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Sample records for age ca controls

  1. Age-related increases in motivation among children with mental retardation and MA- and CA-matched controls.

    PubMed

    Blair, C; Greenberg, M; Crnic, K

    2001-11-01

    Child positive affect and task orientation in response to a series of cognitively demanding puzzle tasks were assessed at two time points separated by a 12-month interval in children with mild mental retardation and MA- and CA-matched controls (age range 1 to 5 years). At the first assessment, children with mild mental retardation exhibited mastery behavior appropriate for MA but not CA. At the second assessment, the goal-directed behavior of children with mild mental retardation was no different from that of both the MA and CA controls. Correlates of motivation were similar for children with mild mental retardation and typically developing children. Implications for the developmental study of children with mild mental retardation are discussed. PMID:11708937

  2. Age-Related Increases in Motivation among Children with Mental Retardation and MA- and CA-Matched Controls.

    ERIC Educational Resources Information Center

    Blair, Clancy; Greenberg, Mark; Crnic, Keith

    2001-01-01

    Child positive affect and task orientation in response to cognitively demanding puzzle tasks were assessed at two time points separated by 12 months in children with mild mental retardation and mental age and chronological age matched controls (ages 1-5 years). Results suggested correlates of motivation were similar for children with mild mental…

  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

    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 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

  7. Propagation of Intracellular Ca2+ Signals in Aged Exocrine Cells.

    PubMed

    Martin-Cano, Francisco E; Camello-Almaraz, Cristina; Macías, Jesús González; Pozo, Maria J; Camello, Pedro J

    2016-02-01

    There is little information on the effects of aging in the propagation of calcium signals and its underlying mechanisms. We studied the effects of aging on propagation of Ca(2+) signals in pancreatic acinar cells. Fura-2 loaded cells isolated from young (3-4 months old) and aged (24 months old) mouse responded to acetylcholine (ACh) and cholecystokinin (CCK) with a polarized Ca(2+) response initiated at the secretory pole before spreading to the basal one. Aging slowed down the propagation of the response to ACh but enhanced the velocity of the CCK response. This pattern can be explained by the age-induced depolarization of mitochondria, because it can be reproduced in young cells by mitochondrial inhibitors. Aging also increased the role of acidic stores in the CCK signal, as judged by the folimycin-induced suppression of the polarization in aged but not in young cells. The involvement of ryanodine receptors in the ACh response was also enhanced, as indicated by the loss of polarization after the treatment with 8Br-cyclic ADP ribose. Therefore, we conclude that aging modifies differentially the propagation of ACh and CCK-evoked Ca(2+) signals through mitochondrial depolarization and changes in the role of the acidic Ca(2+) stores and ryanodine receptors in the initiation of the signals. PMID:25805851

  8. Plasma membrane Ca2+-ATPases in the nervous system during development and ageing

    PubMed Central

    Mata, Ana M; Sepulveda, M Rosario

    2010-01-01

    Calcium signaling is used by neurons to control a variety of functions, including cellular differentiation, synaptic maturation, neurotransmitter release, intracellular signaling and cell death. This review focuses on one of the most important Ca2+ regulators in the cell, the plasma membrane Ca2+-ATPase (PMCA), which has a high affinity for Ca2+ and is widely expressed in brain. The ontogeny of PMCA isoforms, linked to specific requirements of Ca2+ during development of different brain areas, is addressed, as well as their function in the adult tissue. This is based on the high diversity of variants in the PMCA family in brain, which show particular kinetic differences possibly related to specific localizations and functions of the cell. Conversely, alterations in the activity of PMCAs could lead to changes in Ca2+ homeostasis and, consequently, to neural dysfunction. The involvement of PMCA isoforms in certain neuropathologies and in brain ageing is also discussed. PMID:21537478

  9. Similar enhancement of BK(Ca) channel function despite different aerobic exercise frequency in aging cerebrovascular myocytes.

    PubMed

    Li, N; Liu, B; Xiang, S; Shi, L

    2016-07-18

    Aerobic exercise showed beneficial influence on cardiovascular systems in aging, and mechanisms underlying vascular adaption remain unclear. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play critical roles in regulating cellular excitability and vascular tone. This study determined the effects of aerobic exercise on aging-associated functional changes in BK(Ca) channels in cerebrovascular myocytes, Male Wistar rats aged 20-22 months were randomly assigned to sedentary (O-SED), low training frequency (O-EXL), and high training frequency group (O-EXH). Young rats were used as control. Compared to young rats, whole-cell BK(Ca) current was decreased, and amplitude of spontaneous transient outward currents were reduced. The open probability and Ca(2+)/voltage sensitivity of single BK(Ca) channel were declined in O-SED, accompanied with a reduction of tamoxifen-induced BK(Ca) activation; the mean open time of BK(Ca) channels was shortened whereas close time was prolonged. Aerobic exercise training markedly alleviated the aging-associated decline independent of training frequency. Exercise three times rather than five times weekly may be a time and cost-saving training volume required to offer beneficial effects to offset the functional declines of BK(Ca) during aging. PMID:27070745

  10. Hippocampal CA1 Transcriptional Profile of Sleep Deprivation: Relation to Aging and Stress

    PubMed Central

    Porter, Nada M.; Bohannon, Julia H.; Curran-Rauhut, Meredith; Buechel, Heather M.; Dowling, Amy L. S.; Brewer, Lawrence D.; Popovic, Jelena; Thibault, Veronique; Kraner, Susan D.; Chen, Kuey Chu; Blalock, Eric M.

    2012-01-01

    Background Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. Methodology/Principal Findings F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES), and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD -aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. Conclusions/Significance We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular

  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. Nanocomposite containing CaF2 nanoparticles: Thermal cycling, wear and long-term water-aging

    PubMed Central

    Weir, Michael D.; Moreau, Jennifer L.; Levine, Eric D.; Strassler, Howard D.; Chow, Laurence C.; Xu, Hockin H. K.

    2012-01-01

    Objectives Fluoride (F) releasing dental restoratives are promising to promote remineralization and combat caries. The objectives of this study were to develop nanocomposite containing calcium fluoride nanoparticles (nCaF2), and to investigate the long-term mechanical durability including wear, thermal-cycling and long-term water-aging behavior. Methods Two types of fillers were used: nCaF2 with a diameter of 53 nm, and glass particles of 1.4 μm. Four composites were fabricated with fillers of: (1) 0% nCaF2 + 65% glass; (2) 10% nCaF2 + 55% glass; (3) 20% nCaF2 + 45% glass; (4) 30% nCaF2 + 35% glass. Three commercial materials were also tested. Specimens were subjected to thermal-cycling between 5 °C and 60 °C for 105 cycles, three-body wear for 4×105 cycles, and water-aging for 2 years. Results After thermal-cycling, the nCaF2 nanocomposites had flexural strengths in the range of 100-150 MPa, five times higher than the 20-30 MPa for resin-modified glass ionomer (RMGI). The wear scar depth showed an increasing trend with increasing nCaF2 filler level. Wear of nCaF2 nanocomposites was within the range of wear for commercial controls. Water-aging decreased the strength of all materials. At 2 years, flexural strength was 94 MPa for nanocomposite with 10% nCaF2, 60 MPa with 20% nCaF2, and 48 MPa with 30% nCaF2. They are 3-6 fold higher than the 15 MPa for RMGI (p < 0.05). SEM revealed air bubbles and cracks in a RMGI, while composite control and nCaF2 nanocomposites appeared dense and solid. Significance Combining nCaF2 with glass particles yielded nanocomposites with long-term mechanical properties that were comparable to those of a commercial composite with little F release, and much better than those of RMGI controls. These strong long-term properties, together with their F release being comparable to RMGI as previously reported, indicate that the nCaF2 nanocomposites are promising for load-bearing and caries-inhibiting restorations. PMID:22429937

  14. Roles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic tone.

    PubMed

    Charles, Shelton M; Zhang, Lubo; Cipolla, Marilyn J; Buchholz, John N; Pearce, William J

    2010-10-01

    In light of evidence that immature arteries contain a higher proportion of noncontractile smooth muscle cells than found in fully differentiated mature arteries, the present study explored the hypothesis that age-related differences in the smooth muscle phenotype contribute to age-related differences in contractility. Because Ca(2+) handling differs markedly between contractile and noncontractile smooth muscle, the present study specifically tested the hypothesis that the relative contributions of Ca(2+) influx and myofilament sensitization to myogenic tone are upregulated, whereas Ca(2+) release is downregulated, in immature [14 days postnatal (P14)] compared with mature (6 mo old) rat middle cerebral arteries (MCAs). Myofilament Ca(2+) sensitivity measured in β-escin-permeabilized arteries increased with pressure in P14 but not adult MCAs. Cyclopiazonic acid (an inhibitor of Ca(2+) release from the sarcoplasmic reticulum) increased diameter and reduced Ca(2+) in adult MCAs but increased diameter with no apparent change in Ca(2+) in P14 MCAs. La(3+) (Ca(2+) influx inhibitor) increased diameter and decreased Ca(2+) in adult MCAs, but in P14 MCAs, La(3+) increased diameter with no apparent change in Ca(2+). After treatment with both La(3+) and CPA, diameters were passive in both adult and P14 MCAs, but Ca(2+) was decreased only in adult MCAs. To quantify the fraction of smooth muscle cells in the fully differentiated contractile phenotype, extents of colocalization between smooth muscle α-actin and SM2 myosin heavy chain were determined and found to be at least twofold greater in adult than pup MCAs. These data suggest that compared with adult MCAs, pup MCAs contain a greater proportion of noncontractile smooth muscle and, as a consequence, rely more on myofilament Ca(2+) sensitization and Ca(2+) influx to maintain myogenic reactivity. The inability of La(3+) to reduce cytosolic Ca(2+) in the pup MCA appears due to La(3+)-insensitive noncontractile smooth muscle

  15. The Effect of Age, Sex, Speed and Practice on C/A Performance of Children.

    ERIC Educational Resources Information Center

    Dunham, Paul, Jr.

    This study investigated whether age, sex, speed, and practice affects the acquisition of coincidence-anticipation (C/A) performance accuracy of children ages seven to twelve. (C/A refers to the ability to make a motor response coincident with the arrival of an object at a designated point.) The subjects used in this study were 84 elementary…

  16. An epigenetic clock controls aging.

    PubMed

    Mitteldorf, Josh

    2016-02-01

    We are accustomed to treating aging as a set of things that go wrong with the body. But for more than twenty years, there has been accumulating evidence that much of the process takes place under genetic control. We have seen that signaling chemistry can make dramatic differences in life span, and that single molecules can significantly affect longevity. We are frequently confronted with puzzling choices the body makes which benefit neither present health nor fertility nor long-term survival. If we permit ourselves a shift of reference frame and regard aging as a programmed biological function like growth and development, then these observations fall into place and make sense. This perspective suggests that aging proceeds under control of a master clock, or several redundant clocks. If this is so, we may learn to reset the clocks with biochemical interventions and make an old body behave like a young body, including repair of many of the modes of damage that we are accustomed to regard as independent symptoms of the senescent phenotype, and for which we have assumed that the body has no remedy. PMID:26608516

  17. β-Cell Ca(2+) dynamics and function are compromised in aging.

    PubMed

    Barker, Christopher J; Li, Luosheng; Köhler, Martin; Berggren, Per-Olof

    2015-01-01

    Defects in pancreatic β-cell function and survival are key components in type 2 diabetes (T2D). An age-dependent deterioration in β-cell function has also been observed, but little is known about the molecular mechanisms behind this phenomenon. Our previous studies indicate that the regulation of cytoplasmic free Ca(2+) concentration ([Ca(2+)]i) may be critical and that this is dependent on the proper function of the mitochondria. The [Ca(2+)]i dynamics of the pancreatic β-cell are driven by an interplay between glucose-induced influx of extracellular Ca(2+) via voltage-dependent Ca(2+) channels and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-mediated liberation of Ca(2+) from intracellular stores. Our previous work has indicated a direct relationship between disruption of Ins(1,4,5)P3-mediated Ca(2+) regulation and loss of β-cell function, including disturbed [Ca(2+)]i dynamics and compromised insulin secretion. To investigate these processes in aging we used three mouse models, a premature aging mitochondrial mutator mouse, a mature aging phenotype (C57BL/6) and an aging-resistant phenotype (129). Our data suggest that age-dependent impairment in mitochondrial function leads to modest changes in [Ca(2+)]i dynamics in mouse β-cells, particularly in the pattern of [Ca(2+)]i oscillations. These changes are driven by modifications in both PLC/Ins(1,4,5)P3-mediated Ca(2+) mobilization from intracellular stores and decreased β-cell Ca(2+) influx over the plasma membrane. Our findings underscore an important concept, namely that even relatively small, time-dependent changes in β-cell signal-transduction result in compromised insulin release and in a diabetic phenotype. PMID:25282681

  18. Precise age determinations and petrogenetic studies using the K-Ca method

    NASA Astrophysics Data System (ADS)

    Marshall, B. D.; Depaolo, D. J.

    1982-12-01

    New mass spectrometric techniques are used to reassess the capabilities of the K-40 to Ca-40 radioactive decay for yielding precise ages of various geological materials. A brief discussion of the principles underlying the system's use is presented as a preliminary, and the analytical procedures are described. To test the method, a mineral isochron has been obtained on a sample of Pikes Peak granite which has been shown to have concordant K-Ar, Rb-Sr, and U-Pb ages. Plagioclase, K-feldspar, biotite, and whole rock yield an age of 1041 + or 32 m.y., in agreement with previous age determinations. The initial Ca-40/Ca-42 indicates that assimilation of high K/Ca crust was insufficient to affect calcium isotopes. The results show that the K-Ca system can be used as a precise geochronometer for common felsic igneous and metamorphic rocks, and may prove applicable to sedimentary rocks containing authigenic K minerals.

  19. Altered intrinsic excitability of hippocampal CA1 pyramidal neurons in aged PDAPP mice

    PubMed Central

    Tamagnini, Francesco; Novelia, Janet; Kerrigan, Talitha L.; Brown, Jon T.; Tsaneva-Atanasova, Krasimira; Randall, Andrew D.

