocked 100% catecholamine release. 45Ca2+ uptake and cytosolic Ca2+ concentrations ([Ca2+]i) in K(+)-depolarized cells were partially blocked by furnidipine or CTx-MVIIC, and completely inhibited by both agents. The whole cell current through Ca2+ channels carried by Ba2+ (IBa) was partially blocked by CTx-MVIIC. Although omega-conotoxin GVIA (CTx-GVIA, 1 microM) and omega-agatoxin IVA (Aga-IVA, 0.2 microM) partially inhibited 45Ca2+ entry, IBa and the increase in [Ca2+]i, the combination of both toxins did not affect the K(+)-evoked secretory response. The results are compatible with the presence in bovine chromaffin cells of a Q-like Ca2+ channel which has a prominent role in controlling exocytosis. They also suggest that Q- and L-type Ca2+ channels, but not N- or P-types are localized near exocytotic active sites in the plasmalemma.

  10. Sympathetic control of reflex cutaneous vasoconstriction in human aging

    PubMed Central

    Alexander, Lacy M.; Kenney, W. Larry

    2015-01-01

    This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction. PMID:26272321

  11. Sympathetic control of reflex cutaneous vasoconstriction in human aging.

    PubMed

    Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry

    2015-10-01

    This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction.

  12. Does Bilingual Language Control Decline in Older Age?

    PubMed Central

    Ivanova, Iva; Murillo, Mayra; Montoya, Rosa I.; Gollan, Tamar H.

    2016-01-01

    We investigated age-related decline of bilingual language control. Thirteen older and 13 younger bilinguals performed a verbal fluency task (completing the same letter and semantic categories in each language and switching languages after every category), and a non-linguistic flanker task. In letter fluency, bilinguals produced fewer correct responses after switching languages, suggesting inhibition of the previously-used language. However, this testing-order effect did not differ between groups and older bilinguals produced few wrong-language intrusions, implying intact ability to apply inhibition in older age. In contrast, age-related deficits in the flanker task were robust, implying dissociations between language control and domain-general executive control. In semantic fluency, there were no testing-order effects but older bilinguals produced more intrusions than younger bilinguals, and more intrusions than in letter fluency. Thus, bilinguals may flexibly modulate the degree of inhibition when they can benefit from semantic priming between languages, but less efficiently so in older age. PMID:28090222

  13. Control of mitochondrial integrity in ageing and disease.

    PubMed

    Szklarczyk, Radek; Nooteboom, Marco; Osiewacz, Heinz D

    2014-07-05

    Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria.

  14. Effect of component aging on PWR control rod drive systems

    SciTech Connect

    Grove, E.; Gunther, W.; Sullivan, K.

    1992-01-01

    An aging assessment of PWR control rod drive (CRD) systems has been completed as part of the US NRC Nuclear Plant Aging Research (NPAR) Program. The design, construction, maintenance, and operation of the Babcock Wilcox (B W), Combustion Engineering (CE), and Westinghouse (W) systems were evaluated to determine the potential for degradation as each system ages. Operating experience data were evaluated to identify the predominant failure modes, causes, and effects. This, coupled with an assessment of the materials of construction and operating environment, demonstrate that each design is subject to degradation, which if left unchecked, could affect its safety function as the plant ages. An industry survey, conducted with the assistance of EPRI and NUMARC, identified current CRD system maintenance and inspection practices. The results of this survey indicate that some plants have performed system modifications, replaced components, or augmented existing preventive maintenance practices in response to system aging. The survey results also supported the operating experience data, which concluded that the timely replacement of degraded components, prior to failure, was not always possible using existing condition monitoring techniques. The recommendations presented in this study also include a discussion of more advanced monitoring techniques, which provide trendable results capable of detecting aging.

  15. Effect of component aging on PWR control rod drive systems

    SciTech Connect

    Grove, E.; Gunther, W.; Sullivan, K.

    1992-06-01

    An aging assessment of PWR control rod drive (CRD) systems has been completed as part of the US NRC Nuclear Plant Aging Research (NPAR) Program. The design, construction, maintenance, and operation of the Babcock & Wilcox (B & W), Combustion Engineering (CE), and Westinghouse (W) systems were evaluated to determine the potential for degradation as each system ages. Operating experience data were evaluated to identify the predominant failure modes, causes, and effects. This, coupled with an assessment of the materials of construction and operating environment, demonstrate that each design is subject to degradation, which if left unchecked, could affect its safety function as the plant ages. An industry survey, conducted with the assistance of EPRI and NUMARC, identified current CRD system maintenance and inspection practices. The results of this survey indicate that some plants have performed system modifications, replaced components, or augmented existing preventive maintenance practices in response to system aging. The survey results also supported the operating experience data, which concluded that the timely replacement of degraded components, prior to failure, was not always possible using existing condition monitoring techniques. The recommendations presented in this study also include a discussion of more advanced monitoring techniques, which provide trendable results capable of detecting aging.

  16. Microbial Catalysis of CaCO3: Biotic Response Controlling Travertine Deposition

    NASA Astrophysics Data System (ADS)

    Fouke, B. W.; Miller, P. A.; Dwyer, S.; Vescogni, H.; Kandianis, M. T.

    2008-12-01

    Microbial communities inhabiting drainage systems at Mammoth Hot Springs (MHS), Yellowstone National Park, survive increases in flow velocity by catalyzing CaCO3 mineralization (travertine). Our previous experiments have shown that the rate of travertine precipitation is controlled by microbial biomass (e.g. microbial cells and their extra-cellular polymeric substances [EPS]), thus creating a mechanism by which thermophilic microorganisms can survive environmental change and control system-level distributions of CaCO3 precipitation. The most striking example of this occurs in the Apron and Channel Facies of the MHS outflow system (T = 71-65o C; pH = 6-7). As the water flows across a short (1-3 m long) primary flow path, a steep geochemical gradient occurs in dissolved sulfide (125-0 μm) and simultaneously increasing dissolved oxygen. The spring water in the Apron and Channel Facies moves as a shallow (1-2 cm deep) unidirectional advection-dominated turbulent sheet flow that rapidly (< 5 mm/day) precipitates travertine (aragonite) on filamentous microbial mats dominated by Aquificales pBB and Sulfurihydrogenebium. The travertine grows as small (<10 μm) aragonite needle clusters on the surface of the microbial filaments and larger crystals (<100 μm) on the EPS. This forms the distinctive mm- to cm-scale "streamer" fabric common to globally distributed modern and ancient travertine. Fluctuations are common in the velocity of water that emerges from the vents at MHS. Under high flow conditions, it is advantageous for microbes to enhance CaCO3 crystal growth to permit lateral extension of their mats into areas of appropriate temperature, sulfide and oxygen conditions. The extremely rapid travertine precipitation rates (enhanced by the microbial biomass) directly track this extension and permit the associated lateral progradation of the Apron and Channel Facies travertine deposits. Conversely, under lower spring flow conditions, it is beneficial for microbes to

  17. Aging worsens the effects of sleep deprivation on postural control.

    PubMed

    Robillard, Rébecca; Prince, François; Filipini, Daniel; Carrier, Julie

    2011-01-01

    Falls increase with age and cause significant injuries in the elderly. This study aimed to determine whether age modulates the interactions between sleep deprivation and postural control and to evaluate how attention influences these interactions in the elderly. Fifteen young (24±2.7 y.o.) and 15 older adults (64±3.2 y.o.) stood still on a force plate after a night of sleep and after total sleep deprivation. Center of pressure range and velocity were measured with eyes open and with eyes closed while participants performed an interference task, a control task, and no cognitive task. Sleep deprivation increased the antero-posterior range of center of pressure in both age groups and center of pressure speed in older participants only. In elderly participants, the destabilizing effects of sleep deprivation were more pronounced with eyes closed. The interference task did not alter postural control beyond the destabilization induced by sleep loss in older subjects. It was concluded that sleep loss has greater destabilizing effects on postural control in older than in younger participants, and may therefore increase the risk of falls in the elderly.

  18. Practice of contemporary dance promotes stochastic postural control in aging.

    PubMed

    Ferrufino, Lena; Bril, Blandine; Dietrich, Gilles; Nonaka, Tetsushi; Coubard, Olivier A

    2011-01-01

    As society ages and the frequency of falls increases, counteracting gait and posture decline is a challenging issue for countries of the developed world. Previous studies have shown that exercise and hazard management help to improve balance and/or decrease the risks for falling in normal aging. Motor activity based on motor-skill learning, particularly dance, can also benefit balance and decreases falls with age. Recent studies have suggested that older dancers have better balance, posture, or gait than non-dancers. Additionally, clinical or laboratory measures have shown improvements in some aspects of balance after dance interventions in elderly trainees. This study examined the impact of contemporary dance (CD) and of fall prevention (FP) programs on postural control of older adults. Posturography of quiet upright stance was performed in 41 participants aged 59-86 years before and after 4.4-month training in either CD or FP once a week. Though classical statistic scores failed to show any effect, dynamic analyses of the center-of-pressure displacements revealed significant changes after training. Specifically, practice of CD enhanced the critical time interval in diffusion analysis, and reduced recurrence and mathematical stability in recurrence quantification analysis, whereas practice of FP induced or tended to induce the reverse patterns. Such effects were obtained only in the eyes open condition. We suggest that CD training based on motor improvisation favored stochastic posture inducing plasticity in motor control, while FP training based on more stereotyped behaviors did not.

  19. Practice of Contemporary Dance Promotes Stochastic Postural Control in Aging

    PubMed Central

    Ferrufino, Lena; Bril, Blandine; Dietrich, Gilles; Nonaka, Tetsushi; Coubard, Olivier A.

    2011-01-01

    As society ages and the frequency of falls increases, counteracting gait and posture decline is a challenging issue for countries of the developed world. Previous studies have shown that exercise and hazard management help to improve balance and/or decrease the risks for falling in normal aging. Motor activity based on motor-skill learning, particularly dance, can also benefit balance and decreases falls with age. Recent studies have suggested that older dancers have better balance, posture, or gait than non-dancers. Additionally, clinical or laboratory measures have shown improvements in some aspects of balance after dance interventions in elderly trainees. This study examined the impact of contemporary dance (CD) and of fall prevention (FP) programs on postural control of older adults. Posturography of quiet upright stance was performed in 41 participants aged 59–86 years before and after 4.4-month training in either CD or FP once a week. Though classical statistic scores failed to show any effect, dynamic analyses of the center-of-pressure displacements revealed significant changes after training. Specifically, practice of CD enhanced the critical time interval in diffusion analysis, and reduced recurrence and mathematical stability in recurrence quantification analysis, whereas practice of FP induced or tended to induce the reverse patterns. Such effects were obtained only in the eyes open condition. We suggest that CD training based on motor improvisation favored stochastic posture inducing plasticity in motor control, while FP training based on more stereotyped behaviors did not. PMID:22232582

  20. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy.

    PubMed

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A; Zhang, Peng; Dubel, Steve J; Perez-Reyes, Edward; Snutch, Terrance P; Stornetta, Ruth L; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P; Zhu, J Julius

    2015-07-15

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE.

  1. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy

    PubMed Central

    Wang, Guangfu; Bochorishvili, Genrieta; Chen, Yucai; Salvati, Kathryn A.; Zhang, Peng; Dubel, Steve J.; Perez-Reyes, Edward; Snutch, Terrance P.; Stornetta, Ruth L.; Deisseroth, Karl; Erisir, Alev; Todorovic, Slobodan M.; Luo, Jian-Hong; Kapur, Jaideep; Beenhakker, Mark P.; Zhu, J. Julius

    2015-01-01

    CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the brain, yet their general function remains unclear. We discovered that CaV3.2 channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated transmission at rat central synapses. Interestingly, functional CaV3.2 channels primarily incorporate into synapses, replace existing CaV3.2 channels, and can induce local calcium influx to control NMDA transmission strength in an activity-dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked hCaV3.2(C456S) mutant channels have a higher channel open probability, induce more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave discharges and absence-like epilepsy characteristic of CAE patients, which can be suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel antagonists. These results reveal an unexpected role of CaV3.2 channels in regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for human CAE. PMID:26220996

  2. Environmental and cortisol-mediated control of Ca(2+) uptake in tilapia (Oreochromis mossambicus).

    PubMed

    Lin, Chia-Hao; Kuan, Wei-Chun; Liao, Bo-Kai; Deng, Ang-Ni; Tseng, Deng-Yu; Hwang, Pung-Pung

    2016-04-01

    Ca(2+) is a vital element for many physiological processes in vertebrates, including teleosts, which live in aquatic environments and acquire Ca(2+) from their surroundings. Ionocytes within the adult gills or larval skin are critical sites for transcellular Ca(2+) uptake in teleosts. The ionocytes of zebrafish were found to contain transcellular Ca(2+) transporters, epithelial Ca(2+) channel (ECaC), plasma membrane Ca(2+)-ATPase 2 (PMCA2), and Na(+)/Ca(2+) exchanger 1b (NCX1b), providing information about the molecular mechanism of transcellular Ca(2+) transports mediated by ionocytes in fish. However, more evidence is required to establish whether or not a similar mechanism of transcellular Ca(2+) transport also exists in others teleosts. In the present study, ecac, pmca2, and ncx1 were found to be expressed in the branchial ionocytes of tilapia, thereby providing further support for the mechanism of transcellular Ca(2+) transport through ionocytes previously proposed for zebrafish. In addition, we also reveal that low Ca(2+) water treatment of tilapia stimulates Ca(2+) uptake and expression of ecac and cyp11b (the latter encodes a cortisol-synthesis enzyme). Treatment of tilapia with exogenous cortisol (20 mg/l) enhanced both Ca(2+) influx and ecac expression. Therefore, increased cyp11b expression is suggested to enhance Ca(2+) uptake capacity in tilapia exposed to low Ca(2+) water. Furthermore, the application of cortisol receptor antagonists revealed that cortisol may regulate Ca(2+) uptake through glucocorticoid and/or mineralocorticoid receptor (GR and/or MR) in tilapia. Taken together, the data suggest that cortisol may activate GR and/or MR to execute its hypercalcemic action by stimulating ecac expression in tilapia.

  3. What controls the age of subsoil carbon? (Invited)

    NASA Astrophysics Data System (ADS)

    Trumbore, S.; Schrumpf, M.; Khomo, L.; Solly, E.; Herold, N.; Schöning, I.

    2013-12-01

    content of dithionite extractable Fe across a wide range of soil types, also suggesting that transport and sorption/desorption processes control age gradients of mineral-associated OC in soil profiles of the mineral associated OC fraction. By comparison, the age of unprotected OC in the light fraction increases much less with depth than mineral-associated OC, indicating different and less depth-dependent controls of the age of this faction. Other clues for controls on the age of deep soil carbon come from root litter decomposition studies performed at different soil depths. So far our results suggest that reduced microbial activity contributes to the old age of subsoil OC mainly through processes associated with mineral surface stabilization, the age of which is further influenced by transport and sorption along the soil profile.

  4. A UBVI AND uvbyCaH{beta} ANALYSIS OF THE INTERMEDIATE-AGE OPEN CLUSTER, NGC 5822

    SciTech Connect

    Carraro, Giovanni; Anthony-Twarog, Barbara J.; Jones, Bryce J.; Twarog, Bruce A.; Costa, Edgardo E-mail: bjat@ku.edu E-mail: btwarog@ku.edu

    2011-10-15

    NGC 5822 is a richly populated, moderately nearby, intermediate-age open cluster covering an area larger than the full moon on the sky. A CCD survey of the cluster on the UBVI and uvbyCaH{beta} systems shows that the cluster is superposed upon a heavily reddened field of background stars with E(B - V) > 0.35 mag, while the cluster has small and uniform reddening at E(b - y) = 0.075 {+-} 0.008 mag or E(B - V) = 0.103 {+-} 0.011 mag, based upon 48 and 61 probable A and F dwarf single-star members, respectively. The errors quoted include both internal photometric precision and external photometric uncertainties. The metallicity derived from 61 probable single F-star members is [Fe/H] = -0.058 {+-} 0.027 (sem) from m{sub 1} and 0.010 {+-} 0.020 (sem) from hk, for a weighted average of [Fe/H] = -0.019 {+-} 0.023, where the errors refer to the internal errors from the photometry alone. With reddening and metallicity fixed, the cluster age and apparent distance modulus are obtained through a comparison to appropriate isochrones in both VI and BV, producing 0.9 {+-} 0.1 Gyr and 9.85 {+-} 0.15, respectively. The giant branch remains dominated by two distinct clumps of stars, though the brighter clump seems a better match to the core-He-burning phase while the fainter clump straddles the first-ascent red giant branch. Four potential new clump members have been identified, equally split between the two groups. Reanalysis of the UBV two-color data extending well down the main sequence shows it to be optimally matched by reddening near E(B - V) = 0.10 rather than the older value of 0.15, leading to [Fe/H] between -0.16 and 0.00 from the ultraviolet excess of the unevolved dwarfs. The impact of the lower reddening and younger age of the cluster on previous analyses of the cluster is discussed.

  5. PROCEEDINGS: 1989 JOINT SYMPOSIUM ON STATIONARY COMBUSTION NOX CONTROL, SAN FRANCISCO, CA, MARCH 6-9, 1989 VOLUME 1

    EPA Science Inventory

    The proceedings document presentations at the 1989 Joint Symposium on Stationary Combustion NOx Control, held March 6-9, 1989, in San Francisco, CA. The symposium, sponsored by the U. S. EPA and EPRl, was the fifth in a series devoted solely to the discussion of control of NOx em...

  6. PROCEEDINGS: 1989 JOINT SYMPOSIUM ON STATIONARY COMBUSTION NOX CONTROL, SAN FRANCISCO, CA, MARCH 6-9, 1989 VOLUME 2

    EPA Science Inventory

    The proceedings document presentations at the 1989 Joint Symposium on Stationary Combustion NOx Control, held March 6-9. 1989. in San Francisco, CA. The symposium, sponsored by the U.S. EPA and EPRI, was the fifth in a series devoted solely to the discussion of control of NOx emi...

  7. Microbial Controls on the Size, Shape and Porosity of Hot Spring CaCO3 Mineralization

    NASA Astrophysics Data System (ADS)

    Miller, P. A.; Fouke, B. W.; Dwyer, S. E.; Sivaguru, M.; Kandianis, M. T.

    2008-12-01

    Microbial communities inhabiting vent drainage systems at Mammoth Hot Springs in Yellowstone National Park, exert strong controls on the size, shape and porosity of CaCO3 (travertine) mineral deposits at a nanometer to micron scale. Our controlled in situ kinetic experiment (ISKA) has shown that: (1) the natural steady state aragonite precipitation rate is more than twice that when microbial biomass is depleted by 80% via 0.2 um filtration; and (2) ultraviolet (UV) irradiation only slightly reduces the mean aragonite precipitation rate, while keeping all other experimental parameters held constant. An integrated petrographic (plane-light and cathodoluminscence [CL]) and high-resolution inverted fluorescence microscopy (200 nm resolution petrography) were completed on travertine samples collected from the ISKA experiment. Results indicate that, under all experimental conditions, an initial layer of dogtooth to blocky calcite cement (less than 30um) was followed by aragonite needle cement growth (10-50um). The untreated natural control experiment produced an initial layer of small calcite crystals interspersed with densely packed clusters of aragonite needles, which significantly reduced the porosity in this first layer of authigenic crystal growth. The ensuing aragonite needle clusters in the natural control were also present, but in lower concentrations, in the UV- irradiated experiments. The filtration experiment produced the largest calcite crystals with few to no aragonite needles. However, the aragonite needles were on average 40 µm long and are not arranged in dense clusters, producing a higher porosity layer composed of lower crystal densities. Early calcite crystals in both the filtration and UV-irradiation samples exhibit bright orange concentric crystal zonations under CL that were absent in the natural control. Aragonite needles in all samples exhibit no CL. Further, no clear petrographic evidence of diagenesis or mineralogical inversion were observed in

  8. Nonconserved Ca2+/Calmodulin Binding Sites in Munc13s Differentially Control Synaptic Short-Term Plasticity

    PubMed Central

    Lipstein, Noa; Schaks, Sabine; Dimova, Kalina; Kalkhof, Stefan; Ihling, Christian; Kölbel, Knut; Ashery, Uri; Rhee, JeongSeop; Brose, Nils

    2012-01-01

    Munc13s are presynaptic proteins that mediate synaptic vesicle priming and thereby control the size of the readily releasable pool of vesicles. During high synaptic activity, Munc13-1 and its closely related homolog, ubMunc13-2, bind Ca2+/calmodulin, resulting in enhanced priming activity and in changes of short-term synaptic plasticity characteristics. Here, we studied whether bMunc13-2 and Munc13-3, two remote isoforms of Munc13-1 with a neuronal subtype-specific expression pattern, mediate synaptic vesicle priming and regulate short-term synaptic plasticity in a Ca2+/calmodulin-dependent manner. We identified a single functional Ca2+/calmodulin binding site in these isoforms and provide structural evidence that all Munc13s employ a common mode of interaction with calmodulin despite the lack of sequence homology between their Ca2+/calmodulin binding sites. Electrophysiological analysis showed that, during high-frequency activity, Ca2+/calmodulin binding positively regulates the priming activity of bMunc13-2 and Munc13-3, resulting in an increase in the size of the readily releasable pool of vesicles and subsequently in strong short-term synaptic enhancement of neurotransmission. We conclude that Ca2+/calmodulin-dependent regulation of priming activity is structurally and functionally conserved in all Munc13 proteins, and that the composition of Munc13 isoforms in a neuron differentially controls its short-term synaptic plasticity characteristics. PMID:22966208

  9. The effect of aging on anticipatory postural control

    PubMed Central

    Kanekar, Neeta; Aruin, Alexander S.

    2014-01-01

    The aim of the study was to investigate the differences in anticipatory (APAs) postural adjustments between young and older adults and its effect on subsequent control of posture. Ten healthy older adults and thirteen healthy young adults were exposed to predictable external perturbations using the pendulum-impact paradigm. EMG activity of the trunk and leg muscles, the center of pressure (COP), and center of mass (COM) displacements in the anterior-posterior (AP) direction were recorded and analyzed during the anticipatory and compensatory (CPAs) phases of postural control. The effect of aging was seen as delayed anticipatory muscle activity and larger compensatory muscle responses in older adults as compared to young adults. Moreover, in spite of such larger reactive responses, older adults were still more unstable, exhibiting larger COP and COM peak displacements after the perturbation than young adults when exposed to similar postural disturbances. Nonetheless, while APAs are impaired in older adults, the ability to recruit muscles anticipatorily is largely preserved, however, due to their smaller magnitudes and delayed onsets, it is likely that their effectiveness in reducing the magnitude of CPAs is smaller. The outcome of the study lends support towards investigating the ways of improving anticipatory postural control in people with balance impairments due to aging or neurological disorders. PMID:24449006

  10. The effect of aging on anticipatory postural control.

    PubMed

    Kanekar, Neeta; Aruin, Alexander S

    2014-04-01

    The aim of the study was to investigate the differences in anticipatory postural adjustments (APAs) between young and older adults and its effect on subsequent control of posture. Ten healthy older adults and thirteen healthy young adults were exposed to predictable external perturbations using the pendulum impact paradigm. Electromyographic activity of the trunk and leg muscles, the center of pressure (COP), and center of mass (COM) displacements in the anterior-posterior direction were recorded and analyzed during the anticipatory and compensatory postural adjustments (CPAs) phases of postural control. The effect of aging was seen as delayed anticipatory muscle activity and larger compensatory muscle responses in older adults as compared to young adults. Moreover, in spite of such larger reactive responses, older adults were still more unstable, exhibiting larger COP and COM peak displacements after the perturbation than young adults when exposed to similar postural disturbances. Nonetheless, while APAs are impaired in older adults, the ability to recruit muscles anticipatorily is largely preserved; however, due to their smaller magnitudes and delayed onsets, it is likely that their effectiveness in reducing the magnitude of CPAs is smaller. The outcome of the study lends support toward investigating the ways of improving anticipatory postural control in people with balance impairments due to aging or neurological disorders.

  11. Aging interferes central control mechanism for eccentric muscle contraction.

    PubMed

    Yao, Wan X; Li, Jinqi; Jiang, Zhiguo; Gao, Jia-Hong; Franklin, Crystal G; Huang, Yufei; Lancaster, Jack L; Yue, Guang H

    2014-01-01

    Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC) than concentric contraction (CC) despite lower muscle activation level associated with EC vs. CC in healthy, young individuals. It is unknown, however, whether elderly people exhibiting increased difficulties in performing EC than CC possess this unique cortical control mechanism for EC movements. To address this question, we examined functional magnetic resonance imaging (fMRI) data acquired during EC and CC of the first dorsal interosseous (FDI) muscle in 11 young (20-32 years) and 9 old (67-73 years) individuals. During the fMRI experiment, all subjects performed 20 CC and 20 EC of the right FDI with the same angular distance and velocity. The major findings from the behavioral and fMRI data analysis were that (1) movement stability was poorer in EC than CC in the old but not the young group; (2) similar to previous electrophysiological and fMRI reports, the EC resulted in significantly stronger activation in the motor control network consisting of primary, secondary and association motor cortices than CC in the young and old groups; (3) the biased stronger activation towards EC was significantly greater in the old than the young group especially in the secondary and association cortices such as supplementary and premotor motor areas and anterior cingulate cortex; and (4) in the primary motor and sensory cortices, the biased activation towards EC was significantly greater in the young than the old group. Greater activation in higher-order cortical fields for controlling EC movement by elderly adults may reflect activities in these regions to compensate for aging-related impairments in the ability to control complex EC movements. Our finding is useful for potentially guiding the development of targeted therapies to counteract age-related movement deficits and to prevent injury.

  12. Effects of Age on Cognitive Control during Semantic Categorization

    PubMed Central

    Mudar, Raksha A.; Chiang, Hsueh-Sheng; Maguire, Mandy J.; Spence, Jeffrey S.; Eroh, Justin; Michael, A. Kraut; Hart, John

    2015-01-01

    We used event-related potentials (ERPs) to study age effects of perceptual (basic-level) vs. perceptual-semantic (superordinate-level) categorization on cognitive control using the go/nogo paradigm. Twenty-two younger (11 M; 21±2.2 years) and 22 older adults (9 M; 63±5.8 years) completed two visual go/nogo tasks. In the single car task (SiC) (basic), go/nogo responses were made based on single exemplars of a car (go) and a dog (nogo). In the object animal task (ObA) (superordinate), responses were based on multiple exemplars of objects (go) and animals (nogo). Each task consisted of 200 trials: 160 (80%) ‘go’ trials that required a response through button pressing and 40 (20%) ‘nogo’ trials that required inhibition/withholding of a response. ERP data revealed significantly reduced nogo-N2 and nogo-P3 amplitudes in older compared to younger adults, whereas go-N2 and go-P3 amplitudes were comparable in both groups during both categorization tasks. Although the effects of categorization levels on behavioral data and P3 measures were similar in both groups with longer response times, lower accuracy scores, longer P3 latencies, and lower P3 amplitudes in ObA compared to SiC, N2 latency revealed age group differences moderated by the task. Older adults had longer N2 latency for ObA compared to SiC, in contrast, younger adults showed no N2 latency difference between SiC and ObA. Overall, these findings suggest that age differentially affects neural processing related to cognitive control during semantic categorization. Furthermore, in older adults, unlike in younger adults, levels of categorization modulate neural processing related to cognitive control even at the early stages (N2). PMID:25823764

  13. Store-Operated Ca2+ Entry Does Not Control Proliferation in Primary Cultures of Human Metastatic Renal Cellular Carcinoma

    PubMed Central

    Turin, Ilaria; Potenza, Duilio Michele; Bottino, Cinzia; Glasnov, Toma N.; Ferulli, Federica; Mosca, Alessandra; Guerra, Germano; Rosti, Vittorio; Luinetti, Ombretta; Porta, Camillo; Pedrazzoli, Paolo

    2014-01-01

    Store-operated Ca2+ entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca2+ pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca2+ levels within the endoplasmic reticulum (ER) Ca2+ reservoir, and a number of a Ca2+-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1–7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca2+ store, but not by InsP3-dependent Ca2+ release. Metastatic RCC cells express Stim1-2, Orai1–3, and TRPC1–7 transcripts and proteins. In these cells, SOCE was insensitive to BTP-2, 10 µM Gd3+ and Pyr6, while it was inhibited by 100 µM Gd3+, 2-APB, and carboxyamidotriazole (CAI). Neither Gd3+ nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca2+ signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors. PMID:25126575

  14. Local control of β-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca2+-transient1

    PubMed Central

    Heijman, Jordi; Volders, Paul G.A.; Westra, Ronald L.; Rudy, Yoram

    2011-01-01

    Local signaling domains and numerous interacting molecular pathways and substrates contribute to the whole-cell response of myocytes during β-adrenergic stimulation (βARS). We aimed to elucidate the quantitative contribution of substrates and their local signaling environments during βARS to the canine epicardial ventricular myocyte electrophysiology and calcium transient (CaT). We present a computational compartmental model of βARS and its electrophysiological effects. Novel aspects of the model include localized signaling domains, incorporation of β1 and β2 receptor isoforms, a detailed population-based approach to integrate the βAR and Ca2+/Calmodulin kinase (CaMKII) signaling pathways and their effects on a wide range of substrates that affect whole-cell electrophysiology and CaT. The model identifies major roles for phosphodiesterases, adenylyl cyclases, PKA and restricted diffusion in the control of local cAMP levels and shows that activation of specific cAMP domains by different receptor isoforms allows for specific control of action potential and CaT properties. In addition, the model predicts increased CaMKII activity during βARS due to rate-dependent accumulation and increased Ca2+ cycling. CaMKII inhibition, reduced compartmentation, and selective blockade of β1AR are predicted to reduce the occurrence of delayed afterdepolarizations during βARS. Finally, the relative contribution of each PKA substrate to whole-cell electrophysiology is quantified by comparing simulations with and without phosphorylation of each target. In conclusion, this model enhances our understanding of localized βAR signaling and its whole-cell effects in ventricular myocytes by incorporating receptor isoforms, multiple pathways and a detailed representation of multiple-target phosphorylation; it provides a basis for further studies of βARS under pathological conditions. PMID:21345340

  15. P- T- X controls on Ca and Na distribution between Mg-Al tourmaline and fluid

    NASA Astrophysics Data System (ADS)

    Berryman, Eleanor J.; Wunder, Bernd; Rhede, Dieter; Schettler, Georg; Franz, Gerhard; Heinrich, Wilhelm

    2016-04-01

    Ca-Na partitioning between tourmaline and a coexisting fluid is investigated in the system CaO-Na2O-B2O3-Al2O3-MgO-SiO2-H2O-Cl between 0.2-4.0 GPa and 500-700 °C. The synthesis experiments produced a mineral assemblage of tourmaline, coesite/quartz, and in some cases additional phases, typically comprising <1 wt% of the solid product. The synthesized tourmalines are solid solutions of dravite [NaMg3Al6Si6O18(BO3)3(OH)3(OH)], "oxy-uvite" (i.e. "Ca-Mg-O root name") [CaMg3Al6Si6O18(BO3)3(OH)3O], and magnesio-foitite [☐(Mg2Al)Al6Si6O18(BO3)3(OH)3(OH)]. Starting materials comprised a fluid of constant ionic strength (2.00 m) and an oxide mixture with a constant Mg/Al ratio. As a result, the number of vacancies at the X site and the Mg/Al ratio of tourmaline crystals synthesized at the same temperature vary only slightly. The major solid solution is Ca-Na exchange at the X site via the exchange vector X Ca W O[ X Na W (OH)]-1, with the exchange vector X (Ca☐)[ X Na2]-1 serving as a secondary Ca-incorporation mechanism. Tourmaline's X-site composition reflects the fluid composition, whereby the Ca (or Na) concentration in the fluid corresponds with the Ca (or Na) content in tourmaline at each pressure and temperature. At 0.2 GPa, 700 °C, Ca preferentially partitions into tourmaline, producing the most Ca-rich tourmaline crystals synthesized here. At pressures >1.0 GPa, Ca partitions preferentially into the fluid, resulting in Na-dominant tourmaline compositions. Temperature has a secondary effect on Ca-Na partitioning, with higher temperatures correlating with increased Ca incorporation in tourmaline. Based on the experimental findings, tourmaline is expected to have Ca-rich compositions when it forms in low pressure, high-temperature Ca-rich rocks, consistent with the current record of tourmaline occurrence. The bulk Mg/Al ratio and the pH of the tourmaline-forming system may also affect Ca incorporation in tourmaline, but remain to be investigated experimentally.

  16. Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network.

    PubMed

    Pavlov, Ivan; Savtchenko, Leonid P; Song, Inseon; Koo, Jaeyeon; Pimashkin, Alexey; Rusakov, Dmitri A; Semyanov, Alexey

    2014-01-07

    The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABAA depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABAA conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABAA conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABAA conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.

  17. Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

    PubMed Central

    Pavlov, Ivan; Savtchenko, Leonid P.; Song, Inseon; Koo, Jaeyeon; Pimashkin, Alexey; Rusakov, Dmitri A.; Semyanov, Alexey

    2014-01-01

    The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABAA depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABAA conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABAA conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABAA conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns. PMID:24344272

  18. Properties of BK-type Ca++-dependent K+ channel currents in medial prefrontal cortex pyramidal neurons in rats of different ages

    PubMed Central

    Książek, Aneta; Ładno, Wioletta; Szulczyk, Bartłomiej; Grzelka, Katarzyna; Szulczyk, Paweł

    2013-01-01

    The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca++ ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker – paxilline (10 μM) – irreversibly decreased the non-inactivating K+ current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K+ currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K+ channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca++ concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K+ channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC pyramidal

  19. Tonic Firing Rate Controls Dendritic Ca2+ Signaling and Synaptic Gain in Substantia Nigra Dopamine Neurons

    PubMed Central

    Hage, Travis A.

    2015-01-01

    Substantia nigra dopamine neurons fire tonically resulting in action potential backpropagation and dendritic Ca2+ influx. Using Ca2+ imaging in acute mouse brain slices, we find a surprisingly steep relationship between tonic firing rate and dendritic Ca2+. Increasing the tonic rate from 1 to 6 Hz generated Ca2+ signals up to fivefold greater than predicted by linear summation of single spike-evoked Ca2+-transients. This “Ca2+ supralinearity” was produced largely by depolarization of the interspike voltage leading to activation of subthreshold Ca2+ channels and was present throughout the proximal and distal dendrites. Two-photon glutamate uncaging experiments show somatic depolarization enhances NMDA receptor-mediated Ca2+ signals >400 μm distal to the soma, due to unusually tight electrotonic coupling of the soma to distal dendrites. Consequently, we find that fast tonic firing intensifies synaptically driven burst firing output in dopamine neurons. These results show that modulation of background firing rate precisely tunes dendritic Ca2+ signaling and provides a simple yet powerful mechanism to dynamically regulate the gain of synaptic input. PMID:25855191

  20. Voltage control of Ca²⁺ permeation through N-type calcium (Ca(V)2.2) channels.

    PubMed

    Buraei, Zafir; Liang, Haoya; Elmslie, Keith S

    2014-09-01

    Voltage-gated calcium (Ca(V)) channels deliver Ca(2+) to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca(2+) over other cations is thought to involve multiple Ca(2+)-binding sites within the pore. Although the Ca(2+) affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (Ca(V)2.2) channels to investigate the effect of voltage on Ca(2+) flux. We found that the EC50 for Ca(2+) permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca(2+) ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow Ca(V)2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca(2+)-Ba(2+) anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca(2+)-Ba(2+) anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca(2+) permeation through Ca(V)2.2 channels may require at least four Ca(2+)-binding sites. Finally, our results suggest that the high affinity of Ca(2+) for the channel helps to enhance Ca(2+) influx at depolarized voltages relative to other ions (e.g., Ba(2+) or Na(+)), whereas the absence of voltage effects at negative potentials prevents Ca(2+) from becoming a channel blocker. Both effects are needed to maximize Ca(2+) influx over the voltages spanned by action potentials.

  1. Permian U-Pb (CA-TIMS) zircon ages from Australia and China: Constraining the time scale of environmental and biotic change

    NASA Astrophysics Data System (ADS)

    Denyszyn, S. W.; Mundil, R.; Metcalfe, I.; He, B.

    2010-12-01

    In eastern Australia, the interconnected Bowen and Sydney Basins are filled with terrestrial sediments of late Paleozoic to early Mesozoic age. These sedimentary units record significant evolutionary events of eastern Gondwana during the time interval between two major mass extinctions (end Middle Permian and Permian-Triassic), and also provide lithological evidence for the Carboniferous-Permian Late Paleozoic Ice Age of southern Pangea, considered to be divisible into up to seven discrete glaciation events in Australia [e.g., 1]. These glaciations are currently assigned ages that indicate that the last of the glaciations predate the end Middle Permian mass extinction at ca. 260 Ma. However, the estimates for the time and durations are largely based on biostratigraphy and lithostratigraphy that, in the absence of robust and precise radioisotopic ages, are unacceptably fragile for providing an accurate high-resolution framework. Interbedded with the sediments are numerous tuff layers that contain zircon, many of which are associated with extensive coal measures in the Sydney and Bowen Basins. Published SHRIMP U-Pb zircon ages [2, 3] have been shown to be less precise and inaccurate when compared to ages applying the CA-TIMS method to the same horizons. Also within the late Middle Permian, the eruption of the Emeishan flood basalts in SW China has been proposed to have caused the end Middle Permian mass extinction [e.g., 4], though a causal link between these events demands a rigorous test that can only be provided by high-resolution geochronology. We present new U-Pb (CA-TIMS) zircon ages on tuff layers from the Sydney and Bowen Basins, with the purpose of generating a timescale for the Upper Permian of Australia to allow correlation with different parts of the world. Initial results, with permil precision, date a tuff layer within the uppermost Bandanna Fm. to ca. 252 Ma, a tuff within the Moranbah Coal Measures to ca. 256 Ma, and a tuff within the Ingelara Fm. to

  2. The rate of change in Ca(2+) concentration controls sperm chemotaxis.

    PubMed

    Alvarez, Luis; Dai, Luru; Friedrich, Benjamin M; Kashikar, Nachiket D; Gregor, Ingo; Pascal, René; Kaupp, U Benjamin

    2012-03-05

    During chemotaxis and phototaxis, sperm, algae, marine zooplankton, and other microswimmers move on helical paths or drifting circles by rhythmically bending cell protrusions called motile cilia or flagella. Sperm of marine invertebrates navigate in a chemoattractant gradient by adjusting the flagellar waveform and, thereby, the swimming path. The waveform is periodically modulated by Ca(2+) oscillations. How Ca(2+) signals elicit steering responses and shape the path is unknown. We unveil the signal transfer between the changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) and path curvature (κ). We show that κ is modulated by the time derivative d[Ca(2+)](i)/dt rather than the absolute [Ca(2+)](i). Furthermore, simulation of swimming paths using various Ca(2+) waveforms reproduces the wealth of swimming paths observed for sperm of marine invertebrates. We propose a cellular mechanism for a chemical differentiator that computes a time derivative. The cytoskeleton of cilia, the axoneme, is highly conserved. Thus, motile ciliated cells in general might use a similar cellular computation to translate changes of [Ca(2+)](i) into motion.

  3. Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca(2+)-Independent Phospholipase A₂ Pathways.

    PubMed

    Seo, Jihui; Maeng, Jeehye; Kim, Hwa-Jung

    2016-10-24

    The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [³H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca(2+)]i), the rTCTP-driven effect on dopamine release was mediated by a Ca(2+)-independent pathway, as evidenced by the fact that Ca(2+)-modulating agents such as Ca(2+) chelators and a voltage-gated L-type Ca(2+)-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A₂ (PLA₂) in rTCTP-induced dopamine release, the inhibitor for Ca(2+)-independent PLA₂ (iPLA₂) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca(2+)-dependent cytosolic PLA₂ (cPLA₂) and secretory PLA₂ (sPLA₂) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca(2+)-independent mechanism that involved PLA₂ in the process, suggesting the regulatory role of TCTP in the neuronal functions.

  4. Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca2+-Independent Phospholipase A2 Pathways

    PubMed Central

    Seo, Jihui; Maeng, Jeehye; Kim, Hwa-Jung

    2016-01-01

    The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [3H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca2+]i), the rTCTP-driven effect on dopamine release was mediated by a Ca2+-independent pathway, as evidenced by the fact that Ca2+-modulating agents such as Ca2+ chelators and a voltage-gated L-type Ca2+-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A2 (PLA2) in rTCTP-induced dopamine release, the inhibitor for Ca2+-independent PLA2 (iPLA2) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca2+-dependent cytosolic PLA2 (cPLA2) and secretory PLA2 (sPLA2) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca2+-independent mechanism that involved PLA2 in the process, suggesting the regulatory role of TCTP in the neuronal functions. PMID:27783042

  5. The essence of insect metamorphosis and aging: electrical rewiring of cells driven by the principles of juvenile hormone-dependent Ca(2+)-homeostasis.

    PubMed

    De Loof, Arnold; De Haes, Wouter; Janssen, Tom; Schoofs, Liliane

    2014-04-01

    In holometabolous insects the fall to zero of the titer of Juvenile Hormone ends its still poorly understood "status quo" mode of action in larvae. Concurrently it initiates metamorphosis of which the programmed cell death of all internal tissues that actively secrete proteins, such as the fat body, midgut, salivary glands, prothoracic glands, etc. is the most drastic aspect. These tissues have a very well developed rough endoplasmic reticulum, a known storage site of intracellular Ca(2+). A persistent high [Ca(2+)]i is toxic, lethal and causal to apoptosis. Metamorphosis becomes a logical phenomenon if analyzed from: (1) the causal link between calcium toxicity and apoptosis; (2) the largely overlooked fact that at least some isoforms of Ca(2+)-ATPases have a binding site for farnesol-like endogenous sesquiterpenoids (FRS). The Ca(2+)-ATPase blocker thapsigargin, like JH a sesquiterpenoid derivative, illustrates how absence of JH might work. The Ca(2+)-homeostasis system is concurrently extremely well conserved in evolution and highly variable, enabling tissue-, developmental-, and species specificity. As long as JH succeeds in keeping [Ca(2+)]i low by keeping the Ca(2+)-ATPases pumping, it acts as "the status quo" hormone. When it disappears, its various inhibitory effects are lifted. The electrical wiring system of cells, in particular in the regenerating tissues, is subject to change during metamorphosis. The possibility is discussed that in vertebrates an endogenous farnesol-like sesquiterpenoid, probably farnesol itself, acts as a functional, but hitherto completely overlooked Juvenile anti-aging "Inbrome", a novel concept in signaling.

  6. Expression of Bacillus thuringiensis cytolytic toxin (Cyt2Ca1) in citrus roots to control Diaprepes abbreviatus larvae.

    PubMed

    Mahmoud, Sulley Ben; Ramos, John E; Shatters, Robert G; Hall, David G; Lapointe, Stephen L; Niedz, Randall P; Rougé, Pierre; Cave, Ronald D; Borovsky, Dov

    2017-03-01

    Diaprepes abbreviatus (L.) is an important pest of citrus in the USA. Currently, no effective management strategies of D. abbreviatus exist in citriculture, and new methods of control are desperately sought. To protect citrus against D. abbreviatus a transgenic citrus rootstock expressing Bacillus thuringiensis Cyt2Ca1, an insect toxin protein, was developed using Agrobacterium-mediated transformation of 'Carrizo' citrange [Citrus sinensis (L) Osbeck Poncirus trifoliate (L) Raf]. The transgenic citrus root stock expressed the cytolytic toxin Cyt2Ca1 constitutively under the control of a 35S promoter in the transgenic Carrizo citrange trifoliate hybrid including the roots that are the food source of larval D. abbreviatus. The engineered citrus was screened by Western blot and RT-qPCR analyses for cyt2Ca1 and positive citrus identified. Citrus trees expressing different levels of cyt2Ca1 transcripts were identified (Groups A-C). High expression of the toxin in the leaves (10(9) transcripts/ng RNA), however, retarded plant growth. The transgenic plants were grown in pots and the roots exposed to 3week old D. abbreviatus larvae using no-choice plant bioassays. Three cyt2Ca1 transgenic plants were identified that sustained less root damage belonging to Group B and C. One plant caused death to 43% of the larvae that fed on its roots expressed 8×10(6)cyt2Ca1 transcripts/ng RNA. These results show, for the first time, that Cyt2Ca1 expressed in moderate amounts by the roots of citrus does not retard citrus growth and can protect it from larval D. abbreviatus.

  7. Geology, geophysics and age of a late Miocene, intermediate-silicic, collapsed stratovolcano complex in the northern Mojave Desert, CA

    SciTech Connect

    Sabin, A.E. ); Monastero, F.C.; Katzenstein, A.M. ); Snee, L.W. . Branch of Isotope Geochemistry)

    1993-04-01

    Geologic mapping has revealed that the Myrick Spring-Eagle Crags area of the northern Mojave Desert is an intermediate to silicic volcanic center covering nearly 100 square km. A complex series of flows, tuffs, dikes, sills and flow breccias ranging in composition from calc-alkaline basalt to high slica rhyolite were extruded through at least three different types of NW- to W-trending vents. Alteration associated with these vents includes silicic, propylitic, argillic and minor carbonate. The most intensely altered zones are vent-proximal and are controlled by a set of conjugate NW- and NE-trending fractures. Preliminary analyses reveal anomalously high concentrations of Hg, Sb and Ba with no detectable Au or Ag within these zones. Up to 500 m of vertical offset along an arcuate fault scarp in the central portion of this region describes the topographic rim of a half-graben style caldera with an infered diameter of at least 5 km. The outlow facies to the south of the rim is dominated by thick sequences of volcaniclastic breccias with interlayered rhyolite tuffs. Preliminary results of a detailed gravity survey have precisely delineated one of the largest gravity lows in the region ([minus]140 mgals). This low directly coincides with the topographic rim of the caldera. [sup 40]Ar/[sup 39] Ar age dating of biotite, sanidine and hornblende from dacite and rhyolite flows and tuffs preliminarily bracket the age of this volcanic center between 12.4 [+-].04 and 14.5 [+-].05 Ma.

  8. Reversible structure transition in gap junction under Ca++ control seen by high-resolution electron microscopy.

    PubMed

    Wrigley, N G; Brown, E; Chillingworth, R K

    1984-01-01

    Deoxycholate-extracted rat liver gap junction was studied by high-resolution low-dose electron microscopy. Communicating channels between two adjoining cells supposedly form along the common axis of two apposed hexameric trans-membrane protein assemblies. These double hexamers are often arranged in large plaques on an ordered hexagonal net (8-9 nm lattice constant) and seem able to undergo structural alteration as a possible permeability control mechanism. Calcium is widely reported to uncouple gap junction, and we observed this alteration on exposure to Ca++ down to 10(-4) M concentration. When EGTA was added at matching concentrations, the alteration was reversible several times over one hour, but with considerable variability. It was imaged in the absence of any negative stain to avoid ionic and other complications. The resulting lack of contrast plus low-dose "shot" noise required digital Fourier filtering and reconstruction, but no detail was recovered below 1.8 nm. In other experiments with negative stain at neutral pH, gap junction connexons were apparently locked in the "closed" configuration and no transition could be induced. However, recovery of repeating detail to nearly 1.0 nm was possible, reproducibly showing a fine connective matrix between connexons . Whether this was formed by unfolded portions of the 28,000-dalton gap junction protein is not known, but its existence could explain the observed lattice invariance during the connexon structural transition.

  9. Seawater Mg/Ca controls polymorph mineralogy of microbial CaCO3: a potential proxy for calcite-aragonite seas in Precambrian time.

    PubMed

    Ries, J B; Anderson, M A; Hill, R T

    2008-03-01

    A previously published hydrothermal brine-river water mixing model driven by ocean crust production suggests that the molar Mg/Ca ratio of seawater (mMg/Ca(sw)) has varied significantly (approximately 1.0-5.2) over Precambrian time, resulting in six intervals of aragonite-favouring seas (mMg/Ca(sw) > 2) and five intervals of calcite-favouring seas (mMg/Ca(sw) < 2) since the Late Archaean. To evaluate the viability of microbial carbonates as mineralogical proxy for Precambrian calcite-aragonite seas, calcifying microbial marine biofilms were cultured in experimental seawaters formulated over the range of Mg/Ca ratios believed to have characterized Precambrian seawater. Biofilms cultured in experimental aragonite seawater (mMg/Ca(sw) = 5.2) precipitated primarily aragonite with lesser amounts of high-Mg calcite (mMg/Ca(calcite) = 0.16), while biofilms cultured in experimental calcite seawater (mMg/Ca(sw) = 1.5) precipitated exclusively lower magnesian calcite (mMg/Ca(calcite) = 0.06). Furthermore, Mg/Ca(calcite )varied proportionally with Mg/Ca(sw). This nearly abiotic mineralogical response of the biofilm CaCO3 to altered Mg/Ca(sw) is consistent with the assertion that biofilm calcification proceeds more through the elevation of , via metabolic removal of CO2 and/or H+, than through the elevation of Ca2+, which would alter the Mg/Ca ratio of the biofilm's calcifying fluid causing its pattern of CaCO3 polymorph precipitation (aragonite vs. calcite; Mg-incorporation in calcite) to deviate from that of abiotic calcification. If previous assertions are correct that the physicochemical properties of Precambrian seawater were such that Mg/Ca(sw) was the primary variable influencing CaCO3 polymorph mineralogy, then the observed response of the biofilms' CaCO3 polymorph mineralogy to variations in Mg/Ca(sw), combined with the ubiquity of such microbial carbonates in Precambrian strata, suggests that the original polymorph mineralogy and Mg/Ca(calcite )of well

  10. Model of Ca(2+) Concentration Controlled by Sarcoplasmic Reticulum of Skeletal Muscle, Using the State Transition

    DTIC Science & Technology

    2007-11-02

    SR T tubule half sarcomere CS voltage sensor on TT V-channel Ca2+ pump C-channel Ca2+ nerve impulse A B C D TC LSR Fig.2 Model...Aff = σ /τ. III. MODEL STRUCTURE Let us focus on a half sarcomere . We approximate the form as a cylinder with a height of 1.1 µm, a radius 0.5 µm and...a volume of 0.86 µm3 [5]. The half sarcomere is divided into 4 parts: CS, V-channels, C-channels and Ca2+ pumps as illustrated in Fig.2. The

  11. Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

    PubMed Central

    Kumar, Ashok

    2011-01-01

    Synaptic plasticity in the mammalian central nervous system has been the subject of intense investigation for the past four decades. Long-term potentiation (LTP), a major reflection of synaptic plasticity, is an activity-driven long-lasting increase in the efficacy of excitatory synaptic transmission following the delivery of a brief, high-frequency train of electrical stimulation. LTP is regarded as a principal candidate for the cellular mechanisms involved in learning and offers an attractive hypothesis of how memories are constructed. There are a number of exceptional full-length reviews published on LTP; the current review intends to present an overview of the research findings regarding hippocampal LTP with special emphasis on aging, diseases, and psychological insults. PMID:21647396

  12. Sustained overexpression of IGF-1 prevents age-dependent decrease in charge movement and intracellular Ca(2+) in mouse skeletal muscle.

    PubMed

    Wang, Zhong-Min; Messi, María Laura; Delbono, Osvaldo

    2002-03-01

    In this work we tested the hypothesis that transgenic sustained overexpression of IGF-1 prevents age-dependent decreases in charge movement and intracellular Ca(2+) in skeletal muscle fibers. To this end, short flexor digitorum brevis (FDB) muscle fibers from 5-7- and 21-24-month-old FVB (wild-type) and S1S2 (IGF-1 transgenic) mice were studied. Fibers were voltage-clamped in the whole-cell configuration of the patch-clamp technique according to described procedures (Wang, Z. M., M. L. Messi, and O. Delbono. 1999. Biophys. J. 77:2709-2716). Charge movement and intracellular Ca(2+) concentration were recorded simultaneously. The maximum charge movement (Q(max)) recorded in young wild-type and transgenic mice was (mean +/- SEM, in nC microF(-1)): 52 +/- 2.1 (n = 46) and 54 +/- 1.9 (n = 38) (non-significant, ns), respectively, whereas in old wild-type and old transgenic mice the values were 36 +/- 2.1 (n = 32) and 49 +/- 2.3 (n = 35), respectively (p < 0.01). The peak intracellular calcium [Ca(2+)](i) recorded in young wild-type and transgenic mice was (in muM): 14.5 +/- 0.9 and 16 +/- 2.1 (ns), whereas in old wild-type and transgenic mice the values were 9.9 +/- 0.1 and 14 +/- 1.1 (p < 0.01), respectively. No significant changes in the voltage distribution or steepness of the Q-V or [Ca(2+)]-V relationship were found. These data support the concept that overexpression of IGF-1 in skeletal muscle prevents age-dependent reduction in charge movement and peak [Ca(2+)](i).

  13. Carbon-14 age and chemical evolution of Ca(HCO3)2-type groundwater of age less than 8,000 years in a confined sandy and muddy Pleistocene aquifer, Japan

    NASA Astrophysics Data System (ADS)

    Machida, Isao; Suzuki, Yohey; Takeuchi, Mio

    2013-09-01

    The Pleistocene Kimitsu aquifer was selected for examination of the relationship between groundwater age and chemical evolution of Ca(HCO3)2-type groundwater. For the most part, the aquifer is confined and composed mainly of quartz and feldspar with a small amount of calcite. The groundwater ages calculated by 14C were adjusted by using a carbon mass-balance method and corrected for effects of 14C diffusion. Groundwater ages in the Kimitsu aquifer vary from modern (upgradient) to approximately 2,400 years at 4.4 km from the edge of the recharge area. The 14C age was verified by groundwater velocity calculated from the hydraulic gradient and hydraulic conductivity. The confined groundwater evolved to Ca(HCO3)2-type around 50 years after recharge and this has been maintained for more than 8,300 years due to low chemical reactivity, derived from equilibrium with calcite, kaolinite and Ca-montmorillonite. In addition, high pH prevents the dissolution of Fe and Mn. Consequently, the rate of increase in electrical conductivity ranges from 10 to 30 μS/cm per 1,000 years. On the other hand, leakage from the deep region, which is recognized from high Cl- levels, causes remarkable increases in CH4 and HCO3 - concentrations, resulting in an apparent sulfidic zone at 500-m depth in most downgradient regions.

  14. Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca2+ signaling

    PubMed Central

    Muñoz, Manuel F.; Puebla, Mariela; Figueroa, Xavier F.

    2015-01-01

    Neuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes. These glial cells are located between neurons and the microvasculature, with the astrocytic endfeet ensheathing the vessels, which allows fine intercellular communication. The neurotransmitters released during neuronal activity reach astrocytic receptors and trigger a Ca2+ signaling that propagates to the endfeet, activating the release of vasoactive factors and arteriolar dilation. The astrocyte Ca2+ signaling is coordinated by gap junction channels and hemichannels formed by connexins (Cx43 and Cx30) and channels formed by pannexins (Panx-1). The neuronal activity-initiated Ca2+ waves are propagated among neighboring astrocytes directly via gap junctions or through ATP release via connexin hemichannels or pannexin channels. In addition, Ca2+ entry via connexin hemichannels or pannexin channels may participate in the regulation of the astrocyte signaling-mediated neurovascular coupling. Interestingly, nitric oxide (NO) can activate connexin hemichannel by S-nitrosylation and the Ca2+-dependent NO-synthesizing enzymes endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are expressed in astrocytes. Therefore, the astrocytic Ca2+ signaling triggered in neurovascular coupling may activate NO production, which, in turn, may lead to Ca2+ influx through hemichannel activation. Furthermore, NO release from the hemichannels located at astrocytic endfeet may contribute to the vasodilation of parenchymal arterioles. In this review, we discuss the mechanisms involved in the regulation of the astrocytic Ca2+ signaling that mediates neurovascular coupling, with a special emphasis in the possible participation of NO in this process

  15. Control of the neurovascular coupling by nitric oxide-dependent regulation of astrocytic Ca(2+) signaling.

    PubMed

    Muñoz, Manuel F; Puebla, Mariela; Figueroa, Xavier F

    2015-01-01

    Neuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes. These glial cells are located between neurons and the microvasculature, with the astrocytic endfeet ensheathing the vessels, which allows fine intercellular communication. The neurotransmitters released during neuronal activity reach astrocytic receptors and trigger a Ca(2+) signaling that propagates to the endfeet, activating the release of vasoactive factors and arteriolar dilation. The astrocyte Ca(2+) signaling is coordinated by gap junction channels and hemichannels formed by connexins (Cx43 and Cx30) and channels formed by pannexins (Panx-1). The neuronal activity-initiated Ca(2+) waves are propagated among neighboring astrocytes directly via gap junctions or through ATP release via connexin hemichannels or pannexin channels. In addition, Ca(2+) entry via connexin hemichannels or pannexin channels may participate in the regulation of the astrocyte signaling-mediated neurovascular coupling. Interestingly, nitric oxide (NO) can activate connexin hemichannel by S-nitrosylation and the Ca(2+)-dependent NO-synthesizing enzymes endothelial NO synthase (eNOS) and neuronal NOS (nNOS) are expressed in astrocytes. Therefore, the astrocytic Ca(2+) signaling triggered in neurovascular coupling may activate NO production, which, in turn, may lead to Ca(2+) influx through hemichannel activation. Furthermore, NO release from the hemichannels located at astrocytic endfeet may contribute to the vasodilation of parenchymal arterioles. In this review, we discuss the mechanisms involved in the regulation of the astrocytic Ca(2+) signaling that mediates neurovascular coupling, with a special emphasis in the possible participation of NO in

  16. Mitochondria Association to Calcium Release Units is Controlled by Age and Muscle Activity

    PubMed Central

    2015-01-01

    Background At the most basic level, skeletal muscle contraction requires Ca2+ and ATP and, thus, is under direct control of two important intracellular organelles: Ca2+ release units (CRUs) - specialized intracellular junctions, also named triads, which are involved in excitation-contraction (EC) coupling - and mitochondria, the organelles deputed to produce the energy required for most cellular functions (i.e. aerobic ATP production). It is now becoming clear that: a) CRUs and mitochondria interact functionally and structurally, as entry of Ca2+ into the mitochondrial matrix is required to stimulate the respiratory chain, and increase production of ATP (Fig. 1) (Sembrowich et al. 1985 1; Brookes et al. 2004 2; Rossi et al. 2009) 3; b) we recently discovered that, in adult skeletal muscle fibers, mitochondria and CRUs are placed in close proximity to each other (Fig. 2) and structurally linked by small strands called tethers (Fig. 3) (Boncompagni et al. 2009)4. Scientific hypothesis of the study Miss-function of mitochondria and functional/structural changes affecting the EC coupling apparatus have been both proposed to contribute to the age-related decline of skeletal muscle performance (Delbono et al. 1995 5; Boncompagni et al. 2006 6). In this study, we tested the following hypothesis: muscle activity improves/maintains the correct association between CRUs and mitochondria, which is challenged by ageing and inactivity. Experimental Plan We have studied the morphology, frequency, and sarcomericlocalization of both CRUs and mitochondria using light, confocal, and electron microscopy (EM) in: a) Extensor Digitorum Longus (EDL) muscles from adult (3-12 months of age) and ageing (≥24 months of age) wild type (WT) mice; and b) in human biopsies from sedentary elderly subjects (70 ± 5 years) and age matched sportmen (69 ± 4 years of age) to determine how EC coupling and mitochondrial apparatuses are affected by age and exercise. Results A Studies in mice revealed

  17. Mitochondrial Ca2+ uptake controls actin cytoskeleton dynamics during cell migration

    PubMed Central

    Prudent, Julien; Popgeorgiev, Nikolay; Gadet, Rudy; Deygas, Mathieu; Rimokh, Ruth; Gillet, Germain

    2016-01-01

    Intracellular Ca2+ signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca2+ pool and Ca2+ pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized. Here, we show that mcu silencing in two human cell lines compromises their migration capacities. This phenotype is characterized by actin cytoskeleton stiffness, a cell polarization loss and an impairment of the focal adhesion proteins dynamics. At the molecular level, these effects appear to be mediated by the reduction of the ER and cytosolic Ca2+ pools, which leads to a decrease in Rho-GTPases, RhoA and Rac1, and Ca2+-dependent Calpain activites, but seem to be independent of intracellular ATP levels. Together, this study highlights the fundamental and evolutionary conserved role of the mitochondrial Ca2+ homeostasis in cytoskeleton dynamics and cell migration. PMID:27827394

  18. Fine structure of the age-chromospheric activity relation in solar-type stars. I. The Ca II infrared triplet: Absolute flux calibration

    NASA Astrophysics Data System (ADS)

    Lorenzo-Oliveira, D.; Porto de Mello, G. F.; Dutra-Ferreira, L.; Ribas, I.

    2016-10-01

    Context. Strong spectral lines are useful indicators of stellar chromospheric activity. They are physically linked to the convection efficiency, differential rotation, and angular momentum evolution and are a potential indicator of age. However, for ages > 2 Gyr, the age-activity relationship remains poorly constrained thus hampering its full application. Aims: The Ca II infrared triplet (IRT lines, λλ 8498, 8542, and 8662) has been poorly studied compared to classical chromospheric indicators. We report in this paper absolute chromospheric fluxes in the three Ca II IRT lines, based on a new calibration tied to up-to-date model atmospheres. Methods: We obtain the Ca II IRT absolute fluxes for 113 FGK stars from high signal-to-noise ratio (S/N) and high-resolution spectra covering an extensive domain of chromospheric activity levels. We perform an absolute continuum flux calibration for the Ca II IRT lines anchored in atmospheric models calculated as an explicit function of effective temperatures (Teff), metallicity ([Fe/H]), and gravities (log g) avoiding the degeneracy usually present in photometric continuum calibrations based solely on color indices. Results: The internal uncertainties achieved for continuum absolute flux calculations are ≈2% of the solar chromospheric flux, one order of magnitude lower than for photometric calibrations. Using Monte Carlo simulations, we gauge the impact of observational errors on the final chromospheric fluxes due to the absolute continuum flux calibration and find that Teffuncertainties are properly mitigated by the photospheric correction leaving [Fe/H] as the dominating factor in the chromospheric flux uncertainty. Conclusions: Across the FGK spectral types, the Ca II IRT lines are sensitive to chromospheric activity. The reduced internal uncertainties reported here enable us to build a new chromospheric absolute flux scale and explore the age-activity relation from the active regime down to very low activity levels and

  19. Ssp1 CaMKK: A Sensor of Actin Polarization That Controls Mitotic Commitment through Srk1 in Schizosaccharomyces pombe

    PubMed Central

    Giménez-Zaragoza, David; López-Avilés, Sandra; Yance-Chávez, Tula; Montserrat, Marta; Pujol, M. Jesús; Bachs, Oriol; Aligue, Rosa

    2015-01-01

    Background Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is required for diverse cellular functions. Mammalian CaMKK activates CaMKs and also the evolutionarily-conserved AMP-activated protein kinase (AMPK). The fission yeast Schizosaccharomyces pombe CaMKK, Ssp1, is required for tolerance to limited glucose through the AMPK, Ssp2, and for the integration of cell growth and division through the SAD kinase Cdr2. Results Here we report that Ssp1 controls the G2/M transition by regulating the activity of the CaMK Srk1. We show that inhibition of Cdc25 by Srk1 is regulated by Ssp1; and also that restoring growth polarity and actin localization of ssp1-deleted cells by removing the actin-monomer-binding protein, twinfilin, is sufficient to suppress the ssp1 phenotype. Conclusions These findings demonstrate that entry into mitosis is mediated by a network of proteins, including the Ssp1 and Srk1 kinases. Ssp1 connects the network of components that ensures proper polarity and cell size with the network of proteins that regulates Cdk1-cyclin B activity, in which Srk1 plays an inhibitory role. PMID:26575035

  20. A comparative study on the effect of high cholesterol diet on the hippocampal CA1 area of adult and aged rats.

    PubMed

    Abo El-Khair, Doaa M; El-Safti, Fatma El-Nabawia A; Nooh, Hanaa Z; El-Mehi, Abeer E

    2014-06-01

    Dementia is one of the most important problems nowadays. Aging is associated with learning and memory impairments. Diet rich in cholesterol has been shown to be detrimental to cognitive performance. This work was carried out to compare the effect of high cholesterol diet on the hippocampus of adult and aged male albino rats. Twenty adult and twenty aged male rats were used in this study. According to age, the rats were randomly subdivided into balanced and high cholesterol diet fed groups. The diet was 15 g/rat/day for adult rats and 20 g/rat/day for aged rats for eight weeks. Serial coronal sections of hippocampus and blood samples were taken from each rat. For diet effect evaluation, Clinical, biochemical, histological, immunohistochemical, and morphometric assessments were done. In compare to a balanced diet fed rat, examination of Cornu Ammonis 1 (CA 1) area in the hippocampus of the high cholesterol diet adult rats showed degeneration, a significant decrease of the pyramidal cells, attenuation and/or thickening of small blood vessels, apparent increase of astrocytes and apparent decrease of Nissl's granules content. Moreover, the high cholesterol diet aged rats showed aggravation of senility changes of the hippocampus together with Alzheimer like pathological changes. In conclusion, the high cholesterol diet has a significant detrimental effect on the hippocampus and aging might pronounce this effect. So, we should direct our attention to limit cholesterol intake in our food to maintain a healthy life style for a successful aging.

  1. Assessing Sedimentation Issues Within Aging Flood Control Reservoirs in Oklahoma

    NASA Astrophysics Data System (ADS)

    Bennet, Sean J.; Cooper, Charles M.; Ritchie, Jerry C.; Dunbar, John A.; Allen, Peter M.; Caldwell, Larry W.; McGee, Thomas M.

    2002-10-01

    Since 1948, the USDA-NRCS has constructed nearly 11,000 flood control dams across the United States, and many of the reservoirs are rapidly filling with sediment. To rehabilitate these structures, the impounded sediment must be assessed to determine the volume of accumulated sediment and the potential hazard this sediment may pose if reintroduced to the environment. An assessment of sedimentation issues within two reservoirs, Sugar Creek No. 12, Hinton, Oklahoma, and Sergeant Major No. 4, Cheyenne, Oklahoma, is presented. Sediment cores obtained using a vibracoring system were composed of alternating layers of gravel, sand, silt, and clay. Stratigraphic analysis coupled with 137Cs dating techniques enabled the discrimination of pre-construction sediment from post-construction deposition. An acoustic profiling system was unencumbered by the relatively shallow water depth at Sugar Creek No. 12 and the seismic horizons agreed well with the sediment core data. Total sediment volume determined from the acoustic survey and the sediment core data for comparable areas differed by only 1.4 percent. The seismic profiling system worked well in the relatively deeper lake of Sergeant Major No. 4 and showed good correspondence to the collected core data. Detailed chemical analyses showed that overall sediment quality was good at both locations and that chemical composition was spatially invariant. Implementation of these techniques will aid action agencies such as the USDA-NRCS in their assessment and effective management of aging flood control reservoirs.

  2. Ca2+-mediated remote control of reversible sieve tube occlusion in Vicia faba.

    PubMed

    Furch, Alexandra C U; Hafke, Jens B; Schulz, Alexander; van Bel, Aart J E

    2007-01-01

    According to an established concept, injury of the phloem triggers local sieve plate occlusion including callose-mediated constriction and, possibly, protein plugging of the sieve pores. Sieve plate occlusion can also be achieved by distant stimuli, depends on the passage of electropotential waves (EPWs), and is reversible in intact plants. The time-course of the wound response was studied in sieve elements of main veins of intact Vicia faba plants using confocal and multiphoton microscopy. Only 15-45 s after burning a leaf tip, forisomes (giant protein bodies specific for legume sieve tubes) suddenly dispersed, as observed at 3-4 cm from the stimulus site. The dispersion was reversible; the forisomes had fully re-contracted 7-15 min after burning. Meanwhile, callose appeared at the sieve pores in response to the heat shock. Callose production reached a maximum after approximately 20 min and was also reversible; callose degraded over the subsequent 1-2 h. The heat induction of both modes of occlusion coincided with the passage of an EPW visualized by electrophysiology or the potential-sensitive dye RH-414. In contrast to burning, cutting of the leaf tip induced neither an EPW nor callose deposition. The data are consistent with a remote-controlled occlusion of sieve plates depending on the longitudinal propagation of an EPW releasing Ca(2+) into the sieve element lumen. It is hypothesized that forisome plugs and callose constriction are removed once the cytosolic calcium level has returned to the initial level in those sieve tubes.

  3. Perceived controllability of expected psychological change across adulthood and old age.

    PubMed

    Heckhausen, J; Baltes, P B

    1991-07-01

    This cross-sectional study focuses on adults' beliefs about the controllability of developmental change in adulthood and old age. Young (n = 33; age range 20-36 years), middle-aged (n = 35; age range 40-55 years), and older (n = 32; age range 60-85 years) adults rated an extensive list of psychological attributes in terms of the degree of expected developmental increase across the adult life span (ages 20-90), the perceived controllability of these changes, their desirability, and their expected age-related timing. The findings indicate a substantial degree of similarity in young, middle-aged, and old adults' overall beliefs about controllability. The three adult age groups agreed in perceiving developmental changes in adulthood as fairly controllable, and with regard to their relative controllability (rank ordering of change-sensitive attributes). Changes expected to occur later in life were consensually perceived to be less desirable, and less desirable changes were perceived as less controllable. However, there were clear age-related differences involving both the age timing of expected changes and the age of respondents. A comparison between the three subject age groups revealed twofold differences: First, the relationship between desirability and perceived controllability was found to increase with subjects' age; second, Q-technique factor analysis showed that large subgroups of the young and the middle-aged adults, but not the old adults, tended to perceive psychological attributes associated with late onset decline as relatively lower in controllability.

  4. The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control

    PubMed Central

    Shang, Xiaojing; Song, Chunqing; Du, Xiaoming; Shao, Hailin; Xu, Donghong; Wang, Xiaolai

    2017-01-01

    Objectives: To investigate whether there is a difference in carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), and neuron-specific enolase (NSE) between diabetic and non-diabetic patients. Methods: A retrospective analysis was performed in 268 type 2 diabetic patients and 95 non-diabetic ones, and their serum levels of CA19-9, CEA, CA72-4, and NSE were compared in our endocrine ward at the Tianjin Fourth Central Hospital, Tianjin, China during the period from January to June 2015. The diabetic patients were divided into 4 groups based on glycosylated hemoglobin (HbA1c) levels to investigate the relationship between levels of tumor markers and glucose status. Results: Diabetic patients had higher levels of tumor markers than non-diabetic subjects (CA19-9: 13.0 versus 7.25U/mL, p=0.000; CEA: 2.55 versus 2.25 ng/mL, p=0.012; CA72-4: 1.95 versus 1.50U/mL, p=0.001; NSE: 11.64 versus 10.22ng/mL, p=0.000). CA19-9 levels increased in a stepwise manner with poor diabetes status. CEA levels were increased in patients with HbA1c ≥9% and CA72-4 elevation was predominant in patients with poor glycemic control (HbA1c ≥11%). NSE levels were not associated with metabolic parameters. Conclusion: Serum levels of CA19-9, CEA, CA72-4, and NSE were elevated in type 2 diabetes; however, only CA19-9, CEA, and CA72-4 levels were associated with hyperglycemia. PMID:28133696

  5. Reduced, reused and recycled: Detrital zircons define a maximum age for the Eoarchean (ca. 3750-3780 Ma) Nuvvuagittuq Supracrustal Belt, Québec (Canada)

    NASA Astrophysics Data System (ADS)

    Cates, Nicole L.; Ziegler, Karen; Schmitt, Axel K.; Mojzsis, Stephen J.

    2013-01-01

    A key discovery from the Hadean (pre-3850 Ma) detrital zircon record has been that the dichotomy of granitic and basaltic crust was established within about 160 Myr of Earth's formation (Harrison, 2009). Understanding the origin and fate of this primordial crust would greatly add to what we know about the geodynamics of the Hadean Earth. Insights emerge from 147,146Sm-143,142Nd isotope data reported from different Eoarchean terranes worldwide, including the Nuvvuagittuq Supracrustal Belt (NSB) in northern Québec. Some Ca-poor (cummingtonite-rich) amphibolites and granitoid gneisses of the NSB preserve lower 142Nd/144Nd than Bulk Silicate Earth (BSE); these also show positive correlations against 147Sm/144Nd that were used by O'Neil et al. (2008, 2012) to assign a ca. 4400 Ma age. Alternatively, the compositions were inherited during the formation of the NSB at around 3800 Ma (Roth et al., 2013; Guitreau et al., 2013). To resolve this discrepancy, ion microprobe U-Pb ages are reported for detrital zircons from NSB meta-sediments from within the same supracrustal successions that preserve low 142Nd/144Nd. The youngest detrital zircon cores of igneous derivation define a maximum age for the NSB of ca. 3780 Ma. This age is about 600 Myr younger than that obtained from 142Nd/144Nd vs. 147Sm-143Nd regressions. Thus, just like the variable 142Nd/144Nd ratios reported for other Eoarchean terranes, non-BSE 142Nd/144Nd values of the NSB were inherited from an older component.

  6. Peripheral cell loss related to calcium binding protein immunocytochemistry in the dorsal cochlear nucleus in CBA/CaJ mice during aging.

    PubMed

    Idrizbegovic, E; Viberg, A; Bogdanovic, N; Canlon, B

    2001-01-01

    The influence of cochlear hair cell and spiral ganglia neuron loss on calcium binding protein immunoreactivity (calretinin, parvalbumin and calbindin) in the dorsal and posteroventral cochlear nuclei (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months) was determined. Since calcium binding proteins have buffering properties against calcium overload, they may have a protective role during aging. It is shown that the percentage of calretinin- and parvalbumin-immunopositive neurons in the DCN showed a statistically significant positive correlation with inner hair cell loss, outer hair cell loss, and spiral ganglion cell loss. A correlation was also found between aging and the auditory periphery, and calcium binding proteins in the DCN. These findings imply that the pathophysiological state of the auditory periphery may influence the neuronal homeostasis in the dorsal cochlear nucleus.

  7. Chemical and physical controls on the transformation of amorphous calcium carbonate into crystalline CaCO3 polymorphs

    NASA Astrophysics Data System (ADS)

    Blue, C. R.; Giuffre, A.; Mergelsberg, S.; Han, N.; De Yoreo, J. J.; Dove, P. M.

    2017-01-01

    Calcite and other crystalline polymorphs of CaCO3 can form by pathways involving amorphous calcium carbonate (ACC). Apparent inconsistencies in the literature indicate the relationships between ACC composition, local conditions, and the subsequent crystalline polymorphs are not yet established. This experimental study quantifies the control of solution composition on the transformation of ACC into crystalline polymorphs in the presence of magnesium. Using a mixed flow reactor to control solution chemistry, ACC was synthesized with variable Mg contents by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within the output suspension under stirred or quiescent conditions while characterizing the evolving solutions and solids. As the ACC transforms into a crystalline phase, the solutions record a polymorph-specific evolution of pH and Mg/Ca. The data provide a quantitative framework for predicting the initial polymorph that forms from ACC based upon the solution aMg2+/aCa2+ and aCO32-/aCa2+ and stirring versus quiescent conditions. This model reconciles discrepancies among previous studies that report on the nature of the polymorphs produced from ACC and supports the previous claim that monohydrocalcite may be an important, but overlooked, transient phase on the way to forming some aragonite and calcite deposits. By this construct, organic additives and extreme pH are not required to tune the composition and nature of the polymorph that forms. Our measurements show that the Mg content of ACC is recorded in the resulting calcite with a ≈1:1 dependence. By correlating composition of these calcite products with the Mgtot/Catot of the initial solutions, we find a ≈3:1 dependence that is approximately linear and general to whether calcite is formed via an ACC pathway or by the classical step-propagation process. Comparisons to calcite grown in synthetic seawater show a ≈1:1 dependence. The relationships suggest that the

  8. Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability*

    PubMed Central

    Aman, Teresa K.; Maki, Bruce A.; Ruffino, Thomas J.; Kasperek, Eileen M.; Popescu, Gabriela K.

    2014-01-01

    Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca2+ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca2+ permeability (PCa/PNa) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca2+ conductance, because neither Na+ conductance nor Ca2+-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca2+ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca2+ permeability. PMID:24847051

  9. Experimental determination of factors controlling U/Ca of aragonite precipitated from seawater: Implications for interpreting coral skeleton

    NASA Astrophysics Data System (ADS)

    DeCarlo, Thomas M.; Gaetani, Glenn A.; Holcomb, Michael; Cohen, Anne L.

    2015-08-01

    The U/Ca ratio of aragonite coral skeleton exhibits coherent patterns of seasonal and interannual variability. In field-sampled corals and those grown in controlled culture experiments, strong correlations have been found between coral skeleton U/Ca and water temperature, pH, carbonate ion concentration, and salinity. However, the mechanism(s) underlying these different correlations remain unclear. We performed abiogenic precipitation experiments designed to evaluate the sensitivity of U partitioning between aragonite and seawater to temperature, pH, and the concentration of carbonate ion in seawater. Aragonite was precipitated from seawater by addition of carbonate alkalinity at rates set to maintain stable carbonate chemistry during precipitation. Experiments were conducted at 20-40 °C, with pH 7.8-9.0 and carbonate ion concentrations of 600-2600 μmol kg-1. U/Ca ratios of the bulk precipitate and fluid were determined by inductively coupled plasma mass spectrometry. Our results show that the U/Ca ratio of aragonite precipitated from seawater decreases with increasing carbonate ion concentration, and is independent of pH and temperature. We use these results as a framework to interpret the skeletal composition of coral aragonite precipitated from a calcifying fluid that is semi-isolated from the external seawater environment. Accordingly, coral U/Ca ratios are consistent with calcifying fluid carbonate ion concentrations that are several times greater than those of ambient seawater. Correlations between coral U/Ca ratios and seawater temperature, carbonate chemistry, and other environmental variables arise indirectly, via the impacts of these variables on the carbonate ion concentration of the coral calcifying fluid.

  10. The ageing and de-ageing behaviour of (Ba0.85Ca0.15)(Ti0.9Zr0.1)O3 lead-free piezoelectric ceramics

    NASA Astrophysics Data System (ADS)

    Zhang, Yichi; Glaum, Julia; Ehmke, Matthias C.; Bowman, Keith J.; Blendell, John E.; Hoffman, Mark J.

    2015-09-01

    Ageing behaviour usually occurs in acceptor-doped piezoelectric materials (e.g., hard lead zirconate titanate) and exhibits the development of a pinched or shifted hysteresis loop over time. Although no pinched hysteresis loop was observed for lead-free (Ba0.85Ca0.15)(Ti0.9Zr0.1)O3 material, this study showed that the piezoelectric properties change over time in the poled state. The shift of the hysteresis loop along the electric field axis and the development of asymmetry in strain and permittivity hysteresis loop were observed during the ageing process. The origin of this ageing behaviour is proposed to be local defect dipoles and the migration of the charged defects to the grain boundaries. The reorientation of the defect dipole contributes to a fast but unstable ageing mechanism in this material while the migration of the charged defects contributes to a slow but more stable mechanism.

  11. Debris Flow Control on Fluvial Hanging Valley Formation in the South Fork Eel River, CA

    NASA Astrophysics Data System (ADS)

    Deshpande, N.; Perkins, J.; Finnegan, N. J.

    2012-12-01

    An understanding of how base level signals are transmitted into landscapes is fundamental to interpreting river long profiles in tectonically active settings. Fluvial hanging valleys, locations where waves of incision have apparently arrested at tributary junctions, suggest that base level propagation is an unsteady process in many settings. A recent hypothesis (Wobus et al., 2006) explains the formation of fluvial hanging valleys via an instability in the saltation abrasion model of Sklar and Dietrich (2004). At locations where small steep tributaries join trunk streams, tributary incision rates can actually decrease with increasing channel slope when subjected to downstream base-level fall. However, we note that in mountainous river networks steep tributaries also commonly convey debris flows into trunk channels. Since these tributary junctions mark the upstream limit of channels whose beds are mobilized on a regular basis during flood events, here we hypothesize that transitions from fluvial to debris flow channels control the location of fluvial hanging valleys. To test our hypothesis, we exploit a natural experiment in base level fall and landscape evolution along the South Fork Eel River, which is argued to be responding to an increase in rock uplift rate associated with the passage of the Mendocino Triple Junction. In order to separate debris flow channels from fluvial channels, we use airborne laser swath mapping (ALSM) to quantify channel slopes and concavities. In our analysis, concavity data are noisy and represent a poor metric for determination of debris flow channels. In lieu of this, we choose a more straightforward metric of channel slope to discriminate where debris flows occur on the landscape. We find that, on average, fluvial hanging valleys are only present in tributaries with average gradients above 0.10, consistent with empirical determinations of the gradient at which debris flow channels transition to fluvial channels (0.03-0.10). Field

  12. Store-operated Ca2+ entry controls ameloblast cell function and enamel development

    PubMed Central

    Eckstein, Miriam; Vaeth, Martin; Fornai, Cinzia; Vinu, Manikandan; Bromage, Timothy G.; Nurbaeva, Meerim K.; Sorge, Jessica L.; Coelho, Paulo G.; Idaghdour, Youssef; Feske, Stefan; Lacruz, Rodrigo S.

    2017-01-01

    Loss-of-function mutations in stromal interaction molecule 1 (STIM1) impair the activation of Ca2+ release–activated Ca2+ (CRAC) channels and store-operated Ca2+ entry (SOCE), resulting in a disease syndrome called CRAC channelopathy that is characterized by severe dental enamel defects. The cause of these enamel defects has remained unclear given a lack of animal models. We generated Stim1/2K14cre mice to delete STIM1 and its homolog STIM2 in enamel cells. These mice showed impaired SOCE in enamel cells. Enamel in Stim1/2K14cre mice was hypomineralized with decreased Ca content, mechanically weak, and thinner. The morphology of SOCE-deficient ameloblasts was altered, showing loss of the typical ruffled border, resulting in mislocalized mitochondria. Global gene expression analysis of SOCE-deficient ameloblasts revealed strong dysregulation of several pathways. ER stress genes associated with the unfolded protein response were increased in Stim1/2-deficient cells, whereas the expression of components of the glutathione system were decreased. Consistent with increased oxidative stress, we found increased ROS production, decreased mitochondrial function, and abnormal mitochondrial morphology in ameloblasts of Stim1/2K14cre mice. Collectively, these data show that loss of SOCE in enamel cells has substantial detrimental effects on gene expression, cell function, and the mineralization of dental enamel. PMID:28352661

  13. Using Varnish Microlaminations to Provide Minimum Ages on Alluvium Associated with Ground Water Discharge Deposits on an Alluvial Fan at Fenner Gap, Cadiz, CA.

    NASA Astrophysics Data System (ADS)

    Erickson, B.; Hemphill-Haley, M. A.

    2015-12-01

    Groundwater discharge (GWD) deposits are situated on three lobes of an alluvial fan at Fenner Gap near Cadiz, CA, between 220-250 m elevations. They are representative of past wetlands that raised base level leading to aggradation upstream on the alluvial fan. This study utilized the varnish microlamination (VML) dating method to provide minimum ages on the alluvium overlying GWD deposits, as well as estimating the age of a remnant older alluvium in Fenner Gap. VML results provide a minimum age of 2.8-4.1 ka on the overlying alluvium at the Chambless GWD deposit; agreeable with previously published OSL dates on the underlying GWD of about 10 ka. A VML age of 8.1 ka was found on the overlying alluvium at the Archer sediments GWD situated on the southern lobe. The oldest remnant alluvium in Fenner Gap is situated < 1 km upstream from the GWD deposits and has a minimum VML age of 17.75 ka. This older alluvium could be indicative of a raise in base level caused by wetlands formed during a ground water highstand associated with the last glacial maximum. These VML minimum age estimates may be too young due to the collection of varnish that may not be the oldest present.

  14. A calcium-redox feedback loop controls human monocyte immune responses: The role of ORAI Ca2+ channels.

    PubMed

    Saul, Stephanie; Gibhardt, Christine S; Schmidt, Barbara; Lis, Annette; Pasieka, Bastian; Conrad, David; Jung, Philipp; Gaupp, Rosmarie; Wonnenberg, Bodo; Diler, Ebru; Stanisz, Hedwig; Vogt, Thomas; Schwarz, Eva C; Bischoff, Markus; Herrmann, Mathias; Tschernig, Thomas; Kappl, Reinhard; Rieger, Heiko; Niemeyer, Barbara A; Bogeski, Ivan

    2016-03-08

    In phagocytes, pathogen recognition is followed by Ca(2+) mobilization and NADPH oxidase 2 (NOX2)-mediated "oxidative burst," which involves the rapid production of large amounts of reactive oxygen species (ROS). We showed that ORAI Ca(2+) channels control store-operated Ca(2+) entry, ROS production, and bacterial killing in primary human monocytes. ROS inactivate ORAI channels that lack an ORAI3 subunit. Staphylococcal infection of mice reduced the expression of the gene encoding the redox-sensitive Orai1 and increased the expression of the gene encoding the redox-insensitive Orai3 in the lungs or in bronchoalveolar lavages. A similar switch from ORAI1 to ORAI3 occurred in primary human monocytes exposed to bacterial peptides in culture. These alterations in ORAI1 and ORAI3 abundance shifted the channel assembly toward a more redox-insensitive configuration. Accordingly, silencing ORAI3 increased the redox sensitivity of the channel and enhanced oxidation-induced inhibition of NOX2. We generated a mathematical model that predicted additional features of the Ca(2+)-redox interplay. Our results identified the ORAI-NOX2 feedback loop as a determinant of monocyte immune responses.

  15. The balance between cytoplasmic and nuclear CaM Kinase-1 signaling controls the operating range of noxious heat avoidance

    PubMed Central

    Schild, Lisa C.; Zbinden, Laurie; Bell, Harold W.; Yu, Yanxun V.; Sengupta, Piali; Goodman, Miriam B.; Glauser, Dominique A.

    2015-01-01

    SUMMARY Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a novel, gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the operating range for nocifensive heat avoidance to higher temperatures. Such analgesia depends on nuclear CMK-1 signaling, while cytoplasmic CMK-1 signaling lowers the threshold for thermal avoidance. CMK-1 acts downstream of heat detection in thermal receptor neurons and controls neuropeptide release. Our results establish CaMKI as a key regulator of the operating range for nocifensive behaviors, and suggest strategies for producing thermal analgesia through the regulation of CaMKI-dependent signaling. PMID:25467982

  16. Valley-fill alluviation during the Little Ice Age (ca. A.D. 1400-1880), Paria River basin and southern Colorado Plateau, United States

    USGS Publications Warehouse

    Hereford, R.

    2002-01-01

    Valley-fill alluvium deposited from ca. A.D. 1400 to 1880 is widespread in tributaries of the Paria River and is largely coincident with the Little Ice Age epoch of global climate variability. Previous work showed that alluvium of this age is a mappable stratigraphic unit in many of the larger alluvial valleys of the southern Colorado Plateau. The alluvium is bounded by two disconformities resulting from prehistoric and historic arroyo cutting at ca. A.D. 1200-1400 and 1860-1910, respectively. The fill forms a terrace in the axial valleys of major through-flowing streams. This terrace and underlying deposits are continuous and interfinger with sediment in numerous small tributary valleys that head at the base of hillslopes of sparsely vegetated, weakly consolidated bedrock, suggesting that eroded bedrock was an important source of alluvium along with in-channel and other sources. Paleoclimatic and high-resolution paleoflood studies indicate that valley-fill alluviation occured during a long-term decrease in the frequency of large, destructive floods. Aggradation of the valleys ended about A.D. 1880, if not two decades earlier, with the beginning of historic arroyo cutting. This shift from deposition to valley entrenchment near the close of the Little Ice Age generally coincided with the beginning of an episode of the largest floods in the preceding 400-500 yr, which was probably caused by an increased recurrence and intensity of flood-producing El Nin??o events beginning at ca. A.D. 1870.

  17. Preparation of CaO as OLED getter material through control of crystal growth of CaCO{sub 3} by block copolymers in aqueous solution

    SciTech Connect

    Park, Jae-Hyung; Oh, Seong-Geun

    2009-01-08

    As the starting materials of organic light-emitting diode (OLED) getter, calcium carbonate (CaCO{sub 3}) particles with various shapes and crystal structures have been successfully prepared with additives (L64 or PEGPG), which contain blocks of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO). These CaCO{sub 3} particles were calcinated into highly crystalline calcium oxide (CaO) nanoparticles with high capacity of water adsorption up to 14.23 wt.%. The CaCO{sub 3} and CaO particles prepared at various conditions were characterized using the field emission scanning electron microscopy (FE-SEM), Fourier transform infrared microscopy (FT-IR), X-ray powder diffraction (XRD), and dynamic vapor sorption (DVS) method.

  18. Autophagy Controls Acquisition of Aging Features in Macrophages

    PubMed Central

    Stranks, Amanda J.; Hansen, Anne Louise; Panse, Isabel; Mortensen, Monika; Ferguson, David J.P.; Puleston, Daniel J.; Shenderov, Kevin; Watson, Alexander Scarth; Veldhoen, Marc; Phadwal, Kanchan; Cerundolo, Vincenzo; Simon, Anna Katharina

    2015-01-01

    Macrophages provide a bridge linking innate and adaptive immunity. An increased frequency of macrophages and other myeloid cells paired with excessive cytokine production is commonly seen in the aging immune system, known as ‘inflamm-aging’. It is presently unclear how healthy macrophages are maintained throughout life and what connects inflammation with myeloid dysfunction during aging. Autophagy, an intracellular degradation mechanism, has known links with aging and lifespan extension. Here, we show for the first time that autophagy regulates the acquisition of major aging features in macrophages. In the absence of the essential autophagy gene Atg7, macrophage populations are increased and key functions such as phagocytosis and nitrite burst are reduced, while the inflammatory cytokine response is significantly increased – a phenotype also observed in aged macrophages. Furthermore, reduced autophagy decreases surface antigen expression and skews macrophage metabolism toward glycolysis. We show that macrophages from aged mice exhibit significantly reduced autophagic flux compared to young mice. These data demonstrate that autophagy plays a critical role in the maintenance of macrophage homeostasis and function, regulating inflammation and metabolism and thereby preventing immunosenescence. Thus, autophagy modulation may prevent excess inflammation and preserve macrophage function during aging, improving immune responses and reducing the morbidity and mortality associated with inflamm-aging. PMID:25764971

  19. Aging is a primary risk factor for cardiac arrhythmias: disruption of intracellular Ca2+ regulation as a key suspect.

    PubMed

    Hatch, Fiona; Lancaster, Matthew K; Jones, Sandra A

    2011-08-01

    Aging is an inevitable time-dependent progression associated with a functional decline of the cardiovascular system even in 'healthy' individuals. Age positively correlates with an increasing risk of cardiac problems including arrhythmias. Not only the prevalence but also the severity of arrhythmias escalates with age. The reasons for this are multifactorial but dysregulation of intracellular calcium within the heart is likely to play a key role in initiating and perpetuating these life-threatening events. We now know that several aspects of cardiac calcium regulation significantly change with advancing age - changes that could produce electrical instability. Further development of knowledge of the mechanisms underlying these changes will allow us to reduce what currently is an inevitable increase in the incidence of arrhythmias in the elderly.

  20. Polo Kinase Phosphorylates Miro to Control ER-Mitochondria Contact Sites and Mitochondrial Ca(2+) Homeostasis in Neural Stem Cell Development.