    2015-01-01

    Amyloidopathy involves the accumulation of insoluble amyloid β (Aβ) species in the brain’s parenchyma and is a key histopathological hallmark of Alzheimer’s disease (AD). Work on transgenic mice that overexpress Aβ suggests that elevated Aβ levels in the brain are associated with aberrant epileptiform activity and increased intrinsic excitability (IE) of CA1 hippocampal neurons. In this study we examined if similar changes could be observed in hippocampal CA1 pyramidal neurons from aged PDAPP mice (20–23 month old, Indiana mutation: V717F on APP gene) compared to their age-matched wild-type littermate controls. Whole-cell current clamp recordings revealed that sub-threshold intrinsic properties, such as input resistance, resting membrane potential and hyperpolarization activated “sag” were unaffected, but capacitance was significantly decreased in the transgenic animals. No differences between genotypes were observed in the overall number of action potentials (AP) elicited by 500 ms supra-threshold current stimuli. PDAPP neurons, however, exhibited higher instantaneous firing frequencies after accommodation in response to high intensity current injections. The AP waveform was narrower and shorter in amplitude in PDAPP mice: these changes, according to our in silico model of a CA1/3 pyramidal neuron, depended on the respective increase and reduction of K+ and Na+ voltage-gated channels maximal conductances. Finally, the after-hyperpolarization, seen after the first AP evoked by a +300 pA current injection and after 50 Hz AP bursts, was more pronounced in PDAPP mice. These data show that Aβ-overexpression in aged mice altered the capacitance, the neuronal firing and the AP waveform of CA1 pyramidal neurons. Some of these findings are consistent with previous work on younger PDAPP; they also show important differences that can be potentially ascribed to the interaction between amyloidopathy and ageing. Such a change of IE properties over time underlies

  20. Dantrolene suppresses spontaneous Ca2+ release without altering excitation-contraction coupling in cardiomyocytes of aged mice

    PubMed Central

    Roberts, Cale J.; Gibson, Anne K.; Hanft, Laurin M.; McDonald, Kerry S.; Segal, Steven S.

    2014-01-01

    Cardiac dysfunction in the aged heart reflects abnormalities in cardiomyocyte Ca2+ homeostasis including altered Ca2+ cycling through the sarcoplasmic reticulum (SR). The ryanodine receptor antagonist dantrolene exerts antiarrhythmic effects by preventing spontaneous diastolic Ca2+ release from the SR. We tested the hypothesis that dantrolene prevents spontaneous Ca2+ release without altering excitation-contraction coupling in aged myocardium. Left ventricular cardiomyocytes isolated from young (3 to 4 mo) and aged (24–26 mo) C57BL/6 mice were loaded with the Ca2+ indicator fluo-4. Amplitudes of action potential-induced Ca2+ transients at 1-Hz pacing were similar between young and aged mice, yet cell shortening was impaired in aged mice. Isoproterenol (1 μM) increased Ca2+ transient amplitude and cell shortening to identical levels in young and aged; dantrolene (1 μM) had no effect on Ca2+ transients or cell shortening during pacing. Under Ca2+ overload conditions induced with 10 mM extracellular Ca2+ concentration, spontaneous Ca2+ waves were of diminished amplitude and associated with lower SR Ca2+ content in aged versus young mice. Despite no effect in young mice, dantrolene increased SR Ca2+ content and Ca2+ wave amplitude in aged mice. In the presence of isoproterenol following rest from 1-Hz pacing, Ca2+ spark frequency was elevated in aged mice, yet the time to spontaneous Ca2+ wave was similar between young and aged mice; dantrolene decreased Ca2+ spark frequency and prolonged the time to Ca2+ wave onset in aged mice with no effect in young mice. Thus dantrolene attenuates diastolic Ca2+ release in the aged murine heart that may prove useful in preventing cardiac dysfunction. PMID:25038147

  1. 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.

  2. Hippocampal glucocorticoid receptor activation enhances voltage-dependent Ca2+ conductances: relevance to brain aging.

    PubMed Central

    Kerr, D S; Campbell, L W; Thibault, O; Landfield, P W

    1992-01-01

    Glucocorticoids (GCs) activate several biochemical/molecular processes in the hippocampus through two receptor types. In addition, GCs influence cognitive behaviors and hippocampal neural activity and can also increase the rate of aging-dependent cell loss in the hippocampus. However, the ionic mechanisms through which GCs modulate hippocampal neuronal function are not well understood. We report here direct evidence that activation of cytosolic steroid receptors, specifically of the type II GC receptor, can enhance voltage-dependent Ca2+ conductances in brain neurons. Ca2+ current was assessed by current-clamp measures of Ca2+ action potentials and by sharp electrode voltage-clamp analyses of voltage-sensitive currents in cesium-, tetrodotoxin-, and tetraethylammonium-treated CA1 neurons in hippocampal slices. Both Ca2+ action potentials and voltage-activated Ca2+ currents (N- and L-like) were increased by 2-hr exposure to the synthetic GC receptor agonist, RU 28362. This effect of RU 28362 was blocked by coincubation with cycloheximide, indicating that the GC receptor-Ca2+ channel interaction depends on de novo protein synthesis. Dysregulated calcium homeostasis is also viewed as a candidate mechanism in brain aging. Thus, present results are consistent with the hypothesis that excessive GC-receptor activation and resultant increased Ca2+ influx may be two sequential phases of a brain-aging process that results initially in impairment of function and eventually in neuronal loss. PMID:1528857

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

    PubMed

    Pietrangelo, Laura; D'Incecco, Alessandra; Ainbinder, Alina; Michelucci, Antonio; Kern, Helmut; Dirksen, Robert T; Boncompagni, Simona; Protasi, Feliciano

    2015-11-01

    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/100 µm2) and CRU-mitochondrial pair density (37.4 ± 0.8 vs. 27.0 ± 0.7 pairs/100 µm2) 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

  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. Advanced age protects microvascular endothelium from aberrant Ca2+ influx and cell death induced by hydrogen peroxide

    PubMed Central

    Socha, Matthew J; Boerman, Erika M; Behringer, Erik J; Shaw, Rebecca L; Domeier, Timothy L; Segal, Steven S

    2015-01-01

    Abstract Endothelial cell Ca2+ signalling is integral to blood flow control in the resistance vasculature yet little is known of how its regulation may be affected by advancing age. We tested the hypothesis that advanced age protects microvascular endothelium by attenuating aberrant Ca2+ signalling during oxidative stress. Intact endothelial tubes (width, ∼60 μm; length, ∼1000 μm) were isolated from superior epigastric arteries of Young (3–4 months) and Old (24–26 months) male C57BL/6 mice and loaded with Fura-2 dye to monitor [Ca2+]i. At rest there was no difference in [Ca2+]i between age groups. Compared to Young, the [Ca2+]i response to maximal stimulation with acetylcholine (3 μm, 2 min) was ∼25% greater in Old, confirming signalling integrity with advanced age. Basal H2O2 availability was ∼33% greater in Old while vascular catalase activity was reduced by half. Transient exposure to elevated H2O2 (200 μm, 20 min) progressively increased [Ca2+]i to ∼4-fold greater levels in endothelium of Young versus Old. With no difference between age groups at rest, Mn2+ quench of Fura-2 fluorescence revealed 2-fold greater Ca2+ influx in Young during elevated H2O2; this effect was attenuated by ∼75% using ruthenium red (5 μm) as a broad-spectrum inhibitor of transient receptor potential channels. Prolonged exposure to H2O2 (200 μm, 60 min) induced ∼7-fold greater cell death in endothelium of Young versus Old. Thus, microvascular endothelium can adapt to advanced age by reducing Ca2+ influx during elevated oxidative stress. Protection from cell death during oxidative stress will sustain endothelial integrity during ageing. Key points Calcium signalling in endothelial cells of resistance arteries is integral to blood flow regulation. Oxidative stress and endothelial dysfunction can prevail during advanced age and we questioned how calcium signalling may be affected. Intact endothelium was freshly isolated from superior epigastric arteries of

  6. FK506-binding protein 1b/12.6: a key to aging-related hippocampal Ca2+ dysregulation?

    PubMed Central

    Gant, JC; Blalock, EM; K-C, Chen; Kadish, I; Porter, NM; Norris, CM; Thibault, O; Landfield, PW

    2014-01-01

    It has been recognized for some time that the Ca2+-dependent slow afterhyperpolarization (sAHP) is larger in hippocampal neurons of aged compared with young animals. In addition, extensive studies since have shown that other Ca2+-mediated electrophysiological responses are increased in hippocampus with aging, including Ca2+ transients, L-type voltage-gated Ca2+ channel activity, Ca2+ spike duration and action potential accommodation. Elevated Ca2+-induced Ca2+ release from ryanodine receptors (RyRs) appears to drive amplification of the Ca2+ responses. Components of this Ca2+ dysregulation phenotype correlate with deficits in cognitive function and plasticity, indicating they may play critical roles in aging-related impairment of brain function. However, the molecular mechanisms underlying aging-related Ca2+ dysregulation are not well understood. FK506-binding proteins 1a and 1b (FKBP1a/1b, also known as FKBP12/12.6) are immunophilin proteins that bind the immunosuppressant drugs FK506 and rapamycin. In muscle cells, FKBP1a/1b also bind RyRs and inhibits Ca2+-induced Ca2+ release, but it is not clear whether FKBPs act similarly in brain cells. Recently, we found that selectively disrupting hippocampal FKBP1b function in young rats, either by microinjecting adeno-associated viral vectors containing siRNA, or by treatment with rapamycin, increases the sAHP and recapitulates much of the hippocampal Ca2+ dysregulation phenotype. Moreover, in microarray studies, we found FKBP1b gene expression was downregulated in hippocampus of aging rats and early-stage Alzheimer’s disease subjects. These results suggest the novel hypothesis that declining FKBP function is a key factor in aging-related Ca2+ dysregulation in the brain and point to potential new therapeutic targets for counteracting unhealthy brain aging. PMID:24291098

  7. Age-dependent changes in Ca2+ homeostasis in peripheral neurones: implications for changes in function.

    PubMed

    Buchholz, John N; Behringer, Erik J; Pottorf, William J; Pearce, William J; Vanterpool, Conwin K

    2007-06-01

    Calcium ions represent universal second messengers within neuronal cells integrating multiple cellular functions, such as release of neurotransmitters, gene expression, proliferation, excitability, and regulation of cell death or apoptotic pathways. The magnitude, duration and shape of stimulation-evoked intracellular calcium ([Ca2+]i) transients are determined by a complex interplay of mechanisms that modulate stimulation-evoked rises in [Ca2+]i that occur with normal neuronal function. Disruption of any of these mechanisms may have implications for the function and health of peripheral neurones during the aging process. This review focuses on the impact of advancing age on the overall function of peripheral adrenergic neurones and how these changes in function may be linked to age-related changes in modulation of [Ca2+]i regulation. The data in this review suggest that normal aging in peripheral autonomic neurones is a subtle process and does not always result in dramatic deterioration in their function. We present studies that support the idea that in order to maintain cell viability peripheral neurones are able to compensate for an age-related decline in the function of at least one of the neuronal calcium-buffering systems, smooth endoplasmic reticulum calcium ATPases, by increased function of other calcium-buffering systems, namely, the mitochondria and plasmalemma calcium extrusion. Increased mitochondrial calcium uptake may represent a 'weak point' in cellular compensation as this over time may contribute to cell death. In addition, we present more recent studies on [Ca2+]i regulation in the form of the modulation of release of calcium from smooth endoplasmic reticulum calcium stores. These studies suggest that the contribution of the release of calcium from smooth endoplasmic reticulum calcium stores is altered with age through a combination of altered ryanodine receptor levels and modulation of these receptors by neuronal nitric oxide containing neurones

  8. 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

  9. Mg/Ca, Sr/Ca and Ca isotope ratios in benthonic foraminifers related to test structure, mineralogy and environmental controls

    NASA Astrophysics Data System (ADS)

    Gussone, Nikolaus; Filipsson, Helena L.; Kuhnert, Henning

    2016-01-01

    We analysed Mg/Ca, Sr/Ca and Ca isotope ratios of benthonic foraminifers from sediment core tops retrieved during several research cruises in the Atlantic Ocean, in order to improve the understanding of isotope fractionation and element partitioning resulting from biomineralisation processes and changes in ambient conditions. Species include foraminifers secreting tests composed of hyaline low magnesium calcite, porcelaneous high magnesium calcite as well as aragonite. Our results demonstrate systematic isotope fractionation and element partitioning patterns specific for these foraminiferal groups. Calcium isotope fractionation is similar in porcelaneous and hyaline calcite tests and both groups demonstrate the previously described anomaly with enrichment of heavy isotopes around 3-4 °C (Gussone and Filipsson, 2010). Calcium isotope ratios of the aragonitic species Hoeglundina elegans, on the other hand, are about 0.4‰ lighter compared to the calcitic species, which is in general agreement with stronger fractionation in inorganic aragonite compared to calcite. However, the low and strongly variable Sr content suggests additional processes during test formation, and we propose that transmembrane ion transport or a precursor phase to aragonite may be involved. Porcelaneous tests, composed of high Mg calcite, incorporate higher amounts of Sr compared to hyaline low Mg calcite, in agreement with inorganic calcite systematics, but also porcelaneous tests with reduced Mg/Ca show high Sr/Ca. While calcium isotopes, Sr/Ca and Mg/Ca in benthonic foraminifers primarily appear to fractionate and partition with a dominant inorganic control, δ44/40Ca temperature and growth rate dependencies of benthonic foraminifer tests favour a dominant contribution of light Ca by transmembrane transport relative to unfractionated seawater Ca to the calcifying fluid, thus controlling the formation of foraminiferal δ44/40Ca and Sr/Ca proxy signals.

  10. Effect of cell ageing on Ca2+ influx into human red cells.

    PubMed

    Romero, P J; Romero, E A

    1999-01-01

    The effect of cell ageing on Ca2+ entry was studied in this work, using sub-populations of young and old human red cells, separated by stringent percoll density gradients. Additionally, the influence of an osmotic gradient was investigated as a model for shear stress. Ca2+ entry was assessed at 37 degrees C, under conditions where the Ca2+ pump was either inhibited by NaVO3 (0.5-10 mM) or inactivated by ATP depletion. The entry was linear with time up to 1 h. No differences in Ca2+ influx between the two sub-populations were detected in isotonic Na(+)-medium. In contrast, after incubation in anisosmotic media, Ca2+ entry into old cells was significantly higher than into younger cells. In hypotonic Na(+)-medium, the entry into old cells was not affected by La3+ (10 microM) whilst it was partially blocked by Gd3+ at a similar level (half-maximal effect attained with about 1 microM Gd3+). The entry into young cells was only slightly stimulated by these lanthanides at low concentrations (10 microM), regardless of the tonicity of incubation medium. Further increasing Gd3+ levels above 10 microM markedly enhanced Ca2+ entry into both cell types. The selective blockade of Ca2+ influx by low Gd3+ concentrations suggests presence of mechano-sensitive channels, that become preferentially activated in old cells. Activation of these channels during in-vivo microcirculation may help to explain the increased Ca2+ content of senescent cells. PMID:10598277

  11. Measuring Ages and Elemental Abundances from Unresolved Stellar Populations: Fe, Mg, C, N, and Ca

    NASA Astrophysics Data System (ADS)

    Graves, Genevieve J.; Schiavon, Ricardo P.