    PubMed

    Lee, Seongsoo; Lee, Kyu-Sun; Huh, Sungun; Liu, Song; Lee, Do-Yeon; Hong, Seung Hyun; Yu, Kweon; Lu, Bingwei

    2016-04-18

    Mitochondria play central roles in buffering intracellular Ca²⁺ transients. While basal mitochondrial Ca²⁺ (Ca²⁺ mito) is needed to maintain organellar physiology, Ca²⁺ mito overload can lead to cell death. How Ca²⁺ mito homeostasis is regulated is not well understood. Here we show that Miro, a known component of the mitochondrial transport machinery, regulates Drosophila neural stem cell (NSC) development through Ca²⁺ mito homeostasis control, independent of its role in mitochondrial transport. Miro interacts with Ca²⁺ transporters at the ER-mitochondria contact site (ERMCS). Its inactivation causes Ca²⁺ mito depletion and metabolic impairment, whereas its overexpression results in Ca²⁺ mito overload, mitochondrial morphology change, and apoptotic response. Both conditions impaired NSC lineage progression. Ca²⁺ mito homeostasis is influenced by Polo-mediated phosphorylation of a conserved residue in Miro, which positively regulates Miro localization to, and the integrity of, ERMCS. Our results elucidate a regulatory mechanism underlying Ca²⁺ mito homeostasis and how its dysregulation may affect NSC metabolism/development and contribute to disease.

  1. Electric Field-Controlled Crystallizing CaCO3 Nanostructures from Solution

    NASA Astrophysics Data System (ADS)

    Qi, Jian Quan; Guo, Rui; Wang, Yu; Liu, Xuan Wen; Chan, Helen Lai Wah

    2016-03-01

    The role of electric field is investigated in determining the structure, morphology, and crystallographic characteristics of CaCO3 nanostructures crystallized from solution. It is found that the lattice structure and crystalline morphology of CaCO3 can be tailed by the electric field applied to the solution during its crystallization. The calcite structure with cubic-like morphology can be obtained generally without electric field, and the vaterite structure with the morphology of nanorod is formed under the high electric field. The vaterite nanorods can be piled up to the petaliform layers. Both the nanorod and the petaliform layer can have mesocrystal structures which are piled up by much fine units of the rods with the size of several nanometers. Beautiful rose-like nanoflowers can be self-arranged by the petaliform layers. These structures can have potential application as carrier for medicine to involve into metabolism of living cell.

  2. Phase controlled synthesis of (Mg, Ca, Ba)-ferrite magnetic nanoparticles with high uniformity

    NASA Astrophysics Data System (ADS)

    Wang, S. F.; Li, Q.; Zu, X. T.; Xiang, X.; Liu, W.; Li, S.

    2016-12-01

    (Mg, Ca, Ba)-ferrite magnetic nanoparticles were successfully synthesized through modifying the atomic ratio of polysaccharide and chelating agent at an optimal sintering temperature. In the process, the polysaccharide plays an important role in drastically shrinking the precursor during the gel drying process. In the metal-complex structure, M2+ ion active sites were coordinated by -OH of the water molecules except for EDTA anions. The MFe2O4 magnetic nanoparticles exhibited enhanced magnetic properties when compared with nano-MFe2O4 of similar particle size synthesized by other synthesis route reported in the literature. In particular, the sintering temperature improves the crystallinity and increases the hysteresis loop squareness ratio of (Mg, Ca, Ba)-ferrite nanoparticles significantly.

  3. Control of membrane gaps by synaptotagmin-Ca2+ measured with a novel membrane distance ruler

    NASA Astrophysics Data System (ADS)

    Lin, Chao-Chen; Seikowski, Jan; Pérez-Lara, Angel; Jahn, Reinhard; Höbartner, Claudia; Walla, Peter Jomo

    2014-12-01

    Fast synchronous neurotransmitter release is triggered by calcium that activates synaptotagmin-1 (syt-1), resulting in fusion of synaptic vesicles with the presynaptic membrane. Syt-1 possesses two Ca2+-binding C2 domains that tether membranes via interactions with anionic phospholipids. It is capable of crosslinking membranes and has recently been speculated to trigger fusion by decreasing the gap between them. As quantitative information on membrane gaps is key to understanding general cellular mechanisms, including the role of syt-1, we developed a fluorescence-lifetime based inter-membrane distance ruler using membrane-anchored DNAs of various lengths as calibration standards. Wild-type and mutant data provide evidence that full-length syt-1 indeed regulates membrane gaps: without Ca2+, syt-1 maintains membranes at distances of ~7-8 nm. Activation with 100 μM Ca2+ decreases the distance to ~5 nm by binding the C2 domains to opposing membranes, respectively. These values reveal that activated syt-1 adjusts membrane distances to the level that promotes SNARE complex assembly.

  4. Spectral Variability in the Aged Brain during Fine Motor Control

    PubMed Central

    Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.

    2016-01-01

    Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231

  5. Spectral Variability in the Aged Brain during Fine Motor Control.

    PubMed

    Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C

    2016-01-01

    Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role.

  6. Mitochondrial proteostasis in the control of aging and longevity.

    PubMed

    Jensen, Martin Borch; Jasper, Heinrich

    2014-08-05

    Mitochondria play a central role in the aging process. Studies in model organisms have started to integrate mitochondrial effects on aging with the maintenance of protein homeostasis. These findings center on the mitochondrial unfolded protein response (UPR(mt)), which has been implicated in lifespan extension in worms, flies, and mice, suggesting a conserved role in the long-term maintenance of cellular homeostasis. Here, we review current knowledge of the UPR(mt) and discuss its integration with cellular pathways known to regulate lifespan. We highlight how insight into the UPR(mt) is revolutionizing our understanding of mitochondrial lifespan extension and of the aging process.

  7. Dynamic control of presynaptic Ca(2+) inflow by fast-inactivating K(+) channels in hippocampal mossy fiber boutons.

    PubMed

    Geiger, J R; Jonas, P

    2000-12-01

    Analysis of presynaptic determinants of synaptic strength has been difficult at cortical synapses, mainly due to the lack of direct access to presynaptic elements. Here we report patch-clamp recordings from mossy fiber boutons (MFBs) in rat hippocampal slices. The presynaptic action potential is very short during low-frequency stimulation but is prolonged up to 3-fold during high-frequency stimulation. Voltage-gated K(+) channels in MFBs inactivate rapidly but recover from inactivation very slowly, suggesting that cumulative K(+) channel inactivation mediates activity-dependent spike broadening. Prolongation of the presynaptic voltage waveform leads to an increase in the number of Ca(2+) ions entering the terminal per action potential and to a consecutive potentiation of evoked excitatory postsynaptic currents at MFB-CA3 pyramidal cell synapses. Thus, inactivation of presynaptic K(+) channels contributes to the control of efficacy of a glutamatergic synapse in the cortex.

  8. Update on the prevention and control of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA).

    PubMed

    Skov, Robert; Christiansen, Keryn; Dancer, Stephanie J; Daum, Robert S; Dryden, Matthew; Huang, Yhu-Chering; Lowy, Franklin D

    2012-03-01

    The rapid dissemination of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) since the early 2000s and the appearance of new successful lineages is a matter of concern. The burden of these infections varies widely between different groups of individuals and in different regions of the world. Estimating the total burden of disease is therefore problematic. Skin and soft-tissue infections, often in otherwise healthy young individuals, are the most common clinical manifestation of these infections. The antibiotic susceptibilities of these strains also vary, although they are often more susceptible to 'traditional' antibiotics than related hospital-acquired strains. Preventing the dissemination of these organisms throughout the general population requires a multifaceted approach, including screening and decolonisation, general hygiene and cleaning measures, antibiotic stewardship programmes and, in the future, vaccination. The current evidence on the prevention and control of CA-MRSA is appraised and summarised in this review.

  9. Discussion on software aging management of nuclear power plant safety digital control system.

    PubMed

    Liang, Huihui; Gu, Pengfei; Tang, Jianzhong; Chen, Weihua; Gao, Feng

    2016-01-01

    Managing the aging of digital control systems ensures that nuclear power plant systems are in adequate safety margins during their life cycles. Software is a core component in the execution of control logic and differs between digital and analog control systems. The hardware aging management for the digital control system is similar to that for the analog system, which has matured over decades of study. However, software aging management is still in the exploratory stage. Software aging evaluation is critical given the higher reliability and safety requirements of nuclear power plants. To ensure effective inputs for reliability assessment, this paper provides the required software aging information during the life cycle. Moreover, the software aging management scheme for safety digital control system is proposed on the basis of collected aging information.

  10. Age Effect on Autonomic Cardiovascular Control in Pilots

    DTIC Science & Technology

    2000-08-01

    Nantcheva**, M. Vukov*** *National Center of Hygiene, Medical Ecology and Nutrition 15 Dimitar Nestorov Blvd. 1431 Sofia, Bulgaria "**Military Medical...cardiovascular derived indices. Most sensitive to aging process from regulation, involve in part autonomic influences. time-domain HRV measures...completing of the mission tasks (15). A components, and baroreflex sensitivity with age (29). number of studies have investigated the impact of the

  11. Ages and Nd, Sr isotopic systematics in the Sierran foothills ophiolite belt, CA: the Smartville and Feather River complexes

    SciTech Connect

    Shaw, H.F.; Niemeyer, S.

    1985-01-01

    Sm-Nd dating has shown the Kings-Kaweah ophiolite to be approx. 480 My old. Its Nd, Sr, and Pb isotopic compositions require an unusually old depleted mantle source. Samples from the Smartville and Feather River complexes have been analyzed in a search for similar highly depleted, early Paleozoic ophiolites in the northern foothills ophiolite belt. Six whole rocks from Smartville, encompassing representative lithologies, plus plagioclase and pyroxene mineral separates define a 183 +/- 22 My Sm-Nd isochron. This age, interpreted as the igneous age, is older than, but within error of, approx. 160 My U-Pb ages previously obtained from plagiogranite zircon analyses. One diabase with unusually high Rb/Sr yields a depleted mantle Sr model age of 200 +/- 25 My, consistent with the Sm-ND age. These compositions are clearly oceanic in character but do not discriminate among possible tectonic settings for the formation of the Smartville complex. Sm-Nd data for flaser gabbros and related rocks from Feather River scatter about an approx. 230 My errorchron with element of/sub Nd/(T) = +6.3 to +8.7. Initial /sup 87/Sr//sup 86/Sr ranges from 0.7028 to 0.7031. These results indicate a complex history with initial isotopic heterogeneities and/or disturbances of the isotopic systems. If primary, the element of/sub Nd/ (T) values are somewhat low, suggesting a possible arc origin for these rocks. Neither the Smartville nor Feather R. complexes appear to be related to the Kings-Kaweah ophiolite which, so far, is unique among foothill ophiolites in having an early Paleozoic age and a clear MORB, as opposed to arc or marginal basin, isotopic signature.

  12. APP Deletion Accounts for Age-Dependent Changes in the Bioenergetic Metabolism and in Hyperphosphorylated CaMKII at Stimulated Hippocampal Presynaptic Active Zones

    PubMed Central

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Neupärtl, Moritz; Array, Tabiwang N.; Harde, Eva; Beckert, Benedikt; Golghalyani, Vahid; Ackermann, Jörg; Koch, Ina; Müller, Ulrike C.; Karas, Michael; Acker-Palmer, Amparo; Volknandt, Walter

    2017-01-01

    Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice. PMID:28163681

  13. APP Deletion Accounts for Age-Dependent Changes in the Bioenergetic Metabolism and in Hyperphosphorylated CaMKII at Stimulated Hippocampal Presynaptic Active Zones.

    PubMed

    Laßek, Melanie; Weingarten, Jens; Wegner, Martin; Neupärtl, Moritz; Array, Tabiwang N; Harde, Eva; Beckert, Benedikt; Golghalyani, Vahid; Ackermann, Jörg; Koch, Ina; Müller, Ulrike C; Karas, Michael; Acker-Palmer, Amparo; Volknandt, Walter

    2017-01-01

    Synaptic release sites are characterized by exocytosis-competent synaptic vesicles tightly anchored to the presynaptic active zone (PAZ) whose proteome orchestrates the fast signaling events involved in synaptic vesicle cycle and plasticity. Allocation of the amyloid precursor protein (APP) to the PAZ proteome implicated a functional impact of APP in neuronal communication. In this study, we combined state-of-the-art proteomics, electrophysiology and bioinformatics to address protein abundance and functional changes at the native hippocampal PAZ in young and old APP-KO mice. We evaluated if APP deletion has an impact on the metabolic activity of presynaptic mitochondria. Furthermore, we quantified differences in the phosphorylation status after long-term-potentiation (LTP) induction at the purified native PAZ. We observed an increase in the phosphorylation of the signaling enzyme calmodulin-dependent kinase II (CaMKII) only in old APP-KO mice. During aging APP deletion is accompanied by a severe decrease in metabolic activity and hyperphosphorylation of CaMKII. This attributes an essential functional role to APP at hippocampal PAZ and putative molecular mechanisms underlying the age-dependent impairments in learning and memory in APP-KO mice.

  14. Ca(2+)-activated ion currents triggered by ryanodine receptor-mediated Ca(2+) release control firing of inhibitory neurons in the prepositus hypoglossi nucleus.

    PubMed

    Saito, Yasuhiko; Yanagawa, Yuchio

    2013-01-01

    Spontaneous miniature outward currents (SMOCs) are known to exist in smooth muscles and peripheral neurons, and evidence for the presence of SMOCs in central neurons has been accumulating. SMOCs in central neurons are induced through Ca(2+)-activated K(+) (K(Ca)) channels, which are activated through Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum via ryanodine receptors (RyRs). Previously, we found that some neurons in the prepositus hypoglossi nucleus (PHN) showed spontaneous outward currents (SOCs). In the present study, we used whole cell recordings in slice preparations of the rat brain stem to investigate the following: 1) the ionic mechanisms of SOCs, 2) the types of neurons exhibiting frequent SOCs, and 3) the effect of Ca(2+)-activated conductance on neuronal firing. Pharmacological analyses revealed that SOCs were induced via the activation of small-conductance-type K(Ca) (SK) channels and RyRs, indicating that SOCs correspond to SMOCs. An analysis of the voltage responses to current pulses of the fluorescence-expressing inhibitory neurons of transgenic rats revealed that inhibitory neurons frequently exhibited SOCs. Abolition of SOCs via blockade of SK channels enhanced the frequency of spontaneous firing of inhibitory PHN neurons. However, abolition of SOCs via blockade of RyRs reduced the firing frequency and hyperpolarized the membrane potential. Similar reductions in firing frequency and hyperpolarization were also observed when Ca(2+)-activated nonselective cation (CAN) channels were blocked. These results suggest that, in inhibitory neurons in the PHN, Ca(2+) release via RyRs activates SK and CAN channels, and these channels regulate spontaneous firing in a complementary manner.

  15. The total number of neurons and calcium binding protein positive neurons during aging in the cochlear nucleus of CBA/CaJ mice: a quantitative study.

    PubMed

    Idrizbegovic, E; Canlon, B; Bross, L S; Willott, J F; Bogdanovic, N

    2001-08-01

    The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and the total number of neurons immunostained with parvalbumin, calbindin-D28k (calbindin), and calretinin in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months old). CBA mice have only a modest sensorineural pathology late in life. An age-related decrease of the total number of neurons was demonstrated in the DCN (r=-0.54, P<0.03), while the total number of neurons in the PVCN did not show any significant age-related differences (r=0.16, P=0.57). In the DCN 5.5% of neurons were parvalbumin positive in the very old (30-39 months) mice, vs. 2.2% in the 1 month old mice. In the DCN 3% of the neurons were calbindin immunopositive in the 30-39 months mice compared to 1.9% in the 1 month old group. In the PVCN, 20% of the neurons in the very old mice were parvalbumin immunopositive, compared to 12% in the young mice. Calbindin did not show any significant age-related differences in the PVCN. The total number of calretinin immunopositive neurons both in the DCN and PVCN did not show any significant change with increasing age. In conclusion, the total neuronal number in the DCN and PVCN was age-related and region-specific. While the neuronal number in the DCN and PVCN was decreased or unchanged, respectively, the calcium binding protein positive neuronal number showed a graded increase during aging in a region-specific and protein-specific manner.

  16. Control of GABA Release at Mossy Fiber-CA3 Connections in the Developing Hippocampus.

    PubMed

    Safiulina, Victoria F; Caiati, Maddalena D; Sivakumaran, Sudhir; Bisson, Giacomo; Migliore, Michele; Cherubini, Enrico

    2010-01-01

    In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABA(A)-mediated postsynaptic currents (MF-GPSCs) exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABA(B) and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons), generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses.

  17. Control of GABA Release at Mossy Fiber-CA3 Connections in the Developing Hippocampus

    PubMed Central

    Safiulina, Victoria F.; Caiati, Maddalena D.; Sivakumaran, Sudhir; Bisson, Giacomo; Migliore, Michele; Cherubini, Enrico

    2010-01-01

    In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. While in adulthood MF, the axons of dentate gyrus granule cells release onto CA3 principal cells and interneurons glutamate, early in postnatal life they release GABA, which exerts into targeted cells a depolarizing and excitatory action. We found that GABAA-mediated postsynaptic currents (MF-GPSCs) exhibited a very low probability of release, were sensitive to L-AP4, a group III metabotropic glutamate receptor agonist, and revealed short-term frequency-dependent facilitation. Moreover, MF-GPSCs were down regulated by presynaptic GABAB and kainate receptors, activated by spillover of GABA from MF terminals and by glutamate present in the extracellular medium, respectively. Activation of these receptors contributed to the low release probability and in some cases to synapses silencing. By pairing calcium transients, associated with network-driven giant depolarizing potentials or GDPs (a hallmark of developmental networks thought to represent a primordial form of synchrony between neurons), generated by the synergistic action of glutamate and GABA with MF activation increased the probability of GABA release and caused the conversion of silent synapses into conductive ones suggesting that GDPs act as coincident detector signals for enhancing synaptic efficacy. Finally, to compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in adulthood or in postnatal development, respectively, a realistic model was constructed taking into account different biophysical properties of these synapses. PMID:21423487

  18. Shape controlled synthesis of CaMoO 4 thin films and their photoluminescence property

    NASA Astrophysics Data System (ADS)

    Marques, Ana Paula de Azevedo; Longo, Valeria M.; de Melo, Dulce M. A.; Pizani, Paulo S.; Leite, Edson R.; Varela, José Arana; Longo, Elson

    2008-05-01

    CaMoO 4 (CMO) disordered and ordered thin films were prepared by the complex polymerization method (CPM). The films were annealed at different temperatures and time in a conventional resistive furnace (RF) and in a microwave (MW) oven. The microstructure and surface morphology of the structure were monitored by atomic force microscopy (AFM) and high-resolution scanning electron microscopy (HRSEM). Order and disorder were characterized by X-ray diffraction (XRD) and optical reflectance. A strong photoluminescence (PL) emission was observed in the disordered thin films and was attributed to complex cluster vacancies. The experimental results were compared with density functional and Hartree-Fock calculations.

  19. Controlled Proteolysis Activates the Plasma Membrane Ca2+ Pump of Higher Plants (A Comparison with the Effect of Calmodulin in Plasma Membrane from Radish Seedlings).

    PubMed Central

    Rasi-Caldogno, F.; Carnelli, A.; De Michelis, M. I.

    1993-01-01

    The effects of calmodulin and of controlled trypsin treatments on the activity of the Ca2+ pump were investigated in plasma membrane purified from radish (Raphanus sativus L.) seedlings. Treatment of the plasma membrane with ethylenediaminetetra-acetate (EDTA), which removed about two-thirds of the plasma membrane-associated calmodulin, markedly increased the stimulation of the Ca2+ pump by calmodulin. In EDTA-treated plasma membrane, stimulation by calmodulin of the Ca2+ pump activity was maximal at low free Ca2+ (2-5 [mu]M) and decreased with the increase of free Ca2+ concentration. The Ca2+ pump activity was stimulated also by a controlled treatment of the plasma membrane with trypsin: the effect of trypsin treatment depended on the concentration of both trypsin and plasma membrane proteins and on the duration of incubation. Stimulation of the Ca2+ pump activity by trypsin treatment of the plasma membrane was similar to that induced by calmodulin both in extent and in dependence on the free Ca2+ concentration in the assay medium. Moreover, the Ca2+ pump of trypsin-treated plasma membrane was insensitive to further stimulation by calmodulin, suggesting that limited proteolysis preferentially cleaves a regulatory domain of the enzyme that is involved in its activation by calmodulin. PMID:12231945

  20. Age-dependent changes in the functional expression of two nicotinic receptor subtypes in CA1 stratum radiatum interneurons in the rat hippocampus.

    PubMed

    Alkondon, Manickavasagom; Pereira, Edna F R; Albuquerque, Edson X

    2007-10-15

    Protein density measurements and mRNA analysis have provided valuable information on age-dependent changes in the distribution of different nicotinic receptor (nAChR) subtypes in various areas of the rat brain, including the hippocampus. However, very little is known regarding the functional expression of nAChRs in individual neuron types at various ages. Likewise, there is paucity of information regarding the functional and pharmacological profile of nAChRs in the mature rat hippocampus. To address these issues, we used the whole-cell patch-clamp technique to record nicotinic responses from CA1 stratum radiatum (SR) interneurons in hippocampal slices from rat pups (5-19 days old) and adult rats (2-5 months old). As previously observed in the hippocampus of rat pups, CA1 SR interneurons in the hippocampus of adult rats responded to choline (10mM, 12s) with whole-cell currents that decayed to the baseline within the agonist pulse, were sensitive to inhibition by methyllycaconitine (10nM) or alpha-bungarotoxin (50 nM), and were, therefore, mediated by alpha7*(1)[1] nAChRs. Likewise, as previously observed in the hippocampus of young rats, in the adult rat hippocampus excitatory postsynaptic currents (EPSCs) were recorded from SR interneurons in response to a pulse of ACh (0.1 mM, 12s) applied in the presence of the GABA(A) receptor antagonist bicuculline. ACh-triggered EPSCs were inhibited by mecamylamine (1 microM) or choline (1 mM) and were, therefore, likely to have resulted from activation of alpha3beta4beta2* nAChR. The magnitude of alpha7* nAChR-mediated responses increased with the age of the animals. In contrast, the magnitude of alpha3beta4beta2* nAChR-mediated responses was highest at the second postnatal week. The distinct age dependency of functional expression of alpha7* and alpha3beta4beta2* nAChRs strongly suggests that the excitability of CA1 SR interneurons is differentially regulated by the nicotinic cholinergic system in the hippocampus of rat pups

  1. Shape controlled synthesis of CaMoO{sub 4} thin films and their photoluminescence property

    SciTech Connect

    Marques, Ana Paula de Azevedo Longo, Valeria M.; Melo, Dulce M.A. de; Pizani, Paulo S.; Leite, Edson R.; Varela, Jose Arana; Longo, Elson

    2008-05-15

    CaMoO{sub 4} (CMO) disordered and ordered thin films were prepared by the complex polymerization method (CPM). The films were annealed at different temperatures and time in a conventional resistive furnace (RF) and in a microwave (MW) oven. The microstructure and surface morphology of the structure were monitored by atomic force microscopy (AFM) and high-resolution scanning electron microscopy (HRSEM). Order and disorder were characterized by X-ray diffraction (XRD) and optical reflectance. A strong photoluminescence (PL) emission was observed in the disordered thin films and was attributed to complex cluster vacancies. The experimental results were compared with density functional and Hartree-Fock calculations. - Graphical abstract: CaMoO{sub 4} thin films were prepared by the complex polymerization method (CPM). The films were annealed at different temperatures and time in a conventional resistive furnace and in a microwave oven. A strong photoluminescence emission was observed in the disordered thin films and was attributed to complex cluster vacancies. The experimental results were confirmed by high level first principle calculations.

  2. A global evaluation of temperature and carbonate ion control on Mg/Ca ratios of ostracoda genus Krithe

    NASA Astrophysics Data System (ADS)

    Elmore, A. C.; Sosdian, S.; Rosenthal, Y.; Wright, J. D.

    2012-09-01

    Improving estimates of past ocean temperatures is paramount to our understanding of ocean circulation and its role in climate change. Magnesium/calcium (Mg/Ca) ratios of carapaces of the benthic ostracod genus Krithe were determined from new, globally distributed core top samples from the Norwegian Sea, Cape Hatteras shelf, Gulf of Mexico, Sulawesi Margin (Indonesia), New Zealand shelf, Ceara Rise, and the North Atlantic. A linear regression of the Krithe Mg/Ca ratios and bottom water temperature (BWT) reveals a significant correlation for locations where temperature during carapace calcification was above ˜3°C, which can be described by the equation Mg/Ca = (0.972 ± 0.152) * BWT + (7.948 ± 1.103) consistent with previous North Atlantic calibrations. Deviations from the global calibration line below ˜3°C follow the same pattern observed for benthic foraminifera, suggesting that the incorporation of magnesium into ostracodal calcite may be secondarily controlled by changes in carbonate ion concentration. Therefore, we propose a linear regression that describes the relationship between magnesium incorporation, temperature, and carbonate saturation for low temperatures (<3°C) Mg/Ca = (0.972 ± 0.152) * BWT + (0.100 ± 0.030) * Δ[CO32-]) + (4.440 ± 1.103) (1 SE = ± 0.3°C). While the standard error of the calibration is small, it requires an accurate knowledge of past Δ[CO32-] concentration, which necessitates additional proxy data. Applying the calibration to glacial samples from the deep North Atlantic Ocean we show that estimates of bottom water temperatures generated from the new Δ[CO32-]- corrected equations are more consistent with results from oxygen isotopes and pore water studies.

  3. TEMPERATURE AND MOISTURE CONTROL OF SEED AGING IN RYE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The interactions between temperature and moisture that regulate seed aging were measured using rye seeds. Experiments include a number of long term storage studies under conditions of varying relative humidity (RH), water content and temperature. Decrease in germination percentage and radicle leng...

  4. Control of nitrogenase recovery from oxygen inactivation by ammonia in the cyanobacterium Anabaena sp. strain CA (ATCC 33047).

    PubMed Central

    Smith, R L; Van Baalen, C; Tabita, F R

    1990-01-01

    The control of nitrogenase recovery from inactivation by oxygen was studied in Anabaena sp. strain CA (ATCC 33047). Nitrogenase activity (acetylene reduction) in cultures grown in 1% CO2 in air was inhibited by exposure to 1% CO2-99% O2 and allowed to recover in the presence of high oxygen tensions. Cultures exposed to hyperbaric levels of oxygen in the presence of 10 mM NH4NO3 were incapable of regaining nitrogenase activity, whereas control cultures returned to 65 to 80% of their original activity within about 3 h after exposure to high oxygen tension. In contrast to the regulation of heterocyst differentiation and nitrogenase synthesis, recovery from oxygen inactivation in this organism was shown to be under the control of NH4+ rather than NO3-. PMID:2110151

  5. Irisin Controls Growth, Intracellular Ca2+ Signals, and Mitochondrial Thermogenesis in Cardiomyoblasts.

    PubMed

    Xie, Chao; Zhang, Yuan; Tran, Tran D N; Wang, Hai; Li, Shiwu; George, Eva Vertes; Zhuang, Haoyang; Zhang, Peilan; Kandel, Avi; Lai, Yimu; Tang, Dongqi; Reeves, Westley H; Cheng, Henrique; Ding, Yousong; Yang, Li-Jun

    2015-01-01

    Exercise offers short-term and long-term health benefits, including an increased metabolic rate and energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well as increased mitochondrial biogenesis and energy expenditure. Remarkably, irisin is highly expressed in myocardium, but its physiological effects in the heart are unknown. The objective of this work is to investigate irisin's potential multifaceted effects on cardiomyoblasts and myocardium. For this purpose, H9C2 cells were treated with recombinant irisin produced in yeast cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on cell proliferation by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and on gene transcription profiles by qRT-PCR. R-irisin and hr-irisin both inhibited cell proliferation and activated genes related to cardiomyocyte metabolic function and differentiation, including myocardin, follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+ signaling and increase cellular oxygen consumption in H9C2 cells. Our study also suggests the existence of irisin-specific receptor on the membrane of H9C2 cells. In conclusion, irisin in a certain concentration rage increased myocardial cell metabolism, inhibited cell proliferation and promoted cell differentiation. These effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to activate expression of exercise-related genes such as follistatin and myocardin. This work supports the value

  6. Irisin Controls Growth, Intracellular Ca2+ Signals, and Mitochondrial Thermogenesis in Cardiomyoblasts

    PubMed Central

    Xie, Chao; Zhang, Yuan; Tran, Tran D. N.; Wang, Hai; Li, Shiwu; George, Eva Vertes; Zhuang, Haoyang; Zhang, Peilan; Kandel, Avi; Lai, Yimu; Tang, Dongqi; Reeves, Westley H.; Cheng, Henrique; Ding, Yousong; Yang, Li-Jun

    2015-01-01

    Exercise offers short-term and long-term health benefits, including an increased metabolic rate and energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well as increased mitochondrial biogenesis and energy expenditure. Remarkably, irisin is highly expressed in myocardium, but its physiological effects in the heart are unknown. The objective of this work is to investigate irisin’s potential multifaceted effects on cardiomyoblasts and myocardium. For this purpose, H9C2 cells were treated with recombinant irisin produced in yeast cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on cell proliferation by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and on gene transcription profiles by qRT-PCR. R-irisin and hr-irisin both inhibited cell proliferation and activated genes related to cardiomyocyte metabolic function and differentiation, including myocardin, follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+ signaling and increase cellular oxygen consumption in H9C2 cells. Our study also suggests the existence of irisin-specific receptor on the membrane of H9C2 cells. In conclusion, irisin in a certain concentration rage increased myocardial cell metabolism, inhibited cell proliferation and promoted cell differentiation. These effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to activate expression of exercise-related genes such as follistatin and myocardin. This work supports the value

  7. Community Involvement, Perceived Control, and Attitudes toward Aging among Lesbians and Gay Men

    ERIC Educational Resources Information Center

    Hostetler, Andrew J.

    2012-01-01

    A person-environment approach was used to explore the relationship between community involvement and attitudes toward aging among middle-age and older lesbians and gay men. Specifically, this study investigated the relationships between participation in gay community activities, perceived control, and aging-related concerns among two…

  8. Hormonal control of aging in rodents: The somatotropic axis

    PubMed Central

    Brown-Borg, Holly M.

    2015-01-01

    There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

  9. Local geology controlled the feasibility of vitrifying Iron Age buildings

    PubMed Central

    Wadsworth, Fabian B.; Heap, Michael J.; Damby, David E.; Hess, Kai-Uwe; Najorka, Jens; Vasseur, Jérémie; Fahrner, Dominik; Dingwell, Donald B.

    2017-01-01

    During European prehistory, hilltop enclosures made from polydisperse particle-and-block stone walling were exposed to temperatures sufficient to partially melt the constituent stonework, leading to the preservation of glassy walls called ‘vitrified forts’. During vitrification, the granular wall rocks partially melt, sinter viscously and densify, reducing inter-particle porosity. This process is strongly dependent on the solidus temperature, the particle sizes, the temperature-dependence of the viscosity of the evolving liquid phase, as well as the distribution and longevity of heat. Examination of the sintering behaviour of 45 European examples reveals that it is the raw building material that governs the vitrification efficiency. As Iron Age forts were commonly constructed from local stone, we conclude that local geology directly influenced the degree to which buildings were vitrified in the Iron Age. Additionally, we find that vitrification is accompanied by a bulk material strengthening of the aggregates of small sizes, and a partial weakening of larger blocks. We discuss these findings in the context of the debate surrounding the motive of the wall-builders. We conclude that if wall stability by bulk strengthening was the desired effect, then vitrification represents an Iron Age technology that failed to be effective in regions of refractory local geology. PMID:28079121

  10. Local geology controlled the feasibility of vitrifying Iron Age buildings.

    PubMed

    Wadsworth, Fabian B; Heap, Michael J; Damby, David E; Hess, Kai-Uwe; Najorka, Jens; Vasseur, Jérémie; Fahrner, Dominik; Dingwell, Donald B

    2017-01-12

    During European prehistory, hilltop enclosures made from polydisperse particle-and-block stone walling were exposed to temperatures sufficient to partially melt the constituent stonework, leading to the preservation of glassy walls called 'vitrified forts'. During vitrification, the granular wall rocks partially melt, sinter viscously and densify, reducing inter-particle porosity. This process is strongly dependent on the solidus temperature, the particle sizes, the temperature-dependence of the viscosity of the evolving liquid phase, as well as the distribution and longevity of heat. Examination of the sintering behaviour of 45 European examples reveals that it is the raw building material that governs the vitrification efficiency. As Iron Age forts were commonly constructed from local stone, we conclude that local geology directly influenced the degree to which buildings were vitrified in the Iron Age. Additionally, we find that vitrification is accompanied by a bulk material strengthening of the aggregates of small sizes, and a partial weakening of larger blocks. We discuss these findings in the context of the debate surrounding the motive of the wall-builders. We conclude that if wall stability by bulk strengthening was the desired effect, then vitrification represents an Iron Age technology that failed to be effective in regions of refractory local geology.

  11. Local geology controlled the feasibility of vitrifying Iron Age buildings

    USGS Publications Warehouse

    Fabian B Wadsworth,; Michael J Heap,; Damby, David; Kai-Uwe Hess,; Jens Najorka,; Jérémie Vasseur,; Dominik Fahrner,; Donald B Dingwell,

    2017-01-01

    During European prehistory, hilltop enclosures made from polydisperse particle-and-block stone walling were exposed to temperatures sufficient to partially melt the constituent stonework, leading to the preservation of glassy walls called ‘vitrified forts’. During vitrification, the granular wall rocks partially melt, sinter viscously and densify, reducing inter-particle porosity. This process is strongly dependent on the solidus temperature, the particle sizes, the temperature-dependence of the viscosity of the evolving liquid phase, as well as the distribution and longevity of heat. Examination of the sintering behaviour of 45 European examples reveals that it is the raw building material that governs the vitrification efficiency. As Iron Age forts were commonly constructed from local stone, we conclude that local geology directly influenced the degree to which buildings were vitrified in the Iron Age. Additionally, we find that vitrification is accompanied by a bulk material strengthening of the aggregates of small sizes, and a partial weakening of larger blocks. We discuss these findings in the context of the debate surrounding the motive of the wall-builders. We conclude that if wall stability by bulk strengthening was the desired effect, then vitrification represents an Iron Age technology that failed to be effective in regions of refractory local geology.

  12. Multi-Centennial Record of North Atlantic Freshwater Variability since the Little Ice Age Archived in Coralline Algal Ba/Ca

    NASA Astrophysics Data System (ADS)

    Chan, P. T. W.; Halfar, J.; Adey, W.; Zack, T.

    2014-12-01

    Declining Arctic sea-ice cover in recent decades has driven large-scale freshwater transport into the North Atlantic, possibly influencing the strength of the Meridional Overturning Circulation and even global climate. However, due to the lack of long-term oceanographic observations, little is known about the natural freshwater variability of the Northwestern Atlantic. Crustose coralline algae Clathromorphum compactum are extremely long-lived shallow marine calcareous plants that are abundant along the subarctic eastern Canadian coastline. They are particularly well-suited as recorders of paleoclimate signals due to the formation of annual growth increments, allowing for the precise calendar dating and geochemical sampling of hard tissue. Here, we provide the first annually-resolved multi-centennial record of coralline algal Ba/Ca from Labrador, Canada, as a proxy for North Atlantic freshwater variability extending well into the Little Ice Age (LIA) (1665 AD). Barium-to-calcium ratios (Ba/Ca) from coralline algae have previously been used as an indicator of freshwater runoff. This is because barium-rich clay sediments are transported by terrestrial runoff into coastal waters, and barium is released from the clay minerals upon encountering more alkaline elements present in seawater. We observe higher algal barium concentrations during the LIA, followed by a steady decline to recent times. In addition, coralline algal Ba/Ca shows significant positive relationships to Hudson Strait runoff, as well as Canadian Arctic and North Atlantic sea-ice extent. This suggests that more riverine Ba is transported from the Hudson Strait into the Labrador Sea during periods of increased sea-ice cover. Multiyear sea-ice can block incoming solar radiation thereby diminishing the effects of nutrient scavenging by phytoplankton, resulting in a more conservative transport of Ba into northern Labrador. However as sea-ice continues to thin, more sunlight is able to penetrate through the

  13. High-fidelity spatial addressing of 43Ca+ qubits using near-field microwave control

    NASA Astrophysics Data System (ADS)

    Prado Lopes Aude Craik, Diana; Linke, Norbert; Allcock, David; Sepiol, Martin; Harty, Thomas; Ballance, Christopher; Stacey, Derek; Steane, Andrew; Lucas, David

    2016-05-01

    Individual addressing of qubits is essential for scalable quantum computation. Spatial addressing allows unlimited numbers of qubits to share the same frequency, whilst enabling arbitrary parallel operations. We present the latest experimental results obtained using a two-zone microfabricated surface trap designed to perform spatial, near-field microwave addressing of long-lived 43Ca+ ``atomic clock'' qubits held in separate trap zones (each of which feature four integrated microwave electrodes). Microwave near fields generated by multi-electrode chip ion traps are often difficult to faithfully simulate and a simple method of characterizing and testing trap chips before placement under ultra-high vacuum would significantly speed up trap design optimization. We describe a printed circuit board antenna for use in mapping microwave near-fields generated by ion-trap electrodes. The antenna is designed to measure fields down to 100 μ m away from trap electrodes and to be impedance matched at a desired spot frequency for an improved signal to noise ratio in field measurements. This work is supported by the US Army Research Office, EPSRC (UK) and the UK National Quantum Technologies Programme.

  14. Aging and Concurrent Task Performance: Cognitive Demand and Motor Control

    ERIC Educational Resources Information Center

    Albinet, Cedric; Tomporowski, Phillip D.; Beasman, Kathryn

    2006-01-01

    A motor task that requires fine control of upper limb movements and a cognitive task that requires executive processing--first performing them separately and then concurrently--was performed by 18 young and 18 older adults. The motor task required participants to tap alternatively on two targets, the sizes of which varied systematically. The…

  15. Learned Helplessness: A Theory for the Age of Personal Control.

    ERIC Educational Resources Information Center

    Peterson, Christopher; And Others

    Experiences with uncontrollable events may lead to the expectation that future events will elude control, resulting in disruptions in motivation, emotion, and learning. This text explores this phenomenon, termed learned helplessness, tracking it from its discovery to its entrenchment in the psychological canon. The volume summarizes and integrates…

  16. Global Research in an Age of Export Controls

    ERIC Educational Resources Information Center

    Monastersky, Richard

    2008-01-01

    When a jury convicted a Tennessee professor this month of illegally exporting information to foreign countries via his graduate students and a trip to China, it sent a message to colleges that they need to scrupulously monitor their faculty members' research and their compliance with the often confusing universe of export-control regulations. In…

  17. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  18. Revisiting carbonate chemistry controls on planktic foraminifera Mg / Ca: implications for sea surface temperature and hydrology shifts over the Paleocene-Eocene Thermal Maximum and Eocene-Oligocene transition

    NASA Astrophysics Data System (ADS)

    Evans, David; Wade, Bridget S.; Henehan, Michael; Erez, Jonathan; Müller, Wolfgang

    2016-04-01

    Much of our knowledge of past ocean temperatures comes from the foraminifera Mg / Ca palaeothermometer. Several nonthermal controls on foraminifera Mg incorporation have been identified, of which vital effects, salinity, and secular variation in seawater Mg / Ca are the most commonly considered. Ocean carbonate chemistry is also known to influence Mg / Ca, yet this is rarely examined as a source of uncertainty, either because (1) precise pH and [CO32-] reconstructions are sparse or (2) it is not clear from existing culture studies how a correction should be applied. We present new culture data of the relationship between carbonate chemistry and Mg / Ca for the surface-dwelling planktic species Globigerinoides ruber and compare our results to data compiled from existing studies. We find a coherent relationship between Mg / Ca and the carbonate system and argue that pH rather than [CO32-] is likely to be the dominant control. Applying these new calibrations to data sets for the Paleocene-Eocene Thermal Maximum (PETM) and Eocene-Oligocene transition (EOT) enables us to produce a more accurate picture of surface hydrology change for the former and a reassessment of the amount of subtropical precursor cooling for the latter. We show that pH-adjusted Mg / Ca and δ18O data sets for the PETM are within error of no salinity change and that the amount of precursor cooling over the EOT has been previously underestimated by ˜ 2 °C based on Mg / Ca. Finally, we present new laser-ablation data of EOT-age Turborotalia ampliapertura from St. Stephens Quarry (Alabama), for which a solution inductively coupled plasma mass spectrometry (ICPMS) Mg / Ca record is available (Wade et al., 2012). We show that the two data sets are in excellent agreement, demonstrating that fossil solution and laser-ablation data may be directly comparable. Together with an advancing understanding of the effect of Mg / Casw, the coherent picture of the relationship between Mg / Ca and pH that we outline

  19. Infection control in the new age of genomic epidemiology.

    PubMed

    Tang, Patrick; Croxen, Matthew A; Hasan, Mohammad R; Hsiao, William W L; Hoang, Linda M

    2017-02-01

    With the growing importance of infectious diseases in health care and communicable disease outbreaks garnering increasing attention, new technologies are playing a greater role in helping us prevent health care-associated infections and provide optimal public health. The microbiology laboratory has always played a large role in infection control by providing tools to identify, characterize, and track pathogens. Recently, advances in DNA sequencing technology have ushered in a new era of genomic epidemiology, where traditional molecular diagnostics and genotyping methods are being enhanced and even replaced by genomics-based methods to aid epidemiologic investigations of communicable diseases. The ability to analyze and compare entire pathogen genomes has allowed for unprecedented resolution into how and why infectious diseases spread. As these genomics-based methods continue to improve in speed, cost, and accuracy, they will be increasingly used to inform and guide infection control and public health practices.

  20. Optimal Control of Markov Processes with Age-Dependent Transition Rates

    SciTech Connect

    Ghosh, Mrinal K. Saha, Subhamay

    2012-10-15

    We study optimal control of Markov processes with age-dependent transition rates. The control policy is chosen continuously over time based on the state of the process and its age. We study infinite horizon discounted cost and infinite horizon average cost problems. Our approach is via the construction of an equivalent semi-Markov decision process. We characterise the value function and optimal controls for both discounted and average cost cases.

  1. Ca cycling and isotopic fluxes in forested ecosystems in Hawaii

    NASA Astrophysics Data System (ADS)

    Wiegand, B. A.; Chadwick, O. A.; Vitousek, P. M.; Wooden, J. L.

    2005-06-01

    Biogeochemical processes fractionate Ca isotopes in plants and soils along a 4 million year developmental sequence in the Hawaiian Islands. We observed that plants preferentially take up 40Ca relative to 44Ca, and that biological fractionation and changes in the relative contributions from volcanic and marine sources produce a significant increase in 44Ca in soil exchangeable pools. Our results imply moderate fluxes enriched in 44Ca from strongly nutrient-depleted old soils, in contrast with high 40Ca fluxes in young and little weathered environments. In addition, biological fractionation controls divergent geochemical pathways of Ca and Sr in the plant-soil system. While Ca depletes progressively with increasing soil age, Sr/Ca ratios increase systematically. Sr isotope ratios provide a valuable tracer for provenance studies of alkaline earth elements in forested ecosystems, but its usefulness is limited when deciphering biogeochemical processes involved in the terrestrial Ca cycle. Ca isotopes in combination with Sr/Ca ratios reveal more complex processes involved in the biogeochemistry of Ca and Sr.

  2. Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

    PubMed Central

    Evenepoel, Pieter; Curzi, Mario P.; González, Maria Teresa; Husserl, Fred E.; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

    2009-01-01

    Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg2/dl2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. PMID:19696213

  3. The Lake Forest Tuff Ring, Lake Tahoe, CA: Age and Geochemistry of a Post-arc Phreatomagmatic Eruption

    NASA Astrophysics Data System (ADS)

    Cousens, B. L.; Henry, C. D.; Pauly, B. D.

    2007-12-01

    The Lake Tahoe region of the northern Sierra Nevada consists of Mesozoic plutonic rocks blanketed by Mio- Pliocene arc volcanic rocks and locally overlain by < 2.5 Ma post-arc lavas. Several volcanic features along the Lake Tahoe shoreline indicate that magmas commonly erupted into shallow regions of the lake during the last 2.5 Ma, including the Eagle Rock vent (Kortemeier and Schweickert 2007), Tahoe City pillow lavas and palagonite layers, and the Lake Forest tuff ring (Sylvester et al., 2007). Here we report on the age and composition of the rocks at Lake Forest, aiming to identify the source of the volcanic rocks compared to arc and post-arc lavas in the area. The low-relief Lake Forest tuff ring, located on the lakeshore west of Dollar Point, consists of radially outward-dipping layers composed primarily of loosely-cemented angular, microvesicular lava fragments with minor basaltic bombs and a scoria pile at the east end of the exposed ring. Most fragments are poorly phyric, and two samples are andesites similar to post-arc lavas sampled at higher elevations. The bombs are vesicular, poorly olivine/plagioclase-phyric basaltic andesites with chilled margins and glassy matrices. Scoria in the scoria pile, which we tentatively interpret as a slump, are similar texturally to the bombs but are more silica-rich. Chemically, the fragments, bombs and scoria are more primitive (higher Mg number) than local post-arc and arc lavas, and have trace element ratios and normalized incompatible element patterns similar to, but not identical to, local post-arc lava flows. Thus the Lake Forest tuff ring was the product of a shoreline eruptive event and did not form from lavas flowing downslope into the water. The fragments, bombs and scoria each have different radiogenic isotopic compositions and incompatible element ratios, indicating that primary magma compositions varied during the eruption(s) that produced the tuff ring. Our ongoing geochronological analyses will help

  4. Control of magnetic, nonmagnetic, and superconducting states in annealed Ca(Fe1–xCox)₂As₂

    DOE PAGES

    Ran, S.; Bud'ko, S. L.; Straszheim, W. E.; ...