    2008-08-01

    We present a method for determining mean light-weighted ages and abundances of Fe, Mg, C, N, and Ca from medium-resolution spectroscopy of unresolved stellar populations. The method is implemented in a publicly available code called EZ_Ages. The method and error estimation are described, and the results tested for accuracy and consistency, by application to integrated spectra of well-known Galactic globular and open clusters. Ages and abundances from integrated light analysis agree with studies of resolved stars to within ±0.1 dex for most clusters, and to within ±0.2 dex for nearly all cases. The results are robust to the choice of Lick indices used in the fitting to within ±0.1 dex, except for a few systematic deviations that are clearly categorized. The realism of our error estimates is checked through comparison with detailed Monte Carlo simulations. Finally, we apply EZ_Ages to the sample of galaxies presented in Thomas et al. (2005) and compare our derived values of age, [Fe/H], and [α/Fe] to their analysis. We find that [α/Fe] is very consistent between the two analyses, that ages are consistent for old (age > 10 Gyr) populations but show modest systematic differences at younger ages, and that [Fe/H] is fairly consistent, with small systematic differences related to the age systematics. Overall, EZ_Ages provides accurate estimates of fundamental parameters from medium-resolution spectra of unresolved stellar populations in the old and intermediate-age regime, for the first time allowing quantitative estimates of the abundances of C, N, and Ca in these unresolved systems.

  12. Age-dependent changes in diastolic Ca2+ and Na+ concentrations in dystrophic cardiomyopathy: Role of Ca2+ entry and IP3

    PubMed Central

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

    2014-01-01

    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 Ca2+ concentration ([Ca2+]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 (Gd3+)-sensitive Ca2+ entry and inositol triphosphate (IP3) signaling pathways in abnormal [Ca2+]d and [Na+]d were investigated. Our results showed an age-dependent increase in both [Ca2+]d and [Na+]d in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd3+ treatment significantly reduced both [Ca2+]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 Gd3+ normalized both [Ca2+]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 Ca2+ and Na+ overload mediated at least in part by enhanced Ca2+ entry through Gd3+ sensitive transient receptor potential channels (TRPC), and by IP3 receptors. PMID:25242522

  13. 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

    2014-10-01

    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. PMID:25242522

  14. The neuron-astrocyte-microglia triad involvement in neuroinflammaging mechanisms in the CA3 hippocampus of memory-impaired aged rats.

    PubMed

    Lana, Daniele; Iovino, Ludovica; Nosi, Daniele; Wenk, Gary L; Giovannini, Maria Grazia

    2016-10-01

    We examined the effects of inflammaging on memory encoding, and qualitative and quantitative modifications on proinflammatory proteins, apoptosis, neurodegeneration and morphological changes of neuron-astrocyte-microglia triads in CA3 Stratum Pyramidale (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of young (3months) and aged rats (20months). Aged rats showed short-term memory impairments in the inhibitory avoidance task, increased expression of iNOS and activation of p38MAPK in SP, increase of apoptotic neurons in SP and of ectopic neurons in SL, and decrease of CA3 pyramidal neurons. The number of astrocytes and their branches length decreased in the three CA3 subregions of aged rats, with morphological signs of clasmatodendrosis. Total and activated microglia increased in the three CA3 subregions of aged rats. In aged rats CA3, astrocytes surrounded ectopic degenerating neurons forming "micro scars" around them. Astrocyte branches infiltrated the neuronal cell body, and, together with activated microglia formed "triads". In the triads, significantly more numerous in CA3 SL and SR of aged rats, astrocytes and microglia cooperated in fragmentation and phagocytosis of ectopic neurons. Inflammaging-induced modifications of astrocytes and microglia in CA3 of aged rats may help clearing neuronal debris derived from low-grade inflammation and apoptosis. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Targeting the triads may represent a therapeutic strategy which may control inflammatory processes and spread of further cellular damage to neighboring cells. PMID:27466072

  15. Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons: increased effect with age in culture.

    PubMed

    Norris, C M; Blalock, E M; Chen, K-C; Porter, N M; Landfield, P W

    2002-01-01

    The Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, modulates a number of key Ca(2+) signaling pathways in neurons, and has been implicated in Ca(2+)-dependent negative feedback inactivation of N-methyl-D-aspartate receptors and voltage-sensitive Ca(2+) 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 Ca(2+) channel currents by up to 40% in cultured hippocampal neurons, suggesting that calcineurin acts to enhance Ca(2+) currents. This effect occurred with Ba(2+) or Ca(2+) as charge carrier, and with or without intracellular Ca(2+) buffered by EGTA. Ca(2+)-dependent inactivation of Ca(2+) channels was not affected by FK-506. The immunosuppressant, rapamycin, and the protein phosphatase 1/2A inhibitor, okadaic acid, did not decrease Ca(2+) channel current, showing specificity for effects on calcineurin. Blockade of L-type Ca(2+) channels with nimodipine fully negated the effect of FK-506 on Ca(2+) channel current, while blockade of N-, and P-/Q-type Ca(2+) channels enhanced FK-506-mediated inhibition of the remaining L-type-enriched current. FK-506 also inhibited substantially more Ca(2+) 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 Ca(2+) channel activity in neurons. Moreover, this action appears to be increased concomitantly with the well-characterized increase in L-type Ca(2+) channel availability in hippocampal neurons with age-in-culture. PMID:11958864

  16. Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity.

    PubMed

    Vaeth, Martin; Eckstein, Miriam; Shaw, Patrick J; Kozhaya, Lina; Yang, Jun; Berberich-Siebelt, Friederike; Clancy, Robert; Unutmaz, Derya; Feske, Stefan

    2016-06-21

    T follicular helper (Tfh) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (Tfr) cells limit the GC reaction. Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Conditional deletion of Stim1 and Stim2 genes in T cells abolished SOCE and strongly reduced antibody-mediated immune responses following viral infection caused by impaired differentiation and function of Tfh cells. Conversely, aging Stim1Stim2-deficient mice developed humoral autoimmunity with spontaneous autoantibody production due to abolished Tfr cell differentiation in the presence of residual Tfh cells. Mechanistically, SOCE controlled Tfr and Tfh cell differentiation through NFAT-mediated IRF4, BATF, and Bcl-6 transcription-factor expression. SOCE had a dual role in controlling the GC reaction by regulating both Tfh and Tfr cell differentiation, thus enabling protective B cell responses and preventing humoral autoimmunity. PMID:27261277

  17. 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.

  18. Perceived Control over Memory Aging: Developmental and Intervention Perspectives.

    ERIC Educational Resources Information Center

    Lachman, Margie E.

    1991-01-01

    Examines age differences in control beliefs for several domains, including intellectual aging and memory, for 200 adults aged 20-89 years. In domains of health and intellectual aging, older adults have lower internal control and higher external control beliefs than young and middle-age adults. A memory training program is described. (SLD)

  19. Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro aged mouse eggs

    PubMed Central

    Zhang, Nan; Wakai, Takuya; Fissore, Rafael. A.

    2011-01-01

    The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others found that in these eggs the intracellular calcium ([Ca2+]i) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca2+ release is not well known. Here, we investigated if the function of IP3R1, the major Ca2+ release channel at fertilization, was undermined in in vitro aged mouse eggs. We found that in aged eggs IP3R1 displayed reduced function, as many of the changes acquired during maturation that enhance IP3R1 Ca2+ conductivity such as phosphorylation, receptor reorganization and increased Ca2+ store content ([Ca2+]ER) were lost with increasing postovulatory time. IP3R1 fragmentation, possibly associated with the activation of caspase-3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP3R1 function and maintained [Ca2+]ER content. Caffeine also maintained mitochondrial membrane potential as measured by JC-1 fluorescence. We therefore conclude that [Ca2+]i responses in aged eggs are undermined by reduced IP3R1 sensitivity, decreased [Ca2+]ER and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs. PMID:22095868

  20. The influence of solution stoichiometry on surface-controlled Ca isotope fractionation during Ca carbonate precipitation from Mono Lake, California

    NASA Astrophysics Data System (ADS)

    Nielsen, L. C.; Depaolo, D. J.

    2010-12-01

    much higher Ca2+:CO32- activity ratios. We attribute this similarity to the constant detachment frequency of Ca2+ from the mineral surface. Based on a model developed by DePaolo (2010), detachment frequency controls the dependence of isotope fractionation on growth rate, while excess ion attachment relative to detachment controls the rate itself. The frequency of ion attachment depends on ion activity and solution stoichiometry, whereas detachment frequency is solely defined by the solubility product and ion attachment rate constants (Zhang & Nancollas, J. Colloid Interface Sci., 1998). Thus, the Ca detachment flux from CaCO3 surfaces and the rate dependence of Δ44/40Cas-f should be independent of solution stoichiometry, consistent with our findings in the Mono Lake system.

  1. Interactions of hearing loss and diabetes mellitus in the middle age CBA/CaJ mouse model of presbycusis.

    PubMed

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

    2009-03-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects [Frisina, S.T., Mapes, F., Kim, S., Frisina, D.R., Frisina, R.D., 2006. Characterization of hearing loss in aged type II diabetics. Hear. Res. 211, 103-113]. 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 broad-band noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (approximately 32 g), but there was a significant (approximately 5 g) decline in the T1DM, while T2DM exhibited approximately 10 g 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

  2. Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca(2+) biomarkers of aging.

    PubMed

    Maimaiti, Shaniya; DeMoll, Chris; Anderson, Katie L; Griggs, Ryan B; Taylor, Bradley K; Porter, Nada M; Thibault, Olivier

    2015-09-24

    Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca(2+) dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca(2+) dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca(2+) imaging techniques, we show that Ca(2+)levels at rest or during synaptic stimulation, the Ca(2+)-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25451110

  3. 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...

  4. An integrative model of the cardiac ventricular myocyte incorporating local control of Ca2+ release.

    PubMed Central

    Greenstein, Joseph L; Winslow, Raimond L

    2002-01-01

    The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type Ca(2+) current tightly controls Ca(2+) release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type Ca(2+) channels (LCCs) and ryanodine receptors (RyRs). These local interactions give rise to smoothly graded Ca(2+)-induced Ca(2+) release (CICR), which exhibits high gain. In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of Ca(2+) release units (CaRUs) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions where junctional SR membrane and transverse-tubular membrane are in close proximity. The CaRUs are embedded within and interact with the global systems of the myocyte describing ionic and membrane pump/exchanger currents, SR Ca(2+) uptake, and time-varying cytosolic ion concentrations to form a model of the cardiac action potential (AP). The model can reproduce both the detailed properties of EC coupling, such as variable gain and graded SR Ca(2+) release, and whole-cell phenomena, such as modulation of AP duration by SR Ca(2+) release. Simulations indicate that the local control paradigm predicts stable APs when the L-type Ca(2+) current is adjusted in accord with the balance between voltage- and Ca(2+)-dependent inactivation processes as measured experimentally, a scenario where common pool models become unstable. The local control myocyte model provides a means for studying the interrelationship between microscopic and macroscopic behaviors in a manner that would not be possible in experiments. PMID:12496068

  5. 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

  6. 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.

  7. Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling.

    PubMed

    Plattner, Helmut; Verkhratsky, Alexei

    2016-08-01

    unholy alliance into a fascinating success story.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377729

  8. Inhibition of cytoplasmic p53 differentially modulates Ca(2+) signaling and cellular viability in young and aged striata.

    PubMed

    Ureshino, Rodrigo Portes; Hsu, Yi-Te; do Carmo, Lúcia Garcez; Yokomizo, César Henrique; Nantes, Iseli Lourenço; Smaili, Soraya Soubhi

    2014-10-01

    The p53 protein, a transcription factor with many gene targets, can also trigger apoptosis in the cytoplasm. The disruption of cell homeostasis, such as Ca(2+) signaling and mitochondrial respiration, contributes to the loss of viability and ultimately leads to cell death. However, the link between Ca(2+) signaling and p53 signaling remains unclear. During aging, there are alterations in cell physiology that are commonly associated with a reduced adaptive stress response, thus increasing cell vulnerability. In this work, we examined the effects of a cytoplasmic p53 inhibitor (pifithrin μ) in the striatum of young and aged rats by evaluating Ca(2+) signaling, mitochondrial respiration, apoptotic protein expression, and tissue viability. Our results showed that pifithrin μ differentially modulated cytoplasmic and mitochondrial Ca(2+) in young and aged rats. Cytoplasmic p53 inhibition appeared to reduce the mitochondrial respiration rate in both groups. In addition, p53 phosphorylation and Bax protein levels were elevated upon cytoplasmic p53 inhibition and could contribute to the reduction of tissue viability. Following glutamate challenge, pifithrin μ improved cell viability in aged tissue, reduced reactive oxygen species (ROS) generation, and reduced mitochondrial membrane potential (ΔΨm). Taken together, these results indicate that cytoplasmic p53 may have a special role in cell viability by influencing cellular Ca(2+) homeostasis and respiration and may produce differential effects in the striatum of young and aged rats. PMID:25084214

  9. Control of action potential propagation by intracellular Ca2+ in cultured rat dorsal root ganglion cells.

    PubMed Central

    Lüscher, C; Lipp, P; Lüscher, H R; Niggli, E

    1996-01-01

    1. To assess the role of intracellular Ca2+ in action potential (AP) propagation, whole-cell recordings of cultured dorsal root ganglion (DRG) cells were carried out while Ca2+ was simultaneously measured with a laser-scanning confocal microscope. 2. Flash photolytic liberation of a Ca2+ buffer during trains of APs which partly failed to invade the DRG cell body immediately lowered intracellular Ca2+ and restored safe AP propagation. Furthermore, the speed of the propagated AP was reduced considerably when intracellular Ca2+ was increased by flash photolysis of caged Ca2+. 3. Both results suggest that intracellular Ca2+ regulates the safety factor for AP propagation and may thus provide a control mechanism for synaptic integration, which acts pre- as well as postsynaptically. Images Figure 1 Figure 3 PMID:8821131

  10. 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. PMID:26288989

  11. 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.

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

    NASA Astrophysics Data System (ADS)

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-10-01

    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.

  13. Role of Na+/Ca2+ exchanger (NCX) in modulating postovulatory aging of mouse and rat oocytes.

    PubMed

    Zhang, Chuan-Xin; Cui, Wei; Zhang, Min; Zhang, Jie; Wang, Tian-Yang; Zhu, Jiang; Jiao, Guang-Zhong; Tan, Jing-He

    2014-01-01

    We studied the role of the Na+/Ca2+ exchanger (NCX) in modulating oocyte postovulatory aging by observing changes in NCX contents and activities in aging mouse and rat oocytes. Whereas the NCX activity was measured by observing oocyte activation following culture with NCX inhibitor or activator, the NCX contents were determined by immunohistochemical quantification. Although NCX was active in freshly-ovulated rat oocytes recovered 13 h post hCG injection and in aged oocytes recovered 19 h post hCG in both species, it was not active in freshly-ovulated mouse oocytes. However, NCX became active when the freshly-ovulated mouse oocytes were activated with ethanol before culture. Measurement of cytoplasmic Ca2+ revealed Ca2+ increases always before NCX activation. Whereas levels of the reactive oxygen species (ROS) and the activation susceptibility increased, the density of NCX member 1 (NCX1) decreased significantly with oocyte aging in both species. While culture with H2O2 decreased the density of NCX1 significantly, culture with NaCl supplementation sustained the NCX1 density in mouse oocytes. It was concluded that (a) the NCX activity was involved in the modulation of oocyte aging and spontaneous activation; (b) ROS and Na+ regulated the NCX activity in aging oocytes by altering its density as well as functioning; and (c) cytoplasmic Ca2+ elevation was essential for NCX activation in the oocyte. PMID:24695407

  14. Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment

    PubMed Central

    LeBlanc, A C; Ramcharitar, J; Afonso, V; Hamel, E; Bennett, D A; Pakavathkumar, P; Albrecht, S

    2014-01-01

    Active Caspase-6 is abundant in the neuropil threads, neuritic plaques and neurofibrillary tangles of Alzheimer disease brains. However, its contribution to the pathophysiology of Alzheimer disease is unclear. Here, we show that higher levels of Caspase-6 activity in the CA1 region of aged human hippocampi correlate with lower cognitive performance. To determine whether Caspase-6 activity, in the absence of plaques and tangles, is sufficient to cause memory deficits, we generated a transgenic knock-in mouse that expresses a self-activated form of human Caspase-6 in the CA1. This Caspase-6 mouse develops age-dependent spatial and episodic memory impairment. Caspase-6 induces neuronal degeneration and inflammation. We conclude that Caspase-6 activation in mouse CA1 neurons is sufficient to induce neuronal degeneration and age-dependent memory impairment. These results indicate that Caspase-6 activity in CA1 could be responsible for the lower cognitive performance of aged humans. Consequently, preventing or inhibiting Caspase-6 activity in the aged may provide an efficient novel therapeutic approach against Alzheimer disease. PMID:24413155

  15. Calcium and sodium transport processes in patients with cystic fibrosis 2. Mg2+- dependent, Ca2+ ATPase activity in fibroblast membrane preparations from cystic fibrosis patients and controls.

    PubMed

    Katz, S

    1978-03-01

    Mg2+-dependent Ca2+-ATPase activity was determined in membrane preparations of fibroblasts grown from skin biopsies of cystic fibrosis patients and age-matched controls. This enzyme was stimulated by increasing free calcium concentrations with an apparent Kdiss for calcium of approximately 45 micron. Although there was a great deal of variation in Ca2+-ATPase activity observed between individual strains, there was a significant decrease in the maximal activation of the Ca2+-ATPase in membrane preparations of fibroblasts obtained from cystic fibrosis patients compared to the controls (P less than 0.05). This observation indicates that decreased Ca2+-ATPase activity is a generalized phenomenon in cystic fibrosis found in more than one cell-type. This decrease in Ca2+-ATPase activity may have a number of implications that may explain some of the manifestations of the disease. PMID:148720

  16. 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…

  17. Crystallization and assembling behavior of calcium carbonate controlled by Ca-organic fibers

    NASA Astrophysics Data System (ADS)

    Chen, Anliang; Ma, Peiyan; Fu, Zhengyi; Wu, Yan; Kong, Wei

    2013-08-01

    Calcium carbonate (CaCO3) crystals with different phases were obtained on the basis of one-dimensional Ca-deoxycholate fibers (Ca-DC fibers) under ambient conditions. Ca-DC fibers were prepared by the combination of Ca2+ ions and sodium deoxycholate (SDC) before the addition of sodium bicarbonate. Vaterite dominated mixtures could be easily obtained in the presence of Ca-DC fibers in the aqueous system at 10 °C. As the temperature was increased to 30 and 120 °C, pure vaterite and aragonite with novel morphologies were obtained, respectively. The framework formed by one-dimensional Ca-DC fibers was demonstrated to be the key role in mediating the crystallization and assembling behaviors of calcium carbonate. In this study, Ca-DC fibers, prepared as a novel insoluble organic polymorph controller, could even play an important role in the industrial production of CaCO3 with different polymorphs in future and other similar Ca-organic fibers are believed to have same functions as well.

  18. Development of multiple laser frequency control system for Ca+ isotope ion cooling

    NASA Astrophysics Data System (ADS)

    Jung, Kyunghun; Yamamoto, Yuta; Hasegawa, Shuichi

    2015-11-01

    We here developed and evaluated a laser frequency control system which synchronizes the laser frequency to the resonance of target Ca + isotope ion whose having more than 8 GHz of isotope shift based on the Fringe Offset Lock method for simple operation of ICPMS-ILECS (Inductively Coupled Plasma Mass Spectrometry - Ion trap Laser Cooling Spectroscopy) The system fulfilled the minimum requirements of four slave lasers stability for Doppler cooling of Ca + ions. A performance of the system was evaluated by cooling 40Ca + ions with the stabilized slave lasers. All the stable even Ca + isotope ions were trapped and their fluorescence was observed by switching laser frequencies using the system. An odd calcium isotope 43Ca +cooling was also succeeded by the control system.

  19. 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.

  20. 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.

  1. Control of Ca2+ Influx and Calmodulin Activation by SK-Channels in Dendritic Spines

    PubMed Central

    Griffith, Thom; Tsaneva-Atanasova, Krasimira; Mellor, Jack R.

    2016-01-01

    The key trigger for Hebbian synaptic plasticity is influx of Ca2+ into postsynaptic dendritic spines. The magnitude of [Ca2+] increase caused by NMDA-receptor (NMDAR) and voltage-gated Ca2+ -channel (VGCC) activation is thought to determine both the amplitude and direction of synaptic plasticity by differential activation of Ca2+ -sensitive enzymes such as calmodulin. Ca2+ influx is negatively regulated by Ca2+ -activated K+ channels (SK-channels) which are in turn inhibited by neuromodulators such as acetylcholine. However, the precise mechanisms by which SK-channels control the induction of synaptic plasticity remain unclear. Using a 3-dimensional model of Ca2+ and calmodulin dynamics within an idealised, but biophysically-plausible, dendritic spine, we show that SK-channels regulate calmodulin activation specifically during neuron-firing patterns associated with induction of spike timing-dependent plasticity. SK-channel activation and the subsequent reduction in Ca2+ influx through NMDARs and L-type VGCCs results in an order of magnitude decrease in calmodulin (CaM) activation, providing a mechanism for the effective gating of synaptic plasticity induction. This provides a common mechanism for the regulation of synaptic plasticity by neuromodulators. PMID:27232631

  2. 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

  3. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).

    PubMed

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

    2015-01-01

    Mitochondrial Ca(2+) 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 Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) 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

  4. Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Badwi, Syarifah Azizah Wan Ahmadul; Phillips, Natalie A; Rennie, Jaime L; Levi, Christopher R; Drysdale, Karen A; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2016-02-01

    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age. PMID:26511789

  5. Strong biological controls on Sr/Ca ratios in aragonitic marine bivalve shells

    NASA Astrophysics Data System (ADS)

    Gillikin, David Paul; Lorrain, Anne; Navez, Jacques; Taylor, James W.; André, Luc; Keppens, Eddy; Baeyens, Willy; Dehairs, Frank

    2005-05-01

    It is well known that skeletal remains of carbonate secreting organisms can provide a wealth of information about past environments. Sr/Ca ratios have been successfully used as a temperature proxy in corals and sclerosponges. Previous work on aragonitic bivalve shells has not been conclusive but suggests a major control of growth rate on Sr/Ca ratios. As many studies have used bivalve growth rates to determine temperature, we tested if Sr/Ca ratios could predict temperature through its relationship with growth rate. Shells from the two species of clams from the same family (veneroidea) studied here, Saxidomus giganteus and Mercenaria mercenaria, show vastly different seasonal Sr/Ca profiles. A strong relationship between average annual Sr/Ca ratios and annual growth rate was found in S. giganteus shells from both Washington (R2 = 0.87) and Alaska (R2 = 0.64), USA, but not in M. mercenaria shells from North Carolina, USA. Furthermore, the Sr/Ca-growth rate relationship was also evident upon a more detailed inspection of subannual growth rates in S. giganteus (R2 = 0.73). Although there were significant positive correlations between Sr/Ca ratios and temperature in S. giganteus shells, the correlations were weak (0.09 < R2 < 0.27), and thus Sr/Ca ratios cannot be used as a reliable temperature proxy in these species of aragonitic bivalves. It is clear from this study that Sr/Ca ratios are not under thermodynamic control in either clam species, since thermodynamics predict a negative correlation between Sr/Ca ratios and temperature in aragonite. This points toward dominance of biological processes in the regulation of Sr2+. This is also reflected by the largely differing Sr/Ca partition coefficients (DSr) in these shells (DSr ≈ 0.25), when compared to inorganic, coral, and sclerosponge studies (DSr ≈ 1), all of which show a negative dependence of Sr/Ca on temperature. We suggest that caution be taken when using Sr/Ca in any biogenic aragonite as a temperature proxy

  6. αCaMKII Autophosphorylation Controls the Establishment of Alcohol Drinking Behavior

    PubMed Central

    Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P

    2013-01-01

    The α-Ca2+/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a ‘molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKIIT286A mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKIIT286A mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKIIT286A mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKIIT286A mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA–5-HT balance as a putative mechanism. PMID:23459588

  7. Control of ciliary motility by Ca sup 2+ : Integration of Ca sup 2+ -dependent functions and targets for Ca sup 2+ action

    SciTech Connect

    Evans, T.C.

    1988-01-01

    To identify functions that regulate Ca{sup 2+}-induced ciliary reversal in Paramecium, mutants defective in terminating depolarization-induced backward swimming were selected. Six independent recessive mutations (k-shy) comprising two complementation groups, k-shyA and k-shyB, were identified. All mutants exhibited prolonged backward swimming in depolarizing solutions. Voltage clamp studies revealed that mutant Ca{sup 2+} current amplitudes were reduced, but could be restored to wild type levels by EGTA injection. The recovery of the mutant Ca{sup 2+} current from Ca{sup 2+}-dependent inactivation, and the decay of the Ca{sup 2+}-dependent K{sup +} and Ca{sup 2+}-dependent Na{sup +} currents after depolarization were slow in k-shy compared to wild type. To identify protein targets of Ca{sup 2+} action, ciliary proteins that interact with calmodulin (CaM) were characterized. With a {sup 125}I-CaM blot assay, several CaM-binding proteins were identified including axonemal, soluble, and membrane-bound polypeptides. Competitive displacement studies with unlabeled Paramecium CaM, bovine CaM, and troponinC suggested that both protein types bind CaM with high affinity and specificity. To examine the presence of CaM-binding sites in intact axonemes, a filtration binding assay was developed.

  8. 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

  9. The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca(2+)-Induced Inactivation.

    PubMed

    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 Ca(2+). At the same time, they are themselves inhibited by the elevation of intracellular Ca(2+) concentration. It is unclear however, whether the Ca(2+) 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 Ca(2+) buffers. Loading of pyramidal cells with exogenous Ca(2+) 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 Ca(2+) influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg(2+) concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca(2+) buffer capacity of postsynaptic neurons. PMID:26858606

  10. Age and Family Control Influences on Children's Television Viewing.

    ERIC Educational Resources Information Center

    Rubin, Alan M.

    1986-01-01

    Indicates that (1) age and family control did not influence children's television viewing levels; (2) age influenced program preferences of children; (3) cartoon preferences related negatively to family control for the youngest groups; and (4) comedy and children's program preferences and television realism related positively to family control for…

  11. Control of IP3-mediated Ca2+ puffs in Xenopus laevis oocytes by the Ca2+-binding protein parvalbumin

    PubMed Central

    John, Linu M; Mosquera-Caro, Monica; Camacho, Patricia; Lechleiter, James D

    2001-01-01

    Elementary events of Ca2+ release (Ca2+ puffs) can be elicited from discrete clusters of inositol 1,4,5 trisphosphate receptors (IP3Rs) at low concentrations of IP3. Ca2+ puffs have rarely been observed unless elicited by either hormone treatment or introduction of IP3 into the cell. However, cells appear to have sufficient concentrations of IP3 (0.1-3.0 μM) to induce Ca2+ release under resting conditions. Here, we investigated Ca2+ puff activity in non-stimulated Xenopus oocytes using confocal microscopy. The fluorescent Ca2+ dye indicators Calcium Green 1 and Oregon Green 488 BAPTA-2 were injected into oocytes to monitor basal Ca2+ activity. In this preparation, injection or overexpression of parvalbumin, an EF-hand Ca2+-binding protein (CaBP), induced Ca2+ puffs in resting Xenopus oocytes. This activity was inhibited by heparin, an IP3R channel blocker, and by mutation of the Ca2+-binding sites in parvalbumin. Ca2+ puff activity was also evoked by injection of low concentrations of the Ca2+ chelator EGTA, but not by calbindin D28k, another member of the EF-hand CaBP superfamily. BAPTA and the Ca2+ indicator dye Oregon Green 488 BAPTA-1 evoked Ca2+ puff activity, while the dextran conjugate of Oregon Green 488 BAPTA-1 did not. These data indicate that a Ca2+ buffer must be mobile in order to increase Ca2+ puff activity. Together, the data indicate that some IP3Rs spontaneously release Ca2+ under resting concentrations of IP3. These elementary Ca2+ events appear to be below the level of detection of current imaging techniques. We suggest that parvalbumin evokes Ca2+ puffs by coordinating the activity of elementary IP3R channel openings. We conclude that Ca2+ release can be evoked not only by hormone-induced increases in IP3, but also by expression of mobile cytosolic CaBPs under resting concentrations of IP3. PMID:11507154

  12. Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors.