    2012-06-22

    We have grown single-crystal samples of Co substituted CaFe₂As₂ using an FeAs flux and systematically studied the effects of annealing/quenching temperature on the physical properties of these samples. Whereas the as-grown samples (quenched from 960°C) all enter the collapsed tetragonal phase upon cooling, annealing/quenching temperatures between 350 and 800°C can be used to tune the system to low-temperature antiferromagnetic/orthorhomic or superconducting states as well. The progression of the transition temperature versus annealing/quenching temperature (T-Tanneal) phase diagrams with increasing Co concentration shows that, by substituting Co, the antiferromagnetic/orthorhombic and the collapsed tetragonal phase lines are separated and bulk superconductivity is revealed.more » We established a 3D phase diagram with Co concentration and annealing/quenching temperature as two independent control parameters. At ambient pressure, for modest x and Tanneal values, the Ca(Fe₁₋xCox)₂As₂ system offers ready access to the salient low-temperature states associated with Fe-based superconductors: antiferromagnetic/orthorhombic, superconducting, and nonmagnetic/collapsed tetragonal.« less

  5. Aging commuter aeroplanes: Fatigue evaluation and control methods

    NASA Technical Reports Server (NTRS)

    Emmerson, A. J.

    1992-01-01

    The loss of reliability in aircraft is caused by two broad classes of problems. There are those problems which are self evident and hazardous rather than catastrophic. These are the problem areas where characteristically there have been multiple overhauls, repairs, and replacements, and where aging really means the results of repair ineffectiveness that accumulates. The other class of the problem is the insidious and potentially catastrophic class. It includes the progressive deterioration of items that are not maintained, and often cannot be maintained because the deterioration cannot be seen. It includes the loss of physical properties in adhesives and other organic compounds, corrosion, and the response of repeated loads. Dealt with here is a currently unnecessarily troublesome aspect of that response. Although we must remain concerned about those types of aircraft which have been certified under a design standard or operational rule which embodies the elementary fail-safe concept and which have not been subjected to a subsequent structural audit, the focus here is on types of aircraft for which fatigue and damage tolerance evaluation was not required as a condition of certification.

  6. A controlled study of suicide in middle-aged and older people: personality traits, age, and psychiatric disorders.

    PubMed

    Draper, Brian; Kõlves, Kairi; De Leo, Diego; Snowdon, John

    2014-04-01

    Personality traits were examined using the NEO Five-Factor Inventory-Revised in an Australian psychological autopsy study involving 259 suicide deaths and 181 sudden death controls aged 35 years and over. Interviews included the Structured Clinical Interview for DSM-IV to determine the presence of psychiatric disorder. Personality traits of suicide deaths differed significantly from those of controls, scoring higher in the Neuroticism and Openness to Experience domains and lower on the Agreeableness and Extraversion domains. These findings varied with the presence of psychiatric disorder and by age. High Neuroticism scores were the most consistent finding in people who died by suicide, although these scores decreased in older suicides.

  7. Electronic control of Ca2+ signalling in neuronal cells using an organic electronic ion pump.

    PubMed

    Isaksson, Joakim; Kjäll, Peter; Nilsson, David; Robinson, Nathaniel D; Berggren, Magnus; Richter-Dahlfors, Agneta

    2007-09-01

    Cells and tissues use finely regulated ion fluxes for their intra- and intercellular communication. Technologies providing spatial and temporal control for studies of such fluxes are however, limited. We have developed an electrophoretic ion pump made of poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulphonate) (PEDOT:PSS) to mediate electronic control of the ion homeostasis in neurons. Ion delivery from a source reservoir to a receiving electrolyte via a PEDOT:PSS thin-film channel was achieved by electronic addressing. Ions are delivered in high quantities at an associated on/off ratio exceeding 300. This induces physiological signalling events that can be recorded at the single-cell level. Furthermore, miniaturization of the device to a 50-microm-wide channel allows for stimulation of individual cells. As this technology platform allows for electronic control of ion signalling in individual cells with proper spatial and temporal resolution, it will be useful in further studies of communication in biological systems.

  8. Executive Control in a Modified Antisaccade Task: Effects of Aging and Bilingualism

    ERIC Educational Resources Information Center

    Bialystok, Ellen; Craik, Fergus I. M.; Ryan, Jennifer

    2006-01-01

    Two studies are reported that assess differences associated with aging and bilingualism in an executive control task. Previous work has suggested that bilinguals have an advantage over monolinguals in nonlinguistic tasks involving executive control; the major purpose of the present article is to ascertain which aspects of control are sensitive…

  9. Does Verbal Labeling Influence Age Differences in Proactive and Reactive Cognitive Control?

    ERIC Educational Resources Information Center

    Kray, Jutta; Schmitt, Hannah; Heintz, Sonja; Blaye, Agnès

    2015-01-01

    The main goal of this study was to examine whether different types of verbal labeling can influence age-related changes in the dynamic control of behavior by inducing either a proactive or reactive mode of control. Proactive control is characterized by a strong engagement in maintaining task-relevant information to be optimally prepared while…

  10. Waveform generation is controlled by phosphorylation and swimming direction is controlled by Ca2+ in sperm from the mosquito Culex quinquefasciatus.

    PubMed

    Thaler, Catherine D; Miyata, Haruhiko; Haimo, Leah T; Cardullo, Richard A

    2013-12-01

    Most animal sperm are quiescent in the male reproductive tract and become activated after mixing with accessory secretions from the male and/or female reproductive tract. Sperm from the mosquito Culex quinquefasciatus initiate flagellar motility after mixing with male accessory gland components, and the sperm flagellum displays three distinct motility patterns over time: a low amplitude, a long wavelength form (Wave A), a double waveform consisting of two superimposed waveforms over the length of the flagellum (Wave B), and finally, a single helical waveform that propels the sperm at high velocity (Wave C). This flagellar behavior is replicated by treating quiescent sperm with trypsin. When exposed to either broad spectrum or tyrosine kinase inhibitors, sperm activated by accessory gland secretions exhibited motility through Wave B but were unable to progress to Wave C. The MEK1/2 inhibitor UO126 and the ERK1/2 inhibitor FR180204 each blocked the transition from Wave B to Wave C, indicating a role for MAPK activity in the control of waveform and, accordingly, progressive movement. Furthermore, a MAPK substrate antibody stained the flagellum of activated sperm. In the absence of extracellular Ca(2+), a small fraction of sperm swam backwards, whereas most could not be activated by either accessory glands or trypsin and were immotile. However, the phosphatase inhibitor okadaic acid in the absence of extracellular Ca(2+) induced all sperm to swim backwards with a flagellar waveform similar to Wave A. These results indicate that flagellar waveform generation and direction of motility are controlled by protein phosphorylation and Ca(2+) levels, respectively.

  11. Demonstration of a Groundwater Age Determination Using 39Ar in Support of a Multi-Tracer Groundwater Analysis of Wells in Fresno, CA

    NASA Astrophysics Data System (ADS)

    Wurstner White, S.; Brandenberger, J. M.; Kulongoski, J. T.; Aalseth, C.; Williams, R. M.; Mace, E. K.; Humble, P.; Seifert, A.; Cloutier, J. M.

    2015-12-01

    Argon-39 has a half-life of 269 years, making it an ideal tracer for groundwater dating in the age range of 50-1000 years. In September 2014, two production wells within the San Joaquin Valley Aquifer System, located in Fresno, CA were sampled and analyzed for a suite of inorganic and organic contaminants and isotopic constituents. The radiotracers 3H (< 50 years) and 14C (> 1000 years) are routinely measured as part of the U. S. Geological Survey (USGS) National Water Quality Assessment (NAWQA) Enhanced Trends Network project. Adding 39Ar to the suite of tracers provides age data in the intermediate range to refine the groundwater age distribution of mixed waters and establishes groundwater residence times and flow rates. Characterizing the groundwater recharge and flow rate is of particular interest at these wells for determining the sources and movement of contaminants in groundwater, particularly nitrate, DBCP, and perchlorate. The sampled wells were pumped and purged. The sample collection for the 39Ar measurements required extracting the dissolved gases from 3000-5000 L of groundwater using a membrane degasification system with a maximum flow rate of 50 gpm (11.4 m^3/hr). The membranes are plastic hollow fibers that are hydrophobic. The gas was collected in duplicate large aluminum coated plastic sample bags. The gas was purified and then counted via direct beta counting using ultra-low background proportional counters loaded with a mixture of geologic Ar and methane to enhance the sensitivity for Ar measurements. The activity of 39Ar is 1.01 Bq/kg Ar, corresponding to an abundance of 0.808 ppq. The estimated absolute ages of the samples from the two groundwater wells were 23.3 and 27.0 percent of modern Ar. The comparison of the groundwater residence times determined using the suite of radiotracers (3H, 39Ar, and 14C) highlighted the value of knowing the intermediate age of groundwater when determining contaminant fate and transport pathways.

  12. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  13. Revisiting carbonate chemistry controls on planktic foraminifera Mg / Ca: implications for sea surface temperature and hydrology shifts over the Paleocene-Eocene Thermal Maximum and Eocene-Oligocene Transition

    NASA Astrophysics Data System (ADS)

    Evans, D.; Wade, B. S.; Henehan, M.; Erez, J.; Müller, W.

    2015-07-01

    Much of our knowledge of past ocean temperatures comes from the foraminifera Mg / Ca palaeothermometer. Several non-thermal controls on foraminifera Mg incorporation have been identified, of which vital-effects, salinity and secular variation in seawater Mg / Ca are the most commonly considered. Ocean carbonate chemistry is also known to influence Mg / Ca, yet this is rarely considered as a source of uncertainty either because (1) precise pH and [CO32-] reconstructions are sparse, or (2) it is not clear from existing culture studies how a correction should be applied. We present new culture data of the relationship between carbonate chemistry for the surface-dwelling planktic species Globigerinoides ruber, and compare our results to data compiled from existing studies. We find a coherent relationship between Mg / Ca and the carbonate system and argue that pH rather than [CO32-] is likely to be the dominant control. Applying these new calibrations to datasets for the Paleocene-Eocene Thermal Maximum (PETM) and Eocene-Oligocene Transition (EOT) enable us to produce a more accurate picture of surface hydrology change for the former, and a reassessment of the amount of subtropical precursor cooling for the latter. We show that properly corrected Mg / Ca and δ18O datasets for the PETM imply no salinity change, and that the amount of precursor cooling over the EOT has been previously underestimated by ∼ 2 °C based on Mg / Ca. Finally, we present new laser-ablation data of EOT-age Turborotalia ampliapertura from St Stephens Quarry (Alabama), for which a solution ICPMS Mg / Ca record is available (Wade et al., 2012). We show that the two datasets are in excellent agreement, demonstrating that fossil solution and laser-ablation data may be directly comparable. Together with an advancing understanding of the effect of Mg / Casw, the coherent picture of the relationship between Mg / Ca and pH that we outline here represents a step towards producing accurate and

  14. High-fidelity spatial and polarization addressing of +43Ca qubits using near-field microwave control

    NASA Astrophysics Data System (ADS)

    Aude Craik, D. P. L.; Linke, N. M.; Sepiol, M. A.; Harty, T. P.; Goodwin, J. F.; Ballance, C. J.; Stacey, D. N.; Steane, A. M.; Lucas, D. M.; Allcock, D. T. C.

    2017-02-01

    Individual addressing of qubits is essential for scalable quantum computation. Spatial addressing allows unlimited numbers of qubits to share the same frequency, while enabling arbitrary parallel operations. We demonstrate addressing of long-lived +43Ca "atomic clock" qubits held in separate zones (960 μ m apart) of a microfabricated surface trap with integrated microwave electrodes. Such zones could form part of a "quantum charge-coupled device" architecture for a large-scale quantum information processor. By coherently canceling the microwave field in one zone we measure a ratio of Rabi frequencies between addressed and nonaddressed qubits of up to 1400, from which we calculate a spin-flip probability on the qubit transition of the nonaddressed ion of 1.3 ×10-6 . Off-resonant excitation then becomes the dominant error process, at around 5 ×10-3 . It can be prevented either by working at higher magnetic field, or by polarization control of the microwave field. We implement polarization control with error 2 ×10-5 , which would suffice to suppress off-resonant excitation to the ˜10-9 level if combined with spatial addressing. Such polarization control could also enable fast microwave operations.

  15. Age Differences in Life Satisfaction, Locus of Control, and Self-Concept.

    ERIC Educational Resources Information Center

    Nehrke, Milton F.; And Others

    1980-01-01

    Veterans Administration domiciliary residents in three age groups over age 50 completed measures of life satisfaction, locus of control and self-concept. Older veterans had resolved ego integrity v despair crisis more adequately than younger veterans. An institutional environment that facilitates self-esteem and satisfaction of elderly residents…

  16. Age, education, and the gender gap in the sense of control.

    PubMed

    Slagsvold, Britt; Sørensen, Annemette

    2008-01-01

    High sense of control is related to benefits in many aspects of life, and education is known to be strongly related to sense of control. In this article we explore why women tend to feel a lower sense of control than men, and why the sense of control tends to be lower among the elderly than among younger people. In particular we explore the role played by education in explaining age- and gender differences in sense of control. The analysis is based on data from the first wave of the Norwegian NorLAG study, with a representative sample of adults aged 40-79 in 30 municipalities. We find that education accounts for some of the age and gender differences in sense of control, but the mediating effects of education are rather modest. We find an increasing gender gap in sense of control with age, and this increasing gap is completely explained by differences in education. Gender differences in sense of control is explained completely by four factors, which are related to resources and power; physical health, education, living with a partner, and leadership experience. Age differences in sense of control are only partially explained. Education, physical health and employment status cuts the age effect on sense of control to half. The effect of education on sense of control is partly mediated through what we suggest are tangible benefits of education, namely health, employment, and leadership experience. Education also influences individuals through socialization mechanisms. We view agentive orientation as a psychological benefit of education, and measure this characteristic with Bem's (1981) sex-role scale on masculinity. Agentive orientation completely explains the remaining effect of education on sense of control.

  17. Controlled crystallization of CaCO(3) on hyperbranched polyglycerol adsorbed to self-assembled monolayers.

    PubMed

    Balz, Mathias; Barriau, Emilie; Istratov, Vladislav; Frey, Holger; Tremel, Wolfgang

    2005-04-26

    The formation of biominerals by living organisms is governed by the cooperation of soluble and insoluble macromolecules with peculiar interfacial properties. To date, most of the studies on mineralization processes involve model systems that only account for the existence of one organic matrix and thus disregard the interaction between the soluble and insoluble organic components that is crucial for a better understanding of the processes taking place at the inorganic-organic interface. We have set up a model system composed of a matrix surface, namely, a self-assembled monolayer (SAM), and a soluble component, hyperbranched polyglycerol. The model mineral calcium carbonate displays diverse polymorphism. It could be demonstrated that the phase selection of calcium carbonate is controlled by the cooperative interaction of the SAM and hyperbranched polyglycerol of different molecular weights (M(n) = 500-6000 g/mol) adsorbed to the SAM. Our studies showed that hyperbranched polyglycerol is adsorbed to polar as well as to nonpolar SAMs. This effect can be related to its highly flexible structure and its amphiphilic character. The adsorption of hyperbranched polyglycerol to the SAMs with different surface polarities resulted in the formation of aragonite for alkyl-terminated SAMs and no phase selection for carboxylate-terminated SAMs.

  18. Assessing the solubility controls on vanadium in groundwater, northeastern San Joaquin Valley, CA

    USGS Publications Warehouse

    Wright, Michael T.; Stollenwerk, Kenneth G.; Belitz, Kenneth

    2014-01-01

    The solubility controls on vanadium (V) in groundwater were studied due to concerns over possible harmful health effects of ingesting V in drinking water. Vanadium concentrations in the northeastern San Joaquin Valley ranged from 25 μg/L) and lowest in samples collected from anoxic groundwater (70% 2VO4−. Adsorption/desorption reactions with mineral surfaces and associated oxide coatings were indicated as the primary solubility control of V5+ oxyanions in groundwater. Environmental data showed that V concentrations in oxic groundwater generally increased with increasing groundwater pH. However, data from adsorption isotherm experiments indicated that small variations in pH (7.4–8.2) were not likely as an important a factor as the inherent adsorption capacity of oxide assemblages coating the surface of mineral grains. In suboxic groundwater, accurate SM modeling was difficult since Eh measurements of source water were not measured in this study. Vanadium concentrations in suboxic groundwater decreased with increasing pH indicating that V may exist as an oxycationic species [e.g. V(OH)3+]. Vanadium may complex with dissolved inorganic and organic ligands under suboxic conditions, which could alter the adsorption behavior of V in groundwater. Speciation modeling did not predict the existence of V-inorganic ligand complexes and organic ligands were not collected as part of this study. More work is needed to determine processes governing V solubility under suboxic groundwater conditions. Under anoxic groundwater conditions, SM predicts that aqueous V exists as the uncharged V(OH)3 molecule. However, exceedingly low V concentrations show that V is sparingly soluble in anoxic conditions. Results indicated that V may be precipitating as V3+- or mixed V3+/Fe3+-oxides in anoxic groundwater, which is consistent with results of a previous study. The fact that V appears insoluble in anoxic (Fe reducing) redox conditions indicates that the behavior of V is different than

  19. Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

    PubMed

    Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-08-01

    Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window.

  20. Origin of low temperature memory and aging effects in spin glass like La0.7Ca0.3MnO3 nanomanganite

    NASA Astrophysics Data System (ADS)

    Karmakar, Shilpi; Chaudhuri, B. K.; Chan, C. L.; Yang, H. D.

    2010-12-01

    Interesting low temperature memory phenomena have been observed from equilibrium and out of equilibrium magnetic measurements on the La0.7Ca0.3MnO3 nanomanganite system. The observed phenomenon were screened for atomic spin glass (SG), super spin glass (SSG), cluster glass (CG), and superparamagnetic behavior. The results evidences of SG like behavior at low temperature (<40 K) in this manganite system consisting of ferromagnetic nanoparticles. In the temperature region between 40 K and the ferromagnetic Curie point TC˜217 K, a ferromagnetic CG state develops with a relatively weaker interparticle interaction than that of the low temperature SG phase. The dynamic magnetization shows aging, chaos and memory effects. Moreover, we have also noticed asymmetric response in magnetic relaxation in response to positive and negative temperature cycling protocols. The origin and nature of the low-temperature SG state in this system is discussed within the framework of hierarchical organization of metastable states. The results show existence of various time and length scales in the system, which can be explained by considering the nanoparticles with grain boundary spin disorder and the presence of noncompact ferromagnetic clusters.

  1. Effect of age and sex on maturation of sensory systems and balance control.

    PubMed

    Steindl, R; Kunz, K; Schrott-Fischer, A; Scholtz, A W

    2006-06-01

    Maintenance of postural balance requires an active sensorimotor control system. Current data are limited and sometimes conflicting regarding the influence of the proprioceptive, visual, and vestibular afferent systems on posture control in children. This study investigated the development of sensory organization according to each sensory component in relation to age and sex. A total of 140 children (70 males, 70 females; mean age 10y [SD 4y]; age range 3y 5mo-16y 2mo) and 20 adults (10 males, 10 females; mean age 30y 6mo [SD 8y 4mo]; age range 17y 2mo-49y 1mo) were examined using the Sensory Organization Test. Participants were tested in three visual conditions (eyes open, blindfolded, and sway-referenced visual enclosure) while standing on either a fixed or a sway-referenced force platform. Mean equilibrium scores for the six balance conditions showed rapid increases and maturation ceiling levels for age-related development of the sensorimotor control system. Proprioceptive function seemed to mature at 3 to 4 years of age. Visual and vestibular afferent systems reached adult level at 15 to 16 years of age, revealing differences between young males and females. Characterizing balance impairments can contribute to the diagnostic evaluation of neuromotor disorders.

  2. Idiosyncratic responding during movie-watching predicted by age differences in attentional control.

    PubMed

    Campbell, Karen L; Shafto, Meredith A; Wright, Paul; Tsvetanov, Kamen A; Geerligs, Linda; Cusack, Rhodri; Tyler, Lorraine K

    2015-11-01

    Much is known about how age affects the brain during tightly controlled, though largely contrived, experiments, but do these effects extrapolate to everyday life? Naturalistic stimuli, such as movies, closely mimic the real world and provide a window onto the brain's ability to respond in a timely and measured fashion to complex, everyday events. Young adults respond to these stimuli in a highly synchronized fashion, but it remains to be seen how age affects neural responsiveness during naturalistic viewing. To this end, we scanned a large (N = 218), population-based sample from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) during movie-watching. Intersubject synchronization declined with age, such that older adults' response to the movie was more idiosyncratic. This decreased synchrony related to cognitive measures sensitive to attentional control. Our findings suggest that neural responsivity changes with age, which likely has important implications for real-world event comprehension and memory.

  3. Idiosyncratic responding during movie-watching predicted by age differences in attentional control

    PubMed Central

    Campbell, Karen L.; Shafto, Meredith A.; Wright, Paul; Tsvetanov, Kamen A.; Geerligs, Linda; Cusack, Rhodri; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Henson, Rik; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Price, Darren; Taylor, Jason; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Dixon, Marie; Barnes, Dan; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Tyler, Lorraine K.

    2015-01-01

    Much is known about how age affects the brain during tightly controlled, though largely contrived, experiments, but do these effects extrapolate to everyday life? Naturalistic stimuli, such as movies, closely mimic the real world and provide a window onto the brain's ability to respond in a timely and measured fashion to complex, everyday events. Young adults respond to these stimuli in a highly synchronized fashion, but it remains to be seen how age affects neural responsiveness during naturalistic viewing. To this end, we scanned a large (N = 218), population-based sample from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) during movie-watching. Intersubject synchronization declined with age, such that older adults' response to the movie was more idiosyncratic. This decreased synchrony related to cognitive measures sensitive to attentional control. Our findings suggest that neural responsivity changes with age, which likely has important implications for real-world event comprehension and memory. PMID:26359527

  4. Peripheral mechanisms of thermoregulatory control of skin blood flow in aged humans

    PubMed Central

    Kenney, W. Larry

    2010-01-01

    Human skin blood flow is controlled via dual innervation from the sympathetic nervous system. Reflex cutaneous vasoconstriction and vasodilation are both impaired with primary aging, rendering the aged more vulnerable to hypothermia and cardiovascular complications from heat-related illness. Age-related alterations in the thermoregulatory control of skin blood flow occur at multiple points along the efferent arm of the reflex, including 1) diminished sympathetic outflow, 2) altered presynaptic neurotransmitter synthesis, 3) reduced vascular responsiveness, and 4) impairments in downstream (endothelial and vascular smooth muscle) second-messenger signaling. This mechanistic review highlights some of the recent findings in the area of aging and the thermoregulatory control of skin blood flow. PMID:20413421

  5. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    PubMed

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    the basal but not the apical dendrites of CA1 pyramidal neurons from rats chronically treated with caffeine, in comparison with their age- and littermate-matched controls. Altogether, the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging, and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain.

  6. CONTROLS OF EXTENSION ON MIOCENE ARC MAGMATISM IN THE CENTRAL SIERRA NEVADA (CA)

    NASA Astrophysics Data System (ADS)

    Busby, C.; Putirka, K. D.; Hagan, J. C.; Koerner, A.; Melosh, B. L.

    2009-12-01

    Ancestral Cascades arc volcanism in the central Sierra Nevada occurred in three Miocene pulses, at about 16-13 Ma, 11-9 Ma, and 7-6 Ma. Our work in the Carson Pass to Sonora Pass areas shows that range-front faults clearly controlled the positions of volcanic centers during the second and third magmatic pulses. Voluminous high-K volcanic rocks of the 11-9 Ma Stanislaus Group record the onset of transtensional calving of the Sierra Nevada microplate off the western edge of the Nevadaplano. The Little Walker Caldera or Center formed at a releasing stepover in range-front faults at Sonora Pass, and erupted widesperad trachydacite ignimbrite in three distinct phases (Eureka Valley Tuff). Interstratified with these ignimbrites are widespread trachyandesite (latite), basaltic-trachyandesite (shoshonite) and trachydacite lava flows, in sections up to 500 m thick, whose vents have never been discovered (e.g. Table Mountain Latite). Although some of these lavas may have erupted from vents buried beneath the Little Walker Center, we recognize intrusions and vent facies for them along Sierran range-front and range-crest faults that emanate northwestward from the Little Walker Center between Sonora Pass and Ebbetts Pass. The biggest volcanic centers of the third magmatic pulse also include silicic volcanic rocks, and are sited along normal faults; they include the Markleeville Center southeast of Carson Pass, and the Ebbetts Pass Center. The 8 km diameter Markleeville Center consists of andesites and dacites that formed within the Hope Valley graben. The next fault to the east of the Hope Valley graben, which we name the Grover Hot Springs fault, extends southward to Ebbetts Pass, where it forms an overlapping right (releasing) step with the Noble Canyon fault to the west. The Ebbetts Pass Center lies above this releasing step along the Sierran crest. The base of the Ebbetts Pass Center is 10 km in diameter and is formed of radially-dipping basaltic andesite lava flows and

  7. Analysis of postural control and muscular performance in young and elderly women in different age groups

    PubMed Central

    Gomes, Matheus M.; Reis, Júlia G.; Carvalho, Regiane L.; Tanaka, Erika H.; Hyppolito, Miguel A.; Abreu, Daniela C. C.

    2015-01-01

    BACKGROUND: muscle strength and power are two factors affecting balance. The impact of muscle strength and power on postural control has not been fully explored among different age strata over sixty. OBJECTIVES: the aim of the present study was to assess the muscle strength and power of elderly women in different age groups and determine their correlation with postural control. METHOD: eighty women were divided into four groups: the young 18-30 age group (n=20); the 60-64 age group (n=20); the 65-69 age group (n=20); and the 70-74 age group (n=20). The participants underwent maximum strength (one repetition maximum or 1-RM) and muscle power tests to assess the knee extensor and flexor muscles at 40%, 70%, and 90% 1-RM intensity. The time required by participants to recover their balance after disturbing their base of support was also assessed. RESULTS: the elderly women in the 60-64, 65-69, and 70-74 age groups exhibited similar muscle strength, power, and postural control (p>0.05); however, these values were lower than those of the young group (p<0.05) as expected. There was a correlation between muscle strength and power and the postural control performance (p<0.05). CONCLUSION: despite the age difference, elderly women aged 60 to 74 years exhibited similar abilities to generate strength and power with their lower limbs, and this ability could be one factor that explains the similar postural control shown by these women. PMID:25651132

  8. The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants Is Controlled by Cytosolic pH.

    PubMed

    Hao, Meng-Shu; Jensen, Anna M; Boquist, Ann-Sofie; Liu, Yun-Jun; Rasmusson, Allan G

    2015-01-01

    NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O2 and decylubiquinone as electron acceptors. The K0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K0.5(Ca2+) for NADPH oxidation was high (≈100 μM), yet 20-fold lower K0.5(Ca2+) values were determined at pH 6.8. Lower K0.5(Ca2+) values were observed with decylubiquinone than with O2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene.

  9. Stimulus-response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+

    PubMed Central

    Villalón, M; Hinds, T R; Verdugo, P

    1989-01-01

    Changes of cytosolic [Ca2+] have been proposed to couple stimulation of ciliary movement, however, quantitative measurements of fluctuations of intracellular free [Ca2+] associated with stimulation of ciliated cells have not been investigated. In primary cultures of rabbit oviductal ciliated cells, the stimulation of ciliary activity produced by micromolar concentrations of adenosine triphosphate (ATP) and prostaglandin F2 alpha (PGF2 alpha) was associated with a transient increase of intracellular [Ca2+]. Whereas the increase of cytosolic [Ca2+] and beat frequency produced by ATP were inhibited by the Ca-channel blocker LaCl3, the rise of cytosolic [Ca2+] and frequency of ciliary beat produced by PGF2 alpha was not affected by LaCl3. These results are the first direct demonstration that fluctuations of cytosolic [Ca2+] are associated with increased ciliary beat frequency in mammalian epithelial cells. The present findings suggest two different calcium-dependent mechanisms for stimulus-coupling in ciliary epithelium: ATP acting via purinergic receptor coupled to transmembrane influx of Ca2+, and PGF2 alpha acting via receptor-mediated release of intracellular sequestered Ca. PMID:2611335

  10. The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants Is Controlled by Cytosolic pH

    PubMed Central

    Hao, Meng-Shu; Jensen, Anna M.; Boquist, Ann-Sofie; Liu, Yun-Jun; Rasmusson, Allan G.

    2015-01-01

    NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O2 and decylubiquinone as electron acceptors. The K0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K0.5(Ca2+) for NADPH oxidation was high (≈100 μM), yet 20-fold lower K0.5(Ca2+) values were determined at pH 6.8. Lower K0.5(Ca2+) values were observed with decylubiquinone than with O2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene. PMID:26413894

  11. Environmental vs microbial control on ca-carbonate precipitation in fluvial tufa (NW Calabria-Italy)

    NASA Astrophysics Data System (ADS)

    Manzo, E.; Perri, E.; Tucker, M. E.

    2009-04-01

    -shaped lobes and on the upper downstream face of the dams. Vacuolar tufas, which are observable on the upstream surface of the dams, compose the inner part of the dams and the core of the tongue-shaped bodies. Lamination of stromatolitic tufa is almost even and regular with only gentle doming. Laminae, which are 1-2 mm in thickness, originate by the alternation of two main types of microstructure: dendrolitic and detrital layers. Dendrolites, up to 1-1.5 mm thick contain mineralised upward-branching filaments a few micron in diameter, forming bush-likes fans. Filaments coalesce upward to form a solid carbonate layer. Filaments coalesce upwards to form a solid carbonate layer. They are formed by an envelope of micritic crystals of calcite around the sheath of individual cyanobacterial filaments. Detrital layers consist of a minor amount of mineralised cyanobacterial filaments, which appear mainly in transverse section. Carbonate minerals form thin radiating fibrous crystals around the filaments. Micron sized platy crystals of clay minerals and allochthonous dolomitic grains are abundant in such layers. Laminae of stromatolitic tufa also are characterized by the presence of empty tubes, subspherical/lenticular in section, probably originated by insect encrusted larvae. Vacuolar tufas consist of calcified plant remains that contain abundant large voids. Plant leaves, often with a preferred orientation, are the main component, with stems, twigs and mosses. Sub-millimetric carbonate crusts, which form around the plant material, consist of micro-spar fan-shaped calcite crystals 50-100 μm thick. Remains of cyanobacteria filaments, fungal hyphae and diatoms are absent within these calcite crusts, probably since no was biofilm on their external synsedimentary surface. Calcium carbonate tufa precipitation in the Parmenta stream is probably strongly controlled by the calcite supersaturation of the water, since the saturation index is about 0,7. Calcite in vacuolar tufas lacking evidence

  12. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    PubMed

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  13. Aging and insulin signaling differentially control normal and tumorous germline stem cells

    PubMed Central

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-01-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. PMID:25470527

  14. Optimal control of an influenza model with seasonal forcing and age-dependent transmission rates.

    PubMed

    Lee, Jeehyun; Kim, Jungeun; Kwon, Hee-Dae

    2013-01-21

    This study considers an optimal intervention strategy for influenza outbreaks. Variations in the SEIAR model are considered to include seasonal forcing and age structure, and control strategies include vaccination, antiviral treatment, and social distancing such as school closures. We formulate an optimal control problem by minimizing the incidence of influenza outbreaks while considering intervention costs. We examine the effects of delays in vaccine production, seasonal forcing, and age-dependent transmission rates on the optimal control and suggest some optimal strategies through numerical simulations.

  15. Using Large-Scale Roughness Elements to Control Sand and Dust Flux at the Keeler Dunes, Keeler, CA

    NASA Astrophysics Data System (ADS)

    Gillies, John; McCarley-Holder, Grace

    2014-05-01

    Controlling dust emission from areas that subsequently degrade air quality and threaten human and animal health and reduce the quality of life for people residing in proximity to such sources is necessary, but also challenging. Recent research has indicated that arrays of large roughness elements (height >0.3 m) can be used effectively to modulate sand transport and the associated dust emissions. Prediction of the rate of sand flux reduction as a function of downwind distance upon entering an array of roughness elements, and the equilibrium flux reduction in the interior of the array is possible using the known geometric properties of the roughness elements, their number, and published relationships. Air quality in the town of Keeler, CA (36 deg 29' 17.92" N, 117 deg 52' 24.62" W) is degraded by levels of particulate matter <10 µm aerodynamic diameter (PM10) during periods of elevated wind speeds due to sand transport and dust emissions in the nearby Keeler Dunes. A demonstration project was designed to evaluate the effectiveness of an array of roughness elements composed of solid elements and managed vegetation to meet sand and dust flux reduction criteria. This project has two major goals: 1) to demonstrate that solid roughness elements placed on areas of the Keeler Dunes immediately arrest sand movement to specified levels (target of 85% reduction), and 2) to assess whether native plant species, planted in the sheltered area of the solid roughness elements can effectively thrive and subsequently replace the solid roughness to achieve the desired sand flux reduction control efficiency. This poster describes the results related mostly to objective one, as considerable time has to pass before sufficient data will be obtained to evaluate the success of the planted and managed vegetation to achieve a control level provided by the solid element roughness array.

  16. Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust long-term survival and integration and suppress aberrant mossy fiber sprouting in the injured middle-aged hippocampus.

    PubMed

    Rao, Muddanna S; Hattiangady, Bharathi; Shetty, Ashok K

    2006-02-01

    Cell transplants that successfully replace the lost neurons and facilitate the reconstruction of the disrupted circuitry in the injured aging hippocampus are invaluable for treating acute head injury, stroke and status epilepticus in the elderly. This is because apt graft integration has the potential to prevent the progression of the acute injury into chronic epilepsy in the elderly. However, neural transplants into the injured middle-aged or aged hippocampus exhibit poor cell survival, suggesting that apt graft augmentation strategies are critical for robust integration of grafted cells into the injured aging hippocampus. We examined the efficacy of pre-treatment and grafting of donor fetal CA3 cells with a blend of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) for lasting survival and integration of grafted cells in the injured middle-aged (12 months old) hippocampus of F344 rats. Grafts were placed at 4 days after the kainic-acid-induced hippocampal injury and were analyzed at 6 months post-grafting. We demonstrate that 80% of grafted cells exhibit prolonged survival and 71% of grafted cells differentiate into CA3 pyramidal neurons. Grafts also receive a robust afferent input from the host mossy fibers and project efferent axons into the denervated zones of the dentate gyrus and the CA1 subfield. Consequently, the aberrant sprouting of the dentate mossy fibers, an epileptogenic change that typically ensues after the hippocampal injury, was suppressed. Thus, grafts of fetal CA3 cells enriched with FGF-2 and BDNF exhibit robust integration and dampen the abnormal mossy fiber sprouting in the injured middle-aged hippocampus. Because the aberrantly sprouted mossy fibers contribute to the generation of seizures, the results suggest that the grafting intervention using FGF-2 and BDNF is efficacious for suppressing epileptogenesis in the injured middle-aged hippocampus.

  17. Ethylenediamine-Assisted Hydrothermal Synthesis of NaCaSiO3OH: Controlled Morphology, Mechanism, and Luminescence Properties by Doping Eu(3+)/Tb(3).

    PubMed

    Chen, Mingyue; Xia, Zhiguo; Liu, Quanlin

    2016-11-07

    This paper demonstrates a facile hydrothermal method using ethylenediamine (EDA) as a "shape modifier" for the controlled synthesis of rod bunch, decanedron, spindle, flakiness, and flowerlike NaCaSiO3OH microarchitectures. The set of experimental conditions is important to obtain adjustable shape and size of NaCaSiO3OH particles, as the change in either the amount of EDA/H2O or reaction time, or the amount of NaOH. Accordingly, the crystal growth mechanism during the synthesis process is proposed, and it is found that the EDA, acting as the chelating agent and shape modifier, plays a crucial role in fine-tuning the NaCaSiO3OH morphology. Morphology evolution process of flowerlike NaCaSiO3OH as a function of NaOH is also explained in detail. Eu(3+)/Tb(3+) doped NaCaSiO3OH samples exhibit strong red and green emission under ultraviolet excitation, corresponding to the characteristic electronic transitions of Eu(3+) and Tb(3+). These results imply that the morphology-tunable NaCaSiO3OH:Eu(3+)/Tb(3+) microarchitectures with tunable luminescence properties are expected to have promising applications for micro/nano optical functional devices.

  18. The effect of paternal age on offspring intelligence and personality when controlling for paternal trait level.

    PubMed

    Arslan, Ruben C; Penke, Lars; Johnson, Wendy; Iacono, William G; McGue, Matt

    2014-01-01

    Paternal age at conception has been found to predict the number of new genetic mutations. We examined the effect of father's age at birth on offspring intelligence, head circumference and personality traits. Using the Minnesota Twin Family Study sample we tested paternal age effects while controlling for parents' trait levels measured with the same precision as offspring's. From evolutionary genetic considerations we predicted a negative effect of paternal age on offspring intelligence, but not on other traits. Controlling for parental intelligence (IQ) had the effect of turning an initially positive association non-significantly negative. We found paternal age effects on offspring IQ and Multidimensional Personality Questionnaire Absorption, but they were not robustly significant, nor replicable with additional covariates. No other noteworthy effects were found. Parents' intelligence and personality correlated with their ages at twin birth, which may have obscured a small negative effect of advanced paternal age (<1% of variance explained) on intelligence. We discuss future avenues for studies of paternal age effects and suggest that stronger research designs are needed to rule out confounding factors involving birth order and the Flynn effect.

  19. Metabolic control by target of rapamycin and autophagy during ageing - a mini-review.

    PubMed

    Markaki, Maria; Tavernarakis, Nektarios

    2013-01-01

    The conserved target of rapamycin (TOR) pathway integrates signals from nutrient and energy availability, growth factors and stress to regulate cell growth and proliferation, development and metabolism. Growing evidence suggests that TOR signalling controls the rate at which cells and tissues age, thereby contributing to whole-organism ageing. Although significant progress has been made in the last decades towards understanding fundamental aspects of the ageing process, the precise mechanisms underlying the age-related effects of TOR are still not fully understood. TOR interfaces with several cellular processes, such as DNA transcription, mRNA translation, protein turnover and autophagy, among others. Interestingly, TOR regulates various aspects of metabolism including mitochondrial function and lipid metabolism. Inhibition of TOR activity stimulates autophagy, a conserved lysosomal catabolic pathway that controls the degradation and turnover of macromolecules and organelles. Autophagy also has an important role in maintaining metabolic homeostasis at both the cellular and whole-organism level. Ageing in diverse organisms ranging from yeast to mammals appears to be associated with insufficient autophagy. Here, we summarize recent developments that outline how TOR and autophagy modulate the ageing process, with special emphasis on their role in the regulation of metabolism. A better understanding of the complex interplay between TOR, autophagy and ageing will pave the way for the development of novel therapeutic strategies to treat age-related pathologies.

  20. [Calmodulin can induce and control damping oscillations in the plasma membrane Ca2+ -ATPase activity: a kinetic model].

    PubMed

    Gol'dshtein, B N; Aksirov, A M; Zakrzhevskaia, D T

    2007-01-01

    Plasma membrane Ca2+-ATPase is the calcium pump that extrudes calcium ions from cells using ATP hydrolisis for the maintenance of low Ca2+ concentrations in the cell. Calmodulin stimulates Ca2+-ATPase by binding to the autoinhibitory enzyme domain, which allows the access of cytoplasmic ATP and Ca2+ to the active and transport cites. Our kinetic model predicts damped oscillations in the enzyme activity and interprets the known nonmonotonous kinetic behavior of the enzyme in the presence of calmodulin. For the parameters close to the experimental ones, the kinetic model explains the changes in frequency and damping factor of the oscillatory enzyme activity, as dependent on calmodulin concentration. The calculated pre-steady-state curves fit well the known experimental data. The kinetic analysis allows us to assign Ca2+-ATPase to the hysteretic enzymes exhibiting activity oscillations in open systems.

  1. Inositol polyphosphate 5-phosphatase-controlled Ins(1,4,5)P3/Ca2+ is crucial for maintaining pollen dormancy and regulating early germination of pollen.

    PubMed

    Wang, Yuan; Chu, Yu-Jia; Xue, Hong-Wei

    2012-06-01

    Appropriate pollen germination is crucial for plant reproduction. Previous studies have revealed the importance of dehydration in maintaining pollen dormancy; here, we show that phosphatidylinositol pathway-controlled Ins(1,4,5)P(3)/Ca(2+) levels are crucial for maintaining pollen dormancy in Arabidopsis thaliana. An interesting phenotype, precocious pollen germination within anthers, results from a disruption of inositol polyphosphate 5-phosphatase 12 (5PT12). The knockout mutant 5pt12 has normal early pollen development and pollen dehydration, and exhibits hypersensitive ABA responses, indicating that precocious pollen germination is not caused either by abnormal dehydration or by suppressed ABA signaling. Deficiency of 5PT13 (a close paralog of 5PT12) synergistically enhances precocious pollen germination. Both basal Ins(1,4,5)P(3) levels and endogenous Ca(2+) levels are elevated in pollen from 5pt12 mutants, and 5pt12 5pt13 double mutants show an even higher precocious germination rate along with much higher levels of Ins(1,4,5)P(3)/Ca(2+). Strikingly, exogenous Ca(2+) stimulates the germination of wild-type pollen at floral stage 12, even in very low humidity, both in vitro and in vivo, and treatment with BAPTA, a [Ca(2+)](cyt) inhibitor, reduces the precocious pollen germination rates of 5pt12, 5pt13 and 5pt12 5pt13 mutants. These results indicate that the increase in the levels of Ins(1,4,5)P(3)/Ca(2+) caused by deficiency of inositol polyphosphate 5-phosphatases is sufficient to break pollen dormancy and to trigger early germination. The study reveals that independent of dehydration, the control of Ins(1,4,5)P(3)/Ca(2+) levels by Inositol polyphosphate 5-phosphatases is crucial for maintaining pollen dormancy.

  2. SERCA2a controls the mode of agonist-induced intracellular Ca2+ signal, transcription factor NFAT and proliferation in human vascular smooth muscle cells

    PubMed Central

    Bobe, Regis; Hadri, Lahouaria; Lopez, Jose J.; Sassi, Yassine; Atassi, Fabrice; Karakikes, Ioannis; Liang, Lifan; Limon, Isabelle; Lompré, Anne-Marie; Hatem, Stephane N.; Hajjar, Roger J.; Lipskaia, Larissa

    2011-01-01

    In blood vessels, tone is maintained by agonist-induced cytosolic Ca2+ oscillations of quiescent/contractile vascular smooth muscle cells (VSMCs). However, in synthetic/proliferative VSMCs, Gq/phosphoinositide receptor-coupled agonists trigger a steady-state increase in cytosolic Ca2+ followed by a Store Operated Calcium Entry (SOCE) which translates into activation of the proliferation-associated transcription factor NFAT. Here, we report that in human coronary artery smooth muscle cells (hCASMCs), the sarco/endoplasmic reticulum calcium ATPase type 2a (SERCA2a) expressed in the contractile form of the hCASMCs, controls the nature of the agonist-induced Ca2+ transient and the resulting down-stream signaling pathway. Indeed, restoring SERCA2a expression by gene transfer in synthetic hCASMCs 1) increased Ca2+ storage capacity; 2) modified agonist-induced IP3R Ca2+ release from steady-state to oscillatory mode (the frequency of agonist-induced IP3R Ca2+ signal was 11.66 ± 1.40/100 sec in SERCA2a-expressing cells (n=39) vs 1.37 ± 0.20/100 sec in control cell (n=45), p<0.01); 3) suppressed SOCE by preventing interactions between SR calcium sensor STIM1 and pore forming unit ORAI1; 4) inhibited calcium regulated transcription factor NFAT and its down-stream physiological function such as proliferation and migration. This study provides evidence for the first time that oscillatory and steady-state patterns of Ca2+ transients have different effects on calcium-dependent physiological functions in smooth muscle cells. PMID:21195084

  3. Calcium-activated K+ Channels of Mouse β-cells are Controlled by Both Store and Cytoplasmic Ca2+

    PubMed Central

    Goforth, P.B.; Bertram, R.; Khan, F.A.; Zhang, M.; Sherman, A.; Satin, L.S.

    2002-01-01

    A novel calcium-dependent potassium current (Kslow) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic β-cells (Göpel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renström, and P. Rorsman. 1999. J. Gen. Physiol. 114:759–769). Kslow activation may help terminate the cyclic bursts of Ca2+-dependent action potentials that drive Ca2+ influx and insulin secretion in β-cells. Here, we report that when [Ca2+]i handling was disrupted by blocking Ca2+ uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1–5 μM) or insulin (200 nM), Kslow was transiently potentiated and then inhibited. Kslow amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of Kslow by SERCA blockers could not be explained by a minimal mathematical model in which [Ca2+]i is divided between two compartments, the cytosol and the ER, and Kslow activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which Kslow activation is mediated by a localized pool of [Ca2+] in a subspace located between the ER and the plasma membrane. In this model, the subspace [Ca2+] follows changes in cytosolic [Ca2+] but with a gradient that reflects Ca2+ efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of Kslow and [Ca2+] handling in influencing β-cell electrical activity and insulin secretion. PMID:12198088

  4. Apart from its known function, the plasma membrane Ca²⁺ATPase can regulate Ca²⁺ signaling by controlling phosphatidylinositol 4,5-bisphosphate levels.