    PubMed

    Xu, Changqing; Cui, Changhai; Alkon, Daniel L

    2009-08-01

    Changes in hippocampal synaptic networks during aging may contribute to age-dependent compromise of cognitive functions such as learning and memory. Previous studies have demonstrated that GABAergic synaptic transmission exhibits age-dependent changes. To better understand such age-dependent changes of GABAergic synaptic inhibition, we performed whole-cell recordings from pyramidal cells in the CA1 area of acute hippocampal slices on aged (24-26 months old) and young (2-4 months old) Brown-Norway rats. We found that the frequency and amplitude of spontaneous inhibitory postsynaptic current (IPSCs) were significantly increased in aged rats, but the frequency and amplitude of mIPSCs were decreased. Furthermore, the regulation of GABAergic synaptic transmission by GluR5 containing kainate receptors was enhanced in aged rats, which was revealed by using LY382884 (a GluR5 kainate receptor antagonist) and ATPA (a GluR5 kainate receptor agonist). Moreover, we demonstrated that vesicular glutamate transporters are involved in the kainate receptor dependent regulation of sIPSCs. Taken together, these results suggest that GABAergic synaptic transmission is potentiated in aged rats, and GluR5 containing kainate receptors regulate the inhibitory synaptic transmission through endogenous glutamate. These alterations of GABAergic input with aging could contribute to age-dependent cognitive decline. PMID:19123252

  13. Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism - a role for Ca(2+) ?

    PubMed

    R Oliveira, Sara; Queiroga, Cláudia S F; Vieira, Helena L A

    2016-08-01

    Carbon monoxide (CO) is an endogenously produced gasotransmitter with important biological functions: anti-inflammation, anti-apoptosis, vasomodulation and cell metabolism modulation. The most recognized cellular target for CO is the mitochondria. Physiological concentrations of CO generate mitochondrial reactive oxygen species (ROS), which are signalling molecules for CO-induced pathways. Indeed, small amounts of ROS promote cytoprotection by a preconditioning effect. Furthermore, CO prevents cell death by limiting mitochondrial membrane permeabilization, which inhibits the release of pro-apoptotic factors into the cytosol; both events are ROS dependent. CO also increases the ability of mitochondria to take up Ca(2+) . Mitochondrial metabolism is modulated by CO, namely by increasing TCA cycle rate, oxidative phosphorylation and mitochondrial biogenesis, which, in turn, increases ATP production. CO's modulation of metabolism might be important for cellular response to diseases, namely cancer and ischaemic diseases. Finally, another cytoprotective role of CO involves the control of Ca(2+) channels. By limiting the activity of T-type and L-type Ca(2+) channels, CO prevents excitotoxicity-induced cell death and modulates cell proliferation. Several questions concerning Ca(2+) signalling, mitochondria and CO can be asked, for instance whether CO modulation of cell metabolism would be dependent on the mitochondrial Ca(2+) uptake capacity, since small amounts of Ca(2+) can increase mitochondrial metabolism. Whether CO controls Ca(2+) communication between mitochondria and endoplasmic reticulum is another open field of research. In summary, CO emerges as a key gasotransmitter in the control of several cellular functions of mitochondria: metabolism, cell death and Ca(2+) signalling. PMID:26377343

  14. Seawater temperature and salinity controls on Li/Ca ratios in Mytilus edulis (bivalvia) shells

    NASA Astrophysics Data System (ADS)

    Clarke, L. J.; Wanamaker, A. D., Jr.; Kreutz, K. J.; Borns, H. W., Jr.; Introne, D. S.

    2009-04-01

    In this study we have investigated the effects of seawater temperature and salinity on Li/Ca ratios in newly precipitated shell calcite in Mytilus edulis shells, since this potential temperature proxy has not been widely applied beyond brachiopods and inorganic calcite. Juvenile specimens of M. edulis collected from western Greenland were cultured in laboratory aquaria using a four-by-three factorial design that consisted of four circulating temperature baths and three salinities. New shell growth precipitated during the constrained culturing experiment was identified carefully and subsequently dissected from the shells. Following acid dissolution, Li/Ca ratios were measured by ICP-MS, enabling an assessment of temperature and salinity controls on shell Li/Ca ratios. Furthermore, measurement of Li/Ca ratios in the aquaria seawaters has enabled calculation of Li/Ca ratio partition coefficients and direct comparison to Li/Ca ratio to temperature relationships observed for brachiopods and inorganic calcite. The results of this study suggest that bivalve shell Li/Ca ratios can be used as a new temperature proxy.

  15. 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

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

    PubMed

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

    2005-08-01

    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

  17. 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

  18. αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

    PubMed

    Easton, A C; Lourdusamy, A; Havranek, M; Mizuno, K; Solati, J; Golub, Y; Clarke, T-K; Vallada, H; Laranjeira, R; Desrivières, S; Moll, G H; Mössner, R; Kornhuber, J; Schumann, G; Giese, K P; Fernandes, C; Quednow, B B; Müller, C P

    2014-01-01

    Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects. PMID:25290264

  19. αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans

    PubMed Central

    Easton, A C; Lourdusamy, A; Havranek, M; Mizuno, K; Solati, J; Golub, Y; Clarke, T-K; Vallada, H; Laranjeira, R; Desrivières, S; Moll, G H; Mössner, R; Kornhuber, J; Schumann, G; Giese, K P; Fernandes, C; Quednow, B B; Müller, C P

    2014-01-01

    Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca2+/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKIIT286A mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg−1, intraperitoneal). In vivo microdialysis revealed that αCaMKIIT286A mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg−1, intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKIIT286A mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects. PMID:25290264

  20. 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

  1. NAADP-Dependent Ca(2+) Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis.

    PubMed

    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 Ca(2+). In the present report the possible involvement of NAADP-controlled Ca(2+) 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, Ca(2+) imaging experiments showed that the response of B16 cells to VEGF stimulation is NAADP-dependent. The whole of these observations indicate that NAADP-controlled Ca(2+) signaling can be relevant not only for neoangiogenesis but also for direct control of tumor cells. PMID:26733361

  2. Self-Perceptions of Intellectual Control and Aging.

    ERIC Educational Resources Information Center

    Cornelius, Steven W.; Caspi, Avshalom

    1986-01-01

    Investigated beliefs about intellectual control and aging in 86 middle-aged and older adults. Perceptions of internal control over intellectual functioning appeared to be relatively stable during middle adulthood and to decline for older adults. Even with effects of education partialled, there was a decline in perceptions of intellectual…

  3. Prenatal exposure to bisphenol A impacts neuronal morphology in the hippocampal CA1 region in developing and aged mice.

    PubMed

    Kimura, Eiki; Matsuyoshi, Chieri; Miyazaki, Wataru; Benner, Seico; Hosokawa, Mayuko; Yokoyama, Kazuhito; Kakeyama, Masaki; Tohyama, Chiharu

    2016-03-01

    Bisphenol A (BPA), a widely used raw component of polycarbonate plastics and epoxy resins, has been reported to induce developmental neurotoxicity in offspring born to dams exposed to low doses of BPA; however, the toxicity mechanism remains elusive. To study the effects of in utero BPA exposure on neuronal morphology, we studied spine density and dendritic growth in the hippocampal CA1 of aged mice and developing mice prenatally exposed to low doses of BPA. Pregnant mice were orally administered BPA at a low dose of 0, 40, or 400 μg/kg body weight/day on gestational days 8.5-17.5/18.5. Mouse progenies were euthanized at 3 weeks or 14 months, and their brains were analyzed for dendritic arborization of GFP-expressing neurons or spine densities of Golgi-stained neurons in the hippocampal CA1. Regardless of the dose, in utero BPA exposure reduced spine densities in the hippocampal CA1 of the 14-month-old mice. In the developing brain from the 3-week-old mice born to dams exposed to BPA at a dose of 400 μg/kg body weight/day, overall length and branching number of basal dendrites but not apical dendrites were decreased. In utero low doses of BPA exposure disrupts hippocampal CA1 neuronal morphology during development, and this disruption is believed to persist in adulthood. PMID:25804199

  4. Aging and Executive Control: Reports of a Demise Greatly Exaggerated

    PubMed Central

    Verhaeghen, Paul

    2015-01-01

    I report a series of meta-analyses on aging and executive control. A first set of analyses failed to find evidence for specific age-related deficits in tasks of selective attention (inhibition of return, negative priming, flanker, and Stroop) or tasks tapping local task-shifting costs (reading with distractors is an exception) but found evidence for specific age-related deficits in tasks of divided attention (dual tasking and global task-shifting costs). The second set examined whether executive control explained any age-related variance in complex cognition (episodic memory, reasoning, spatial abilities) over and beyond the effects of speed and working memory; it did not. Thus, the purported decline in executive control with advancing age is clearly not general, and it may ultimately play only a small role in explaining age-related deficits in complex cognition. PMID:25866452

  5. 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.

  6. 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…

  7. T-Type Ca2+ Channel Regulation by CO: A Mechanism for Control of Cell Proliferation.

    PubMed

    Duckles, Hayley; Al-Owais, Moza M; Elies, Jacobo; Johnson, Emily; Boycott, Hannah E; Dallas, Mark L; Porter, Karen E; Boyle, John P; Scragg, Jason L; Peers, Chris

    2015-01-01

    T-type Ca(2+) channels regulate proliferation in a number of tissue types, including vascular smooth muscle and various cancers. In such tissues, up-regulation of the inducible enzyme heme oxygenase-1 (HO-1) is often observed, and hypoxia is a key factor in its induction. HO-1 degrades heme to generate carbon monoxide (CO) along with Fe(2+) and biliverdin. Since CO is increasingly recognized as a regulator of ion channels (Peers et al. 2015), we have explored the possibility that it may regulate proliferation via modulation of T-type Ca(2+) channels.Whole-cell patch-clamp recordings revealed that CO (applied as the dissolved gas or via CORM donors) inhibited all 3 isoforms of T-type Ca(2+) channels (Cav3.1-3.3) when expressed in HEK293 cells with similar IC(50) values, and induction of HO-1 expression also suppressed T-type currents (Boycott et al. 2013). CO/HO-1 induction also suppressed the elevated basal [Ca(2+) ](i) in cells expressing these channels and reduced their proliferative rate to levels seen in non-transfected control cells (Duckles et al. 2015).Proliferation of vascular smooth muscle cells (both A7r5 and human saphenous vein cells) was also suppressed either by T-type Ca(2+) channel inhibitors (mibefradil and NNC 55-0396), HO-1 induction or application of CO. Effects of these blockers and CO were non additive. Although L-type Ca(2+) channels were also sensitive to CO (Scragg et al. 2008), they did not influence proliferation. Our data suggest that HO-1 acts to control proliferation via CO modulation of T-type Ca(2+) channels. PMID:26303493

  8. 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. PMID:26222899

  9. Is reproductive ageing controlled by the brain?

    PubMed

    Gore, Andrea C

    2007-08-01

    Female reproductive function is controlled by complex interactions of the brain, pituitary gland and ovary. Each of these organs produces unique hormones, and each hormone acts upon the other organs to affect a response. Differentiating the causes and the consequences of reproductive senescence in mammals is thus a 'chicken and egg' puzzle. Surprisingly, recent evidence indicates a more important role for the brain in the initiation and transition to reproductive senescence. PMID:17620108

  10. Synchrony of Cardiomyocyte Ca2+ Release is Controlled by t-tubule Organization, SR Ca2+ Content, and Ryanodine Receptor Ca2+ Sensitivity

    PubMed Central

    Øyehaug, Leiv; Loose, Kristian Ø.; Jølle, Guro F.; Røe, Åsmund T.; Sjaastad, Ivar; Christensen, Geir; Sejersted, Ole M.; Louch, William E.

    2013-01-01

    Recent work has demonstrated that cardiomyocyte Ca2+release is desynchronized in several pathological conditions. Loss of Ca2+ release synchrony has been attributed to t-tubule disruption, but it is unknown if other factors also contribute. We investigated this issue in normal and failing myocytes by integrating experimental data with a mathematical model describing spatiotemporal dynamics of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). Heart failure development in postinfarction mice was associated with progressive t-tubule disorganization, as quantified by fast-Fourier transforms. Data from fast-Fourier transforms were then incorporated in the model as a dyadic organization index, reflecting the proportion of ryanodine receptors located in dyads. With decreasing dyadic-organization index, the model predicted greater dyssynchrony of Ca2+ release, which exceeded that observed in experimental line-scan images. Model and experiment were reconciled by reducing the threshold for Ca2+ release in the model, suggesting that increased RyR sensitivity partially offsets the desynchronizing effects of t-tubule disruption in heart failure. Reducing the magnitude of SR Ca2+ content and release, whether experimentally by thapsigargin treatment, or in the model, desynchronized the Ca2+ transient. However, in cardiomyocytes isolated from SERCA2 knockout mice, RyR sensitization offset such effects. A similar interplay between RyR sensitivity and SR content was observed during treatment of myocytes with low-dose caffeine. Initial synchronization of Ca2+ release during caffeine was reversed as SR content declined due to enhanced RyR leak. Thus, synchrony of cardiomyocyte Ca2+ release is not only determined by t-tubule organization but also by the interplay between RyR sensitivity and SR Ca2+ content. PMID:23601316

  11. Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress

    PubMed Central

    Awad, Salma; Al-Haffar, Kamar Mohamed Adib; Marashly, Qussay; Quijada, Pearl; Kunhi, Muhammad; Al-Yacoub, Nadya; Wade, Fallou S; Mohammed, Shamayel Faheem; Al-Dayel, Fouad; Sutherland, George; Assiri, Abdullah; Sussman, Mark; Bers, Donald; Al-Habeeb, Waleed; Poizat, Coralie

    2015-01-01

    Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin-dependent protein kinase II δ (CaMKIIδ), which are resistant to pathological cardiac stress, we show that CaMKIIδ regulates the phosphorylation of histone H3 at serine-10 during pressure overload hypertrophy. H3 S10 phosphorylation is strongly increased in the adult mouse heart in the early phase of cardiac hypertrophy and remains detectable during cardiac decompensation. This response correlates with up-regulation of CaMKIIδ and increased expression of transcriptional drivers of pathological cardiac hypertrophy and of fetal cardiac genes. Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3. Robust H3 phosphorylation is detected in both adult ventricular myocytes and in non-cardiac cells in the stressed myocardium, and these signals are abolished in CaMKIIδ-deficient mice after pressure overload. Mechanistically, fetal cardiac genes are activated by increased recruitment of CaMKIIδ and enhanced H3 phosphorylation at hypertrophic promoter regions, both in mice and in human failing hearts, and this response is blunted in CaMKIIδ-deficient mice under stress. We also document that the chaperone protein 14–3–3 binds phosphorylated H3 in response to stress, allowing proper elongation of fetal cardiac genes by RNA polymerase II (RNAPII), as well as elongation of transcription factors regulating cardiac hypertrophy. These processes are impaired in CaMKIIδ-KO mice after pathological stress. The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.

  12. 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

  13. Differential effects of PKA-controlled CaMKK2 variants on neuronal differentiation

    PubMed Central

    Cao, Wenguang; Sohail, Muhammad; Liu, Guodong; Koumbadinga, Geremy A; Lobo, Vincent G

    2011-01-01

    Regulation between protein kinases is critical for the establishment of signaling pathways/networks to orchestrate cellular processes. Besides posttranslational phosphorylation, alternative pre-mRNA splicing is another way to control kinase properties, but splicing regulation between two kinases and the effect of resulting variants on cells have not been explored. We examined the effect of the protein kinase A (PKA) pathway on the alternative splicing and variant properties of the Ca++/calmodulin-dependent protein kinase kinase 2 (CaMKK2) gene in B35 neuroblastoma cells. Inclusion of the exon 16 of CaMKK2 was significantly reduced by H89, a PKA selective inhibitor. Consistently, overexpressed PKA strongly promoted the exon inclusion in a CaMKK2 sequence-dependent way in splicing reporter assays. In vitro, purified CaMKK2 variant proteins were kinase-active. In cells, they were differentially phosphorylated by PKA. In RNA interference assays, CaMKK2 was required for forskolin-induced neurite growth. Interestingly, overexpression of the variant without exon 16 (−E16) promoted neurite elongation while the other one (+E16) promoted neurite branching; in contrast, reduction of the latter variant enhanced neurite elongation. Moreover, the variants are differentially expressed and the exon 16-containing transcripts highly enriched in the brain, particularly the cerebellum and hippocampus. Thus, PKA regulates the alternative splicing of CaMKK2 to produce variants that differentially modulate neuronal differentiation. Taken together with the many distinct variants of kinases, alternative splicing regulation likely adds another layer of modulation between protein kinases in cellular signaling networks. PMID:21957496

  14. 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

  15. Effect of Aging on ERP Components of Cognitive Control.

    PubMed

    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

  16. Calmodulin-controlled spatial decoding of oscillatory Ca2+ signals by calcineurin

    PubMed Central

    Mehta, Sohum; Aye-Han, Nwe-Nwe; Ganesan, Ambhighainath; Oldach, Laurel; Gorshkov, Kirill; Zhang, Jin

    2014-01-01

    Calcineurin is responsible for mediating a wide variety of cellular processes in response to dynamic calcium (Ca2+) signals, yet the precise mechanisms involved in the spatiotemporal control of calcineurin signaling are poorly understood. Here, we use genetically encoded fluorescent biosensors to directly probe the role of cytosolic Ca2+ oscillations in modulating calcineurin activity dynamics in insulin-secreting MIN6 β-cells. We show that Ca2+ oscillations induce distinct temporal patterns of calcineurin activity in the cytosol and plasma membrane vs at the ER and mitochondria in these cells. Furthermore, we found that these differential calcineurin activity patterns are determined by variations in the subcellular distribution of calmodulin (CaM), indicating that CaM plays an active role in shaping both the spatial and temporal aspects of calcineurin signaling. Together, our findings provide new insights into the mechanisms by which oscillatory signals are decoded to generate specific functional outputs within different cellular compartments. DOI: http://dx.doi.org/10.7554/eLife.03765.001 PMID:25056880

  17. 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…

  18. 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.

  19. 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

  20. FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca2+/CREB pathway

    PubMed Central

    Liu, Xin-Mei; Chan, Hsiao Chang; Ding, Guo-Lian; Cai, Jie; Song, Yang; Wang, Ting-Ting; Zhang, Dan; Chen, Hui; Yu, Mei Kuen; Wu, Yan-Ting; Qu, Fan; Liu, Ye; Lu, Yong-Chao; Adashi, Eli Y; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    Increased fat mass and fat redistribution are commonly observed in aging populations worldwide. Although decreased circulating levels of sex hormones, androgens and oestrogens have been observed, the exact mechanism of fat accumulation and redistribution during aging remains obscure. In this study, the receptor of follicle-stimulating hormone (FSH), a gonadotropin that increases sharply and persistently with aging in both males and females, is functionally expressed in human and mouse fat tissues and adipocytes. Follicle-stimulating hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH could also alter the secretion of leptin and adiponectin, but not hyperplasia, in vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to the Gαi protein; as a result, Ca2+ influx is stimulated, cAMP-response-element-binding protein is phosphorylated, and an array of genes involved in lipid biosynthesis is activated. The present findings depict the potential of FSH receptor-mediated lipodystrophy of adipose tissues in aging. Our results also reveal the mechanism of fat accumulation and redistribution during aging of males and females. PMID:25754247

  1. 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

  2. Electrical and Pharmacological Stimuli Reveal a Greater Susceptibility for CA3 Network Excitability in Hippocampal Slices from Aged vs. Adult Fischer 344 Rats

    PubMed Central

    Kanak, Daniel J.; Jones, Ryan T.; Tokhi, Ashish; Willingham, Amy L.; Zaveri, Hitten P.; Rose, Gregory M.; Patrylo, Peter R.

    2011-01-01

    Clinical data and experimental studies in rats have shown that the aged CNS is more susceptible to the proconvulsive effects of the excitotoxic glutamate analogues kainate (KA) and domoate (DA), which bind high-affinity receptors localized at mossy fiber (MF) synapses in the CA3 subregion of the hippocampus. Although decreased renal clearance appears to play a role in the hypersensitivity of the aged hippocampus to systemically-administered DA, it is unclear if the excitability of the CA3 network is also altered with age. Therefore, this study monitored CA3 field potential activity in hippocampal slices from aged and adult male Fischer 344 rats in response to electrical and pharmacological network stimulation targeted to the MF-CA3 circuit. Network challenges with repetitive hilar stimulation or bath application of nanomolar concentrations of KA more readily elicited excitable network activity (e.g. population spike facilitation, multiple population spikes, and epileptiform bursts) in slices from aged vs. adult rats, although basal network excitability was comparable between age groups. Additionally, exposure to 200 nM KA often abolished epileptiform activity and revealed theta or gamma oscillations instead. However, slices from aged rats were less sensitive to the rhythmogenic effects of 200 nM KA. Taken together, these findings suggest that aging decreases the capacity of the CA3 network to constrain the spread of excitability during focal excitatory network challenges. PMID:22396884

  3. Effects of camptothecin, etoposide and Ca2+ on caspase-3 activity and myofibrillar disruption of chicken during postmortem ageing.

    PubMed

    Chen, Lin; Feng, Xian Chao; Lu, Feng; Xu, Xing Lian; Zhou, Guang Hong; Li, Qing Yun; Guo, Xiang Ying

    2011-03-01

    Recently, a novel consideration has focused on the potential relationship of apoptosis and the protease caspases and the underlying mechanism for meat postmortem tenderization. In this study, apoptosis inducers, camptothecin and etoposide as well as Ca(2+) were used to treat chicken muscle immediately after slaughter and follow the changes in caspase-3 activities and changes in the myofibrillar structures during 7 days of ageing. All three treatments resulted in significantly higher caspase-3 activities during storage (p<0.05), with the natural substrates, whereas Western blotting analysis of the α-spectrin cleavage product, 120 kDa peptide (SBDP 120), showed that Ca(2+) was more effective than either camptothecin or etopside, and all were most active up to day 3 (p<0.01). According to SDS-PAGE, each treatment enhanced the accumulation of the 30 kD Troponin-T degradation product, especially during the first 3 days (p<0.05), and this was supported by the degradation of myofibrils observed by electron microscopy (TEM). TEM images showed the treatments resulted in enlargement of the I-bands and shrinkage of A-bands; however Z-lines were only slightly affected, even at day 7. The findings revealed that the three apoptosis inducers could increase myofibrillar dissociation and proteolysis during the first 3 days of chicken meat ageing. Because of the high activity of caspase-3 during the early postmortem period, it is possible that caspase-3 contributes to the conversion of muscle into meat. PMID:21055882

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

    PubMed

    Simkin, Dina; Hattori, Shoai; Ybarra, Natividad; Musial, Timothy F; Buss, Eric W; Richter, Hannah; Oh, M Matthew; Nicholson, Daniel A; Disterhoft, John F

    2015-09-23

    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

  5. 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

  6. 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…

  7. 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…

  8. Practice effects in bimanual force control: does age matter?

    PubMed

    Vieluf, Solveig; Godde, Ben; Reuter, Eva-Maria; Temprado, Jean-Jacques; Voelcker-Rehage, Claudia

    2015-01-01

    The authors examined age-related differences in fine motor control during a bimanual coordination task. The task required the modulation of fingertip forces in the precision grip according to a visually presented sinusoidal antiphase pattern (force range 2-12 N; frequency 0.2 Hz). Thirty-four right-handed participants of three age groups (young, early middle-aged, and late middle-aged) practiced 30 trials of the task. Accuracy and variability of relative timing and relative forces at minima and maxima of the sine wave were analyzed for hand-hand and hand-stimulus couplings and compared between age groups. Analysis showed for relative timing and force weaker hand-hand than hand-stimulus coupling as well as lower accuracy and higher variability for minima as compared to maxima. Further, we analyzed practice effects by comparing the first and last trials and characterized the course of practice by detecting the transition of a steeper to a shallower acquisition slope for the different age groups. Late middle-aged participants demonstrated poorer performance than both other groups for all parameters. All groups improved performance to a similar amount. However, an age-related difference in acquisition strategy is visible. Late middle-aged participants seemed to have focused on improvement of force amplitude, whereas young and early middle-aged focused on timing. PMID:25575223

  9. 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

  10. 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. PMID:25941121

  11. /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.

  12. The L-type voltage-dependent Ca2+ channel EGL-19 controls body wall muscle function in Caenorhabditis elegans

    PubMed Central

    Jospin, Maëlle; Jacquemond, Vincent; Mariol, Marie-Christine; Ségalat, Laurent; Allard, Bruno

    2002-01-01

    Caenorhabditis elegans is a powerful model system widely used to investigate the relationships between genes and complex behaviors like locomotion. However, physiological studies at the cellular level have been restricted by the difficulty to dissect this microscopic animal. Thus, little is known about the properties of body wall muscle cells used for locomotion. Using in situ patch clamp technique, we show that body wall muscle cells generate spontaneous spike potentials and develop graded action potentials in response to injection of positive current of increasing amplitude. In the presence of K+ channel blockers, membrane depolarization elicited Ca2+ currents inhibited by nifedipine and exhibiting Ca2+-dependent inactivation. Our results give evidence that the Ca2+ channel involved belongs to the L-type class and corresponds to EGL-19, a putative Ca2+ channel originally thought to be a member of this class on the basis of genomic data. Using Ca2+ fluorescence imaging on patch-clamped muscle cells, we demonstrate that the Ca2+ transients elicited by membrane depolarization are under the control of Ca2+ entry through L-type Ca2+ channels. In reduction of function egl-19 mutant muscle cells, Ca2+ currents displayed slower activation kinetics and provided a significantly smaller Ca2+ entry, whereas the threshold for Ca2+ transients was shifted toward positive membrane potentials. PMID:12391025

  13. Parallel circuits control temperature preference in Drosophila during ageing

    PubMed Central

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

    2015-01-01

    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. PMID:26178754

  14. 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

    2015-01-01

    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. PMID:26178754

  15. ESTROGEN AND AGING AFFECT THE SYNAPTIC DISTRIBUTION OF ESTROGEN RECEPTOR BETA-IMMUNOREACTIVITY IN THE CA1 REGION OF FEMALE RAT HIPPOCAMPUS

    PubMed Central

    Waters, Elizabeth M.; Yildirim, Murat; Janssen, William G.M.; Lou, W.Y. Wendy; McEwen, Bruce S.; Morrison, John H.; Milner, Teresa A.

    2010-01-01

    Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young females rats express more estrogen receptor α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor β (ERβ) expression in spine synapse complexes may be altered by age or E treatment. Young (3–4 months) and aged (22–23 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ERβ immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERβ-ir was more prominent postsynaptically than presynaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ERβ-ir (i.e., within 60 nm of the pre- and post-synaptic membranes), E treatment increased synaptic ERβ in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERβ-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERβ-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERβ may be a more responsive target to E, particularly in aged females. PMID:20875808

  16. 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.

  17. 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.

  18. Improved control of anthracnose rot in loquat fruit by a combination treatment of Pichia membranifaciens with CaCl(2).

    PubMed

    Cao, Shifeng; Zheng, Yonghua; Tang, Shuangshuang; Wang, Kaituo

    2008-08-15

    The beneficial effect of 2% CaCl(2) (w/v) on the antagonistic yeast Pichia membranifaciens for control of anthracnose rot caused by Colletotrichum acutatum in postharvest loquat fruit (Eriobotrya japonica L.) and the possible mechanisms involved were investigated. The results showed that treatment with P. membranifaciens at 1x10(8) CFU ml(-1) or 2% CaCl(2) alone both resulted in significantly smaller lesion diameter and lower disease incidence of anthracnose rot on loquat fruit wounds compared with the controls. The biocontrol activity of P. membranifaciens on the disease was enhanced by the addition of 2% CaCl(2), the combined treatment of P. membranifaciens with CaCl(2) resulted in a remarkably improved control of the disease in comparison with the treatment of P. membranifaciens or CaCl(2) alone. P. membranifaciens in combination with CaCl(2) induced higher activities of two defense-related enzymes chitinase and beta-1,3-glucanase in loquat fruit than applying the yeast or CaCl(2) alone. The in vitro experiment showed that the addition of 2% CaCl(2) in the suspensions of P. membranifaciens significantly inhibited spore germination and germ tube elongation of C. acutatum than the yeast or CaCl(2) alone. However, adding CaCl(2) did not significantly influence the population of P. membranifaciens in NYDB medium or fruit wounds. These results suggest that CaCl(2) could improve the biocontrol activity of P. membranifaciens on anthracnose rot in loquat fruit. It is postulated that the improved control of the disease is directly because of the higher inhibitory effect on pathogen growth and indirectly because of the enhanced disease resistance in loquat fruit by the combination treatment. PMID:18590937

  19. 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

  20. 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. PMID:27066038

  1. 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.

  2. 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. ...

  3. 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

  4. Influence of pH on Ca2+ current and its control of electrical and Ca2+ signaling in ventricular myocytes

    PubMed Central

    Saegusa, Noriko; Moorhouse, Emma; Vaughan-Jones, Richard D.