    PubMed

    Penniston, John T; Padányi, Rita; Pászty, Katalin; Varga, Karolina; Hegedus, Luca; Enyedi, Agnes

    2014-01-01

    Plasma membrane Ca(2+) ATPases (PMCAs, also known as ATP2B1-ATP2B4) are known targets of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂], but if and how they control the PtdIns(4,5)P₂ pool has not been considered. We demonstrate here that PMCAs protect PtdIns(4,5)P₂ in the plasma membrane from hydrolysis by phospholipase C (PLC). Comparison of active and inactive PMCAs indicates that the protection operates by two mechanisms; one requiring active PMCAs, the other not. It appears that the mechanism requiring activity is the removal of the Ca(2+) required for sustained PLC activity, whereas the mechanism not requiring activity is PtdIns(4,5)P₂ binding. We show that in PMCA overexpressing cells, PtdIns(4,5)P₂ binding can lead to less inositol 1,4,5-triphosphate (InsP₃) and diminished Ca(2+) release from intracellular Ca(2+) pools. Inspection of a homology model of PMCA suggests that PMCAs have a conserved cluster of basic residues forming a 'blue collar' at the interface between the membrane core and the cytoplasmic domains. By molecular dynamics simulation, we found that the blue collar forms four binding pockets for the phosphorylated inositol head group of PtdIns(4,5)P₂; these pockets bind PtdIns(4,5)P₂ strongly and frequently. Our studies suggest that by having the ability to bind PtdIns(4,5)P₂, PMCAs can control the accessibility of PtdIns(4,5)P₂ for PLC and other PtdIns(4,5)P₂-mediated processes.

  5. Age-dependent specific changes in area CA2 of the hippocampus and social memory deficit in a mouse model of the 22q11.2 deletion syndrome

    PubMed Central

    Piskorowski, Rebecca A.; Nasrallah, Kaoutsar; Diamantopoulou, Anastasia; Mukai, Jun; Hassan, Sami I.; Siegelbaum, Steven A.; Gogos, Joseph A.; Chevaleyre, Vivien

    2015-01-01

    Several neuropsychiatric disorders are associated with cognitive and social dysfunction. Post-mortem studies of patients with schizophrenia have revealed specific changes in area CA2, a long over-looked region of the hippocampus recently found to be critical for social memory formation. To examine how area CA2 is altered in psychiatric illness, we used the Df(16)A+/− mouse model of the 22q11.2 microdeletion, a genetic risk factor for developing several neuropsychiatric disorders, including schizophrenia. We report several age-dependent CA2 alterations: a decrease in the density of parvalbumin-stained interneurons, a reduction in the amount of feed-forward inhibition and a change in CA2 pyramidal neuron intrinsic properties. Furthermore, we found that area CA2 is less plastic in Df(16)A+/− mice, making it nearly impossible to evoke action potential firing in CA2 pyramidal neurons. Finally, we show that Df(16)A+/− mice display impaired social cognition, providing a potential mechanism and a neural substrate for this impairment in psychiatric disorders. PMID:26748091

  6. Factors controlling the geochemical composition of Limnopolar Lake sediments (Byers Peninsula, Livingston Island, South Shetland Island, Antarctica) during the last ca. 1600 years

    NASA Astrophysics Data System (ADS)

    Martínez Cortizas, A.; Rozas Muñiz, I.; Taboada, T.; Toro, M.; Granados, I.; Giralt, S.; Pla-Rabés, S.

    2014-07-01

    We sampled a short (57 cm) sediment core in Limnopolar Lake (Byers Peninsula, Livingston Island, South Shetland Islands), which spans the last ca. 1600 years. The core was sectioned at high resolution and analyzed for elemental and mineralogical composition, and scanning electron microscope and energy dispersive X-ray spectrometer (SEM-EDS) analysis of glass mineral particles in selected samples. The chemical record was characterized by a contrasted pattern of layers with high Ca, Ti, Zr, and Sr concentrations and layers with higher concentrations of K and Rb. The former were also enriched in plagioclase and, occasionally, in zeolites, while the latter were relatively enriched in 2 : 1 phyllosilicates and quartz. This was interpreted as reflecting the abundance of volcaniclastic material (Ca rich) versus Jurassic-Lower Cretaceous marine sediments (K rich) - the dominant geological material in the lake catchment. SEM-EDS analysis revealed the presence of abundant volcanic shards in the Ca-rich layers, pointing to tephras most probably related to the activity of Deception Island volcano (located 30 km to the SE). The ages of four main peaks of volcanic-rich material (AD ca. 1840-1860 for L1, AD ca. 1570-1650 for L2, AD ca. 1450-1470 for L3, and AD ca. 1300 for L4) matched reasonably well the age of tephra layers (AP1 to AP3) previously identified in lakes of Byers Peninsula. Some of the analyzed metals (Fe, Mn, Cu, and Cr) showed enrichments in the most recent tephra layer (L1), suggesting relative changes in the composition of the tephras as found in previous investigations. No evidence of significant human impact on the cycles of most trace metals (Cu, Zn, Pb) was found, probably due to the remote location of Livingston Island and the modest research infrastructures; local contamination was found by other researchers in soils, waters and marine sediments on areas with large, permanent research stations. Chromium is the only metal showing a steady enrichment in the

  7. Age-Specific Morbidity and Mortality Rates Among U.S. Navy Enlisted Divers and Controls

    DTIC Science & Technology

    1984-07-01

    The purpose of this study was to compare age-specific hospitalization, disability, and mortality rates for diving-related and stress- induced...actions for stress-related disorders were observed among controls than divers. For both groups, medical board, physical evaluation board, and mortality ... rates increased with age as did hospitalization for musculoskeletal disorders, stress-related disorders, and circulatory diseases. Subsequent research

  8. Aging Management Guideline for commercial nuclear power plants: Motor control centers; Final report

    SciTech Connect

    Toman, G.; Gazdzinski, R.; O`Hearn, E.

    1994-02-01

    This Aging Management Guideline (AMG) provides recommended methods for effective detection and mitigation of age-related degradation mechanisms in Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) commercial nuclear power plant motor control centers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein.

  9. Chemical characteristics combined with bioactivity for comprehensive evaluation of Panax ginseng C.A. Meyer in different ages and seasons based on HPLC-DAD and chemometric methods.

    PubMed

    Shan, Si-Ming; Luo, Jian-Guang; Huang, Fang; Kong, Ling-Yi

    2014-02-01

    Panax ginseng C.A. Meyer has been known as a valuable traditional Chinese medicines for thousands years of history. Ginsenosides, the main active constituents, exhibit prominent immunoregulation effect. The present study first describes a holistic method based on chemical characteristic and lymphocyte proliferative capacity to evaluate systematically the quality of P. ginseng in thirty samples from different seasons during 2-6 years. The HPLC fingerprints were evaluated using principle component analysis (PCA) and hierarchical clustering analysis (HCA). The spectrum-efficacy model between HPLC fingerprints and T-lymphocyte proliferative activities was investigated by principal component regression (PCR) and partial least squares (PLS). The results indicated that the growth of the ginsenosides could be grouped into three periods and from August of the fifth year, P. ginseng appeared significant lymphocyte proliferative capacity. Close correlation existed between the spectrum-efficacy relationship and ginsenosides Rb1, Ro, Rc, Rb2 and Re were the main contributive components to the lymphocyte proliferative capacity. This comprehensive strategy, providing reliable and adequate scientific evidence, could be applied to other TCMs to ameliorate their quality control.

  10. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging.

    PubMed

    Czepielewski, Leticia Sanguinetti; Massuda, Raffael; Panizzutti, Bruna; da Rosa, Eduarda Dias; de Lucena, David; Macêdo, Danielle; Grun, Lucas Kich; Barbé-Tuana, Florencia María; Gama, Clarissa Severino

    2016-07-01

    Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

  11. Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.

    PubMed

    Kim, Jinhyun; Wei, Dong-Sheng; Hoffman, Dax A

    2005-11-15

    A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.

  12. Is groundwater age the main control for slow turnover of nitrate in a fractured groundwater system?

    NASA Astrophysics Data System (ADS)

    Osenbrück, Karsten; Schwientek, Marc; Rügner, Hermann; Grathwohl, Peter

    2015-04-01

    Slow transformation processes are known to control the chemical, isotopic, and redox evolution of large-scale aquifers (Edmunds et al., 1982; Katz et al., 1995). However, at the field scale some of the crucial biogeochemical processes governing pollutant turnover and their interrelations with hydrology are poorly understood. Particularly, only little is known about denitrification in fractured rock aquifers. Therefore, the main objective of the presented study is to assess where and how slow turnover of nitrate ans other pollutants in the deeper subsurface take place. The studied fractured and partly karstified aquifer consisting of Triassic black limestones and dolomites is located in the catchment of the Ammer river (ca. 350 km²) close to Tübingen in southern Germany. Near the recharge area, the aquifer is covered by loess allowing intensive agriculture. Further downgradient, the cover consist of a series of mudstones and sandstones of variable permeability. The aquifer is used for drinking water purposes by regional water suppliers. Land-use is dominated by agriculture with arable land covering nearly 50% of the catchment. Over the last years a variety of groundwater samples have been collected from the groundwater system including 6 water supply wells, 4 karstic springs, and 9 monitoring wells in the recharge area. This allowed to identify spatial and temporal patterns of water quality including concentrations of major ions, dissolved organic carbon (DOC), organic pollutants (e.g., pesticides), and environmental isotopes. Groundwater age distributions at most of these locations were derived from tritium, 3He, CFCs and SF6. Groundwaters in the recharge area show high concentrations of nutrients (e.g. 20-51 mg/L of nitrate and 0.2 to 0.05 µg/L of phosphate). Of special concern are disparate nitrate concentrations ranging from below 0.4 to 20 mg/L in water supply wells although screen depths of the production wells are similar. Concentrations of dissolved

  13. The role of neuromuscular changes in aging and knee osteoarthritis on dynamic postural control.

    PubMed

    Takacs, Judit; Carpenter, Mark G; Garland, S Jayne; Hunt, Michael A

    2013-04-01

    Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA.

  14. Control of the superconducting properties of Sr{sub 2−x}Ca{sub x}VO{sub 3}FeAs through isovalent substitution

    SciTech Connect

    Corkett, Alex J.; Free, David G.; Cassidy, Simon J.; Ramos, Silvia; Clarke, Simon J.

    2014-08-15

    The effect of the isovalent substitution of Sr{sup 2+} by Ca{sup 2+} on the structure and superconducting properties of Sr{sub 2−x}Ca{sub x}VO{sub 3}FeAs is described in the compositional range 0≤x≤0.5. SQUID magnetometry measurements reveal that after an initial increase in T{sub c}, which is maximised at 29.5 K in Sr{sub 1.95}Ca{sub 0.05}VO{sub 3}FeAs, a rapid suppression of superconductivity is observed with increasing x. XANES spectra of Sr{sub 2−x}Ca{sub x}VO{sub 3}FeAs collected on the Fe and V absorption K-edges show that the position of both edges are invariant with composition within the experimental uncertainty. A combination of synchrotron X-ray powder diffraction and neutron powder diffraction techniques is used to rationalise the observed changes in T{sub c} with x, in terms of changes to the structure of the FeAs layer upon partial Ca substitution. These findings demonstrate that superconductivity in the Fe-based superconductors is extremely sensitive to the crystal structure with T{sub c} maximised in samples with regular FeAs{sub 4}-tetrahedra. - Graphical abstract: Superconducting transition temperature is controlled by structural parameters in Sr{sub 2−x}Ca{sub x}VO{sub 3}FeAs. - Highlights: • Substitution of Sr by Ca in the superconductor Sr{sub 2}VO{sub 3}FeAs is isovalent. • Relationship between superconducting T{sub c} and structural parameters is demonstrated. • Linear dependence of T{sub c} on structural parameters rather than composition.

  15. Experience-Based Mitigation of Age-Related Performance Declines: Evidence From Air Traffic Control

    PubMed Central

    Nunes, Ashley; Kramer, Arthur F.

    2010-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic control (ATC), would enable older controllers to perform at high levels of proficiency. The authors also investigated whether older controllers would show diminished age-related decrements on domain-relevant cognitive abilities. Both young and old controllers and noncontrollers performed a battery of cognitive and ATC tasks. Results indicate that although high levels of experience can reduce the magnitude of age-related decline on the component processes that underlie complex task performance, this sparing is limited in scope. More important, however, the authors observed experience-based sparing on simulated ATC tasks, with the sparing being most evident on the more complex air traffic control tasks. These results suggest that given substantial experience, older adults may be quite capable of performing at high levels of proficiency on fast-paced demanding real-world tasks. The implications of these findings for global skilled labor shortages are discussed. PMID:19309213

  16. Aging causes a reorganization of cortical and spinal control of posture

    PubMed Central

    Papegaaij, Selma; Taube, Wolfgang; Baudry, Stéphane; Otten, Egbert; Hortobágyi, Tibor

    2013-01-01

    Classical studies in animal preparations suggest a strong role for spinal control of posture. In humans it is now established that the cerebral cortex contributes to postural control of unperturbed and perturbed standing. The age-related degeneration and accompanying functional changes in the brain, reported so far mainly in conjunction with simple manual motor tasks, may also affect the mechanisms that control complex motor tasks involving posture. This review outlines the age-related structural and functional changes at spinal and cortical levels and provides a mechanistic analysis of how such changes may be linked to the behaviorally manifest postural deficits in old adults. The emerging picture is that the age-related reorganization in motor control during voluntary tasks, characterized by differential modulation of spinal reflexes, greater cortical activation and cortical disinhibition, is also present during postural tasks. We discuss the possibility that this reorganization underlies the increased coactivation and dual task interference reported in elderly. Finally, we propose a model for future studies to unravel the structure-function-behavior relations in postural control and aging. PMID:24624082

  17. MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death

    PubMed Central

    Aurora, Arin B.; Mahmoud, Ahmed I.; Luo, Xiang; Johnson, Brett A.; van Rooij, Eva; Matsuzaki, Satoshi; Humphries, Kenneth M.; Hill, Joseph A.; Bassel-Duby, Rhonda; Sadek, Hesham A.; Olson, Eric N.

    2012-01-01

    Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca2+ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca2+ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca2+ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca2+ influx; and to repression of several downstream effectors of Ca2+ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca2+ homeostasis and survival during cardiac injury. PMID:22426211

  18. Morphology control and mechanisms of CaCO3 crystallization on gas-liquid interfaces of CO2/NH3 bubbles in aqueons-glycine solutions

    NASA Astrophysics Data System (ADS)

    Guan, Xiaomei; Huang, Fangzhi; Li, Jian; Li, Shikuo; Zhang, Xiuzhen; Guo, Degui; Shen, Yuhua; Xie, Anjian

    2015-06-01

    As one of the new methods of materials preparing, interface-regulated mineralization, has been developed and used to fabricate the CaCO3 materials with mimetic construction of natural biogenic structures in the present work. Combined with the effect of glycine at different concentrations, novel gas-liquid interfaces of CO2/NH3 bubbles have been substituted for the traditional settled matrix and utilized as new reaction fields of CaCO3. CaCO3 crystals with delicate hierarchical structures and morphologies, such as scallop-shaped, ellipsoidal and spherical structure, have been obtained at the special glycine-mediated gasliquid interfaces. The effect of glycine concentration and the chemical reaction kinetics have been deeply studied. As a result, we have successfully captured in detail the crystallization behaviors of CaCO3 in different stages, which allow us to put forward a general kinetic model to reveal the formation mechanism of CaCO3 and implicate a straightforward mean to control the morphology and structure.

  19. Cognitive control, cognitive reserve, and memory in the aging bilingual brain

    PubMed Central

    Grant, Angela; Dennis, Nancy A.; Li, Ping

    2014-01-01

    In recent years bilingualism has been linked to both advantages in executive control and positive impacts on aging. Such positive cognitive effects of bilingualism have been attributed to the increased need for language control during bilingual processing and increased cognitive reserve, respectively. However, a mechanistic explanation of how bilingual experience contributes to cognitive reserve is still lacking. The current paper proposes a new focus on bilingual memory as an avenue to explore the relationship between executive control and cognitive reserve. We argue that this focus will enhance our understanding of the functional and structural neural mechanisms underlying bilingualism-induced cognitive effects. With this perspective we discuss and integrate recent cognitive and neuroimaging work on bilingual advantage, and suggest an account that links cognitive control, cognitive reserve, and brain reserve in bilingual aging and memory. PMID:25520695

  20. Inhibitory control of sensory gating in a computer model of the CA3 region of the hippocampus

    PubMed Central

    Moxon, Karen A.; Gerhardt, Greg A.; Gulinello, Maria; Adler, Lawrence E.

    2014-01-01

    A model of the CA3 region of the hippocampus was used to simulate the P50 auditory-evoked potential response to repeated stimuli in order to study the neuronal circuits involved in a sensory-processing deficit associated with schizophrenia. Normal subjects have a reduced P50 auditory-evoked potential amplitude in response to the second of two paired auditory click stimuli spaced 0.5 s apart. However, schizophrenic patients do not gate or reduce their response to the second click. They have equal auditory-evoked response amplitudes to both clicks. When schizophrenic patients were medicated with traditional neuroleptics, the evoked potential amplitude to both clicks increased, but gating of the second response was not restored or improved. Animal studies suggest a role for septohippocampal cholinergic activity in sensory gating. We used a computational model of this system in order to study the relative contributions of local processing and afferent activity in sensory gating. We first compared the effect of information representation as average firing rate to information representation as cell assemblies in order to evaluate the best method to represent the response of hippocampal neurons to the auditory click. We then studied the effects of nicotinic cholinergic input on the response of the network and the effect of GABAB receptor activation on the ability of the local network to suppress the test response. The results of our model showed that nicotinic cholinergic input from the septum to the hippocampus can control the flow of sensory information from the cortex into the hippocampus. In addition, postsynaptic GABAB receptor activation was not sufficient to suppress the test response when the interstimulus interval was 500 ms. However, presynaptic GABAB receptor activity may be responsible for the suppression of the test response at this interstimulus interval. PMID:12690484

  1. Age-related changes in postural control to the demands of a precision task.

    PubMed

    Yeh, Ting-Ting; Cinelli, Michael E; Lyons, James L; Lee, Timothy D

    2015-12-01

    Optimal sensorimotor integration is needed to maintain the precision of a visuomotor postural task. Furthermore, cognitive resources have been suggested to be involved in maintaining balance, especially in older adults. This study investigated how older and younger adults differed in employing sensorimotor strategies in a dual-task situation. Older (age 65-84 years) and younger adults (age 19-30 years) performed a visually-based, postural tracking task in different body orientations (from 0° to 45°), which necessitated slightly different task goals. On some trials, participants performed a concurrent silent arithmetic task with the visuomotor tracking task. The results demonstrated that sensorimotor control declined with age. Older adults showed greater medial-lateral center of pressure variability compared to younger adults in the precision task. Younger adults displayed a trend to decrease anterior-posterior variability, but older adults exhibited an opposite trend when the body orientation changed from 0° to 45°. The addition of a dual-task situation decreased overall postural variability in both age groups. Age-related changes in postural control may degrade the flexible coordination of the sensory feedback and motor execution. This study suggested that medial-lateral stability may be more sensitive to this age-related decline and may be closely associated with postural instability and falls.

  2. Age-related changes in the center of mass velocity control during walking.

    PubMed

    Chong, Raymond K Y; Chastan, Nathalie; Welter, Marie-Laure; Do, Manh-Cuong

    2009-07-10

    During walking, the body center of mass oscillates along the vertical plane. Its displacement is highest at mid-swing and lowest at terminal swing during the transition to double support. Its vertical velocity (CoMv) has been observed to increase as the center of mass falls between mid- and late swing but is reduced just before double support. This suggests that braking of the center of mass is achieved with active neural control. We tested whether this active control deteriorates with aging (Experiment 1) and during a concurrent cognitive task (Experiment 2). At short steps of <0.4m, CoMv control was low and similar among all age groups. All groups braked the CoMv at longer steps of >0.4m but older subjects did so to a lesser extent. During the cognitive task, young subjects increased CoMv control (i.e. increase in CoMv braking) while maintaining step length and walking speed. Older subjects on the other hand, did not increase CoMv control but rather maintain it by reducing both step length and walking speed. These results suggest that active braking of the CoM during the transition to double support predominates in steps >0.4m. It could be a manifestation of the balance control system, since the braking occurs at late stance where body weight is being shifted to the contralateral side. The active braking mechanism also appears to require some attentional resource. In aging, reducing step length and speed are strategic to maintaining effective center of mass control during the transition to double support. However, the lesser degree of control in older adults indicates a true age-related deficit.

  3. Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth

    PubMed Central

    Miller, Gregory E.; Yu, Tianyi; Chen, Edith; Brody, Gene H.

    2015-01-01

    There are persistent socioeconomic disparities in many aspects of child development in America. Relative to their affluent peers, children of low socioeconomic status (SES) complete fewer years of education, have a higher prevalence of health problems, and are convicted of more criminal offenses. Based on research indicating that low self-control underlies some of these disparities, policymakers have begun incorporating character-skills training into school curricula and social services. However, emerging data suggest that for low-SES youth, self-control may act as a “double-edged sword,” facilitating academic success and psychosocial adjustment, while at the same time undermining physical health. Here, we examine this hypothesis in a five-wave study of 292 African American teenagers from rural Georgia. From ages 17 to 20 y, we assessed SES and self-control annually, along with depressive symptoms, substance use, aggressive behavior, and internalizing problems. At age 22 y, we obtained DNA methylation profiles of subjects’ peripheral blood mononuclear cells. These data were used to measure epigenetic aging, a methylation-derived biomarker reflecting the disparity between biological and chronological aging. Among high-SES youth, better mid-adolescent self-control presaged favorable psychological and methylation outcomes. However, among low-SES youth, self-control had divergent associations with these outcomes. Self-control forecasted lower rates of depressive symptoms, substance use, aggressive behavior, and internalizing problems but faster epigenetic aging. These patterns suggest that for low-SES youth, resilience is a “skin-deep” phenomenon, wherein outward indicators of success can mask emerging problems with health. These findings have conceptual implications for models of resilience, and practical implications for interventions aimed at ameliorating social and racial disparities. PMID:26170291

  4. Compliance instead of flexibility? On age-related differences in cognitive control during visual search.

    PubMed

    Mertes, Christine; Wascher, Edmund; Schneider, Daniel

    2017-02-11

    The effect of healthy aging on cognitive control of irrelevant visual information was investigated by using event-related potentials. Participants performed a spatial cuing task where an irrelevant color cue that was either contingent (color search) or noncontingent (shape search) on the attentional set was presented before a target with different stimulus-onset asynchronies. In the contingent condition, attentional capture appeared independent of age and persisted over the stimulus-onset asynchronies but was markedly pronounced for elderly people. Accordingly, event-related potential analyses revealed that both older and younger adults initially selected the irrelevant cue when it was contingent on the attentional set and transferred spatial cue information into working memory. However, only younger adults revealed inhibitory mechanisms to compensate for attentional capture. It is proposed that this age-related lack of reactive inhibition leads to stickiness in visual processing whenever information is contingent on the attentional set, unveiling older adults' "Achilles' heel" in cognitive control.

  5. The Influence of Task Difficulty and Participant Age on Balance Control in ASD

    ERIC Educational Resources Information Center

    Graham, Sarah A.; Abbott, Angela E.; Nair, Aarti; Lincoln, Alan J.; Müller, Ralph-Axel; Goble, Daniel J.

    2015-01-01

    Impairments in sensorimotor integration are reported in Autism Spectrum Disorder (ASD). Poor control of balance in challenging balance tasks is one suggested manifestation of these impairments, and is potentially related to ASD symptom severity. Reported balance and symptom severity relationships disregard age as a potential covariate, however,…

  6. Relationship of Air Traffic Control Specialist Age to En Route Operational Errors

    DTIC Science & Technology

    2005-12-01

    to the preservation of human life. This calls for recognition of the highly important fact that early retirement is not solely a matter of fairness...increased with age. This finding casts doubt on the explicit characterization of the mandatory early retirement of controllers as “primarily a safety

  7. Ageing vessel configuration for continuous redox potential-controlled very-high-gravity fermentation.

    PubMed

    Liu, Chen-Guang; Lin, Yen-Han; Bai, Feng-Wu

    2011-01-01

    The development of continuous very-high-gravity (VHG) fermentation is hindered by ineffective glucose uptake in order to result in zero discharge in the effluent stream. To overcome the problem, we proposed a continuous redox potential-controlled fermentation configuration, consisting of a Chemostat vessel connected with two ageing vessels installed in parallel, and the relevant design criteria are also specified. The Chemostat vessel is subjected to redox potential control to maintain yeast viability, and the ageing vessels are used to completely utilize glucose before discharging to next process unit. Two ageing vessels are scheduled alternatively, resulting in continuously-like operation. The size of ageing vessel is governed by the Chemostat size, dilution rate and filling time. The guideline to choose proper dilution rate is provided and the selection criterion of the proposed continuous configuration over batch fermentation is derived. The excess ethanol produced by the proposed continuous configuration over batch fermenter is quantified. As an illustration, a bio-ethanol plant is typically operated 8000 h per annum and the downtime between batches is 6h. Given that the fermenter size of 100 m(3) for both batch fermenter and Chemostat vessel, and glucose fed at 300 g/l, if the proposed continuous redox potential-controlled fermentation configuration (operated at 0.028 h(-1) and controlled at -50 mV) is selected, it will take 191 h for this configuration to outperform the batch counterpart, and the excess amount of ethanol being produced will be 1142 t.

  8. Aging Labels: The Decline of Control and the Fall of Self-Esteem.

    ERIC Educational Resources Information Center

    Rodin, Judith; Langer, Ellen

    1980-01-01

    Describes studies that investigate how labeling and stigmatization of the elderly might contribute to behavior that would confirm prevalent stereotypes of old age and lead to lowered self esteem and diminished feelings of control. Also discusses suggested strategies for social change. (Author/GC)

  9. Effects of Attentional Focus and Age on Suprapostural Task Performance and Postural Control

    ERIC Educational Resources Information Center

    McNevin, Nancy; Weir, Patricia; Quinn, Tiffany

    2013-01-01

    Purpose: Suprapostural task performance (manual tracking) and postural control (sway and frequency) were examined as a function of attentional focus, age, and tracking difficulty. Given the performance benefits often found under external focus conditions, it was hypothesized that external focus instructions would promote superior tracking and…

  10. Relationship between the Onset Age of Bilingualism and Development of Cognitive Control among Nigerians

    ERIC Educational Resources Information Center

    Al-Shujairi, Yasir Bdaiwi Jasim; Buba, Jamila AbdulAzeez; Ya'u, Mohammed Sani

    2016-01-01

    An increasing body of studies suggests that bilingual persons are better than monolinguals on a variety of cognitive measures. Thus, the present study investigates the relationship between the onset age of bilingual and the development of cognitive control among Nigerians. 10 bilingual students studying at University Putra Malaysia have been…

  11. Opiate Exposure State Controls a D2-CaMKIIα-Dependent Memory Switch in the Amygdala-Prefrontal Cortical Circuit

    PubMed Central

    Rosen, Laura G; Zunder, Jordan; Renard, Justine; Fu, Jennifer; Rushlow, Walter; Laviolette, Steven R

    2016-01-01

    The mammalian basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) comprise a functionally interconnected circuit that is critical for processing opiate-related associative memories. In the opiate-naïve state, reward memory formation in the BLA involves a functional link between dopamine (DA) D1 receptor (D1R) and extracellular signal-related kinase 1/2 (ERK1/2) signaling substrates, but switches to a DA D2 (D2R)/Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-dependent memory substrate following chronic opiate exposure and spontaneous withdrawal. Using conditioned place preference (CPP) in rats paired with molecular analyses, we examined the role of intra-mPFC CaMKII, ERK and DAergic activity during the formation of opiate associative memories, and how opiate exposure state may regulate the functions of these molecular memory pathways. We report that the role of CaMKIIα signaling is functionally reversed within the BLA-mPFC pathway depending on opiate exposure state. Thus, in the opiate-naïve state, intra-mPFC but not intra-BLA blockade of CaMKII signaling prevents formation of opiate reward memory. However, following chronic opiate exposure and spontaneous withdrawal, the role of CaMKII signaling in the BLA-mPFC is functionally reversed. This behavioral memory switch corresponds to a selective increase in the expression of D2R and CaMKIIα, but not other calcium/calmodulin-related molecules, nor D1R expression levels within the mPFC. PMID:26174594

  12. DNA aptamer raised against advanced glycation end products (AGEs) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing AGE-RAGE axis.

    PubMed

    Ojima, A; Matsui, T; Nakamura, N; Higashimoto, Y; Ueda, S; Fukami, K; Okuda, S; Yamagishi, S

    2015-04-01

    Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements.

  13. Aging into Perceptual Control: A Dynamic Causal Modeling for fMRI Study of Bistable Perception

    PubMed Central

    Dowlati, Ehsan; Adams, Sarah E.; Stiles, Alexandra B.; Moran, Rosalyn J.

    2016-01-01

    Aging is accompanied by stereotyped changes in functional brain activations, for example a cortical shift in activity patterns from posterior to anterior regions is one hallmark revealed by functional magnetic resonance imaging (fMRI) of aging cognition. Whether these neuronal effects of aging could potentially contribute to an amelioration of or resistance to the cognitive symptoms associated with psychopathology remains to be explored. We used a visual illusion paradigm to address whether aging affects the cortical control of perceptual beliefs and biases. Our aim was to understand the effective connectivity associated with volitional control of ambiguous visual stimuli and to test whether greater top-down control of early visual networks emerged with advancing age. Using a bias training paradigm for ambiguous images we found that older participants (n = 16) resisted experimenter-induced visual bias compared to a younger cohort (n = 14) and that this resistance was associated with greater activity in prefrontal and temporal cortices. By applying Dynamic Causal Models for fMRI we uncovered a selective recruitment of top-down connections from the middle temporal to Lingual gyrus (LIN) by the older cohort during the perceptual switch decision following bias training. In contrast, our younger cohort did not exhibit any consistent connectivity effects but instead showed a loss of driving inputs to orbitofrontal sources following training. These findings suggest that perceptual beliefs are more readily controlled by top-down strategies in older adults and introduce age-dependent neural mechanisms that may be important for understanding aberrant belief states associated with psychopathology. PMID:27064235

  14. CaCO3/Tetraethylenepentamine-Graphene Hollow Microspheres as Biocompatible Bone Drug Carriers for Controlled Release.

    PubMed

    Li, Jie; Jiang, Hongkun; Ouyang, Xiao; Han, Shihui; Wang, Jun; Xie, Rui; Zhu, Wenting; Ma, Ning; Wei, Hao; Jiang, Zhongyi

    2016-11-09

    CaCO3 is one kind of important biological mineral, which widely exists in coral, shell, and other organisms. Since it is similar to bone tissue elements and has good biocompatibility, it was very suitable as a candidates for bone drug carriers. In this work, we used tetraethylenepentamine-graphene (rGO-TEPA) sheet matrices induction of CaCO3 mineralization and successfully constructed CaCO3/rGO-TEPA drug carriers with a hollow structure and rough surface. As potential drug carriers, doxorubicin (DOX) loading and release measurements were carried out. It showed that load efficiency was 94.7% and the release efficiencies were 13.8% and 91.7% at values of pH 7.4 and 5.0. The as-prepared drug carriers showed some appealing advantages, such as the pH-sensitive release characteristics and mild storage-release behaviors. The excellent biocompatibility and nontoxicity of CaCO3/rGO-TEPA hybrid microspheres were tested by the cell viability of mouse preosteoblast cells (MC3T3-E1). And cytotoxicity with human osteosarcoma cells (MG-63) was carried out to demonstrate the drug release effect in the cells system. Therefore, the CaCO3/rGO-TEPA hybrid microspheres would be a competitive alternative in bone drug carriers.

  15. The control of translational accuracy is a determinant of healthy ageing in yeast

    PubMed Central

    Leadsham, Jane E.; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S.; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F.; Gourlay, Campbell W.

    2017-01-01

    Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. PMID:28100667

  16. The control of translational accuracy is a determinant of healthy ageing in yeast.

    PubMed

    von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

    2017-01-01

    Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing.

  17. Antecedents and Outcomes of Level and Rates of Change in Perceived Control: The Moderating Role of Age

    ERIC Educational Resources Information Center

    Infurna, Frank J.; Okun, Morris A.

    2015-01-01

    Perceived control is interrelated with aging-related outcomes across adulthood and old age. Relatively little is known, however, about resources as antecedents of longitudinal change in perceived control and the role of perceived control as a buffer against mortality risk when these resources are low. We examined functional limitations, depressive…

  18. Everything under Control? The Effects of Age, Gender, and Education on Trajectories of Perceived Control in a Nationally Representative German Sample

    ERIC Educational Resources Information Center

    Specht, Jule; Egloff, Boris; Schmukle, Stefan C.

    2013-01-01

    Perceived control is an important variable for various demands involved in successful aging. However, perceived control is not set in stone but rather changes throughout the life course. The aim of this study was to identify cross-sectional age differences and longitudinal mean-level changes as well as rank-order changes in perceived control with…

  19. Age effects on transfer index performance and executive control in baboons (Papio papio).

    PubMed

    Bonté, Elodie; Kemp, Caralyn; Fagot, Joël

    2014-01-01

    Reversal performance in the transfer index (TI) task is known to improve from prosimians to apes, suggesting that this task is a marker of cognitive evolution within the primate taxa (Rumbaugh, 1970). However, the cognitive processes recruited by this task remain unclear. In the present study, 19 socially-housed baboons (Papio papio) from 1.6 to 14.3 years of age were tested on a computerized version of the TI task, using an automated self-testing procedure. Age was a significant factor in the level of success, with the younger baboons outperforming the adults. The younger baboons learned the pre-reversal discrimination faster and improved their post-reversal performance more rapidly than adult baboons. As 17 of these baboons had already been tested in previous studies on inhibitory control and cognitive flexibility tasks, comparison across tasks provide indicators of the underlying cognitive processes. Age variations in performance were similar between the TI task and in an adaptation of the Wisconsin Card Sorting Task (WCST) measuring cognitive flexibility (Bonté et al., 2011). This contrasts previous results from a task requiring motor inhibitory control (Fagot et al., 2011). Therefore, these findings suggest that cognitive flexibility was a central component of the cognitive system that evolved within non-human primates. They also implicate a decline in executive control with age that begins during early adulthood in this baboon species.

  20. Ca2+-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients

    PubMed Central

    2013-01-01

    Background Nitric oxide is key to endothelial regeneration, but it is still unknown whether endothelial cell (EC) loss results in an increase in NO levels at the wound edge. We have already shown that endothelial damage induces a long-lasting Ca2+ entry into surviving cells though connexin hemichannels (CxHcs) uncoupled from their counterparts on ruptured cells. The physiological outcome of injury-induced Ca2+ inflow is, however, unknown. Methods In this study, we sought to determine whether and how endothelial scraping induces NO production (NOP) in the endothelium of excised rat aorta by exploiting the NO-sensitive fluorochrome, DAF-FM diacetate and the Ca2+-sensitive fluorescent dye, Fura-2/AM. Results We demonstrated that injury-induced NOP at the lesion site is prevented in presence of the endothelial NO synthase inhibitor, L-NAME, and in absence of extracellular Ca2+. Unlike ATP-dependent NO liberation, the NO response to injury is insensitive to BTP-2, which selectively blocks store-operated Ca2+ inflow. However, injury-induced NOP is significantly reduced by classic gap junction blockers, and by connexin mimetic peptides specifically targeting Cx37Hcs, Cx40HCs, and Cx43Hcs. Moreover, disruption of caveolar integrity prevents injury-elicited NO signaling, but not the accompanying Ca2+ response. Conclusions The data presented provide the first evidence that endothelial scraping stimulates NO synthesis at the wound edge, which might both exert an immediate anti-thrombotic and anti-inflammatory action and promote the subsequent re-endothelialization. PMID:24266895

  1. Conspiracy beliefs about birth control: barriers to pregnancy prevention among African Americans of reproductive age.

    PubMed

    Thorburn, Sheryl; Bogart, Laura M

    2005-08-01

    This article examines the endorsement of conspiracy beliefs about birth control (e.g., the belief that birth control is a form of Black genocide) and their association with contraceptive attitudes and behavior among African Americans. The authors conducted a telephone survey with a random sample of 500 African Americans (aged 15-44). Many respondents endorsed birth control conspiracy beliefs, including conspiracy beliefs about Black genocide and the safety of contraceptive methods. Stronger conspiracy beliefs predicted more negative attitudes toward contraceptives. In addition, men with stronger contraceptive safety conspiracy beliefs were less likely to be currently using any birth control. Among current birth control users, women with stronger contraceptive safety conspiracy beliefs were less likely to be using contraceptive methods that must be obtained from a health care provider. Results suggest that conspiracy beliefs are a barrier to pregnancy prevention. Findings point to the need for addressing conspiracy beliefs in public health practice.

  2. The Effect of Aging on the Dynamics of Reactive and Proactive Cognitive Control of Response Interference

    PubMed Central

    Xiang, Ling; Zhang, Baoqiang; Wang, Baoxi; Jiang, Jun; Zhang, Fenghua; Hu, Zhujing

    2016-01-01

    A prime-target interference task was used to investigate the effects of cognitive aging on reactive and proactive control after eliminating frequency confounds and feature repetitions from the cognitive control measures. We used distributional analyses to explore the dynamics of the two control functions by distinguishing the strength of incorrect response capture and the efficiency of suppression control. For reactive control, within-trial conflict control and between-trial conflict adaption were analyzed. The statistical analysis showed that there were no reliable between-trial conflict adaption effects for either young or older adults. For within-trial conflict control, the results revealed that older adults showed larger interference effects on mean RT and mean accuracy. Distributional analyses showed that the decline mainly stemmed from inefficient suppression rather than from stronger incorrect responses. For proactive control, older adults showed comparable proactive conflict resolution to young adults on mean RT and mean accuracy. Distributional analyses showed that older adults were as effective as younger adults in adjusting their responses based on congruency proportion information to minimize automatic response capture and actively suppress the direct response activation. The results suggest that older adults were less proficient at suppressing interference after conflict was detected but can anticipate and prevent inference in response to congruency proportion manipulation. These results challenge earlier views that older adults have selective deficits in proactive control but intact reactive control. PMID:27847482

  3. Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines

    NASA Technical Reports Server (NTRS)

    Sooy, K.; Schermerhorn, T.; Noda, M.; Surana, M.; Rhoten, W. B.; Meyer, M.; Fleischer, N.; Sharp, G. W.; Christakos, S.

    1999-01-01

    The role of the calcium-binding protein, calbindin-D(28k) in potassium/depolarization-stimulated increases in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release was investigated in pancreatic islets from calbindin-D(28k) nullmutant mice (knockouts; KO) or wild type mice and beta cell lines stably transfected and overexpressing calbindin. Using single islets from KO mice and stimulation with 45 mM KCl, the peak of [Ca(2+)](i) was 3.5-fold greater in islets from KO mice compared with wild type islets (p < 0.01) and [Ca(2+)](i) remained higher during the plateau phase. In addition to the increase in [Ca(2+)](i) in response to KCl there was also a significant increase in insulin release in islets isolated from KO mice. Evidence for modulation by calbindin of [Ca(2+)](i) and insulin release was also noted using beta cell lines. Rat calbindin was stably expressed in betaTC-3 and betaHC-13 cells. In response to depolarizing concentrations of K(+), insulin release was decreased by 45-47% in calbindin expressing betaTC cells and was decreased by 70-80% in calbindin expressing betaHC cells compared with insulin release from vector transfected betaTC or betaHC cells (p < 0.01). In addition, the K(+)-stimulated intracellular calcium peak was markedly inhibited in calbindin expressing betaHC cells compared with vector transfected cells (225 nM versus 1,100 nM, respectively). Buffering of the depolarization-induced rise in [Ca(2+)](i) was also observed in calbindin expressing betaTC cells. In summary, our findings, using both isolated islets from calbindin-D(28k) KO mice and beta cell lines, establish a role for calbindin in the modulation of depolarization-stimulated insulin release and suggest that calbindin can control the rate of insulin release via regulation of [Ca(2+)](i).

  4. Multisubject Decomposition of Event-related Positivities in Cognitive Control: Tackling Age-related Changes in Reactive Control.

    PubMed

    Enriquez-Geppert, Stefanie; Barceló, Francisco

    2016-08-13

    Age-related neurocognitive effects have been observed at different levels ranging from reduced amplitudes of even-related potentials and brain oscillations, to topography changes of brain activity. However, their association remains incompletely understood. We investigated time-frequency and time-course effects in functional networks underlying the P300 and their involvement in reactive control. Electroencephalographic (EEG) data of three different age groups (30 young: 18-26 years, 30 mid-aged: 49-58 years, 30 elderly: 65-75 years) was measured while they performed a cued colour/thickness switching task. Neural data was analysed concerning the targets. To consider restart, mixing, and switching processes, the targets´ position after a cue (first or third target) as well as their context in the single-task (distractor cue) or the mixed-task block (switch- or repeat cue) was analysed. P300 EEG data was decomposed by means of group-independent component and time-frequency analyses focusing on theta and beta oscillations. RTs generally slowed down with age (main effect group), and effects were specifically strong in targets after a switching cue (larger Cohens d). Peaking at around 300 ms, we detected five functionally independent networks reflecting the multicomponent process underlying task-switching. These networks differed in terms of their topography (parietal and frontal), their involvement in task processes (switch-specific, mixing-, restart-, and single-task processes) and in terms of frequency effects. All were affected by age, as indicated by amplitude changes of the target-P300 and power reductions most consistently shown in beta oscillations. Most extensive age-related changes were observed in one parietal network sensitive to mixing and restart processes. Changes included a topography shift, P300 and beta amplitudes, and were ongoing in the elderly group.

  5. Expression of Bacillus thuringiensis cytolytic toxin (Cyt2Ca1) in citrus roots to control Diaprepes abbreviatus larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diaprepes abbreviatus (L.) is an important pest of citrus in the USA. Currently, no effective management strategies of Diaprepes abbreviatus exist in citriculture. To protect citrus against Diaprepes abbreviatus a transgenic citrus rootstock expressing Bacillus thuringiensis Cyt2Ca1, an insect toxin...

  6. Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

    PubMed Central

    Coletta, Rocio R D; Jorge, Alexander A L; D' Alva, Catarina Brasil; Pinto, Emília M; Billerbeck, Ana Elisa C; Pachi, Paulo R; Longui, Carlos A; Garcia, Ricardo M; Boguszewski, Margaret; Arnhold, Ivo J P; Mendonca, Berenice B; Costa, Elaine M F

    2013-01-01

    OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance. PMID:23778474

  7. Cognitive Control Modulates Effects of Episodic Simulation on Delay Discounting in Aging

    PubMed Central

    Sasse, Laura K.; Peters, Jan; Brassen, Stefanie

    2017-01-01

    Enhancing prospective thinking by tagging the future with specific episodic events has been shown to reduce delay discounting in young age (“tag-effect”). So far, it is unclear whether such beneficial effect extends to old adulthood. Since the general ability of future thinking and cognitive control are crucial modulators of temporal discounting in young age, potential age-related decline in these functions might impact on the effect. We focused on this issue by combining functional magnetic resonance imaging (fMRI) with an established intertemporal choice task including episodic “tags” in healthy older participants. Future thinking ability was assessed using autobiographical interviews for future event simulations and a visual search task was applied to assess participants’ cognitive control ability. In contrast to previous data in young adults, the group of older participants did not benefit from tagging the future with episodic events. Older participants’ cognitive control function was directly associated with discounting rates in the episodic conditions: the less the older adults were able to focus their attention the less they benefited from the inclusion of episodic events. Consistent with this, imaging results revealed that: (a) subjective value (SV) signals in the hippocampus and the anterior cingulate cortex (ACC) as well as; (b) hippocampal-striatal coupling during the episodic condition were positively related to participants’ control capacity. Our findings highlight the critical role of executive functioning for the simultaneous integration of episodic information with future value computation in aging. Boosting delay gratification by including episodic tags might hence be limited in older individuals with pronounced decline in distraction control. PMID:28352226

  8. Age and Expertise Effects in Aviation Decision Making and Flight Control in a Flight Simulator

    PubMed Central

    Kennedy, Quinn; Taylor, Joy L.; Reade, Gordon; Yesavage, Jerome A.

    2010-01-01

    Introduction Age (due to declines in cognitive abilities necessary for navigation) and level of aviation expertise are two factors that may affect aviation performance and decision making under adverse weather conditions. We examined the roles of age, expertise, and their relationship on aviation decision making and flight control performance during a flight simulator task. Methods Seventy-two IFR-rated general aviators, aged 19–79 yr, made multiple approach, holding pattern entry, and landing decisions while navigating under Instrument Flight Rules weather conditions. Over three trials in which the fog level varied, subjects decided whether or not to land the aircraft. They also completed two holding pattern entries. Subjects’ flight control during approaches and holding patterns was measured. Results Older pilots (41+ yr) were more likely than younger pilots to land when visibility was inadequate (older pilots’ mean false alarm rate: 0.44 vs 0.25). They also showed less precise flight control for components of the approach, performing 0.16 SD below mean approach scores. Expertise attenuated an age-related decline in flight control during holding patterns: older IFR/CFI performed 0.73 SD below mean score; younger IFR/CFI, younger CFII/ATP, older CFII/ATP: 0.32, 0.26, 0.03 SD above mean score. Additionally, pilots with faster processing speed (by median split) had a higher mean landing decision false alarm rate (0.42 vs 0.28), yet performed 0.14 SD above the mean approach control score. Conclusions Results have implications regarding specialized training for older pilots and for understanding processes involved in older adults’ real world decision making and performance. PMID:20464816

  9. Cognitive Control Modulates Effects of Episodic Simulation on Delay Discounting in Aging.

    PubMed

    Sasse, Laura K; Peters, Jan; Brassen, Stefanie

    2017-01-01

    Enhancing prospective thinking by tagging the future with specific episodic events has been shown to reduce delay discounting in young age ("tag-effect"). So far, it is unclear whether such beneficial effect extends to old adulthood. Since the general ability of future thinking and cognitive control are crucial modulators of temporal discounting in young age, potential age-related decline in these functions might impact on the effect. We focused on this issue by combining functional magnetic resonance imaging (fMRI) with an established intertemporal choice task including episodic "tags" in healthy older participants. Future thinking ability was assessed using autobiographical interviews for future event simulations and a visual search task was applied to assess participants' cognitive control ability. In contrast to previous data in young adults, the group of older participants did not benefit from tagging the future with episodic events. Older participants' cognitive control function was directly associated with discounting rates in the episodic conditions: the less the older adults were able to focus their attention the less they benefited from the inclusion of episodic events. Consistent with this, imaging results revealed that: (a) subjective value (SV) signals in the hippocampus and the anterior cingulate cortex (ACC) as well as; (b) hippocampal-striatal coupling during the episodic condition were positively related to participants' control capacity. Our findings highlight the critical role of executive functioning for the simultaneous integration of episodic information with future value computation in aging. Boosting delay gratification by including episodic tags might hence be limited in older individuals with pronounced decline in distraction control.