    2011-01-01

    Modulation of L-type Ca2+ current (ICa,L) by H+ ions in cardiac myocytes is controversial, with widely discrepant responses reported. The pH sensitivity of ICa,L was investigated (whole cell voltage clamp) while measuring intracellular Ca2+ (Ca2+i) or pHi (epifluorescence microscopy) in rabbit and guinea pig ventricular myocytes. Selectively reducing extracellular or intracellular pH (pHo 6.5 and pHi 6.7) had opposite effects on ICa,L gating, shifting the steady-state activation and inactivation curves to the right and left, respectively, along the voltage axis. At low pHo, this decreased ICa,L, whereas at low pHi, it increased ICa,L at clamp potentials negative to 0 mV, although the current decreased at more positive potentials. When Ca2+i was buffered with BAPTA, the stimulatory effect of low pHi was even more marked, with essentially no inhibition. We conclude that extracellular H+ ions inhibit whereas intracellular H+ ions can stimulate ICa,L. Low pHi and pHo effects on ICa,L were additive, tending to cancel when appropriately combined. They persisted after inhibition of calmodulin kinase II (with KN-93). Effects are consistent with H+ ion screening of fixed negative charge at the sarcolemma, with additional channel block by H+o and Ca2+i. Action potential duration (APD) was also strongly H+ sensitive, being shortened by low pHo, but lengthened by low pHi, caused mainly by H+-induced changes in late Ca2+ entry through the L-type Ca2+ channel. Kinetic analyses of pH-sensitive channel gating, when combined with whole cell modeling, successfully predicted the APD changes, plus many of the accompanying changes in Ca2+ signaling. We conclude that the pHi-versus-pHo control of ICa,L will exert a major influence on electrical and Ca2+-dependent signaling during acid–base disturbances in the heart. PMID:22042988

  5. TiO2 controlling photoluminescence of AWO4 (A =Ca,Sr,Ba) nanofilms

    NASA Astrophysics Data System (ADS)

    Jia, Runping; Zhang, Guoxin; Wu, Qingsheng; Ding, Yaping

    2006-07-01

    AWO4 (A =Ca,Sr,Ba) nanofilms are prepared by a self-inventive technique using collodion to disperse nanoparticles and form film, and their photoluminescence (PL) properties are controlled by a nano-TiO2 doping method. This cannot only reach the results of uniform film and PL enhancement, but also realize a PL increase/decrease shift effect. The PL behaviors of AWO4 nanofilms doped by TiO2 are in good agreement with Gaussion function relation. In addition, there is a positive correlation between the critical concentrations of TiO2 in AWO4-TiO2 nanofilm series and A's ionic potential.

  6. Kinetic Control of Multiple Forms of Ca2+ Spikes by Inositol Trisphosphate in Pancreatic Acinar Cells

    PubMed Central

    Ito, Koichi; Miyashita, Yasushi; Kasai, Haruo

    1999-01-01

    The mechanisms of agonist-induced Ca2+ spikes have been investigated using a caged inositol 1,4,5-trisphosphate (IP3) and a low-affinity Ca2+ indicator, BTC, in pancreatic acinar cells. Rapid photolysis of caged IP3 was able to reproduce acetylcholine (ACh)-induced three forms of Ca2+ spikes: local Ca2+ spikes and submicromolar (<1 μM) and micromolar (1–15 μM) global Ca2+ spikes (Ca2+ waves). These observations indicate that subcellular gradients of IP3 sensitivity underlie all forms of ACh-induced Ca2+ spikes, and that the amplitude and extent of Ca2+ spikes are determined by the concentration of IP3. IP3-induced local Ca2+ spikes exhibited similar time courses to those generated by ACh, supporting a role for Ca2+-induced Ca2+ release in local Ca2+ spikes. In contrast, IP3- induced global Ca2+ spikes were consistently faster than those evoked with ACh at all concentrations of IP3 and ACh, suggesting that production of IP3 via phospholipase C was slow and limited the spread of the Ca2+ spikes. Indeed, gradual photolysis of caged IP3 reproduced ACh-induced slow Ca2+ spikes. Thus, local and global Ca2+ spikes involve distinct mechanisms, and the kinetics of global Ca2+ spikes depends on that of IP3 production particularly in those cells such as acinar cells where heterogeneity in IP3 sensitivity plays critical role. PMID:10427093

  7. Cortisol Response to Challenge Involving Low Controllability: The Role of Control Beliefs and Age

    PubMed Central

    Agrigoroaei, Stefan; Polito, Michael; Lee, Angela; Kranz-Graham, Eileen; Seeman, Teresa; Lachman, Margie E.

    2013-01-01

    Cortisol responses are typically more pronounced under low controllability conditions, yet little is known about the role of individual differences. This study examined whether cortisol response to a situation with low controllability differs as a function of preexisting control beliefs and age. We manipulated level of controllability using a driving simulator. Control beliefs were assessed prior to the lab session. Salivary cortisol was measured before and after the driving simulation. Participants were 152 adults aged 22-84 from a Boston area sample. In comparison to the normal controllability condition, those in the low controllability condition reported less perceived control over driving, supporting the effectiveness of the manipulation. In the low controllability condition those with higher control beliefs showed a greater cortisol response than those with low control beliefs. Older adults showed a greater cortisol response than younger adults during the challenge. Implications of acute cortisol responses for performance outcomes are discussed. PMID:23348557

  8. The Growth and Aggressive Behavior of Human Osteosarcoma Is Regulated by a CaMKII-Controlled Autocrine VEGF Signaling Mechanism

    PubMed Central

    Daft, Paul G.; Yang, Yang; Napierala, Dobrawa; Zayzafoon, Majd

    2015-01-01

    Osteosarcoma (OS) is a hyperproliferative malignant tumor that requires a high vascular density to maintain its large volume. Vascular Endothelial Growth Factor (VEGF) plays a crucial role in angiogenesis and acts as a paracrine and autocrine agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin kinase two (α-CaMKII) protein is an important regulator of OS growth. Here, we investigate the role of α-CaMKII-induced VEGF in the growth and tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of α-CaMKII results in decreases in VEGF gene expression (50%) and protein secretion (55%), while α- CaMKII overexpression increases VEGF gene expression (250%) and protein secretion (1,200%). We show that aggressive OS cells (143B) express high levels of VEGF receptor 2 (VEGFR-2) and respond to exogenous VEGF (100nm) by increasing intracellular calcium (30%). This response is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF results in autocrine stimulated α-CaMKII activation. Furthermore, we show that VEGF and α-CaMKII inhibition decreases the transactivation of the HIF-1α and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation assay shows significantly decreased binding of HIF-1α and AP-1 to their responsive elements in the VEGF promoter. These data suggest that α-CaMKII regulates VEGF transcription by controlling HIF-1α and AP-1 transcriptional activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor) and combination therapy significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF inhibitors could be a promising therapy against this devastating adolescent disease. PMID:25860662

  9. 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

  10. Aging assessment of BWR control rod drive systems

    SciTech Connect

    Greene, R.H.

    1991-01-01

    This study examines the aging phenomena associated with boiling water reactor (BWR) control rod drive mechanisms (CRDMs) and assess the merits of various methods of managing this aging. Information for this study was acquired from (1) the results of a special CRDM aging questionnaire distributed to each US BWR utility, (2) a first-of-its-kind workshop held to discuss CRDM aging and maintenance concerns, (3) an analysis of Nuclear Plant Reliability Data System (NPRDS) failure cases attributed to the CRD system, and (4) personal information exchange with industry experts. As part of this study, nearly 3500 NPRDS failure reports have been analyzed to examine the prevailing failure trends for CRD system components. An investigation was conducted to summarize the occurrence frequency of these component failures, discovery methods, reported failure causes, their respective symptoms, and actions taken by utilities to restore component and system service. The results of this research have identified the predominant CRDM failure modes and causes. In addition, recommendations are presented that identify specific actions utilities can implement to mitigate CRDM aging. An evaluation has also been made of certain maintenance practices and tooling which have enabled some utilities to reduce ALARA exposures received from routine CRDM replacement and rebuilding activities. 5 refs., 8 figs., 2 tabs.

  11. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    PubMed Central

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. PMID:19850077

  12. Oxidative stress and mitochondrial protein quality control in aging.

    PubMed

    Lionaki, Eirini; Tavernarakis, Nektarios

    2013-10-30

    Mitochondrial protein quality control incorporates an elaborate network of chaperones and proteases that survey the organelle for misfolded or unfolded proteins and toxic aggregates. Repair of misfolded or aggregated protein and proteolytic removal of irreversibly damaged proteins are carried out by the mitochondrial protein quality control system. Initial maturation and folding of the nuclear or mitochondrial-encoded mitochondrial proteins are mediated by processing peptidases and chaperones that interact with the protein translocation machinery. Mitochondrial proteins are subjected to cumulative oxidative damage. Thus, impairment of quality control processes may cause mitochondrial dysfunction. Aging has been associated with a marked decline in the effectiveness of mitochondrial protein quality control. Here, we present an overview of the chaperones and proteases involved in the initial folding and maturation of new, incoming precursor molecules, and the subsequent repair and removal of oxidized aggregated proteins. In addition, we highlight the link between mitochondrial protein quality control mechanisms and the aging process. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine. PMID:23563202

  13. Acute Seizures in Old Age Leads to a Greater Loss of CA1 Pyramidal Neurons, an Increased Propensity for Developing Chronic TLE and a Severe Cognitive Dysfunction.

    PubMed

    Hattiangady, Bharathi; Kuruba, Ramkumar; Shetty, Ashok K

    2011-02-01

    The aged population displays an enhanced risk for developing acute seizure (AS) activity. However, it is unclear whether AS activity in old age would result in a greater magnitude of hippocampal neurodegeneration and inflammation, and an increased predilection for developing chronic temporal lobe epilepsy (TLE) and cognitive dysfunction. Therefore, we addressed these issues in young-adult (5-months old) and aged (22-months old) F344 rats after three-hours of AS activity, induced through graded intraperitoneal injections of kainic acid (KA), and terminated through a diazepam injection. During the three-hours of AS activity, both young adult and aged groups exhibited similar numbers of stage-V motor seizures but the numbers of stage-IV motor seizures were greater in the aged group. In both age groups, three-hour AS activity induced degeneration of 50-55% of neurons in the dentate hilus, 22-32% of neurons in the granule cell layer and 49-52% neurons in the CA3 pyramidal cell layer without showing any interaction between the age and AS activity. However, degeneration of neurons in the CA1 pyramidal cell layer showed a clear interaction between the age and AS activity (12% in the young adult group and 56% in the aged group), suggesting that an advanced age makes the CA1 pyramidal neurons more susceptible to die with AS activity. The extent of inflammation measured through the numbers of activated microglial cells was similar between the two age groups. Interestingly, the predisposition for developing chronic TLE at 2-3 months after AS activity was 60% for young adult rats but 100% for aged rats. Moreover, both frequency & intensity of spontaneous recurrent seizures in the chronic phase after AS activity were 6-12 folds greater in aged rats than in young adult rats. Furthermore, aged rats lost their ability for spatial learning even in a scrupulous eleven-session water maze learning paradigm after AS activity, in divergence from young adult rats which retained the

  14. 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.

  15. Chronic estradiol treatment increases CA1 cell survival but does not improve visual or spatial recognition memory after global ischemia in middle-aged female rats

    PubMed Central

    De Butte-Smith, M.; Gulinello, M.; Zukin, R.S.; Etgen, A.M.

    2008-01-01

    Transient global ischemia induces selective, delayed neuronal death in the hippocampal CA1 and cognitive deficits. Physiological levels of 17β-estradiol ameliorate ischemia-induced neuronal death and cognitive impairments in young animals. In view of concerns regarding hormone therapy in postmenopausal women, we investigated whether chronic estradiol treatment initiated 14 days prior to ischemia attenuates ischemia-induced CA1 cell loss and impairments in visual and spatial memory, in ovariohysterectomized (OVX), middle-aged (9-11 months) female rats. To determine whether the duration of hormone withdrawal affects the efficacy of estradiol treatment, hormone treatment was initiated immediately (0 week), 1 week, or 8 weeks after OVX. Age-matched, OVX and gonadally intact females were studied at each OVX interval. Ischemia was induced 1 week after animals were pretested on a variety of behavioral tasks. Global ischemia produced significant neuronal loss in the CA1 and impaired performance on visual and spatial recognition. Chronic estradiol modestly but significantly increased the number of surviving CA1 neurons in animals at all OVX durations. However, in contrast with previous results in young females, estradiol did not preserve visual or spatial memory performance in middle-aged females. All animals displayed normal locomotion, spontaneous alternation and social preference, indicating the absence of global behavioral impairments. Therefore, the neuroprotective effects of estradiol are different in middle-aged than in young rats. These findings highlight the importance of using older animals in studies assessing potential treatments for focal and global ischemia. PMID:19124025

  16. 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. PMID:26220996

  17. 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

  18. CA-LOD: Collision Avoidance Level of Detail for Scalable, Controllable Crowds

    NASA Astrophysics Data System (ADS)

    Paris, Sébastien; Gerdelan, Anton; O'Sullivan, Carol

    The new wave of computer-driven entertainment technology throws audiences and game players into massive virtual worlds where entire cities are rendered in real time. Computer animated characters run through inner-city streets teeming with pedestrians, all fully rendered with 3D graphics, animations, particle effects and linked to 3D sound effects to produce more realistic and immersive computer-hosted entertainment experiences than ever before. Computing all of this detail at once is enormously computationally expensive, and game designers as a rule, have sacrificed the behavioural realism in favour of better graphics. In this paper we propose a new Collision Avoidance Level of Detail (CA-LOD) algorithm that allows games to support huge crowds in real time with the appearance of more intelligent behaviour. We propose two collision avoidance models used for two different CA-LODs: a fuzzy steering focusing on the performances, and a geometric steering to obtain the best realism. Mixing these approaches allows to obtain thousands of autonomous characters in real time, resulting in a scalable but still controllable crowd.