  10. Controlling polymorphic structures and investigating electric properties of Ca-doped zirconia using solid state ceramic method

    SciTech Connect

    Emam, W.I.; Mabied, Ahmed F.; Hashem, H.M.; Selim, M.M.; El-Shabiny, A.M.; Ahmed Farag, I.S.

    2015-08-15

    Structural study of Zr{sub 1−x}Ca{sub x}O{sub 2−x} samples with x=0.01–0.15 were prepared using solid state ceramic method. X-ray diffraction analysis revealed a mixture of the high temperature phase and the monoclinic one for the samples with x≤0.05. On the other hand, the formation of a single high temperature cubic phase was observed within a concentration range of x=0.06–0.10. At concentrations higher than 0.10 the calcium zirconate phase was observed besides the dominant high temperature one. Rietveld refinement of the single phase data clearly revealed, that substitution of zirconium by calcium increases both the lattice parameters as well as the tetrahedral bond length. Ionic to electronic conductivity ratio enhanced considerably as Ca-doping level ascends. The dielectric constant shows strong temperature dependence at lower frequencies. The dielectric loss factor increases rapidly with the increase in temperature at lower frequencies, while decreases with the increase in frequency at higher temperatures. The ionic conduction is considered as the dominant process at higher temperatures. - Graphical abstract: Forming a high temperature cubic zirconia phase at 1200 °C using ceramic solid state method and aliovalent cation. - Highlights: • Formation the high temperature cubic polymorph of zirconia using Ca-doping. • Solid state ceramic method was used for preparing the cubic Ca-doped zirconia. • Substitution of zirconium by calcium increases the lattice parameters and the bond length. • Ionic to electronic conductivity ratio enhanced considerably as Ca-doping level increases.

  11. Comparison of Brachial Artery Vasoreactivity in Elite Power Athletes and Age-Matched Controls

    PubMed Central

    Welsch, Michael A.; Blalock, Paul; Credeur, Daniel P.; Parish, Tracie R.

    2013-01-01

    Elite endurance athletes typically have larger arteries contributing to greater skeletal muscle blood flow, oxygen and nutrient delivery and improved physical performance. Few studies have examined structural and functional properties of arteries in power athletes. Purpose To compare the size and vasoreactivity of the brachial artery of elite power athletes to age-matched controls. It was hypothesized brachial artery diameters of athletes would be larger, have less vasodilation in response to cuff occlusion, but more constriction after a cold pressor test than age-matched controls. Methods Eight elite power athletes (age = 23±2 years) and ten controls (age = 22±1 yrs) were studied. High-resolution ultrasonography was used to assess brachial artery diameters at rest and following 5 minutes of forearm occlusion (Brachial Artery Flow Mediated Dilation = BAFMD) and a cold pressor test (CPT). Basic fitness measures included a handgrip test and 3-minute step test. Results Brachial arteries of athletes were larger (Athletes 5.39±1.51 vs. Controls: 3.73±0.71 mm, p<0.05), had greater vasodilatory (BAFMD%: Athletes: 8.21±1.78 vs. Controls: 5.69±1.56%) and constrictor (CPT %: Athletes: -2.95±1.07 vs. Controls: −1.20±0.48%) responses, compared to controls. Vascular operating range (VOR = Peak dilation+Peak Constriction) was also greater in athletes (VOR: Athletes: 0.55±0.15 vs. Controls: 0.25±0.18 mm, p<0.05). Athletes had superior handgrip strength (Athletes: 55.92±17.06 vs. Controls: 36.77±17.06 kg, p<0.05) but similar heart rate responses at peak (Athletes: 123±16 vs. Controls: 130±25 bpm, p>0.05) and 1 minute recovery (Athletes: 88±21 vs. Controls: 98±26 bpm, p>0.05) following the step test. Conclusion Elite power athletes have larger brachial arteries, and greater vasoreactivity (greater vasodilatory and constrictor responses) than age-matched controls, contributing to a significantly greater VOR. These data extend the existence of an

  12. Relationships among aging, IQ, and intracranial volume in alcoholics and control subjects.

    PubMed

    Schottenbauer, Michele A; Momenan, Reza; Kerick, Michael; Hommer, Daniel W

    2007-05-01

    The current article examined the relationships among aging, intelligence, intracranial volume, and brain shrinkage in alcoholics and nonalcoholic controls. Magnetic resonance imaging was used to measure intracranial and cerebral volumes in 146 subjects with alcohol use disorders and 42 comparison subjects who were not alcoholic. The authors' findings show that performance on Block Design decreases as alcoholics age, and this decrease is predicted by brain shrinkage. This is consistent with a process of cumulative brain damage related to alcohol use. However, the authors' data also show that vocabulary does not decrease with age and is correlated with premorbid brain size as measured by intracranial volume, suggesting that lower verbal ability precedes heavy alcohol use and may be a risk factor for alcoholism.

  13. Age-related changes in human posture control: Sensory organization tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural control was measured in 214 human subjects ranging in age from 7 to 81 years. Sensory organization tests measured the magnitude of anterior-posterior body sway during six 21 s trials in which visual and somatosensory orientation cues were altered (by rotating the visual surround and support surface in proportion to the subject's sway) or vision eliminated (eyes closed) in various combinations. No age-related increase in postural sway was found for subjects standing on a fixed support surface with eyes open or closed. However, age-related increases in sway were found for conditions involving altered visual or somatosensory cues. Subjects older than about 55 years showed the largest sway increases. Subjects younger than about 15 years were also sensitive to alteration of sensory cues. On average, the older subjects were more affected by altered visual cues whereas younger subjects had more difficulty with altered somatosensory cues.

  14. Aging assessment of the boiling-water reactor (BWR) standby liquid control system. Phase 1

    SciTech Connect

    Orton, R.D.; Johnson, A.B.; Buckley, G.D.; Larson, L.L.

    1992-10-01

    Pacific Northwest Laboratory conducted a Phase I aging assessment of the standby liquid control (SLC) system used in boiling-water reactors. The study was based on detailed reviews of SLC system component and operating experience information obtained from the Nuclear Plant Reliability Database System, the Nuclear Document System, Licensee Event Reports, and other databases. Sources dealing with sodium pentaborate, borates, boric acid, and the effects of environment and corrosion in the SLC system were reviewed to characterize chemical properties and corrosion characteristics of borated solutions. The leading aging degradation concern to date appears to be setpoint drift in relief valves, which has been discovered during routine surveillance and is thought to be caused by mechanical wear. Degradation was also observed in pump seals and internal valves. In general, however, the results of the Phase I study suggest that age-related degradation of SLC systems has not been serious.

  15. Aging assessment of the boiling-water reactor (BWR) standby liquid control system

    SciTech Connect

    Orton, R.D.; Johnson, A.B.; Buckley, G.D.; Larson, L.L.

    1992-10-01

    Pacific Northwest Laboratory conducted a Phase I aging assessment of the standby liquid control (SLC) system used in boiling-water reactors. The study was based on detailed reviews of SLC system component and operating experience information obtained from the Nuclear Plant Reliability Database System, the Nuclear Document System, Licensee Event Reports, and other databases. Sources dealing with sodium pentaborate, borates, boric acid, and the effects of environment and corrosion in the SLC system were reviewed to characterize chemical properties and corrosion characteristics of borated solutions. The leading aging degradation concern to date appears to be setpoint drift in relief valves, which has been discovered during routine surveillance and is thought to be caused by mechanical wear. Degradation was also observed in pump seals and internal valves. In general, however, the results of the Phase I study suggest that age-related degradation of SLC systems has not been serious.

  16. Parenting clinically anxious versus healthy control children aged 4-12 years.

    PubMed

    van der Sluis, C M; van Steensel, F J A; Bögels, S M

    2015-05-01

    This study investigated whether parenting behaviors differed between parents of 68 clinically anxious children and 106 healthy control children aged 4-12 years. The effects of parent gender, child gender and child age on parenting were explored. Mothers and fathers completed a questionnaire to assess parenting behaviors in for children hypothetically anxious situations. Results showed that parents of clinically anxious children reported more anxiety-enhancing parenting (reinforcement of dependency and punishment) as well as more positive parenting (positive reinforcement). For the clinical sample, fathers reported using more modeling/reassurance than mothers, and parents reported using more force with their 4-7-year-olds than with their 8-12-year-olds. No interaction effects were found for child gender with child anxiety status on parenting. Results indicate that for intervention, it is important to measure parenting behaviors, and to take into account father and mother differences and the age of the child.

  17. Presynaptic Control of Glycine Transporter 2 (GlyT2) by Physical and Functional Association with Plasma Membrane Ca2+-ATPase (PMCA) and Na+-Ca2+ Exchanger (NCX)*

    PubMed Central

    de Juan-Sanz, Jaime; Núñez, Enrique; Zafra, Francisco; Berrocal, María; Corbacho, Isaac; Ibáñez, Ignacio; Arribas-González, Esther; Marcos, Daniel; López-Corcuera, Beatriz; Mata, Ana M.; Aragón, Carmen

    2014-01-01

    Fast inhibitory glycinergic transmission occurs in spinal cord, brainstem, and retina to modulate the processing of motor and sensory information. After synaptic vesicle fusion, glycine is recovered back to the presynaptic terminal by the neuronal glycine transporter 2 (GlyT2) to maintain quantal glycine content in synaptic vesicles. The loss of presynaptic GlyT2 drastically impairs the refilling of glycinergic synaptic vesicles and severely disrupts neurotransmission. Indeed, mutations in the gene encoding GlyT2 are the main presynaptic cause of hyperekplexia in humans. Here, we show a novel endogenous regulatory mechanism that can modulate GlyT2 activity based on a compartmentalized interaction between GlyT2, neuronal plasma membrane Ca2+-ATPase (PMCA) isoforms 2 and 3, and Na+/Ca2+-exchanger 1 (NCX1). This GlyT2·PMCA2,3·NCX1 complex is found in lipid raft subdomains where GlyT2 has been previously found to be fully active. We show that endogenous PMCA and NCX activities are necessary for GlyT2 activity and that this modulation depends on lipid raft integrity. Besides, we propose a model in which GlyT2·PMCA2–3·NCX complex would help Na+/K+-ATPase in controlling local Na+ increases derived from GlyT2 activity after neurotransmitter release. PMID:25315779

  18. Discrimination of speech sounds by children with dyslexia: comparisons with chronological age and reading level controls.

    PubMed

    Bogliotti, C; Serniclaes, W; Messaoud-Galusi, S; Sprenger-Charolles, L

    2008-10-01

    Previous studies have shown that children suffering from developmental dyslexia have a deficit in categorical perception of speech sounds. The aim of the current study was to better understand the nature of this categorical perception deficit. In this study, categorical perception skills of children with dyslexia were compared with those of chronological age and reading level controls. Children identified and discriminated /do-to/ syllables along a voice onset time (VOT) continuum. Results showed that children with dyslexia discriminated among phonemically contrastive pairs less accurately than did chronological age and reading level controls and also showed higher sensitivity in the discrimination of allophonic contrasts. These results suggest that children with dyslexia perceive speech with allophonic units rather than phonemic units. The origin of allophonic perception in the course of perceptual development and its implication for reading acquisition are discussed.

  19. FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging.

    PubMed

    Li, Hanjun; Liu, Pei; Xu, Shuqin; Li, Yinghua; Dekker, Joseph D; Li, Baojie; Fan, Ying; Zhang, Zhenlin; Hong, Yang; Yang, Gong; Tang, Tingting; Ren, Yongxin; Tucker, Haley O; Yao, Zhengju; Guo, Xizhi

    2017-04-03

    A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A. Conditional depletion of Foxp1 in bone marrow MSCs led to premature aging characteristics, including increased bone marrow adiposity, decreased bone mass, and impaired MSC self-renewal capacity in mice. At the molecular level, FOXP1 regulated cell-fate choice of MSCs through interactions with the CEBPβ/δ complex and recombination signal binding protein for immunoglobulin κ J region (RBPjκ), key modulators of adipogenesis and osteogenesis, respectively. Loss of p16INK4A in Foxp1-deficient MSCs partially rescued the defects in replication capacity and bone mass accrual. Promoter occupancy analyses revealed that FOXP1 directly represses transcription of p16INK4A. These results indicate that FOXP1 attenuates MSC senescence by orchestrating their cell-fate switch while maintaining their replicative capacity in a dose- and age-dependent manner.

  20. Hydrologic control of carbon cycling and aged carbon discharge in the Congo River basin

    NASA Astrophysics Data System (ADS)

    Schefuß, Enno; Eglinton, Timothy I.; Spencer-Jones, Charlotte L.; Rullkötter, Jürgen; de Pol-Holz, Ricardo; Talbot, Helen M.; Grootes, Pieter M.; Schneider, Ralph R.

    2016-09-01

    The age of organic material discharged by rivers provides information about its sources and carbon cycling processes within watersheds. Although elevated ages in fluvially transported organic matter are usually explained by erosion of soils and sedimentary deposits, it is commonly assumed that mainly young organic material is discharged from flat tropical watersheds due to their extensive plant cover and rapid carbon turnover. Here we present compound-specific radiocarbon data of terrigenous organic fractions from a sedimentary archive offshore the Congo River, in conjunction with molecular markers for methane-producing land cover reflecting wetland extent. We find that the Congo River has been discharging aged organic matter for several thousand years, with apparently increasing ages from the mid- to the Late Holocene. This suggests that aged organic matter in modern samples is concealed by radiocarbon from atmospheric nuclear weapons testing. By comparison to indicators for past rainfall changes we detect a systematic control of organic matter sequestration and release by continental hydrology, mediating temporary carbon storage in wetlands. As aridification also leads to exposure and rapid remineralization of large amounts of previously stored labile organic matter, we infer that this process may cause a profound direct climate feedback that is at present underestimated in carbon cycle assessments.

  1. Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging.

    PubMed

    Crane, Justin D; MacNeil, Lauren G; Lally, James S; Ford, Rebecca J; Bujak, Adam L; Brar, Ikdip K; Kemp, Bruce E; Raha, Sandeep; Steinberg, Gregory R; Tarnopolsky, Mark A

    2015-08-01

    Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging.

  2. Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging

    PubMed Central

    Crane, Justin D; MacNeil, Lauren G; Lally, James S; Ford, Rebecca J; Bujak, Adam L; Brar, Ikdip K; Kemp, Bruce E; Raha, Sandeep; Steinberg, Gregory R; Tarnopolsky, Mark A

    2015-01-01

    Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging. PMID:25902870

  3. Challenges in Recruiting Aging Women Holocaust Survivors to a Case Control Study of Breast Cancer.

    PubMed

    Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

    2015-01-01

    Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel.

  4. Age Differences in the Demand–Control Model of Work Stress

    PubMed Central

    Shultz, Kenneth S.; Wang, Mo; Crimmins, Eileen M.; Fisher, Gwenith G.

    2010-01-01

    There have been many tests of Karasek’s demand–control model of work stress. However, no studies have examined how the model may differentially apply to older versus younger workers. Due to age changes in cognitive processing, the psychological demands of jobs may interact differently with controls for younger versus older workers. Therefore, the study uses data from the Eurobarometer to examine how the demand–control model of work stress may function differently for older versus younger workers. The results indicate that different controls may in fact buffer different types of job demands for younger versus older workers. The findings reveal that only the interaction between problem solving and time to complete tasks was significant for younger workers. For older workers, however, the interactions between time deadlines and having sufficient time to complete tasks, autonomy, and the interaction between problem solving and schedule flexibility are significant predictors of self-reported stress. PMID:20948986

  5. A proteomic study of protein variation between osteopenic and age-matched control bone tissue.

    PubMed

    Chaput, Christopher D; Dangott, Lawrence J; Rahm, Mark D; Hitt, Kirby D; Stewart, Donald S; Wayne Sampson, H

    2012-05-01

    The focus of this study was to identify changes in protein expression within the bone tissue environment between osteopenic and control bone tissue of human femoral neck patients with osteoarthritis. Femoral necks were compared from osteopenic patients and age-matched controls. A new method of bone protein extraction was developed to provide a swift, clear view of the bone proteome. Relative changes in protein expression between control and osteopenic samples were quantified using difference gel electrophoresis (DIGE) technology after affinity chromatographic depletion of albumin and IgG. The proteins that were determined to be differentially expressed were identified using standard liquid chromatography mass spectrometry (LC/MS/MS) and database searching techniques. In order to rule out blood contamination, blood from age-matched osteoporotic, osteopenic and controls were analyzed in a similar manner. Image analysis of the DIGE gels indicated that 145 spots in the osteopenic bone samples changed at least ± 1.5-fold from the control samples (P < 0.05). Three of the proteins were identified by LC/MS/MS. Of the proteins that increased in the osteopenic femurs, two were especially significant: carbonic anhydrase I and phosphoglycerate kinase 1. Apolipoprotein A-I was the most prominent protein that significantly decreased in the osteopenic femurs. The blood samples revealed no significant differences between groups for any of these proteins. In conclusion, carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis.

  6. Does age affect the relationship between control at work and sleep disturbance for shift workers?

    PubMed

    Loudoun, Rebecca Jane; Muurlink, Olav; Peetz, David; Murray, Georgina

    2014-12-01

    Among miners, shift work, aging and lack of control at work may be factors leading to increased sleep problems. Such risk factors may also operate in interaction, resulting in an even increased harm for sleep disruption. The present study aims at evaluating these relationships drawing on a sample of Australian mine and energy workers and their partners. The workers were mainly men. All performed shift work that included either nights (95%) or multiple shifts (92%), usually both (87%), while 36% were aged 50 years or above. The results show that low latitude over work activities is associated with higher sleep disturbances across the sample, though the effects are clearer amongst younger workers. By contrast, for younger workers, control over shift scheduling is not associated with sleep disturbances but for workers aged 50 or more, low control results in more sleep disturbance. Misalignment between shift workers and partner work schedules, and partner dissatisfaction with shift worker's employment and shift worker's work-life balance, are also associated with more sleep disturbances amongst shift workers.

  7. Effects of incentives, age, and behavior on brain activation during inhibitory control: a longitudinal fMRI study.

    PubMed

    Paulsen, David J; Hallquist, Michael N; Geier, Charles F; Luna, Beatriz

    2015-02-01

    We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control.

  8. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  9. Release of the Biological Control Agent Puccinia jaceae var. solstitialis for Management of Yellow Starthistle at Fort Hunter Liggett, CA

    DTIC Science & Technology

    2010-07-01

    DiTomaso 2005). Seed germination starts in the fall and can continue into winter and spring depending on moisture availability (Benefield et al. 2001...Fort Hunter Liggett, CA. Note the spines on the seed heads. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the...Following germination , the plant allocates resources initially to root growth and then to leaf expansion, stem development, and flower production

  10. Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

    PubMed

    Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

    2016-06-01

    Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

  11. Brain-derived neurotrophic factor controls activity-dependent maturation of CA1 synapses by downregulating tonic activation of presynaptic kainate receptors.

    PubMed

    Sallert, Marko; Rantamäki, Tomi; Vesikansa, Aino; Anthoni, Heidi; Harju, Kirsi; Yli-Kauhaluoma, Jari; Taira, Tomi; Castren, Eero; Lauri, Sari E

    2009-09-09

    Immature hippocampal synapses express presynaptic kainate receptors (KARs), which tonically inhibit glutamate release. Presynaptic maturation involves activity-dependent downregulation of the tonic KAR activity and consequent increase in release probability; however, the molecular mechanisms underlying this developmental process are unknown. Here, we have investigated whether brain derived neurotrophic factor (BDNF), a secreted protein implicated in developmental plasticity in several areas of the brain, controls presynaptic maturation by regulating KARs. Application of BDNF in neonate hippocampal slices resulted in increase in synaptic transmission that fully occluded the immature-type KAR activity in area CA1. Conversely, genetic ablation of BDNF was associated with delayed synaptic maturation and persistent presynaptic KAR activity, suggesting a role for endogenous BDNF in the developmental regulation of KAR function. In addition, our data suggests a critical role for BDNF TrkB signaling in fast activity-dependent regulation of KARs. Selective acute inhibition of TrkB receptors using a chemical-genetic approach prevented rapid change in synapse dynamics and loss of tonic KAR activity that is typically seen in response to induction of LTP at immature synapses. Together, these data show that BDNF-TrkB-dependent maturation of glutamatergic synapses is tightly associated with a loss of endogenous KAR activity. The coordinated action of these two receptor mechanisms has immediate physiological relevance in controlling presynaptic efficacy and transmission dynamics at CA3-CA1 synapses at a stage of development when functional contact already exists but transmission is weak.

  12. Controllable synthesis of hierarchical nanostructures of CaWO{sub 4} and SrWO{sub 4} via a facile low-temperature route

    SciTech Connect

    Chen, Z.; Gong, Q.; Zhu, J.; Yuan, Y.P.; Qian, L.W.; Qian, X.F.

    2009-01-08

    CaWO{sub 4} and SrWO{sub 4} nanostructures have been synthesized via a simple microemulsion-mediated route. With careful control of the fundamental experimental parameters including the concentration of reactants, the reaction time and the temperature, the products with different morphologies of dumbbell, coral, rod and dendrite have been obtained, respectively. The possible formation mechanism of these unique morphologies has been proposed based on surfactant self-assembly under different experimental conditions. The as-synthesized CaWO{sub 4} samples with various morphologies exhibit different photoluminescence properties. X-ray powder diffraction, transmission electron microscopy, field-emission scanning electron microscopy, and luminescence spectroscopy were used to characterize these products.

  13. Control of mean ionic radius at Ca site by Sr co-doping for Ce doped LiCaAlF6 single crystals and the effects on optical and scintillation properties

    NASA Astrophysics Data System (ADS)

    Yokota, Yuui; Yamaji, Akihiro; Kurosawa, Shunsuke; Kamada, Kei; Yoshikawa, Akira

    2014-10-01

    Sr co-doped Ce:LiCaAlF6 [Ce:Li(Ca,Sr)AlF6] crystals with various Ca/Sr ratios were grown by a micro-pulling-down (μ-PD) method and effects of Sr co-doping on crystal structure, chemical composition, optical and scintillation properties for Ce:LiCaAlF6 crystals were investigated as a neutron scintillator. High transparent Ce2%:Li(Ca,Sr)AlF6 crystals with 2% and 5% Sr contents were obtained while Ce2%:Li(Ca,Sr)AlF6 crystals with 10% and 20% Sr contents included milky parts in the crystals. a- and c-axis lengths of Ce:Li(Ca,Sr)AlF6 phase systematically increased with an increase of Sr content. In addition to the emission at 284 and 308 nm from Ce3+ ion, emission peaks at 367 nm appeared by Sr co-doping.

  14. A Case-Controlled Study of Successful Aging in Older Adults with HIV

    PubMed Central

    Moore, Raeanne C.; Moore, David J.; Thompson, Wesley; Vahia, Ipsit V.; Grant, Igor; Jeste, Dilip V.

    2013-01-01

    OBJECTIVES There is a growing public health interest in the aging HIV-infected (HIV+) population, although there is a dearth of research on successful aging with HIV. This study aimed to understand the risk and protective factors associated with self-rated successful aging (SRSA) with HIV. DESIGN Cross-sectional, case-controlled. SETTING HIV Neurobehavioral Research Program and the Stein Institute for Research on Aging at University of California, San Diego. PARTICIPANTS Eighty-three community-dwelling HIV+ and 83 demographically matched HIV-uninfected (HIV−) individuals, enrolled between 12/1/11 and 5/10/12, mean age of 59 years, primarily Caucasian males, 69% with AIDS, who had been living with an HIV diagnosis for 16 years. Diagnostic criteria for HIV/AIDS was obtained through a blood draw. MEASUREMENTS Participants provided ratings of SRSA as part of a comprehensive survey which included measures of physical and emotional functioning and positive psychological traits. Relationships between how the different variables related to SRSA were explored. RESULTS While SRSA was lower in the HIV+ individuals than their HIV− counterparts, 66% of adults with HIV reported scores of 5 or higher on a 10-point scale of SRSA. Despite worse physical and mental functioning and greater psychosocial stress among the HIV+ participants, the two groups had comparable levels of optimism, personal mastery, and social support. SRSA in HIV+ individuals was associated with better physical and emotional functioning and positive psychological factors, but not HIV disease status or negative life events. CONCLUSION Successful psychosocial aging is possible in older HIV+ individuals. Positive psychological traits such as resilience, optimism, and sense of personal mastery have stronger relationship with SRSA than duration or severity of HIV disease. Research on interventions to enhance these positive traits in HIV+ adults is warranted. PMID:23759460

  15. Prenatal Methamphetamine Exposure and Inhibitory Control among Young School-Age Children

    PubMed Central

    Derauf, Chris; LaGasse, Linda L.; Smith, Lynne M.; Newman, Elana; Shah, Rizwan; Neal, Charles; Arria, Amelia; Huestis, Marilyn A.; Grotta, Sheri Della; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.

    2012-01-01

    Objective To examine the association between prenatal methamphetamine exposure and inhibitory control in 66 month old children followed since birth in the multicenter, longitudinal Infant Development, Environment and Lifestyle Study. Study design The sample included 137 children with prenatal methamphetamine exposure and 130 comparison children, matched for race, birth weight, maternal education and type of insurance. Inhibitory control, an executive function related to emotional and cognitive control, was assessed using a computerized Stroop-like task developed for young children. Hierarchical linear modeling tested the relationship between the extent (heavy, some and no use) of prenatal methamphetamine exposure and accuracy and reaction time outcomes, adjusting for prenatal exposure to alcohol, tobacco and marijuana, age, sex, socioeconomic status, caregiver IQ and psychological symptoms, child protective services report of physical or sexual abuse, and site. Results In adjusted analyses, heavy prenatal methamphetamine exposure was related to reduced accuracy in both the incongruent and mixed conditions on the Stroop task. Caregiver psychological symptoms and Child Protective Services (CPS) report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed, and incongruent conditions, respectively. Conclusions Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, is related to subtle deficits in inhibitory control during the early school-aged years. PMID:22424953

  16. Age and Sex Differences in Controlled Force Exertion Measured by a Computing Bar Chart Target-Pursuit System

    ERIC Educational Resources Information Center

    Nagasawa, Yoshinori; Demura, Shinichi

    2009-01-01

    This study aimed to examine the age and sex differences in controlled force exertion measured by the bar chart display in 207 males (age 42.1 [plus or minus] 19.8 years) and 249 females (age 41.7 [plus or minus] 19.1 years) aged 15 to 86 years. The subjects matched their submaximal grip strength to changing demand values, which appeared as a…

  17. Influence of BCL2-938C>A and BAX-248G>A promoter polymorphisms in the development of AML: case-control study from South India.

    PubMed

    Cingeetham, Anuradha; Vuree, Sugunakar; Dunna, Nageswara Rao; Gorre, Manjula; Nanchari, Santhoshi Rani; Edathara, Prajitha Mohandas; Meka, Phannibhushann; Annamaneni, Sandhya; Digumarthi, Raghunadharao; Sinha, Sudha; Satti, Vishnupriya

    2015-09-01

    B-cell lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) proteins are anti-apoptotic and pro-apoptotic determinants of mitochondrial-mediated apoptosis, and their relative expression determines the cell fate. The promoter polymorphisms in these genes were shown to alter the protein function or expression and exert an impact on apoptosis regulation. Deregulation in the expression of any of these genes leads to disruption of cellular homeostasis and malignant transformation. The present study was aimed to determine the association of BCL2-938C>A and BAX-248G>A promoter polymorphisms with origin and progression of acute myeloid leukemia (AML). We also have performed combined genotype analysis to evaluate the cumulative effect of risk genotypes in the AML development. These polymorphisms were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in 221 AML patients and 305 age- and sex-matched healthy controls. Our study revealed that BCL2-938CA (p = 0.018) and BAX-248GG (0.043) genotypes were significantly associated with increased risk for AML occurrence. BAX-248A allele had shown decreased risk for AML. The combined analysis had shown that BCL2-938CA+AA-BAX-248GG group had a 1.63-fold (95 % CI: 1.08-2.45, p = 0.02) increased risk for AML. None of the clinical variables had shown any significant association with both polymorphisms. With respect to complete remission (CR) rate, BAX-248GG genotype (p = 0.002) and G allele (p = 0.009) had conferred significant risk for complete remission failure. Although the log rank test was not significant, survival analysis had shown a trend where BCL2-938CA genotype, and BAX-248GG had reduced median disease-free survival (DFS) of 9 and 10 months, respectively. In conclusion, BCL2-938C>A and BAX-248G>A gene polymorphisms might contribute to the origin of AML. Moreover, influence of BAX-248GG genotype on CR and DFS rate suggests that the BAX-248G>A polymorphism can serve as

  18. The Origin of Aging: Imperfectness-Driven Non-Random Damage Defines the Aging Process and Control of Lifespan

    PubMed Central

    Gladyshev, Vadim N.

    2013-01-01

    Physico-chemical properties preclude ideal biomolecules and perfect biological functions. This inherent imperfectness leads to the generation of damage by every biological process, at all levels, from small molecules to cells. The damage is too numerous to be repaired, is partially invisible to natural selection and manifests as aging. I propose that it is the inherent imperfectness of biological systems that is the true root of the aging process. As each biomolecule generates specific forms of damage, the cumulative damage is largely non-random and is indirectly encoded in the genome. I consider this concept in light of other proposed theories of aging and integrate these disparate ideas into a single model. I also discuss the evolutionary significance of damage accumulation and strategies for reducing damage. Finally, I suggest ways to test this integrated model of aging. PMID:23769208

  19. Spatial protein quality control and the evolution of lineage-specific ageing

    PubMed Central

    Nyström, Thomas

    2011-01-01

    Propagation of a species requires periodic cell renewal to avoid clonal extinction. Sexual reproduction and the separation of germ cells from the soma provide a mechanism for such renewal, but are accompanied by an apparently mandatory ageing of the soma. Data obtained during the last decade suggest that a division of labour exists also between cells of vegetatively reproducing unicellular organisms, leading to the establishment of a soma-like and germ-like lineage with distinct fitness and longevity characteristics. This division of labour in both bacteria and yeast entails segregation of damaged and aggregated proteins such that the germ-like lineage is kept free of damage to the detriment of the soma-like lineage. In yeast, this spatial protein quality control (SQC) encompasses a CCT-chaperonin-dependent translocation and merging of cytotoxic protein aggregates. This process is regulated by Sir2, a protein deacetylase that modulates the rate of ageing in organisms ranging from yeast to worms and flies. Recent data also demonstrate that SQC is intimately integrated with the machinery establishing proper cell polarity and that this machinery is required for generating a soma-like and germ-like lineage in yeast. Deciphering the details of the SQC network may increase our understanding of the development of age-related protein folding disorders and shed light on the selective forces that paved the way for polarity and lineage-specific ageing to evolve. PMID:21115532

  20. Effects of physical training on age-related balance and postural control.

    PubMed

    Lelard, T; Ahmaidi, S

    2015-11-01

    In this paper, we review the effects of physical activity on balance performance in the elderly. The increase in the incidence of falls with age reflects the disorders of balance-related to aging. We are particularly interested in age-related changes in the balance control system as reflected in different static and dynamic balance tests. We report the results of studies demonstrating the beneficial effects of physical activity on postural balance. By comparing groups of practitioners of different physical activities, it appears that these effects on postural control depend on the type of activity and the time of practice. Thus, we have focused in the present review on "proprioceptive" and "strength" activities. Training programs offering a combination of several activities have demonstrated beneficial effects on the incidence of falls, and we present and compare the effects of these two types of training activities. It emerges that there are differential effects of programs of activities: while all activities improve participants' confidence in their ability, the "proprioceptive" activities rather improve performance in static tasks, while "strength" activities tend to improve performance in dynamic tasks. These effects depend on the targeted population and will have a greater impact on the frailest subjects. The use of new technologies in the form of "exergames" may also be proposed in home-based exercises.

  1. Age-dependent Maintenance of Motor Control and Corticostriatal Innervation by Death Receptor 3

    PubMed Central

    Twohig, Jason Peter; Roberts, Malcolm I.; Gavalda, Nuria; Rees-Taylor, Emma L.; Giralt, Albert; Adams, Debbie; Brooks, Simon P.; Bull, Melanie J.; Calder, Claudia J.; Cuff, Simone; Yong, Audrey A.; Alberch, Jordi; Davies, Alun; Dunnett, Stephen B.; Tolkovsky, Aviva M.; Wang, Eddie C. Y.

    2010-01-01

    Death Receptor 3 is a proinflammatory member of the immunomodulatory tumour necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats and humans although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region specific pattern. Behavioural studies on DR3-deficient (DR3ko) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3ko mice progressively developed behavioral defects characterised by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3ko mice. These studies indicate that DR3 plays a key non-redundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease. PMID:20220013

  2. Effect of a quality-controlled fermented nutraceutical on skin aging markers: An antioxidant-control, double-blind study

    PubMed Central

    BERTUCCELLI, GIUSEPPE; ZERBINATI, NICOLA; MARCELLINO, MASSIMILIANO; NANDA KUMAR, NAVALPUR SHANMUGAM; HE, FANG; TSEPAKOLENKO, VLADIMIR; CERVI, JOSEPH; LORENZETTI, ALDO; MAROTTA, FRANCESCO

    2016-01-01

    The aim of the present study was to determine whether oral supplementation with a fermented papaya preparation (FPP-treated group) or an antioxidant cocktail (antioxidant-control group, composed of 10 mg trans-resveratrol, 60 µg selenium, 10 mg vitamin E and 50 mg vitamin C) was able to improve the skin antioxidant capacity and the expression of key skin genes, while promoting skin antiaging effects. The study enrolled 60 healthy non-smoker males and females aged 40–65 years, all of whom showed clinical signs of skin aging. The subjects were randomly divided into two matched groups, and were administered FPP or antioxidant treatment of a 4.5 g/day sachet sublingually twice a day for 90 days in a double-blind fashion. The parameters investigated were: Skin surface, brown spots, skin evenness, skin moisturization, elasticity (face), redox balance, nitric oxide (NO) concentration, and the expression levels of key genes (outer forearm sample). As compared with the baseline (day 0) and antioxidant-control values, FPP-treated subjects showed a significant improvement in skin evenness, moisturization and elasticity. The two treatments improved the MDA and SOD skin concentrations, but only the FPP-treated group showed a higher SOD level and a significant NO increase, along with significant upregulation of acquaporin-3 and downregulation of the potentially pro-aging/carcinogenetic cyclophilin-A and CD147 genes (P<0.05). Progerin was unaffected in both treatment groups. In conclusion, these findings suggest that orally-administered FPP showed a consistent biological and gene-regulatory improvement in the skin, as was also demonstrated in previous experimental and clinical trials testing other tissues, while common oral antioxidants had only a minor effect. PMID:26998011

  3. Controls on the age of vascular plant biomarkers in Black Sea sediments

    NASA Astrophysics Data System (ADS)

    Kusch, Stephanie; Rethemeyer, Janet; Schefuß, Enno; Mollenhauer, Gesine

    2010-12-01

    Transfer of organic carbon (OC) from the terrestrial to the oceanic carbon pool is largely driven by riverine and aeolian transport. Before transport, however, terrigenous organic matter can be retained in intermediate terrestrial reservoirs such as soils. Using compound-specific radiocarbon analysis of terrigenous biomarkers their average terrestrial residence time can be evaluated. Here we show compound-specific radiocarbon ( 14C) ages of terrigenous biomarkers and bulk 14C ages accompanied by geochemical proxy data from core top samples collected along transects in front of several river mouths in the Black Sea. 14C ages of long chain n-alkanes, long chain n-fatty acids and total organic carbon (TOC) are highest in front of the river mouths, correlating well with BIT (branched and isoprenoid tetraether) indices, which indicates contribution of pre-aged, soil-derived terrigenous organic matter. The radiocarbon ages decrease further offshore towards locations where organic matter is dominated by marine production and aeolian input potentially contributes terrigenous organic matter. Average terrestrial residence times of vascular plant biomarkers deduced from n-C 29+31 alkanes and n-C 28+30 fatty acids ages from stations directly in front of the river mouths range from 900 ± 70 years to 4400 ± 170 years. These average residence times correlate with size and topography in climatically similar catchments, whereas the climatic regime appears to control continental carbon turnover times in morphologically similar drainage areas of the Black Sea catchment. Along-transect data imply petrogenic contribution of n-C 29+31 alkanes and input via different terrigenous biomarker transport modes, i.e., riverine and aeolian, resulting in aged biomarkers at offshore core locations. Because n-C 29+31 alkanes show contributions from petrogenic sources, n-C 28+30 fatty acids likely provide better estimates of average terrestrial residence times of vascular plant biomarkers

  4. Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism.

    PubMed

    Lebeau, Paul; Al-Hashimi, Ali; Sood, Sudesh; Lhoták, Šárka; Yu, Pei; Gyulay, Gabriel; Paré, Guillaume; Chen, S R Wayne; Trigatti, Bernardo; Prat, Annik; Seidah, Nabil G; Austin, Richard C

    2017-01-27

    Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER-localized transcription factor that directly up-regulates sterol regulatory genes, including PCSK9 Given that PCSK9 contributes to atherosclerosis by targeting low density lipoprotein (LDL) receptor (LDLR) degradation, this study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression. Herein, we demonstrate the existence of two independent effects of ER stress on PCSK9 expression and secretion. In cultured HuH7 and HepG2 cells, agents or conditions that cause ER Ca(2+) depletion, including thapsigargin, induced SREBP2-dependent up-regulation of PCSK9 expression. In contrast, a significant reduction in the secreted form of PCSK9 protein was observed in the media from both thapsigargin- and tunicamycin (TM)-treated HuH7 cells, mouse primary hepatocytes, and in the plasma of TM-treated C57BL/6 mice. Furthermore, TM significantly increased hepatic LDLR expression and reduced plasma LDL concentrations in mice. Based on these findings, we propose a model in which ER Ca(2+) depletion promotes the activation of SREBP2 and subsequent transcription of PCSK9. However, conditions that cause ER stress regardless of their ability to dysregulate ER Ca(2+) inhibit PCSK9 secretion, thereby reducing PCSK9-mediated LDLR degradation and promoting LDLR-dependent hepatic cholesterol uptake. Taken together, our studies provide evidence that the retention of PCSK9 in the ER may serve as a potential strategy for lowering LDL cholesterol levels.

  5. Mitochondrial Haplogroups and Control Region Polymorphisms in Age-Related Macular Degeneration: A Case-Control Study

    PubMed Central

    Eder, Waltraud; Mayr, Johannes A.; Egger, Stefan F.; Nischler, Christian; Oberkofler, Hannes; Reitsamer, Herbert A.; Patsch, Wolfgang; Sperl, Wolfgang; Kofler, Barbara

    2012-01-01

    Background Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. Methodology/Principal Findings Mitochondrial haplogroups (combinations of mtDNA polymorphisms) and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV), in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C), are linked to those haplogroups. Conclusions/Significance It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems to be protective for AMD. PMID:22348027

  6. Aging affects motor skill learning when the task requires inhibitory control.

    PubMed

    Brosseau, Julie; Potvin, Marie-Julie; Rouleau, Isabelle

    2007-01-01

    Few studies have examined the influence of aging on motor skill learning (MSL) tasks involving different skills and conditions. Two tasks, each including two different conditions (repeated and nonrepeated), were used: (a) the Mirror Tracing task, requiring the inhibition of an overlearned response and the learning of a new visuomotor association, and (b) the Pursuit Tracking task, mainly requiring the processing of visuospatial stimuli. We hypothesized that older participants would benefit as much as younger participants from the stimuli repetition and that they would exhibit a slower learning rate exclusively on the Mirror Tracing task. As expected, older and younger participants' MSL were not differentially affected by task conditions. They also showed a similar learning rate on the Pursuit Tracking task and a subgroup of older participants exhibited MSL difficulties on the Mirror Tracing task. Problems in the inhibitory control of competing motor memories could explain these age-related MSL difficulties.

  7. Phosphorylation of bacterial-type phosphoenolpyruvate carboxylase by a Ca2+-dependent protein kinase suggests a link between Ca2+ signalling and anaplerotic pathway control in developing castor oil seeds.

    PubMed

    Hill, Allyson T; Ying, Sheng; Plaxton, William C

    2014-02-15

    The aim of the present study was to characterize the native protein kinase [BTPC (bacterial-type phosphoenolpyruvate carboxylase)-K (BTPC Ser451 kinase)] that in vivo phosphorylates Ser451 of the BTPC subunits of an unusual Class-2 PEP (phosphoenolpyruvate) carboxylase hetero-octameric complex of developing COS (castor oil seeds). COS BTPC-K was highly purified by PEG fractionation and hydrophobic size-exclusion anion-exchange and affinity chromatographies. BTPC-K phosphorylated BTPC strictly at Ser451 (Km=1.0 μM; pH optimum=7.3), a conserved target residue occurring within an intrinsically disordered region, as well as the protein histone III-S (Km=1.7 μM), but not a COS plant-type PEP carboxylase or sucrose synthase or α-casein. Its activity was Ca2+- (K0.5=2.7 μM) and ATP- (Km=6.6 μM) dependent, and markedly inhibited by trifluoperazine, 3-phosphoglycerate and PEP, but insensitive to calmodulin or 14-3-3 proteins. BTPC-K exhibited a native molecular mass of ~63 kDa and was soluble rather than membrane-bound. Inactivation and reactivation occurred upon BTPC-K's incubation with GSSG and then DTT respectively. Ser451 phosphorylation by BTPC-K inhibited BTPC activity by ~50% when assayed under suboptimal conditions (pH 7.3, 1 mM PEP and 10 mM L-malate). Our collective results indicate a possible link between cytosolic Ca2+ signalling and anaplerotic flux control in developing COS.

  8. Age-Related Differences in Vehicle Control and Eye Movement Patterns at Intersections: Older and Middle-Aged Drivers

    PubMed Central

    Yamani, Yusuke; Horrey, William J.; Liang, Yulan; Fisher, Donald L.

    2016-01-01

    Older drivers are at increased risk of intersection crashes. Previous work found that older drivers execute less frequent glances for detecting potential threats at intersections than middle-aged drivers. Yet, earlier work has also shown that an active training program doubled the frequency of these glances among older drivers, suggesting that these effects are not necessarily due to age-related functional declines. In light of findings, the current study sought to explore the ability of older drivers to coordinate their head and eye movements while simultaneously steering the vehicle as well as their glance behavior at intersections. In a driving simulator, older (M = 76 yrs) and middle-aged (M = 58 yrs) drivers completed different driving tasks: (1) travelling straight on a highway while scanning for peripheral information (a visual search task) and (2) navigating intersections with areas potential hazard. The results replicate that the older drivers did not execute glances for potential threats to the sides when turning at intersections as frequently as the middle-aged drivers. Furthermore, the results demonstrate costs of performing two concurrent tasks, highway driving and visual search task on the side displays: the older drivers performed more poorly on the visual search task and needed to correct their steering positions more compared to the middle-aged counterparts. The findings are consistent with the predictions and discussed in terms of a decoupling hypothesis, providing an account for the effects of the active training program. PMID:27736887

  9. Biotic Control of Surface pH and Evidence of Light-Induced H+ Pumping and Ca2+-H+ Exchange in a Tropical Crustose Coralline Alga

    PubMed Central

    Hofmann, Laurie C.; Koch, Marguerite; de Beer, Dirk

    2016-01-01

    Presently, an incomplete mechanistic understanding of tropical reef macroalgae photosynthesis and calcification restricts predictions of how these important autotrophs will respond to global change. Therefore, we investigated the mechanistic link between inorganic carbon uptake pathways, photosynthesis and calcification in a tropical crustose coralline alga (CCA) using microsensors. We measured pH, oxygen (O2), and calcium (Ca2+) dynamics and fluxes at the thallus surface under ambient (8.1) and low (7.8) seawater pH (pHSW) and across a range of irradiances. Acetazolamide (AZ) was used to inhibit extracellular carbonic anhydrase (CAext), which mediates hydrolysis of HCO3-, and 4,4′ diisothiocyanatostilbene-2,2′-disulphonate (DIDS) that blocks direct HCO3- uptake by anion exchange transport. Both inhibited photosynthesis, suggesting both diffusive uptake of CO2 via HCO3- hydrolysis to CO2 and direct HCO3- ion transport are important in this CCA. Surface pH was raised approximately 0.3 units at saturating irradiance, but less when CAext was inhibited. Surface pH was lower at pHSW 7.8 than pHSW 8.1 in the dark, but not in the light. The Ca2+ fluxes were large, complex and temporally variable, but revealed net Ca2+ uptake under all conditions. The temporal variability in Ca2+ dynamics was potentially related to localized dissolution during epithallial cell sloughing, a strategy of CCA to remove epiphytes. Simultaneous Ca2+ and pH dynamics suggest the presence of Ca2+/H+ exchange. Rapid light-induced H+ surface dynamics that continued after inhibition of photosynthesis revealed the presence of a light-mediated, but photosynthesis-independent, proton pump. Thus, the study indicates metabolic control of surface pH can occur in CCA through photosynthesis and light-inducible H+ pumps. Our results suggest that complex light-induced ion pumps play an important role in biological processes related to inorganic carbon uptake and calcification in CCA. PMID:27459463

  10. Aging and balance control in response to external perturbations: role of anticipatory and compensatory postural mechanisms.

    PubMed

    Kanekar, Neeta; Aruin, Alexander S

    2014-06-01

    The ability to maintain balance deteriorates with increasing age. Anticipatory and compensatory postural adjustments (APAs and CPAs, respectively), both, are known to be affected in the elderly. We examined the effect of aging on the ability of older adults to utilize APAs and its effect on subsequent control of posture (CPAs). Ten elderly individuals were exposed to external predictable and unpredictable perturbations applied to the upper body in the sagittal plane. Body kinematics, electromyographic activity of 13 muscles, and ground reaction forces were analyzed during the anticipatory and compensatory phases of postural control. The elderly were capable of recognizing an upcoming predictable perturbation and activated muscles prior to it. However, the older adults used different muscle strategies and sequence of muscle recruitment than that reported in young adults. Additionally, when the perturbations were unpredictable, no APAs were seen which resulted in large CPAs and greater peak displacements of the center of pressure (COP) and center of mass (COM) following perturbations. As opposed to this, when the perturbations were predictable, APAs were seen in older adults resulting in significantly smaller CPAs. The presence and utilization of APAs in older adults also improved postural stability following the perturbation as seen by significantly smaller COP and COM peak displacements. Using APAs in older adults significantly reduces the need for large CPAs, resulting in greater postural stability following a perturbation. The results provide a foundation for investigating the role of training in improving the interplay between anticipatory and compensatory postural control in older adults.

  11. Everything under control? The effects of age, gender, and education on trajectories of perceived control in a nationally representative German sample.

    PubMed

    Specht, Jule; Egloff, Boris; Schmukle, Stefan C

    2013-02-01

    Perceived control is an important variable for various demands involved in successful aging. However, perceived control is not set in stone but rather changes throughout the life course. The aim of this study was to identify cross-sectional age differences and longitudinal mean-level changes as well as rank-order changes in perceived control with respect to gender and education. Furthermore, changes in income and health were analyzed to explain trajectories of perceived control. In a large and representative sample of Germans across all of adulthood, 9,484 individuals gave information about their perceived control twice over a period of 6 years. Using locally weighted smoothing (LOESS) curves and latent structural equation modeling, four main findings were revealed: (a) Perceived control increased until ages 30-40, then decreased until about age 60, and increased slightly afterwards. (b) The rank order of individuals in perceived control was relatively unstable, especially in young adulthood, and reached a plateau at about age 40. (c) Men perceived that they had more control than did women, but there were no gender differences in the development of perceived control. (d) Individuals with more education perceived that they had more control than those with less education, and there were slight differences in the development of perceived control dependent on education. Taken together, these findings offer important insights into the development of perceived control across the life span.

  12. TRPM4-mediated control of FcεRI-evoked Ca2+ elevation comprises enhanced plasmalemmal trafficking of TRPM4 channels in connective tissue type mast cells

    PubMed Central

    Rixecker, Torben; Mathar, Ilka; Medert, Rebekka; Mannebach, Stefanie; Pfeifer, Alexander; Lipp, Peter; Tsvilovskyy, Volodymyr; Freichel, Marc

    2016-01-01

    TRPM4 proteins form Ca2+-activated non selective cation (CAN) channels that affect transmembrane Ca2+-influx by determining the membrane potential. Tight control of the intracellular Ca2+ concentration is essential for mast cell responses. In this study, we analyzed the expression of TRPM4 in peritoneal mast cells (PCMC) as a model for connective tissue type mast cells with respect to FcεRI-evoked calcium changes and the subcellular localization of fluorescently labeled TRPM4 using two viral transduction systems before and following antigen stimulation. Our results show that TRPM4 is expressed in PCMCs, is an essential constituent of the endogenous CAN channels in PCMCs and regulates antigen-evoked increases in intracellular calcium that are significantly enhanced in TRPM4-deficient PCMCs. Compared to PCMCs analyzed before antigen stimulation, the cells depict a substantially increased localization of TRPM4 proteins towards the plasma membrane after FcεRI stimulation. Thus, TRPM4 functions as a limiting factor for antigen evoked calcium rise in connective tissue type mast cells and concurrent translocation of TRPM4 into the plasma membrane is part of this mechanism. PMID:27624684

  13. Control of crystal polymorph in microfluidics using molluscan 28 kDa Ca²(+)-binding protein.

    PubMed

    Ji, Bozhi; Cusack, Maggie; Freer, Andy; Dobson, Phil S; Gadegaard, Nikolaj; Yin, Huabing

    2010-10-01

    Biominerals produced by biological systems in physiologically relevant environments possess extraordinary properties that are often difficult to replicate under laboratory conditions. Understanding the mechanism that underlies the process of biomineralisation can lead to novel strategies in the development of advanced materials. Using microfluidics, we have demonstrated for the first time, that an extrapallial (EP) 28 kDa protein, located in the extrapallial compartment between mantle and shell of Mytilus edulis, can influence, at both micro- and nanoscopic levels, the morphology, structure and polymorph that is laid down in the shell ultrastructure. Crucially, this influence is predominantly dependent on the existence of an EP protein concentration gradient and its consecutive interaction with Ca²(+) ions. Novel lemon-shaped hollow vaterite structures with a clearly defined nanogranular assembly occur only where particular EP protein and Ca²(+) gradients co-exist. Computational fluid dynamics enabled the progress of the reaction to be mapped and the influence of concentration gradients across the device to be calculated. Importantly, these findings could not have been observed using conventional bulk mixing methods. Our findings not only provide direct experimental evidence of the potential influence of EP proteins in crystal formation, but also offer a new biomimetic strategy to develop functional biomaterials for applications such as encapsulation and drug delivery.

  14. Geographic Region, Weather, Pilot Age and Air Carrier Crashes: a Case-Control Study

    PubMed Central

    Li, Guohua; Pressley, Joyce C.; Qiang, Yandong; Grabowski, Jurek G.; Baker, Susan P.; Rebok, George W.

    2009-01-01

    Background Information about risk factors of aviation crashes is crucial for developing effective intervention programs. Previous studies assessing factors associated with crash risk were conducted primarily in general aviation, air taxis and commuter air carriers. Methods A matched case-control design was used to examine the associations of geographic region, basic weather condition, and pilot age with the risk of air carrier (14 CFR Part 121) crash involvement. Cases (n=373) were air carrier crashes involving aircraft made by Boeing, McDonnell Douglas, and Airbus, recorded in the National Transportation Safety Board’s aviation crash database during 1983 through 2002, and controls (n=746) were air carrier incidents involving aircraft of the same three makes selected at random from the Federal Aviation Administration’s aviation incident database. Each case was matched with two controls on the calendar year when the index crash occurred. Conditional logistic regression was used for statistical analysis. Results With adjustment for basic weather condition, pilot age, and total flight time, the risk of air carrier crashes in Alaska was more than three times the risk for other regions [adjusted odds ratio (OR) 3.18, 95% confidence interval (CI) 1.35 – 7.49]. Instrument meteorological conditions were associated with an increased risk for air carrier crashes involving pilot error (adjusted OR 2.26, 95% CI 1.15 – 4.44) and a decreased risk for air carrier crashes without pilot error (adjusted OR 0.57, 95% CI 0.40 – 0.87). Neither pilot age nor total flight time was significantly associated with the risk of air carrier crashes. Conclusions The excess risk of air carrier crashes in Alaska and the effect of adverse weather on pilot-error crashes underscore the importance of environmental hazards in flight safety. PMID:19378910

  15. [Physiological prion and activity of plasma membrane Na+,K(+)- and Ca(2+)-ATPase in the medulla oblongata cells of rats of different ages].

    PubMed

    Kushkevych, M V; Vlizlo, V V; Martyn, Iu V

    2013-01-01

    Based on the results of immunohistochemical analysis of the rat medulla tissue the localization of physiological prion has been established. Specifically, in rats aged one month they are placed in the gray matter near the bodies of neurons and mikrohliocytes and in animals of six and thirty months--in olive kernel core and upward path bodies. Physiological prion is localized along the nerve processes and is absent in the neuron bodies. In the medulla oblongata of animals aged six months its amount is the highest compared to animals of other age. The activity of plasma membrane ATPases in this tissue decreases with age, the content of sodium and calcium ions increases, while that of potassium is almost unchanged.

  16. Enhancer-promoter activity of human papillomavirus type 16 long control regions isolated from cell lines SiHa and CaSki and cervical cancer biopsies.

    PubMed

    Kozuka, T; Aoki, Y; Nakagawa, K; Ohtomo, K; Yoshikawa, H; Matsumoto, K; Yoshiike, K; Kanda, T

    2000-03-01

    Expression of human papillomavirus 16 (HPV-16) oncogenes is markedly higher in cervical cancer cells than in precancerous cells, and the elevated expression is believed to be required for the malignant phenotypes. We compared cancer cell lines CaSki (with 200 to 400 copies of HPV-16 DNA per cell) and SiHa (with one to two copies of HPV-16 DNA per cell) for the E7 expression in cells and the enhancer-promoter activity of the isolated viral long control region (LCR). Although these parameters per cell were 10-fold higher in CaSki than in SiHa, the levels of the E7 mRNA and protein per HPV DNA copy were 10- to 20-fold higher in SiHa than in CaSki. Characterization of the isolated LCRs showed that, whereas the LCR from CaSki resembled the prototype in structure and activity, the LCR from SiHa, with a deletion of 38 base pairs, enhanced transcription from P97 as assayed by using a plasmid capable of expressing luciferase. The upregulation appeared to be due to removal of one of the silencer YY1-binding sites. Furthermore, we isolated and characterized LCRs from 51 cervical cancer patients' biopsies. Among them, one with a deletion including YY1-binding sites and the other with a substitution in a YY1-motif were found to enhance the transcription. These findings suggest that mutation affecting YY1-motifs in the LCR is one of the mechanisms enhancing the viral oncogene expression in the course of progression of cancer cells.

  17. Does verbal labeling influence age differences in proactive and reactive cognitive control?

    PubMed

    Kray, Jutta; Schmitt, Hannah; Heintz, Sonja; Blaye, Agnès

    2015-03-01

    The main goal of this study was to examine whether different types of verbal labeling can influence age-related changes in the dynamic control of behavior by inducing either a proactive or reactive mode of control. Proactive control is characterized by a strong engagement in maintaining task-relevant information to be optimally prepared while reactive control is characterized by a reactivation of task-related information during responding. To investigate dynamic shifts between these control modes, we applied the AX-Continuous-Performance-Task in 2 experiments that differed in the complexity of stimuli and types of labeling in children (range = 7-10 years), younger (range = 19-33 years), and older adults (range = 69-83 years). We expected that labeling the cue information would promote a shift from a reactive to a proactive control mode primarily in children and older adults, while labeling the probe information would result in a shift from a proactive to a reactive control mode primarily in younger adults. Results of both experiments indicated that children, younger, and older adults were equally engaged in cue processing and performed the task in a proactive manner. While cue labeling did not further promote performing the task proactively, probe labeling induced a shift to a reactive control mode, especially in children. In the first experiment, including younger children than in the second experiment, children had more problems than adults to reactivate cue information to overcome a strong response tendency. These findings support the view that verbal labeling can influence the regulation of behavior by selectively attracting attention to relevant information in a given task.

  18. The design of mobile robot control system for the aged and the disabled

    NASA Astrophysics Data System (ADS)

    Qiang, Wang; Lei, Shi; Xiang, Gao; Jin, Zhang

    2017-01-01

    This paper designs a control system of mobile robot for the aged and the disabled, which consists of two main parts: human-computer interaction and drive control module. The data of the two parts is transferred via universal asynchronous receiver/transmitter. In the former part, the speed and direction information of the mobile robot is obtained by hall joystick. In the latter part, the electronic differential algorithm is developed to implement the robot mobile function by driving two-wheel motors. In order to improve the comfort of the robot when speed or direction is changed, the least squares algorithm is used to optimize the speed characteristic curves of the two motors. Experimental results have verified the effectiveness of the designed system.

  19. Loss of control eating disorder in children age 12 years and younger: proposed research criteria.

    PubMed

    Tanofsky-Kraff, Marian; Marcus, Marsha D; Yanovski, Susan Z; Yanovski, Jack A

    2008-08-01

    Binge eating is common in middle childhood (6-12 years) and often presents in concert with disordered eating attitudes, emotional distress, overweight and adiposity. Binge eating is also predictive of excessive weight gain and is associated with energy intake. However, few children meet DSM-IV-TR criteria for binge eating disorder, thereby making treatment recommendations a challenge. We propose criteria for a new diagnosis, Loss of Control Eating Disorder in Children age 12 years and younger, for further study. The criteria put forward are a revision of Marcus and Kalarchian's [Marcus, M.D., & Kalarchian, M.A. (2003). Binge eating in children and adolescents. International Journal of Eating Disorders, 34 Suppl, S47-S57.] provisional binge eating disorder research criteria for children 14 years and younger, and are based upon the evolving literature in children with binge and loss of control eating episodes. A rationale for the new criteria set is provided, and future research directions are proposed.

  20. Online games training aging brains: limited transfer to cognitive control functions.

    PubMed

    van Muijden, Jesse; Band, Guido P H; Hommel, Bernhard

    2012-01-01

    The prevalence of age-related cognitive decline will increase due to graying of the global population. The goal of the present study was to test whether playing online cognitive training games can improve cognitive control (CC) in healthy older adults. Fifty-four older adults (age 60-77) played five different cognitive training games online for 30 min a day over a period of seven weeks (game group). Another group of 20 older adults (age 61-73) instead answered quiz questions about documentaries online (documentary group). Transfer was assessed by means of a cognitive test battery administered before and after the intervention. The test battery included measures of working memory updating, set shifting, response inhibition, attention, and inductive reasoning. Compared with the documentary group, the game group showed larger improvement of inhibition (Stop-Signal task) and inductive reasoning (Raven-SPM), whereas the documentary group showed more improvement in selective attention (UFoV-3). These effects qualify as transfer effects, because response inhibition, inductive reasoning and selective attention were not targeted by the interventions. However, because seven other indicators of CC did not show benefits of game training and some of those that did suffered from potential baseline differences, the study as a whole provides only modest support for the potential of videogame training to improve CC in healthy older adults.

  1. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  2. Mid-life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ-associated pathology and positively influences synaptic and cognitive health in healthy ageing.

    PubMed

    Stuart, Kimberley E; King, Anna E; Fernandez-Martos, Carmen M; Dittmann, Justin; Summers, Mathew J; Vickers, James C

    2016-12-17

    Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APPSWE /PS1dE9 ) from 6 months of age. After 6 months of housing in standard laboratory cages, APPSWE /PS1dE9 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APPSWE /PS1dE9 mice. However, a significant increase in synaptophysin immunolabelled puncta in the hippocampal subregion, CA1, in APPSWE /PS1dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APPSWE /PS1dE9 mice exposed to EE, however no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition. This article is protected by copyright. All rights reserved.

  3. Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology

    PubMed Central

    Van Dijk, Koene R. A.; Shire, Emily H.; Sperling, Reisa A.; Johnson, Keith A.; Buckner, Randy L.

    2012-01-01

    Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes. PMID:21765181

  4. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.

    PubMed

    Hecker, Laura A; Edwards, Albert O; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H; Brown, William L; Charbel Issa, Peter; Scholl, Hendrik P; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E; Bailey, Kent R; Oppermann, Martin

    2010-01-01

    Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.

  5. Training for improved neuro-muscular control of balance in middle aged females.

    PubMed

    Anderson, Gregory S; Deluigi, Fabio; Belli, Guido; Tentoni, Claudio; Gaetz, Michael B

    2016-01-01

    This study examined improvements in static balance and muscle electromyographic (EMG) activity following a four week progressive training program in 16 middle aged females (mean age = 46.9 ± 8.7 yrs; height 161.1 ± 6.0 cm; weight 65.4 ± 11.2 kg). Participants trained 3 times per week for 4 weeks, for 50 min per session, progressing base of support, stability, vision, resistance and torque in each of six basic exercises. Pre and post training measures of balance included feet together standing, a tandem stance and a one-leg stand (unsupported leg in the saggital plane) performed with the eyes closed, and a Stork Stand (unsupported leg in the frontal plane) with both eyes open and closed. In each position postural deviations were tallied for each individual while muscle recruitment was determined using root mean squared (RMS) EMG activity for the soleus, biceps femoris, erector spinae, rectus abdominis and internal oblique muscles of the dominant foot side. Balance scores were significantly improved post training in both the Balance Error Score System (p < 0.05) and stork stand positions (p < 0.01). Muscle activity was reduced post-training in all muscles in each condition except the soleus in the tandem position, although not all significantly. Reduced biceps femoris activity suggest that improved core stability allowed participants to move from a hip to an ankle postural control strategy through improved coordination of muscles involved in balance and reduced body sway. The core muscles were able to control body position with less activity post training suggesting improved muscle coordination and efficiency. These results suggest that short term progressive floor to BOSU™ balance training can improve standing balance in middle aged women.

  6. Effect of aging on the PWR Chemical and Volume Control System

    SciTech Connect

    Grove, E.J.; Travis, R.J.; Aggarwal, S.K.

    1995-06-01

    The PWR Chemical and Volume Control System (CVCS) is designed to provide both safety and non-safety related functions. During normal plant operation it is used to control reactor coolant chemistry, and letdown and charging flow. In many plants, the charging pumps also provide high pressure injection, emergency boration, and RCP seal injection in emergency situations. This study examines the design, materials, maintenance, operation and actual degradation experiences of the system and main sub-components to assess the potential for age degradation. A detailed review of the Nuclear Plant Reliability Data System (NPRDS) and Licensee Event Report (LER) databases for the 1988--1991 time period, together with a review of industry and NRC experience and research, indicate that age-related degradations and failures have occurred. These failures had significant effects on plant operation, including reactivity excursions, and pressurizer level transients. The majority of these component failures resulted in leakage of reactor coolant outside the containment. A representative plant of each PWR design (W, CE, and B and W) was visited to obtain specific information on system inspection, surveillance, monitoring, and inspection practices. The results of these visits indicate that adequate system maintenance and inspection is being performed. In some instances, the frequencies of inspection were increase in response to repeated failure events. A parametric study was performed to assess the effect of system aging on Core Damage Frequency (CDF). This study showed that as motor-operated valve (MOV) operating failures increased, the contribution of the High Pressure Injection to CDF also increased.

  7. Controlling Factors of Soil CO2 Efflux in Pinus yunnanensis across Different Stand Ages.

    PubMed

    Wang, Shaojun; Zhao, Jixia; Chen, Qibo

    2015-01-01

    The characteristics of soil respiration (Rs) across different stand ages have not been well investigated. In this study, we identified temporal variation of Rs and its driving factors under three nature forest stands (e.g. 15-yr-old, 30-yr-old, and 45-yr-old) of Pinus yunnanensis in the Plateau of Mid-Yunnan, China. No consistent tendency was found on the change of Rs with the stand ages. Rs was ranked in the order of 30-yr-old > 45-yr-old >15-yr-old. Rs in 15-yr-old stand was the most sensitive to soil temperature (Ts) among the three sites. However, Ts only explained 30-40% of the seasonal dynamics of Rs at the site. Soil water content (Sw) was the major controlling factor of temporal variation at the three sites. Sw explained 88-93% of seasonal variations of Rs in the 30-yr-old stand, and 63.7-72.7% in the 15-yr-old and 79.1-79.6% in the 45-yr-old stands. In addition, we found that pH, available nitrogen (AN), C/N and total phosphorus (TP) contributed significantly to the seasonal variation of Rs. Sw was significantly related with pH, total nitrogen (TN), AN and TP, suggesting that Sw can affect Rs through improving soil acid-base property and soil texture, and increasing availability of soil nutrient. The results indicated that besides soil water, soil properties (e. g. pH, AN, C/N and TP) were also the important in controlling the temporal variations of Rs across different stand ages in the nature forestry.

  8. Safety and efficacy of nurse-controlled analgesia in patients less than 1 year of age

    PubMed Central

    Walia, Hina; Tumin, Dmitry; Wrona, Sharon; Martin, David; Bhalla, Tarun; Tobias, Joseph D

    2016-01-01

    Background The management of acute pain presents unique challenges in the younger pediatric population. Although patient-controlled devices are frequently used in patients ≥6 years of age, alternative modes of analgesic delivery are needed in infants. Objective To examine the safety and efficacy of nurse-controlled analgesia (NCA) in neonates less than 1 year of age. Methods Data from patients <1 year of age receiving NCA as ordered by the Acute Pain Service at our institution were collected over a 5-year period and reviewed retrospectively. The primary outcomes were activation of the institution’s Rapid Response Team (RRT) or Code Blue, signifying severe adverse events. Pain score after NCA initiation was a secondary outcome. Results Among 338 girls and 431 boys, the most common opioid used for NCA was fentanyl, followed by morphine and hydromorphone. There were 39 (5%) cases involving RRT or Code Blue activation, of which only one (Code Blue) was activated due to a complication of NCA (apnea). Multivariable logistic regression demonstrated morphine NCA to be associated with greater odds of RRT activation (OR=3.29, 95% CI=1.35, 8.03, P=0.009) compared to fentanyl NCA. There were no statistically significant differences in pain scores after NCA initiation across NCA agents. Conclusion NCA is safe in neonates and infants, with comparable efficacy demonstrated for the three agents used. The elevated incidence of RRT activation in patients receiving morphine suggests caution in its use and consideration of alternative agents in this population. PMID:27358574

  9. Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E- cadherin

    PubMed Central

    1991-01-01

    Gap junctional intercellular communication (GJIC) of cultured mouse epidermal cells is mediated by a gap junction protein, connexin 43, and is dependent on the calcium concentration in the medium, with higher GJIC in a high-calcium (1.2 mM) medium. In several mouse epidermal cell lines, we found a good correlation between the level of GJIC and that of immunohistochemical staining of E-cadherin, a calcium-dependent cell adhesion molecule, at cell-cell contact areas. The variant cell line P3/22 showed both low GJIC and E-cadherin protein expression in low- and high-Ca2+ media. P3/22 cells showed very low E-cadherin mRNA expression. To test directly whether E-cadherin is involved in the Ca(2+)-dependent regulation of GJIC, we transfected the E-cadherin expression vector into P3/22 cells and obtained several stable clones which expressed high levels of E-cadherin mRNA. All transfectants expressed E-cadherin molecules at cell-cell contact areas in a calcium- dependent manner. GJIC was also observed in these transfectants and was calcium dependent. These results suggest that Ca(2+)-dependent regulation of GJIC in mouse epidermal cells is directly controlled by a calcium-dependent cell adhesion molecule, E-cadherin. Furthermore, several lines of evidence suggest that GJIC control by E-cadherin involves posttranslational regulation (assembly and/or function) of the gap junction protein connexin 43. PMID:1650371

  10. As we age: Does slippage of quality control in the immune system lead to collateral damage?

    PubMed

    Müller, Ludmila; Pawelec, Graham

    2015-09-01

    The vertebrate adaptive immune system is remarkable for its possession of a very broad range of antigen receptors imbuing the system with exquisite specificity, in addition to the phagocytic and inflammatory cells of the innate system shared with invertebrates. This system requires strict control both at the level of the generation the cells carrying these receptors and at the level of their activation and effector function mediation in order to avoid autoimmunity and mitigate immune pathology. Thus, quality control checkpoints are built into the system at multiple nodes in the response, relying on clonal selection and regulatory networks to maximize pathogen-directed effects and minimize collateral tissue damage. However, these checkpoints are compromised with age, resulting in poorer immune control manifesting as tissue-damaging autoimmune and inflammatory phenomena which can cause widespread systemic disease, paradoxically compounding the problems associated with increased susceptibility to infectious disease and possibly cancer in the elderly. Better understanding the reasons for slippage of immune control will pave the way for developing rational strategies for interventions to maintain appropriate immunity while reducing immunopathology.

  11. The unconventional doping in YBa2Cu3O7-x/La0.7Ca0.3MnO3 heterostructures by termination control

    NASA Astrophysics Data System (ADS)

    Tra, V. T.; Huang, R.; Gao, X.; Chen, Y.-J.; Liu, Y. T.; Kuo, W. C.; Chin, Y. Y.; Lin, H. J.; Chen, J. M.; Lee, J. M.; Lee, J. F.; Shi, P. S.; Jiang, M. G.; Duan, C. G.; Juang, J. Y.; Chen, C. T.; Jeng, H. T.; He, Q.; Chuang, Y.-D.; Lin, J.-Y.; Chu, Y.-H.

    2017-01-01

    In strongly correlated oxides, heterostructures provide a powerful route to manipulate the charge, spin, orbital, and lattice degrees of freedom to create distinctive functionalities. In this work, we have achieved atomically precise interface control in YBa2Cu3O7-x/La0.7Ca0.3MnO3 (YBCO/LCMO) heterostructures and find a hidden effective doping. This mechanism is responsible for higher Tc in the sample with the MnO2-terminated interface than in that with the La0.7Ca0.3O-terminated interface. The MnO2-terminated sample also shows a larger magnetic moment of Mn together with a lower valence state. For more than a decade, the control of Tc in these heterostructures prior to this work has been solely via the variation of YBCO or LCMO thickness. This work hints at an alternative way of exploiting and exploring the interactions between superconductivity and magnetism in this system.

  12. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

    PubMed Central

    Ferreira, Leandro; Tanaka, Kátia; Santos-Galduróz, Ruth Ferreira; Galduróz, José Carlos Fernandes

    2015-01-01

    Background Inadequate oxygenation may cause lesions and brain atrophy during aging. Studies show a positive association between pulmonary function and the cognitive performance of individuals from middle age on. Objective To investigate the effect of aerobic physical exercises and respiratory training on the blood oxygenation, pulmonary functions, and cognition of the elderly. Design This was a randomized and controlled trial with three parallel groups. A total of 195 community-dwelling elderly were assessed for eligibility; only n=102 were included and allocated into the three groups, but after 6 months, n=68 were analyzed in the final sample. Participants were randomized into a social interaction group (the control group), an aerobic exercise group (the “walking” group), or a respiratory training group (the “breathing” group). The main outcome measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic–abdominal circumference); oxygen saturation in arterial blood (SpO2), and hemogram. Results No differences were observed for any of the blood parameters. Aerobic exercise and respiratory training were effective in improving the pulmonary parameters. Better cognitive performance was observed for the breathing group as regards abstraction and mental flexibility. The walking group remained stable in the cognitive performance of most of the tests, except attention. The control group presented worst performance in mental manipulation of information, abstraction, mental flexibility, and attention. Conclusion Our results showed that both the walking and breathing groups presented improvement of pulmonary function. However, only the breathing group showed improved cognitive function (abstraction, mental flexibility). The improvement in cognitive functions cannot be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and hematocrit. PMID:25848235

  13. A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations.

    PubMed

    Adebanjo, O A; Moonga, B S; Haddad, J G; Huang, C L; Zaidi, M

    1998-08-28

    Upon removal of its sialic acid or galactose residue, vitamin D-binding protein (DBP) becomes a potent macrophage-activating factor, DBP-MAF. Here we document a new function of DBP-MAF and its parent molecule, DBP, in osteoclast control. We show that all DBPs potently inhibit extracellular Ca2+ (cation) sensing at low nanomolar concentrations with the following rank order of potency: native DBP = sialidase-treated DBP > beta-galactosidase-treated DBP. This attenuation remains unaffected despite co-incubation either with the native DBP ligand, 1,25-dihydroxyvitamin D3, or with an asialoglycoprotein receptor modulator, asialoorosomucoid. Taken together, the results suggest that circulating DBP may play a role in the systemic control of osteoclastic bone resorption, a hitherto unrecognized action of the protein.

  14. Age and Individual Differences in Controlled Force Exertion Measured by a Computer-Generated Sinusoidal and Quasi-Random Display

    ERIC Educational Resources Information Center

    Nagasawa, Yoshinori; Demura, Shinichi

    2010-01-01

    This study examined age group and individual differences in controlled force exertion by emulating sinusoidal and quasi-random waveforms in 222 right-handed female adults aged 20 to 86 years. The subjects matched their submaximal grip strength by the dominant hand to changing demand values displayed as either a sinusoidal or a quasi-random…

  15. School-Age Children of Alcoholics and Non-Alcoholics: Their Anxiety, Self-Esteem, and Locus of Control.

    ERIC Educational Resources Information Center

    Post, Phyllis; Robinson, Bryan E.

    1998-01-01

    Using sample of 108 students from fourth to eighth grades, study seeks to further clarify three major psychological dimensions among school-aged young children of alcoholics (YCOAs). Self-esteem, anxiety level, and locus of control were compared among school-aged children with and without alcoholic parents. YCOAs reported lower self-esteem, higher…

  16. Changes in Angiotensin Receptor Distribution and in Aortic Morphology Are Associated with Blood Pressure Control in Aged Metabolic Syndrome Rats

    PubMed Central

    Guarner-Lans, Verónica; Soria-Castro, Elizabeth; Torrico-Lavayen, Rocío; Patrón-Soberano, Araceli; Carvajal-Aguilera, Karla G.; Castrejón-Tellez, Vicente; Rubio-Ruiz, María Esther

    2016-01-01

    The role of the renin-angiotensin system (RAS) in blood pressure regulation in MS during aging is unknown. It participates in metabolic syndrome (MS) and aging regulating vascular tone and remodeling. RAS might participate in a compensatory mechanism decreasing blood pressure and allowing MS rats to reach 18 months of age and it might form part of therapeutical procedures to ameliorate MS. We studied histological changes and distribution of RAS receptors in aortas of MS aged rats. Electron microscopy images showed premature aging in MS since the increased fibrosis, enlarged endothelium, and invasion of this layer by muscle cells that was present in control 18-month-old aortas were also found in 6-month-old aortas from MS rats. AT1, AT2, and Mas receptors mediate the effects of Ang II and Ang 1-7, respectively. Fluorescence from AT2 decreased with age in control and MS aortas, while fluorescence of AT1 increased in aortas from MS rats at 6 months and diminished during aging. Mas expression increased in MS rats and remained unchanged in control rats. In conclusion, there is premature aging in the aortas from MS rats and the elevated expression of Mas receptor might contribute to decrease blood pressure during aging in MS. PMID:27293881

  17. Age and Educational Inequalities in Smoking Cessation Due to Three Population-Level Tobacco Control Interventions: Findings from the International Tobacco Control (ITC) Netherlands Survey

    ERIC Educational Resources Information Center

    Nagelhout, Gera E.; Crone, Matty R.; van den Putte, Bas; Willemsen, Marc C.; Fong, Geoffrey T.; de Vries, Hein

    2013-01-01

    This study aimed to examine age and educational inequalities in smoking cessation due to the implementation of a tobacco tax increase, smoke-free legislation and a cessation campaign. Longitudinal data from 962 smokers aged 15 years and older were used from three survey waves of the International Tobacco Control (ITC) Netherlands Survey. The 2008…

  18. Modafinil improves attention, inhibitory control, and reaction time in healthy, middle-aged rats.

    PubMed

    Morgan, Russell E; Crowley, Jaime M; Smith, Roland H; LaRoche, Ronee B; Dopheide, Marsha M

    2007-03-01

    This study examined the effect of the novel psychostimulant modafinil (Provigil) on a variety of cognitive and behavioral measures including associative learning, sustained attention, inhibitory control, and reaction time. Middle-aged female rats (18-20 months old) were administered oral doses of modafinil (0, 8, 32, and 64 mg/kg) and tested in a 3-choice visual discrimination and sustained attention task. Modafinil produced a dose-dependent pattern of improved response accuracy and impulse control (fewer premature responses) and shorter response latencies, without affecting omission errors, motivation or motor control. Although the biochemical mechanism of modafinil is unknown, these results suggest a profile differing from typical psychostimulants (e.g., amphetamine). The implications of these findings for treatment of narcolepsy, ADHD, and various arousal-related disorders are considered. Further research is needed to examine the relative safety, effectiveness, and addictive potential of modafinil, as well as, its effects in comparison with other performance-enhancing drugs (e.g., caffeine, nicotine, and amphetamines).

  19. Age-related deficits in voluntary control over saccadic eye movements: consideration of electrical brain stimulation as a therapeutic strategy.

    PubMed

    Chen, Po Ling; Machado, Liana

    2016-05-01

    Sudden changes in our visual environment trigger reflexive eye movements, so automatically they often go unnoticed. Consequently, voluntary control over reflexive eye movements entails considerable effort. In relation to frontal-lobe deterioration, adult aging adversely impacts voluntary saccadic eye movement control in particular, which compromises effective performance of daily activities. Here, we review the nature of age-related changes in saccadic control, focusing primarily on the antisaccade task because of its assessment of 2 key age-sensitive control functions: reflexive saccade inhibition and voluntary saccade generation. With an ultimate view toward facilitating development of therapeutic strategies, we systematically review the neuroanatomy underpinning voluntary control over saccadic eye movements and natural mechanisms that kick in to compensate for age-related declines. We then explore the potential of noninvasive electrical brain stimulation to counteract aging deficits. Based on evidence that anodal transcranial direct current stimulation can confer a range of benefits specifically relevant to aging brains, we put forward this neuromodulation technique as a therapeutic strategy for improving voluntary saccadic eye movement control in older adults.

  20. Higher education is an age-independent predictor of white matter integrity and cognitive control in late adolescence.

    PubMed

    Noble, Kimberly G; Korgaonkar, Mayuresh S; Grieve, Stuart M; Brickman, Adam M

    2013-09-01

    Socioeconomic status is an important predictor of cognitive development and academic achievement. Late adolescence provides a unique opportunity to study how the attainment of socioeconomic status (in the form of years of education) relates to cognitive and neural development, during a time when age-related cognitive and neural development is ongoing. During late adolescence it is possible to disambiguate age- and education-related effects on the development of these processes. Here we assessed the degree to which higher educational attainment was related to performance on a cognitive control task, controlling for age. We then used diffusion tensor imaging (DTI) to assess the degree to which white matter microstructure might mediate this relationship. When covarying age, significant associations were found between educational attainment and fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and cingulum bundle (CB). Further, when covarying age, FA in these regions was associated with cognitive control. Finally, mediation analyses revealed that the age-independent association between educational attainment and cognitive control was completely accounted for by FA in these regions. The uncinate fasciculus, a late-myelinated control region not implicated in cognitive control, did not mediate this effect.

  1. Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans.

    PubMed

    Sidhu, Simranjit K; Weavil, Joshua C; Venturelli, Massimo; Rossman, Matthew J; Gmelch, Benjamin S; Bledsoe, Amber D; Richardson, Russell S; Amann, Markus

    2015-11-01

    We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL (P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. Interestingly, in terms of peripheral hemodynamics, while group III/IV-mediated feedback plays a clear role in increasing LVC during exercise in the YNG, these afferents seem to actually reduce LVC in OLD. These peripheral findings may help explain the limited exercise-induced peripheral vasodilation often associated with aging.

  2. Crystal structures of CaSiO3 polymorphs control growth and osteogenic differentiation of human mesenchymal stem cells on bioceramic surfaces.

    PubMed

    Zhang, Nianli; Molenda, James A; Mankoci, Steven; Zhou, Xianfeng; Murphy, William L; Sahai, Nita

    2013-10-01

    The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure-reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, β-CaSiO3) and wollastonite (wol, α-CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X-ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were more

  3. Crystal structures of CaSiO3 polymorphs control growth and osteogenic differentiation of human mesenchymal stem cells on bioceramic surfaces†

    PubMed Central

    Zhang, Nianli; Molenda, James A.; Mankoci, Steven; Zhou, Xianfeng; Murphy, William L.

    2014-01-01

    The repair and replacement of damaged or diseased human bone tissue requires a stable interface between the orthopedic implant and living tissue. The ideal material should be both osteoconductive (promote bonding to bone) and osteoinductive (induce osteogenic differentiation of cells and generate new bone). Partially resorbable bioceramic materials with both properties are developed by expensive trial-and-error methods. Structure–reactivity relationships for predicting the osteoinductive properties of ceramics would significantly increase the efficiency of developing materials for bone tissue engineering. Here we propose the novel hypothesis that the crystal structure of a bioceramic controls the release rates, subsequent surface modifications due to precipitation of new phases, and thus, the concentrations of soluble factors, and ultimately, the attachment, viability and osteogenic differentiation of human Mesenchymal Stem Cells (hMSCs). To illustrate our hypothesis, we used two CaSiO3 polymorphs, pseudo-wollastonite (psw, β-CaSiO3) and wollastonite (wol, α-CaSiO3) as scaffolds for hMSC culture. Polymorphs are materials which have identical chemical composition and stoichiometry, but different crystal structures. We combined the results of detailed surface characterizations, including environmental Scanning Electron Microscopy (SEM) back-scattered imaging, and spot-analysis and 2D elemental mapping by SEM-Energy Dispersive X-ray (SEM-EDX), High Resolution Transmission Electron Microscopy (HRTEM) and surface roughness analysis; culture medium solution analyses; and molecular/genetic assays from cell culture. Our results confirmed the hypothesis that the psw polymorph, which has a strained silicate ring structure, is more osteoinductive than the wol polymorph, which has a more stable, open silicate chain structure. The observations could be attributed to easier dissolution (resorption) of psw compared to wol, which resulted in concentration profiles that were

  4. EFFECTS OF AGE AND ACUTE MUSCLE FATIGUE ON REACTIVE POSTURAL CONTROL IN HEALTHY ADULTS

    PubMed Central

    Papa, Evan V.; Foreman, K. Bo; Dibble, Lee E.

    2015-01-01

    BACKGROUND Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults. METHODS A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-minutes (T15) and 30-minutes (T30) of rest. FINDINGS Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found. INTERPRETATION Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 minutes of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults. PMID:26351001

  5. Age-related differences in inhibitory control and memory updating in boys with Asperger syndrome.

    PubMed

    Weiss, Elisabeth M; Gschaidbauer, Bianca; Kaufmann, Liane; Fink, Andreas; Schulter, Günter; Mittenecker, Erich; Papousek, Ilona

    2016-12-26

    Deficits in specific executive domains are highly prevalent in autism spectrum disorder; however, age-related improvements in executive functions (reflecting prefrontal maturational changes) have been reported even in individuals diagnosed with autism. The current study examined two components of cognitive flexibility (inhibition of prepotent responses and memory monitoring/updating) by using a random-motor-generation task (MPT) in a group of 23 boys with Asperger syndrome (AS) and 23 matched healthy controls. We found poorer inhibition and more repetitive responses in younger AS children solely, but comparable memory monitoring/updating skills across groups. Overall, our findings correspond well with previous studies and reveal that even in AS specific EFs may improve with age and, thus, call for a more differentiated view of executive (dys) function profiles in children diagnosed with AS. Tests such as the random-motor-generation task may help to disentangle more specific processes of executive deficits in autism spectrum disorder as compared to the more classical tests.

  6. Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma

    PubMed Central

    Galamb, Orsolya; Kalmár, Alexandra; Barták, Barbara Kinga; Patai, Árpád V; Leiszter, Katalin; Péterfia, Bálint; Wichmann, Barnabás; Valcz, Gábor; Veres, Gábor; Tulassay, Zsolt; Molnár, Béla

    2016-01-01

    with significantly increased SFRP1 mRNA levels in children compared to normal adult samples (P < 0.05). In CRC tissue the mRNA expression of 117 age-related genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue (P < 0.05, logFC > 0.5). The change of expression for several genes including SYNE1, CLEC3B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes (e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the mRNA expression of certain CRC- and adenoma-related key control genes. PMID:28058013

  7. Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls.

    PubMed Central

    Gengo, F M; Fagan, S C; Krol, G; Bernhard, H

    1987-01-01

    Six biopsy proven cirrhotics and five age-matched controls (mean 55.3 vs 52.4 years) were randomly given single 60 mg p.o. and 30 mg s.l. doses of nimodipine. Serum concentrations and blood pressure were measured regularly over the subsequent 24 h period. The clearance of nimodipine was reduced in the patients with cirrhosis. Apparent oral clearance of nimodipine in the cirrhotic group was significantly lower than that observed in the normal group (187 +/- 163 l h-1 vs 469.6 +/- 198.4 l h-1, P less than 0.01). There were no significant changes in mean arterial pressure (MAP) in the normal subjects. There were, however, significant reductions in MAP following oral nimodipine in the cirrhotics. These reductions were significantly related to nimodipine concentrations in individual patients (P less than 0.05). PMID:3814462

  8. Respiratory Sinus Arrhythmia, Shyness, and Effortful Control in Preschool-Age Children

    PubMed Central

    Sulik, Michael J.; Eisenberg, Nancy; Silva, Kassondra M.; Spinrad, Tracy L.; Kupfer, Anne

    2015-01-01

    Resting respiratory sinus arrhythmia (RSA) and shyness were examined as predictors of effortful control (EC) in a sample of 101 preschool-age children. Resting RSA was calculated from respiration and heart rate data collected during a neutral film; shyness was measured using parents’, preschool teachers’, and classroom observers’ reports; and EC was measured using four laboratory tasks in addition to questionnaire measures. Principal components analysis was used to create composite measures of EC and shyness. The relation between RSA and EC was moderated by shyness, such that RSA was positively related to EC only for children high in shyness. This interaction suggests that emotional reactivity affects the degree to which RSA can be considered a correlate of EC. This study also draws attention to the need to consider the measurement context when assessing resting psychophysiology measures; shy individuals may not exhibit true baseline RSA responding in an unfamiliar laboratory setting. PMID:23127725

  9. Synthesis and characterization of CaCO3-biopolymer hybrid nanoporous microparticles for controlled release of doxorubicin.

    PubMed

    Bosio, Valeria E; Cacicedo, Maximiliano L; Calvignac, Brice; León, Ignacio; Beuvier, Thomas; Boury, Frank; Castro, Guillermo R

    2014-11-01

    Doxorubicin (Dox) is a hydrophilic drug extensively used for treatment of breast, lung, and ovarian cancer, among others; it is highly toxic and can cause serious side effects on nontargeted tissues. We developed and studied a hybrid nanoporous microparticle (hNP) carrier based on calcium carbonate and biopolymers derivatized with folic acid (FA) and containing Dox as a chemotherapeutic drug model. The hNPs were characterized by X-ray diffraction, and Raman and Fourier transform infrared (FTIR) spectroscopies. The X-ray diffraction patterns of calcium carbonate particles showed about 30-70% vaterite-calcite polymorphisms and up to 95% vaterite, depending on the absence or the presence of biopolymers as well as their type. Scanning electron microcopy images revealed that all types of hNPs were approximately spherical and porous with average diameter 1-5 μm, and smaller than CaCO3 microparticles. The presence of biopolymers in the matrices was confirmed after derivatization with a fluorescein isothiocyanate probe by means of confocal microscopy and FTIR synchrotron beamline analysis. In addition, the coupling of lambda carrageenan (λ-Car) to FA in the microparticles (FA-λ-Car-hNPs) increased the cancer-cell targeting and also extended the specific surface area by up to ninefold (26.6 m2 g(-1)), as determined by the Brunauer-Emmett-Teller isotherm. A nanostructured porous surface was found in all instances, and the FA-λ-Car-hNP pore size was about 30 nm, as calculated by means of the Barrett-Joyner-Halenda adsorption average. The test of FA-λ-Car-hNP anticancer activity on human osteosarcoma MG-63 cell line showed cell viabilities of 13% and 100% with and without Dox, respectively, as determined by crystal violet staining after 24 h of incubation.

  10. Age-related iron deposition in the basal ganglia of controls and Alzheimer disease patients quantified using susceptibility weighted imaging.

    PubMed

    Wang, Dan; Li, Yan-Ying; Luo, Jian-Hua; Li, Yue-Hua

    2014-01-01

    This study aimed to investigate age-related iron deposition changes in healthy subjects and Alzheimer disease patients using susceptibility weighted imaging. The study recruited 182 people, including 143 healthy volunteers and 39 Alzheimer disease patients. All underwent conventional magnetic resonance imaging and susceptibility weighted imaging sequences. The groups were divided according to age. Phase images were used to investigate iron deposition in the bilateral head of the caudate nucleus, globus pallidus and putamen, and the angle radian value was calculated. We hypothesized that age-related iron deposition changes may be different between Alzheimer disease patients and controls of the same age, and that susceptibility weighted imaging would be a more sensitive method of iron deposition quantification. The results revealed that iron deposition in the globus pallidus increased with age, up to 40 years. In the head of the caudate nucleus, iron deposition peaked at 60 years. There was a general increasing trend with age in the putamen, up to 50-70 years old. There was significant difference between the control and Alzheimer disease groups in the bilateral globus pallidus in both the 60-70 and 70-80 year old group comparisons. In conclusion, iron deposition increased with age in the globus pallidus, the head of the caudate nucleus and putamen, reaching a plateau at different ages. Furthermore, comparisons between the control and Alzheimer disease group revealed that iron deposition changes were more easily detected in the globus pallidus.

  11. Improved age control on early Homo fossils from the upper Burgi Member at Koobi Fora, Kenya.

    PubMed

    Joordens, Josephine C A; Dupont-Nivet, Guillaume; Feibel, Craig S; Spoor, Fred; Sier, Mark J; van der Lubbe, Jeroen H J L; Nielsen, Trine Kellberg; Knul, Monika V; Davies, Gareth R; Vonhof, Hubert B

    2013-12-01

    To address questions regarding the evolutionary origin, radiation and dispersal of the genus Homo, it is crucial to be able to place the occurrence of hominin fossils in a high-resolution chronological framework. The period around 2 Ma (millions of years ago) in eastern Africa is of particular interest as it is at this time that a more substantial fossil record of the genus Homo is first found. Here we combine magnetostratigraphy and strontium (Sr) isotope stratigraphy to improve age control on hominin-bearing upper Burgi (UBU) deposits in Areas 105 and 131 on the Karari Ridge in the eastern Turkana Basin (Kenya). We identify the base of the Olduvai subchron (bC2n) plus a short isolated interval of consistently normal polarity that we interpret to be the Pre-Olduvai event. Combined with precession-forced (~20 kyr [thousands of years]) wet-dry climate cycles resolved by Sr isotope ratios, the magnetostratigraphic data allow us to construct an age model for the UBU deposits. We provide detailed age constraints for 15 hominin fossils from Area 131, showing that key specimens such as cranium KNM-ER 1470, partial face KNM-ER 62000 and mandibles KNM-ER 1482, KNM-ER 1801, and KNM-ER 1802 can be constrained between 1.945 ± 0.004 and 2.058 ± 0.034 Ma, and thus older than previously estimated. The new ages are consistent with a temporal overlap of two species of early Homo that can be distinguished by their facial morphology. Further, our results show that in this time interval, hominins occurred throughout the wet-dry climate cycles, supporting the hypothesis that the lacustrine Turkana Basin was a refugium during regionally dry periods. By establishing the observed first appearance datum of a marine-derived stingray in UBU deposits at 2.058 ± 0.034 Ma, we show that at this time the Turkana Basin was hydrographically connected to the Indian Ocean, facilitating dispersal of fauna between these areas. From a biogeographical perspective, we propose that the Indian Ocean

  12. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing.

    PubMed

    Sengupta, Shomit; Peterson, Timothy R; Laplante, Mathieu; Oh, Stephanie; Sabatini, David M

    2010-12-23

    The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors. Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPARα (peroxisome proliferator activated receptor α), the master transcriptional activator of ketogenic genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPARα, reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis, which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPARα activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPARα function and hepatic ketogenesis and suggest a

  13. Control of magnetic, nonmagnetic, and superconducting states in annealed Ca(Fe1–xCox)₂As₂

    SciTech Connect

    Ran, S.; Bud'ko, S. L.; Straszheim, W. E.; Soh, J.; Kim, M. G.; Kreyssig, A.; Goldman, A. I.; Canfield, P. C.

    2012-06-22

    We have grown single-crystal samples of Co substituted CaFe₂As₂ using an FeAs flux and systematically studied the effects of annealing/quenching temperature on the physical properties of these samples. Whereas the as-grown samples (quenched from 960°C) all enter the collapsed tetragonal phase upon cooling, annealing/quenching temperatures between 350 and 800°C can be used to tune the system to low-temperature antiferromagnetic/orthorhomic or superconducting states as well. The progression of the transition temperature versus annealing/quenching temperature (T-Tanneal) phase diagrams with increasing Co concentration shows that, by substituting Co, the antiferromagnetic/orthorhombic and the collapsed tetragonal phase lines are separated and bulk superconductivity is revealed. We established a 3D phase diagram with Co concentration and annealing/quenching temperature as two independent control parameters. At ambient pressure, for modest x and Tanneal values, the Ca(Fe₁₋xCox)₂As₂ system offers ready access to the salient low-temperature states associated with Fe-based superconductors: antiferromagnetic/orthorhombic, superconducting, and nonmagnetic/collapsed tetragonal.

  14. Age-Related Differences in the Reliance on Executive Control in Working Memory: Role of Task Demand

    PubMed Central

    Isingrini, Michel; Angel, Lucie; Fay, Séverine; Taconnat, Laurence; Lemaire, Patrick; Bouazzaoui, Badiâa

    2015-01-01

    We examined the hypothesis that age-related differences in the reliance on executive control may be better explained by variations of task demand than by a mechanism specifically linked to aging. To this end, we compared the relationship between the performance of young and older adults on two executive functioning tests and an updating working-memory task with different load levels. The results revealed a significant interaction between age, task demand, and individual executive capacities, indicating that executive resources were only involved at lower loads in older adults, and only at higher loads in young adults. Overall, the results are not consistent with the proposition that cognition places greater demand on executive control in older adults. However, they support the view that how much young and older adults rely on executive control to accomplish cognitive tasks depends on task demand. Finally, interestingly these results are consistent with the CRUNCH model accounting for age-related differences in brain activations. PMID:26700019

  15. The Caraguataí syenitic suite, a ca. 2.7 Ga-old alkaline magmatism (petrology, geochemistry and U-Pb zircon ages). Southern Gavião block (São Francisco Craton), Brazil

    NASA Astrophysics Data System (ADS)

    Cruz, Simone Cerqueira Pereira; Peucat, Jean-Jacques; Teixeira, Leo; Carneiro, Maurício Antônio; Marques Martins, Adriano Alberto; Santana, Jocilene dos Santos; de Souza, Jailma Santos; Barbosa, Johildo Salomão Figueiredo; Leal, Ângela Beatriz Menezes; Dantas, Elton; Pimentel, Marcio

    2012-08-01

    The Gavião Block comprises amphibolite- and granulite-facies gneisses and migmatites of tonalitic, granodioritic and granitic compositions and supracrustal sequences including volcanosedimentary layers metamorphosed up to the amphibolite facies. In the region of Abaíra-Jussiape (BA), two main igneous suites, called Caraguataí and Jussiape, are exposed in the core of an anticline. The Caraguataí suite encompasses alkali-feldspar granites, syenites and quartz syenites that contain biotite, magnetite/hematite, apatite, titanite, hastingsite/pargasite and zircon as accessory minerals that were adjusted to the amphibolite facies. White mica and epidote minerals are related to retrograde greenschist facies. These rocks were deformed in dextral to reverse-dextral shear zones, giving origin to protomylonites and augen-mesomylonites to ultramylonites. The ultramylonites have a prominent banding parallel to the main foliation of the rocks. Lithogeochemical studies revealed subalkaline to alkaline, metaluminous to peraluminous, Fe-rich protolith for instead of to these rocks associated with A2-type magmatism and partial melting of igneous continental crust. In situ U-Pb zircon dating using the Laser Ablation ICPMS method was carried out for five samples of the Caraguataí alkaline suite. The ages obtained for an isotropic syenite (SCP 1470: 2680 ± 24 Ma), a foliated syenite (SCP 2035: 2703 ± 11 Ma), a syenitic augen gneiss (SCP 2017: 2706 ± 34 Ma) and two ultramylonitic syenitic banded gneisses (SCP 1446: 2711 ± 34 Ma and SCP 1809: 2698 ± 10 Ma) fall in the same range. The average of the 62 concordant analyses obtained from the five samples allows to determine a mean 207Pb/206Pb age of 2696 ± 5 Ma (±2σ) interpreted as that of the alkaline plutonism. The geochronologic data obtained up to now have not helped to constrain an age for the metamorphism that affected the study area. The A2 type of magmatism, instead of and the TDM model ages (ca. 3.2-3.8 Ga) and the

  16. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    PubMed Central

    2015-01-01

    Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer's disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS) and Heat Shock Proteins (HSPs), in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging. PMID:26078824

  17. Ionic, electronic and ion-diffusion controlled relaxation processes in CaF2, BaF2 and LiBaF3 crystals

    NASA Astrophysics Data System (ADS)

    Ziraps, V.; Kulis, P.; Tale, I.; Veispals, A.

    The ionic, electronic and anion-diffusion controlled thermally stimulated relaxation (TSR) processes at 80-700 K in CaF2 BaF2 and LiBaF3 crystals (X-ray irradiated or non-irradiated) have been investigated by means of ionic conductivity, ionic thermally stimulated (TS) depolarization current (TSDC); as well as current (TSC), luminescence (TSL) and bleaching (TSB) techniques. Above 250-290 K broad and overlapping anion TSDC peaks and correlated TSB stages are detected. The TSB kinetics is initiated and controlled by anion detrapping and interaction with the localized charges, i.e., the anion-diffusion controlled TSR processes take place in fluorides. The TSL and TSC data for LiBaF3 indicate that the lifetime and drift of electrons at 80-250 K is very small because of deep retrapping. The main TSL peaks at 132K, 170K and 220 K are caused by Vk center detrapping and hole-diffusion controlled tunnel recombination within pairs like .

  18. Zircon U-Pb Age Distributions in Cogenetic Crystal-Rich Dacitic and Crystal-Poor Rhyolitic Members of Zoned Ignimbrites in the Southern Rocky Mountains by Chemical Abrasion Inductively-Coupled-Plasma Mass Spectrometry (CA-LA-ICP-MS).

    NASA Astrophysics Data System (ADS)

    Sliwinski, J.; Zimmerer, M. J.; Guillong, M.; Bachmann, O.; Lipman, P. W.

    2015-12-01

    The San Juan locus of the Southern Rocky Mountain Volcanic Field (SRMVF) in SW Colorado represents an erosional remnant of a mid-Tertiary (~37-23 Ma) ignimbrite flare up that produced some of the most voluminous ignimbrites on Earth. A key feature of many SRMVF ignimbrites is compositional zonation, with many volcanic units comprising both dacitic and rhyolitic horizons. Geochemical, field and petrographic evidence suggests that dacites and rhyolites are cogenetic. Here, we report U-Pb zircon ages by chemical abrasion inductively-coupled-plasma mass spectrometry (CA-LA-ICPMS) for rhyolitic and dacitic components in four units: the Bonanza, Rat Creek, Carpenter Ridge and Nelson Mountain Tuffs. All units show zircon age spectra that are either within analytical uncertainty of Ar/Ar ages or are appreciably older, indicating prolonged magma residence times (~500 ka) prior to eruption. Anomalously young Pb-loss zones in zircon have been largely removed by chemical abrasion. Older, inherited zircons and zircon cores (60-2000 Ma) are rare in all samples, suggesting limited assimilation of upper crustal Precambrian country rock or complete resorption during recharge events and magma chamber growth.

  19. Noradrenaline-induced changes in intracellular Ca(2+) and tension in mesenteric arteries from diabetic rats.

    PubMed

    Chow, W L; Zhang, L; MacLeod, K M

    2001-09-01

    1. The purpose of this investigation was to determine whether enhanced contractile responses to noradrenaline (NA) of mesenteric arteries from rats with chronic streptozotocin-induced diabetes are associated with increases in mean cytosolic [Ca(2+)]i. 2. [Ca(2+)]i was measured with fura 2-AM, and was monitored simultaneously with tension in perfused endothelium-denuded mesenteric arterial rings from 12 - 14 week diabetic rats and age- and gender-matched control rats. 3. Basal [Ca(2+)]i (expressed as R(n), the normalized fura 2 ratio) was not significantly different in arteries from control and diabetic rats. Similarly, no differences between control and diabetic arteries in the tension or [Ca(2+)]i responses to 80 mM KCl in the presence of phentolamine were detected. 4. The rate of tension development, peak tension and integrated tension in response to 30 microM NA were all significantly greater in diabetic than control arteries. However, this was not associated with enhancement of the corresponding [Ca(2+)]i responses in the diabetic arteries. 5. Peak contractile responses to perfusion with both 0.3 and 3 microM NA, but peak [Ca(2+)]i only in response to 0.3 microM NA, were significantly greater in diabetic than control arteries. 6. NA (30 microM) produced a greater increase in both peak tension and [Ca(2+)]i in diabetic than control arteries perfused with Ca(2+)-free solution containing 1 mM EGTA. Neither the rate nor the magnitude of NA-induced Ca(2+) influx appeared to be altered in the diabetic arteries. 7. The enhanced sustained contractile response of diabetic arteries to NA appears to be dissociated from increases in [Ca(2+)]i, and may be due to other factors, such as an increase in the Ca(2+) sensitivity of the contractile proteins.

  20. Efficacy of the Lexicon Pirate Strategy Therapy for Improving Lexical Learning in School-Age Children: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Motsch, Hans-Joachim; Marks, Dana-Kristin

    2015-01-01

    Lexicon Pirate was originally developed as a strategy intervention programme to treat lexical disorders of pre-school children. To evaluate the therapy's effectiveness for school-age students, a randomized controlled trial (RCT, N = 157) was conducted. Based on a pre--post-test design, the programme's impacts were compared with a control group…

  1. A child-centered scale of informal social control for Latino parents of preschool-age children: Development and validation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perceived neighborhood informal social control may determine whether parents allow their young children to be physically active in the neighborhood. We developed and validated a scale of neighborhood child-centered informal social control appropriate for Latino parents of preschool-age children. The...

  2. ARRA FEMP Technical Assistance -- Federal Aviation Administration Project 209 -- Control Tower and Support Building, Palm Springs, CA

    SciTech Connect

    Arends, J.; Sandusky, William F.

    2010-03-31

    This report represents findings of a design review team that evaluated construction documents (at the 100% level) and operating specifications for a new control tower and support building that will be built in Palm Springs, California by the Federal Aviation Administration (FAA). The focus of the review was to identify measures that could be incorporated into the final design and operating specifications that would result in additional energy savings for the FAA that would not have otherwise occurred.

  3. Control system for the 2nd generation Berkeley AutoMounters (BAM2) at GM/CA CAT macromolecular crystallography beamlines.

    PubMed

    Makarov, O; Hilgart, M; Ogata, C; Pothineni, S; Cork, C

    2011-09-01

    GM/CA CAT at Sector 23 of the Advanced Photon Source (APS) is an NIH funded facility for crystallographic structure determination of biological macromolecules by X-ray diffraction.A second generation Berkeley automounter is being integrated into the beamline control system at the 23-BM experimental station. This new device replaces the previous all-pneumatic gripper motions with a combination of pneumatics and XYZ motorized linear stages. The latter adds a higher degree of flexibility to the robot including auto-alignment capability, accommodation of a larger capacity sample Dewar of arbitrary shape, and support for advanced operations such as crystal washing, while preserving the overall simplicity and efficiency of the Berkeley automounter design.

  4. Mercury fate in ageing and melting snow: development and testing of a controlled laboratory system.

    PubMed

    Mann, Erin; Meyer, Torsten; Mitchell, Carl P J; Wania, Frank

    2011-10-01

    A snow cover can modify when, to what extent, and in what form atmospherically deposited mercury is released to the underlying surface media and/or back to the atmosphere. Investigations of mercury transport and transformation processes in snow packs are hampered by the difficulty in controlling experimental and melt conditions and due to the huge variability in the composition and physical structure of environmental snow packs. A method was developed that allows the detailed mechanistic investigation of mercury fate in snow that is made, aged and melted under controlled laboratory conditions. A number of control samples established that mercury in indoor air, scavenged during the snow making process, constitutes the dominant source of mercury in the artificial snow. No addition of mercury is required. The amount of mercury in fresh snow was quantitatively (102 and 106% in two experiments) recovered in the dissolved and particulate fractions of the melt water and the vessel head space, confirming a mass balance for mercury and the absence of unquantifiable mercury sources and sinks in the experimental system. In snow made from unmodified tap water, more than half of the mercury present in the snowpack was recovered from the bottom of the snow vessel after all of the snow had melted. Such late elution is indicative of mercury being mostly associated with particles that are filtered by, and retained in, the shrinking snowpack. Addition of salt to the snow-making water at an environmentally realistic pH notably shifted the distribution of mercury in the snowpack from the particulate to the dissolved phase, resulting in more than 60% of the mercury eluting in the dissolved phase of early melt water fractions.

  5. Evolution of Seawater 44Ca/40Ca Through the Late Cretaceous and Cenozoic

    NASA Astrophysics Data System (ADS)

    Castillo, P. R.; Gopalan, K.; Norris, R. D.; MacIsaac, C.; Liu, X.; MacDougall, J. D.

    2009-12-01

    We analyzed the Ca concentrations and 44Ca/40Ca ratios of surface ocean planktonic (Morozovella, Acarinina, Dentoglobigerina) and benthic (Gavelinella) foraminifera of Late Cretaceous to Late Oligocene ages from DSDP and ODP sites in the Pacific, Atlantic and Indian oceans in order to fill a major gap in the Phanerozoic seawater 44Ca/40Ca curve (Farkass et al., Geochim. Cosmochim. Acta 71, 2007). Our new 44Ca/40Ca data indicate a general increase in foraminiferan-based seawater 44Ca/40Ca from ~-1.3 ‰ δ44Ca/40CaSW in Late Cretaceous to ~0.0 ‰ δ44Ca/40CaSW in Early Miocene (Heuser et al., Paleocean. 20, 2005; Sime et al., Geochim. Cosmochim. Acta 71, 2007). In detail, the 44Ca/40Ca ratio stepped abruptly from ~-1.3 ‰ δ44Ca/40CaSW to a slightly higher value of ~-1.1 ‰ δ44Ca/40CaSW across the Cretaceous-Tertiary (K/T) boundary. A slight positive excursion of ~0.2 ‰ above the background value occurred after the Paleocene Thermal Maximum (55 Ma) but otherwise, the Paleocene to Middle Eocene ratio is relatively stable at ~-1.0 ‰ δ44Ca/40CaSW. The most prominent increase in foraminiferan-based seawater 44Ca/40Ca occurred from Late Eocene to Late Oligocene, roughly coincident with the initial phase of the rapid and steady rise of marine carbonate 87Sr/86Sr ratio in the Tertiary (e.g., DePaolo and Ingram, Science 227, 1985).

  6. A conserved splicing mechanism of the LMNA gene controls premature aging.

    PubMed

    Lopez-Mejia, Isabel C; Vautrot, Valentin; De Toledo, Marion; Behm-Ansmant, Isabelle; Bourgeois, Cyril F; Navarro, Claire L; Osorio, Fernando G; Freije, José M P; Stévenin, James; De Sandre-Giovannoli, Annachiara; Lopez-Otin, Carlos; Lévy, Nicolas; Branlant, Christiane; Tazi, Jamal

    2011-12-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and leads to the production of a truncated protein (progerin) with a dominant negative effect. Here we show that HGPS mutation changes the accessibility of the 5'SS of LMNA exon 11 which is sequestered in a conserved RNA structure. Our results also reveal a regulatory role of a subset of serine-arginine (SR)-rich proteins, including serine-arginine rich splicing factor 1 (SRSF1) and SRSF6, on utilization of the 5'SS leading to lamin A or progerin production and a modulation of this regulation in the presence of the c.1824C>T mutation is shown directly on HGPS patient cells. Mutant mice carrying the equivalent mutation in the LMNA gene (c.1827C>T) also accumulate progerin and phenocopy the main cellular alterations and clinical defects of HGPS patients. RNAi-induced depletion of SRSF1 in the HGPS-like mouse embryonic fibroblasts (MEFs) allowed progerin reduction and dysmorphic nuclei phenotype correction, whereas SRSF6 depletion aggravated the HGPS-like MEF's phenotype. We demonstrate that changes in the splicing ratio between lamin A and progerin are key factors for lifespan since heterozygous mice harboring the mutation lived longer than homozygous littermates but less than the wild-type. Genetic and biochemical data together favor the view that physiological progerin production is under tight control of a conserved splicing mechanism to avoid precocious aging.

  7. Women With Polycystic Ovary Syndrome Have Comparable Hip Bone Geometry to Age-Matched Control Women.

    PubMed

    McBreairty, Laura E; Zello, Gordon A; Gordon, Julianne J; Serrao, Shani B; Pierson, Roger A; Chizen, Donna R; Chilibeck, Philip D

    2016-12-26

    Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting women of reproductive age manifesting with polycystic ovaries, menstrual irregularities, hyperandrogenism, hirsutism, and insulin resistance. The oligomenorrhea and amenorrhea characteristic to PCOS are associated with low bone mineral density (BMD); conversely, the hyperandrogenism and hyperinsulinemia may elicit a protective effect on BMD. As bone geometric properties provide additional information about bone strength, the objective of this study was to compare measures of hip geometry in women with PCOS to a healthy female population. Using dual-energy X-ray absorptiometry, BMD and measures of hip geometry were determined in women with PCOS (n = 60) and healthy controls (n = 60) aged 18-35 years. Clinical biochemical measures were also determined in women with PCOS. Measures of hip geometry, including cross-sectional area, cross-sectional moment of inertia, subperiosteal width (SPW), and section modulus, were similar between groups following correction for body mass index (BMI) (all p > 0.05) with intertrochanter SPW significantly lower in women with PCOS (p < 0.05). BMI-corrected whole body BMD as well as the lumbar spine and regions of proximal femur were also comparable between groups. In women with PCOS, BMI-corrected correlations were found between insulin and femoral shaft SPW (r = 0.322, p < 0.05), glucose and femoral neck (r = 0.301, p < 0.05), and trochanter BMD (0.348, p < 0.05), as well as between testosterone and femoral neck BMD (0.376, p < 0.05) and narrow neck cross-sectional area (0.306, p < 0.05). This study demonstrates that women with PCOS may have compromised intertrochanter SPW while oligomenorrhea appears to have no detrimental effect on bone density or geometry in women with PCOS.

  8. Biological controls on coral Sr/Ca and {delta}{sup 18}O reconstructions of sea surface temperatures

    SciTech Connect

    Villiers, S. de; Nelson, B.K.; Archivas, A.R.

    1995-09-01

    Coral strontium/calcium ratios have been used to infer that the tropical sea surface temperature (SST) cooled by as much as 6{degrees}C during the last glacial maximum. In contrast, little or no change has been inferred from other marine-based proxy records. Experimental studies of the effect of growth rate and the magnitude of intraspecific differences indicate that biological controls on coral skeletal strontium/calcium uptake have been underestimated. These results call into question the reliability of strontium/calcium-based SST reconstructions. 17 refs., 2 figs.

  9. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease.

  10. Development of self-control in children aged 3 to 9 years: Perspective from a dual-systems model

    PubMed Central

    Tao, Ting; Wang, Ligang; Fan, Chunlei; Gao, Wenbin

    2014-01-01

    The current study tested a set of interrelated theoretical propositions based on a dual-systems model of self-control. Data were collected from 2135 children aged 3 to 9 years. The results suggest that (a) there was positive growth in good self-control, whereas poor control remained relatively stable; and (b) girls performed better than boys on tests of good self-control. The results are discussed in terms of their implications for a dual-systems model of self-control theory and future empirical work. PMID:25501669

  11. Age-related disorders of sleep and motor control in the rat models of functionally distinct cholinergic neuropathology.

    PubMed

    Ciric, Jelena; Lazic, Katarina; Petrovic, Jelena; Kalauzi, Aleksandar; Saponjic, Jasna

    2016-03-15

    We studied the impact of aging during sleep in the rat models of Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology to determine the possible different and earlier onset of age-related sleep disorder during the neurodegenerative diseases vs. healthy aging. We used the bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during rapid eye movement sleep (REM). EEG delta amplitude attenuation within the sensorimotor cortex (SMCx) during REM was the earliest sign of aging in the NB lesion. EEG sigma amplitude augmentation within the motor cortex (MCx) during REM was the earliest sign of aging in the PPT lesion. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states. Our study provided evidence of distinct REM sleep disorders and sleep state related cortical drives as the signs of aging onset during functionally distinct cholinergic neuropathologies (NB lesion vs. PPT lesion).

  12. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  13. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    PubMed Central

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). Conclusions These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  14. EFFECT OF SEX, AGE, AND BMI ON THE DEVELOPMENT OF LOCOMOTOR SKILLS AND OBJECT CONTROL SKILLS AMONG PRESCHOOL CHILDREN.

    PubMed

    Yang, Shu-Chu; Lin, Shu-Jung; Tsai, Chia-Yen

    2015-12-01

    Purposive sampling was used to recruit 1,200 preschoolers between the ages of three and seven from 12 preschools throughout Taiwan in order to examine locomotor skills, object control skills, and fundamental motor skills with respect to sex, age, and body mass index (BMI). Fundamental motor skills were measured using the TGMD-2. Only age had a significant influence on locomotor skills, object control skills, and fundamental motor skills; sex had a small influence on object control skills, and BMI had a very limited influence on all three categories. The difference from previous studies related to BMI may be due to the different items included in the various tests, the number of trials conducted, and ways in which BMI was categorized.

  15. Age-dependent lower or higher levels of hair mercury in autistic children than in healthy controls.

    PubMed

    Majewska, Maria Dorota; Urbanowicz, Ewa; Rok-Bujko, Paulina; Namyslowska, Irena; Mierzejewski, Paweł

    2010-01-01

    An association between autism and early life exposure to mercury is a hotly debated issue. In this study, 91 autistic Polish children, male and female, 3-4 and 7-9 years old, were compared to 75 age- and sex-matched healthy children with respect to: demographic, perinatal, clinical and developmental measures, parental age, birth order, morphometric measures, vaccination history, and hair mercury content. In demographic and perinatal measures there were no consistent differences between the autistic and control groups. Autistic children had a significantly greater prevalence of adverse reactions after vaccinations and abnormal development than controls. Between 45 and 80% of autistic children experienced developmental regress. Autistic children significantly differed from healthy peers in the concentrations of mercury in hair: younger autistics had lower levels, while older - higher levels than their respective controls. The results suggest that autistic children differ from healthy children in metabolism of mercury, which seems to change with age.

  16. Clinical application of a novel endoscopic mask: A randomized controlled trial in aged patients undergoing painless gastroscopy.

    PubMed

    Cai, Guangyu; Huang, Zhenling; Zou, Tianxiao; He, Miao; Wang, Shanjuan; Huang, Ping; Yu, Bin

    2017-01-01

    Background: Desaturation during painless gastroscopy in aged patients leads to discontinuation of the procedure, prolonged manipulation time and increased risk of severe complications. An endoscopic nasal mask was designed to control hypoxia during the above procedures. A randomized trial was performed to test whether the novel endoscopic mask is helpful for hypoxia during painless gastroscopy in aged patients. Methods: In this randomized, controlled trial, 141 aged patients undergoing painless gastroscopy were randomized into nasal catheter group (69 patients) and endoscopic mask group (65 patients). Primary outcomes were minimum pulse oxygen saturation and incidence of pulse oxygen saturation ≤ 90%. Results: Finally, 134 aged patients were analyzed, including 69 patients in nasal catheter group and 65 patients endoscopic mask group. The minimum pulse oxygen saturation (96.4% ± 4.8%) was higher in the aged endoscopic mask group than in the aged nasal catheter group (94.3% ± 5.6%, P = 0.0075). The incidence of pulse oxygen saturation ≤ 90% did not significantly differ between the endoscopic mask group and nasal catheter group (6.2% VS 15.9%, P = 0.07). There were no severe adverse events in either groups. Conclusion: The endoscopic mask was safely used in aged patients during painless gastroscopy under propofol sedation and significantly improved the minimum pulse oxygen saturation without increasing time to examination or recovery time.

  17. Clinical application of a novel endoscopic mask: A randomized controlled trial in aged patients undergoing painless gastroscopy

    PubMed Central

    Cai, Guangyu; Huang, Zhenling; Zou, Tianxiao; He, Miao; Wang, Shanjuan; Huang, Ping; Yu, Bin

    2017-01-01

    Background: Desaturation during painless gastroscopy in aged patients leads to discontinuation of the procedure, prolonged manipulation time and increased risk of severe complications. An endoscopic nasal mask was designed to control hypoxia during the above procedures. A randomized trial was performed to test whether the novel endoscopic mask is helpful for hypoxia during painless gastroscopy in aged patients. Methods: In this randomized, controlled trial, 141 aged patients undergoing painless gastroscopy were randomized into nasal catheter group (69 patients) and endoscopic mask group (65 patients). Primary outcomes were minimum pulse oxygen saturation and incidence of pulse oxygen saturation ≤ 90%. Results: Finally, 134 aged patients were analyzed, including 69 patients in nasal catheter group and 65 patients endoscopic mask group. The minimum pulse oxygen saturation (96.4% ± 4.8%) was higher in the aged endoscopic mask group than in the aged nasal catheter group (94.3% ± 5.6%, P = 0.0075). The incidence of pulse oxygen saturation ≤ 90% did not significantly differ between the endoscopic mask group and nasal catheter group (6.2% VS 15.9%, P = 0.07). There were no severe adverse events in either groups. Conclusion: The endoscopic mask was safely used in aged patients during painless gastroscopy under propofol sedation and significantly improved the minimum pulse oxygen saturation without increasing time to examination or recovery time. PMID:28260993

  18. A role for synaptic and network plasticity in controlling epileptiform activity in CA1 in the kainic acid-lesioned rat hippocampus in vitro.

    PubMed Central

    Bernard, C; Wheal, H V

    1996-01-01

    , E-S dissociations were independent of the activation of NMDA receptors, hinting at mechanisms different from those of synaptic LTD. We suggest that changes in E-S coupling were caused by a modification of the firing threshold of the CA1 pyramidal neurons. Furthermore, the firing mechanisms controlling NMDA and AMPA receptor-mediated network activity appeared to be different. The possible use of LFS applied to the hippocampus as a clinical intervention to suppress epileptiform activity is discussed. PMID:8866357

  19. Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation

    PubMed Central

    Goldberg, Jesse H; Tamas, Gabor; Yuste, Rafael

    2003-01-01

    GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions. PMID:12844506

  20. Relations of Growth in Effortful Control to Family Income, Cumulative Risk, and Adjustment in Preschool-age Children

    PubMed Central

    Lengua, Liliana J.; Moran, Lyndsey; Zalewski, Maureen; Ruberry, Erika; Kiff, Cara; Thompson, Stephanie

    2014-01-01

    The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50% girls, 50% boys) from families representing a range of income (29% at- or near-poverty; 28% lower-income; 25% middle-income; 18% upper-income), with 4 assessments starting at 36–40 mos. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children’s preschool adjustment. PMID:25253079

  1. Relations of growth in effortful control to family income, cumulative risk, and adjustment in preschool-age children.

    PubMed

    Lengua, Liliana J; Moran, Lyndsey; Zalewski, Maureen; Ruberry, Erika; Kiff, Cara; Thompson, Stephanie

    2015-05-01

    The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50 % girls, 50 % boys) from families representing a range of income (29 % at- or near-poverty; 28 % lower-income; 25 % middle-income; 18 % upper-income), with 4 assessments starting at 36-40 month. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children's preschool adjustment.

  2. Distribution of P, K, Ca, Mg, Cd, Cu, Fe, Mn, Pb and Zn in wood and bark age classes of willows and poplars used for phytoextraction on soils contaminated by risk elements.

    PubMed

    Zárubová, Pavla; Hejcman, Michal; Vondráčková, Stanislava; Mrnka, Libor; Száková, Jiřina; Tlustoš, Pavel

    2015-12-01

    Fast-growing clones of Salix and Populus have been studied for remediation of soils contaminated by risk elements (RE) using short-rotation coppice plantations. Our aim was to assess biomass yield and distributions of elements in wood and bark of highly productive willow (S1--[Salix schwerinii × Salix viminalis] × S. viminalis, S2--Salix × smithiana clone S-218) and poplar (P1--Populus maximowiczii × Populus nigra, P2--P. nigra) clones with respect to aging. The field experiment was established in April 2008 on moderately Cd-, Pb- and Zn- contaminated soil. Shoots were harvested after four seasons (February 2012) and separated into annual classes of wood and bark. All tested clones grew on contaminated soils, with highest biomass production and lowest mortality exhibited by P1 and S2. Concentrations of elements, with exception of Ca and Pb, decreased with age and were higher in bark than in wood. The Salix clones were characterised by higher removal of Cd, Mn and Zn compared to the Populus clones. Despite generally higher RE content in young shoots, partly due to lower wood/bark ratios and higher RE concentrations in bark, the overall removal of RE was higher in older wood classes due to higher biomass yield. Thus, longer rotations seem to be more effective when phytoextraction strategy is considered. Of the four selected clones, S1 exhibited the best removal of Cd and Zn and is a good candidate for phytoextraction.

  3. Age-Related Corresponding Relationships of Controlled Force Exertion Measured by a Computer-Generated Sinusoidal and Quasi-Random Display

    ERIC Educational Resources Information Center

    Nagasawa, Yoshinori; Demura, Shinichi

    2011-01-01

    This study examined age-group corresponding relationships of the controlled force exertion based on sinusoidal and quasi-random waveforms in 175 right-handed male adults aged 20 to 86 years. The subjects were divided into 3 groups based on age-level: 53 young (mean age 24.6, SD = 3.3 years), 71 middle aged (mean age 44.3, SD = 8.7 years), and 51…

  4. Synthesis and photoluminescence control of Ca10.5-1.5xLax(PO4)7:Eu2+ phosphors by aliovalent cation substitution

    NASA Astrophysics Data System (ADS)

    Fan, Yanting; Tang, Miao; Qiu, Zhongxian; Zhang, Jilin; Yu, Liping; Li, Chengzhi; Lian, Shixun; Zhou, Wenli

    2017-02-01

    A range of Ca10.5-1.5xLax(PO4)7:Eu2+phosphors were synthesized by high temperature solid state method. Subsequently we studied the crystal structures and luminescent properties through X-ray diffraction, photoluminescence and photoluminescence excitation, diffuse reflection spectra, Raman spectra and decay curves systematically. Based on the special crystal structure ofβ-Ca3(PO4)2:Eu2+, its emission undergoes a variation from violet-blue to cyan through introducing La3+. The substitution of La3+ for Ca2+ could form some cation vacancies in Ca(4) sites according to the scheme 3Ca2+= 2La3++ □ due to the different ion valence, which compels Eu2+ to migrate from Ca(4) site to other sites. Additionally, the formation of the cation vacancies can further reduce the thermal stability of phosphors.

  5. Implementation of an active aging model in Mexico for prevention and control of chronic diseases in the elderly

    PubMed Central

    Mendoza-Núñez, Víctor Manuel; Martínez-Maldonado, María de la Luz; Correa-Muñoz, Elsa

    2009-01-01

    Background World Health Organization cites among the main challenges of populational aging the dual disease burden: the greater risk of disability, and the need for care. In this sense, the most frequent chronic diseases during old age worldwide are high blood pressure, type 2 diabetes mellitus, cancer, arthritis, osteoporosis, depression, and dementia. Chronic disease-associated dependency represents an onerous sanitary and financial burden for the older adult, the family, and the health care system. Thus, it is necessary to propose community-level models for chronic disease prevention and control in old age. The aim of the present work is to show our experience in the development and implementation of a model for chronic disease prevention and control in old age at the community level under the active aging paradigm. Methods/Design A longitudinal study will be carried out in a sample of 400 elderly urban and rural-dwelling individuals residing in Hidalgo State, Mexico during five years. All participants will be enrolled in the model active aging. This establishes the formation of 40 gerontological promoters (GPs) from among the older adults themselves. The GPs function as mutual-help group coordinators (gerontological nuclei) and establish self-care and self-promotion actions for elderly well-being and social development. It will be conformed a big-net of social network of 40 mutual-help groups of ten elderly adults each one, in which self-care is a daily practice for chronic disease prevention and control, as well as for achieving maximal well-being and life quality in old age. Indicators of the model's impact will be (i) therapeutic adherence; (ii) the incidence of the main chronic diseases in old age; (iii) life expectancy without chronic diseases at 60 years of age; (iv) disability adjusted life years lost; (v) years of life lost due to premature mortality, and (vi) years lived with disability. Discussion We propose that the implementation of the model active

  6. The aging clock and circadian control of metabolism and genome stability.

    PubMed

    Belancio, Victoria P; Blask, David E; Deininger, Prescott; Hill, Steven M; Jazwinski, S Michal

    2014-01-01

    It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN) and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s) of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity, and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable, and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

  7. Controlling reactive oxygen species in skin at their source to reduce skin aging.

    PubMed

    Kern, Dale G; Draelos, Zoe D; Meadows, Christiaan; James Morré, D; Morré, Dorothy M

    2010-01-01

    Activity of an age-related, superoxide-forming, cell-surface oxidase (arNOX) comparing dermis, epidermis, serum, and saliva from female and male subjects ages 28-72 years measured spectrophotometrically using reduction of ferricytochrome c correlated with oxidative skin damage as estimated from autofluoresence of skin using an Advanced Glycation End products Reader (AGE-Reader; DiagnOptics B.V., Netherlands). By reducing arNOX activity in skin with arNOX-inhibitory ingredients (NuSkin's ageLOC technology), skin appearance was improved through decreased protein cross-linking and an accelerated increase in collagen.

  8. Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease.

    PubMed

    Beerman, Isabel; Rossi, Derrick J

    2015-06-04

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This Review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease.

  9. Supralinear dendritic Ca2+ signalling in young developing CA1 pyramidal cells

    PubMed Central

    Pohle, Jörg; Bischofberger, Josef

    2014-01-01

    Although Ca2+ is critically important in activity-dependent neuronal development, not much is known about the regulation of dendritic Ca2+ signals in developing neurons. Here, we used ratiometric Ca2+ imaging to investigate dendritic Ca2+ signalling in rat hippocampal pyramidal cells during the first 1–4 weeks of postnatal development. We show that active dendritic backpropagation of Nav channel-dependent action potentials (APs) evoked already large dendritic Ca2+ transients in animals aged 1 week with amplitudes of ∼150 nm, similar to the amplitudes of ∼160 nM seen in animals aged 4 weeks. Although the AP-evoked dendritic Ca2+ load increased about four times during the first 4 weeks, the peak amplitude of free Ca2+ concentration was balanced by a four-fold increase in Ca2+ buffer capacity κs (∼70 vs. ∼280). Furthermore, Ca2+ extrusion rates increased with postnatal development, leading to a slower decay time course (∼0.2 s vs. ∼0.1 s) and more effective temporal summation of Ca2+ signals in young cells. Most importantly, during prolonged theta-burst stimulation dendritic Ca2+ signals were up to three times larger in cells at 1 week than at 4 weeks of age and much larger than predicted by linear summation, which is attributable to an activity-dependent slow-down of Ca2+ extrusion. As Ca2+ influx is four-fold smaller in young cells, the larger Ca2+ signals are generated using four times less ATP consumption. Taken together, the data suggest that active backpropagations regulate dendritic Ca2+ signals during early postnatal development. Remarkably, during prolonged AP firing, Ca2+ signals are several times larger in young than in mature cells as a result of activity-dependent regulation of Ca2+ extrusion rates. PMID:25239458

  10. Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

    PubMed Central

    Porpora, Maria Grazia; Medda, Emanuela; Abballe, Annalisa; Bolli, Simone; De Angelis, Isabella; di Domenico, Alessandro; Ferro, Annamaria; Ingelido, Anna Maria; Maggi, Antonella; Panici, Pierluigi Benedetti; De Felip, Elena

    2009-01-01

    Background Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. Objective We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. Methods We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. Results We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. Conclusions The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis. PMID:19654915

  11. The use of age-clustered pooled faecal samples for monitoring worm control in horses.

    PubMed

    Eysker, M; Bakker, J; van den Berg, M; van Doorn, D C K; Ploeger, H W

    2008-02-14

    A study was performed on two horse farms to evaluate the use of age-clustered pooled faecal samples for monitoring worm control in horses. In total 109 horses, 57 on farm A and 52 on farm B, were monitored at weekly intervals between 6 and 14 weeks after ivermectin treatment. This was performed through pooled faecal samples of pools of up to 10 horses of the groups 'yearlings' (both farms), '2-year-old' (two pools in farm A), '3-year-old' (farm A) and adult horses (four pools on farm A and five pools on farm B), which were compared with the mean individual faecal egg counts of the same pools. A very high correlation between the faecal egg counts in pooled samples and the mean faecal egg counts was seen and also between the faecal egg counts in pooled samples and larval counts from pooled faecal larval cultures. Faecal egg counts increased more rapidly in yearlings and 2-year-old horses than in older horses. This implied that in these groups of young animals faecal egg counts of more than 200 EPG were reached at or just after the egg reappearance period (ERP) of 8 weeks that is usually indicated for ivermectin. This probably means that, certainly under intensive conditions, repeated treatment at this ERP is warranted in these young animals, with or without monitoring through faecal examination. A different situation is seen in adult animals. Based on the mean faecal egg counts on both farms and on the results of pooled samples in farm A, using 100 EPG as threshold, no justification for treatment was seen throughout the experimental period. However, on farm B values of 100 EPG were seen at 9 and 11, 13 and 14 and 14 weeks after ivermectin treatment in pools 10, 12 and 13, respectively. This coincided with the presence of one or two horses with egg counts above 200 EPG. The conclusion is that random pooled faecal samples of 10 adult horses from a larger herd, starting at the ERP and repeating it at, for instance, 4-week intervals, could be used for decisions on worm

  12. HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of C. elegans.

    PubMed

    Kern, Andreas; Ackermann, Bianca; Clement, Albrecht M; Duerk, Heike; Behl, Christian

    2010-01-05

    Protein stability under changing conditions is of vital importance for the cell and under the control of a fine-tuned network of molecular chaperones. Aging and age-related neurodegenerative diseases are directly associated with enhanced protein instability. Employing C. elegans expressing GFP-tagged luciferase as a reporter for evaluation of protein stability we show that the chaperoning strategy of body wall muscle cells and neurons is significantly different and that both are differently affected by aging. Muscle cells of young worms are largely resistant to heat stress, which is directly mediated by the stress response controlled through Heat Shock Transcription Factor 1. During recovery following heat stress the ability to refold misfolded proteins is missing. Young neurons are highly susceptible to chronic heat stress, but show a high potency to refold or disaggregate proteins during subsequent recovery. The particular proteome instability in neurons results from a delayed induction of the heat shock response. In aged neurons protein stability is increased during heat stress, whereas muscle cells show enhanced protein instability due to a deteriorated heat shock response. An efficient refolding activity is absent in both aged tissues. These results provide molecular insights into the differential protein stabilization capacity in different tissues and during aging.

  13. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    ERIC Educational Resources Information Center

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  14. Posttraumatic Symptoms and Thought Control Strategies among Aging Hidden Jewish Children

    ERIC Educational Resources Information Center

    Fohn, Adeline; Grynberg, Delphine; Luminet, Olivier

    2012-01-01

    This study examined the severity of posttraumatic stress disorder (PTSD) symptoms and the coping strategies of 51 aging hidden children (28 women and 23 men) 65 years after the Holocaust. Results indicated a positive relation between age and PTSD symptoms that was fully mediated by sense of danger and education. Regression analyses showed that…

  15. Movement Control in Older Adults: Does Old Age Mean Middle of the Road?

    ERIC Educational Resources Information Center

    Raw, Rachael K.; Kountouriotis, Georgios K.; Mon-Williams, Mark; Wilkie, Richard M.

    2012-01-01

    Old age is associated with poorer movement skill, as indexed by reduced speed and accuracy. Nevertheless, reductions in speed and accuracy can also reflect compensation as well as deficit. We used a manual tracing and a driving task to identify generalized spatial and temporal compensations and deficits associated with old age. In Experiment 1,…

  16. Age-related changes in human posture control: Motor coordination tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

  17. CaMKII regulates intracellular Ca²⁺ dynamics in native endothelial cells.

    PubMed

    Toussaint, Fanny; Charbel, Chimène; Blanchette, Alexandre; Ledoux, Jonathan

    2015-09-01

    Localized endothelial Ca(2+) signalling, such as Ca(2+) pulsars, can modulate the contractile state of the underlying vascular smooth muscle cell through specific endothelial targets. In addition to K(Ca)3.1 as a target, Ca(2+) pulsars, an IP3R-dependent pulsatile Ca(2+) release from the endoplasmic reticulum (ER) could activate a frequency-sensitive Ca(2+)-dependent kinase such as CaMKII. In the absence of extracellular Ca(2+), acetylcholine increased endothelial CaMKII phosphorylation and activation, thereby suggesting CaMKII activation independently of Ca(2+) influx. Herein, a reciprocal relation where CaMKII controls endothelial Ca(2+) dynamics has been investigated in mesenteric arteries. Both CaMKIIα and β isoforms have been identified in endothelial cells and close proximity (<40 nm) suggests their association in heteromultimers. Intracellular Ca(2+) monitoring with high speed confocal microscopy then showed that inhibition of CaMKII with KN-93 significantly increased the population of Ca(2+) pulsars active sites (+89%), suggesting CaMKII as a major regulator of Ca(2+) pulsars in native endothelium. Mechanistic insights were then sought through the elucidation of the impact of CaMKII on ER Ca(2+) store. ER Ca(2+) emptying was accelerated by CaMKII inhibition and ER Ca(2+) content was assessed using ionomycin. Exposure to KN-93 strongly diminished ER Ca(2+) content (-61%) by relieving CaMKII-dependent inhibition of IP3 receptors (IP3R). Moreover, in situ proximity ligation assay suggested CaMKII-IP3R promiscuity, essential condition for a protein-protein interaction. Interestingly, segregation of IP3R within myoendothelial projection (MEP) appears to be isoform-specific. Hence, only IP3R type 1 and type 2 are detected within fenestrations of the internal elastic lamina, sites of MEP, whilst type 3 is absent from these structures. In summary, CaMKII seems to act as a Ca(2+)-sensitive switch of a negative feedback loop regulating endothelial Ca(2

  18. Interrelationship of the Risser sign, knee epiphysis, and bone age in determining skeletal maturity: a case-control study.

    PubMed

    Kim, Hak Jun; Yoon, Jung-Ro; Modi, Chetna; Modi, Hitesh; Song, Hae-Ryong; Song, Sang-Youn

    2011-05-01

    The purpose of our study was to correlate the chronological age with Risser staging, knee epiphyseal closure, and bone age by the Tanner and Whitehouse (TW3) or Greulich and Pyle (GP) method simultaneously, to find out the most correlated methods used to calculate the age in a Korean population. A case-control study was carried out in 293 children between the age of 9 and 18 years. Skeletal age was estimated by using the atlas of the GP and TW3 methods; knee epiphysis closure and the Risser staging were also noted. Spearman's correlation coefficient test showed that in both the sexes the GP method is more correlated (r=0.58 for female patients, range: 0.55-0.61; and 0.58 for male patients, range: 0.54-0.61) with the Risser staging and physeal stages of the knee joint than the TW3 method (r=0.52 for female patients, range: 0.44-0.61; and 0.55 for male patients, range: 0.48-0.61) in Korean children. Our results suggested that by using the combination of Risser sign, knee epiphyseal closure, and GP bone age, one can calculate a person's chronological age most accurately.

  19. A Randomized Controlled Trial of Two Syntactic Treatment Procedures with Cantonese-Speaking, School-Age Children with Language Disorders

    ERIC Educational Resources Information Center

    To, Carol K. S.; Lui, Hoi Ming; Li, Xin Xin; Lam, Gary Y. H

    2015-01-01

    Purpose: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. Method: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment…

  20. ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

    PubMed Central

    Frankfort, Suzanne V; Doodeman, Valerie D; Bakker, Remco; Tulner, Linda R; van Campen, Jos PCM; Smits, Paul HM; Beijnen, Jos H

    2006-01-01

    Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age