  19. Morphology Control for Al2O3 Inclusion Without Ca Treatment in High-Aluminum Steel

    NASA Astrophysics Data System (ADS)

    He, Shengping; Chen, Gujun; Guo, Yintao; Shen, Boyi; Wang, Qian

    2015-04-01

    Nozzle blockage is a major problem during continuous casting of Al-containing steel. Herein, we analyzed the thermodynamic equilibrium behavior between aluminum and oxygen in steel at 1873 K (1600 °C) and demonstrated that, the dissolved [O] initially decreases with increasing the dissolved [Al] until approximately 0.1 wt pct [Al], and after that, the dissolved [O] increases with dissolved [Al]. Thus, for high-aluminum steel with 1.0 wt pct dissolved [Al], the precipitation of Al2O3 inclusion can be avoided during cooling from deoxidation temperature to the liquidus temperature, if the actual dissolved [O] can be kept from increasing when the dissolved [Al] further increases from 0.1 to 1.0 wt pct. Hence, a method of inclusion control for high-aluminum steel without traditional Ca treatment technology was proposed based on the thermodynamic analysis. Industrial tests confirmed that low-melting point Ca-aluminate inclusions were observed typically through a slag washing with SiO2-minimized high-basicity slag during tapping, accompanied by two-step Al-adding process for production of high-aluminum steel. Moreover, there was no nozzle clogging occurred for five heats of continuous casting.

  20. Structural controls on diffuse degassing in the Las Cañadas caldera, Tenerife, Canary Islands

    NASA Astrophysics Data System (ADS)

    Galindo, I.; Soriano, C.; Martí, J.; Pérez, N.

    2003-04-01

    The Las Cañadas caldera is an elliptical depression located in the central part of the Tenerife Island. The active Teide stratovolcano stands in the centre of the depression, which is limited to the south by the caldera wall, up to 500 m high above the caldera floor. Mapping most of the caldera wall at 1:5000 has provided new insights on its stratigraphy, structure, and geological evolution. Three major ENE-WSW normal faults have been mapped on the caldera wall in the area comprised between El Llano de Ucanca and Los Azulejos, where an intense hydrothermal alteration affects the lower stratigraphic levels of the caldera wall. Hydrothermal alteration is rather distinctive in this area, showing bluish to greenish colours. Most of the phonolitic cone sheets and radial dykes of the caldera wall do not show distinctive hydrothermal features, as do show the phonolitic pyroclastic rocks and lavas of the lower parts of the caldera wall. This suggests the main episodes of dyke intrusion in the Las Cañadas caldera postdate hydrothermal alteration. ENE-WSW normal faults involve dyke swarms and rocks of the upper stratigraphic levels of the caldera wall, and show displacements of up to 100 m. Unfortunately the upper possible age of these faults is poorly constrained since no contact relationship has been observed between fault planes and the rocks of the uppermost stratigraphic levels of the caldera wall. The rocks of the caldera wall adjacent to the faults are intensely fractured at the macro and mesoscale. In addition to field mapping, a soil gas survey was carried out at the caldera depression. Soil CO2 efflux and H2 concentration were measured reaching values of 12 gm-2d-1 and 4 ppmV, respectively. Spatial distribution of these species showed that positive anomalies coincide with the surface expression of the three major faults and their adjacent intensely fractured zone. The high CO2 and H2 values and their coincidence with major normal faults suggests that degassing in

  1. [Age-related factors of psychopathology of impulse control disorders].

    PubMed

    Shiurkute, A

    1999-01-01

    15 children and adolescents with impulse control disorders (mean age 12.9 years) were examined. These disorders were presented as dromomania, kleptomania, aggressive-sadistic actions, tricholillomania, pyromania; a combination of different types was observed in some cases. Schizophrenia was diagnosed in 7 cases, affective disorders--in 8 patients. Independently of the nosologic unity of the disease, development of the impulse control disorders took place in affective disorders which manifested either by monopolar course (depression) (11 cases), or by bypolar attacks with unclear outlines of the phases (4 patients). Psychopathology of impulse control disorders in children and juveniles was analogous to that of the adults, however, their structure wasn't so complex and development of the phases wasn't so clear. PMID:11530454

  2. How to control the scaling of CaCO3: a "fingerprinting technique" to classify additives.

    PubMed

    Verch, Andreas; Gebauer, Denis; Antonietti, Markus; Cölfen, Helmut

    2011-10-01

    A titration set-up coupling ion selective electrodes with pH adjustment was used to analyze the effects of additives present during precipitation of calcium carbonate. Besides industrially well-established antiscalants (sodium triphosphate, citrate, polyacrylate and poly(aspartic acid)), also functional polymers being active in morphosynthesis (polystyrene sulfonate and poly(styrene-alt-maleic acid)) were analyzed. Interestingly each additive acts in its specific way, suggesting the notation "fingerprinting" for a complex interplay of up to five "solution modes" of influencing CaCO(3) precipitation and crystallisation. The results provide new insights into the modes of additive controlled crystallisation, and in the long run, the insights may facilitate the design of precipitation systems that yield complex and tailor-made crystals. PMID:21860865

  3. 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...

  4. 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...

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase

    PubMed Central

    Saotome, Masao; Safiulina, Dzhamilja; Szabadkai, György; Das, Sudipto; Fransson, Åsa; Aspenstrom, Pontus; Rizzuto, Rosario; Hajnóczky, György

    2008-01-01

    Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca2+ targets a yet unidentified cytoplasmic factor that does not seem to be a microtubular motor or a kinase/phosphatase. Here, we have studied the dependence of mitochondrial dynamics on the Miro GTPases that reside in the mitochondria and contain two EF-hand Ca2+-binding domains, in H9c2 cells and primary neurons. At resting cytoplasmic [Ca2+] ([Ca2+]c), movements of the mitochondria were enhanced by Miro overexpression irrespective of the presence of the EF-hands. The Ca2+-induced arrest of mitochondrial motility was also promoted by Miro overexpression and was suppressed when either the Miro were depleted or their EF-hand was mutated. Miro also enhanced the fusion state of the mitochondria at resting [Ca2+]c but promoted mitochondrial fragmentation at high [Ca2+]c. These effects of Miro on mitochondrial morphology seem to involve Drp1 suppression and activation, respectively. In primary neurons, Miro also caused an increase in dendritic mitochondrial mass and enhanced mitochondrial calcium signaling. Thus, Miro proteins serve as a [Ca2+]c-sensitive switch and bifunctional regulator for both the motility and fusion-fission dynamics of the mitochondria. PMID:19098100

  15. The rate of change in Ca2+ concentration controls sperm chemotaxis

    PubMed Central

    Dai, Luru; Friedrich, Benjamin M.; Kashikar, Nachiket D.; Gregor, Ingo; Pascal, René

    2012-01-01

    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 Ca2+ oscillations. How Ca2+ signals elicit steering responses and shape the path is unknown. We unveil the signal transfer between the changes in intracellular Ca2+ concentration ([Ca2+]i) and path curvature (κ). We show that κ is modulated by the time derivative d[Ca2+]i/dt rather than the absolute [Ca2+]i. Furthermore, simulation of swimming paths using various Ca2+ 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 [Ca2+]i into motion. PMID:22371558

  16. Age-related downregulation of the CaV3.1 T-type calcium channel as a mediator of amyloid beta production

    PubMed Central

    Rice, Rachel A.; Berchtold, Nicole C.; Cotman, Carl W.; Green, Kim N.

    2014-01-01

    Alzheimer's is a crippling neurodegenerative disease that largely affects aged individuals. Decades of research have highlighted age-related changes in calcium homeostasis that occur before and throughout the duration of the disease, and the contributions of such dysregulation to Alzheimer's disease pathogenesis. We report an age-related decrease in expression of the CaV3.1 T-type calcium channel at the level of messenger RNA and protein in both humans and mice that is exacerbated with the presence of Alzheimer's disease. Downregulating T-type calcium channels in N2a cells and the 3xTg-AD mouse model of Alzheimer's disease, by way of pharmacologic inhibition with NNC-55-0396, results in a rapid increase in amyloid beta production via reductions in non-amyloidogenic processing, whereas genetic over-expression of the channel in human embryonic kidney cells expressing amyloid precursor protein produces complementary effects. The age-related decline in CaV3.1 expression may therefore contribute to a pro-amyloidogenic environment in the aging brain and represents a novel opportunity to intervene in the course of Alzheimer's disease pathogenesis. PMID:24268883

  17. 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.

  18. 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

  19. 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

  20. Primary and secondary control over age-related changes in physical appearance.

    PubMed

    Thompson, S C; Thomas, C; Rickabaugh, C A; Tantamjarik, P; Otsuki, T; Pan, D; Garcia, B F; Sinar, E

    1998-08-01

    Beliefs about appearance-related changes due to aging were used to test the effects of perceived control and secondary control (acceptance) in a sample of 412 young, early-middle-age, and late-middle-age college-educated adults. Mean difference in aging-related appearance control and hypotheses regarding the adaptiveness of primary and secondary control were examined. Primary control over aging-related appearance was lower in older adults and secondary control was higher. In addition, the results indicated support for the Primacy/Back-Up Model that primary perceived control is important at all levels of actual control. Those with stronger beliefs in their primary control were less distressed. Secondary control served a back-up function in that it was related to less distress only for those who had medium or lower beliefs in primary control. The implications of these findings, that primary control may be advantageous even in low-control circumstances, are discussed. PMID:9728417

  1. Cognitive control, goal maintenance, and prefrontal function in healthy aging.

    PubMed

    Paxton, Jessica L; Barch, Deanna M; Racine, Caroline A; Braver, Todd S

    2008-05-01

    Cognitive control impairments in healthy older adults may partly reflect disturbances in the ability to actively maintain goal-relevant information, a function that depends on the engagement of lateral prefrontal cortex (PFC). In 2 functional magnetic resonance imaging studies, healthy young and older adults performed versions of a task in which contextual cues provide goal-relevant information used to bias processing of subsequent ambiguous probes. In Study 1, a blocked design and manipulation of the cue-probe delay interval revealed a generalized pattern of enhanced task-related brain activity in older adults but combined with a specific delay-related reduction of activity in lateral PFC regions. In Study 2, a combined blocked/event-related design revealed enhanced sustained (i.e., across-trial) activity but a reduction in transient trial-related activation in lateral PFC among older adults. Further analyses of within-trial activity dynamics indicated that, within these and other lateral PFC regions, older adults showed reduced activation during the cue and delay period but increased activation at the time of the probe, particularly on high-interference trials. These results are consistent with the hypothesis that age-related impairments in goal maintenance abilities cause a compensatory shift in older adults from a proactive (seen in young adults) to a reactive cognitive control strategy. PMID:17804479

  2. Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

    PubMed Central

    Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

    2013-01-01

    In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

  3. Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine.

    PubMed

    Sharma, D; Maurya, A K; Singh, R

    1993-01-01

    Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age-related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age-associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration. PMID:8367013

  4. STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry

    PubMed Central

    Shinde, Arti V.; Motiani, Rajender K.; Zhang, Xuexin; Abdullaev, Iskandar F.; Adam, Alejandro P.; González-Cobos, José C.; Zhang, Wei; Matrougui, Khalid; Vincent, Peter A.; Trebak, Mohamed

    2014-01-01

    Endothelial barrier function is critical for tissue fluid homeostasis and its disruption contributes to various pathologies, including inflammation and sepsis. Thrombin is an endogenous agonist that impairs endothelial barrier function. Here, we showed that the thrombin-induced decrease in transendothelial electric resistance of cultured human endothelial cells required the endoplasmic reticulum-localized, calcium-sensing protein STIM1, but was independent of Ca2+ entry across the plasma membrane and the Ca2+ release-activated Ca2+ channel protein Orai1, which is the target of STIM1 in the store-operated calcium entry pathway. We found that STIM1 coupled the thrombin receptor to activation of the guanosine triphosphatase RhoA, stimulation of myosin light chain phosphorylation, formation of actin stress fibers, and loss of cell-cell adhesion. Thus, STIM1 functions in pathways that are dependent and independent of Ca2+entry. PMID:23512989

  5. 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

  6. 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

  7. Kinetic control of skeletal Sr/Ca in a symbiotic coral: Implications for the paleotemperature proxy

    NASA Astrophysics Data System (ADS)

    Cohen, Anne L.; Layne, Graham D.; Hart, Stanley R.; Lobel, Phillip S.

    2001-02-01

    Modeling of past climates is critically dependent on estimates of past sea surface temperatures (SSTs), for which one of the principal techniques used is the measurement of Sr/Ca ratios in corals [Guilderson et al., 1994; McCulloch et al., 1999; Hughen et al., 1999]. The link between coral Sr/Ca and SST is not well-understood and there have been a number of discrepant observations [de Villiers et al., 1995; Alibert, 1998]. Corals with symbiotic zooxanthellae are known to show large diurnal fluctuations in calcification rate associated with the photosynthetic activity of their symbionts. Using detailed measurements with the ion microprobe, we compared the Sr/Ca content of discrete daytime and nighttime skeletal structures in the massive hermatypic coral Porties lutea over the course of 1 year and a seasonal temperature range of 4°C. The Sr/Ca content of daytime skeleton is always lower than that of adjacent nighttime skeleton. While the slope of the nighttime Sr/Ca-SST correlation is close to that seen in inorganic aragonite precipitates, that of the daytime correlation is >4 times as steep. We attribute these differences to the role of photosynthesis in calcification and conclude that bulk Sr/Ca is related principally to daytime calcification rate rather than directly to SST. More reliable estimates of past SST may be arrived at through selective analysis of nighttime skeleton.

  8. Differences in the protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils following transient global cerebral ischemia.

    PubMed

    Lee, Choong Hyun; Park, Joon Ha; Cho, Jeong-Hwi; Ahn, Ji Hyeon; Bae, Eun Joo; Won, Moo-Ho

    2015-08-01

    The thioredoxin (Trx) and peroxiredoxin (Prx) redox system is associated with neuronal damage and neuroprotective effects via the regulation of oxidative stress in brain ischemia. In the present study, ischemia-induced changes in the protein expression levels of Trx2 and Prx3 in the stratum pyramidale (SP) of the hippocampal CA1 region were investigated in adult and aged gerbils, subjected to 5 min of transient global cerebral ischemia, using immunohistochemistry and western blot analysis. In the adult ischemia-group, minimal Trx2 immunoreactivity was detected in the SP 2 days after ischemia-reperfusion. In the aged animals, the Trx2 immunoreactivity in the sham-group was marginally lower compared with that in the adult sham-group. In the aged ischemia-group, Trx2 immunoreactivity in the SP was significantly higher 1, 2 and 4 days post-ischemia, compared with that in the adult ischemia-group and, in the 5 days post-ischemia group, Trx2 immunoreactivity was significantly decreased in the SP. Prx3 immunoreactivity in the SP of the adult ischemia-group was significantly decreased from 4 days after ischemia-reperfusion. In the aged animals, Prx3 immunoreactivity in the sham-group was also marginally lower compared with that in the adult sham-group. Prx3 immunoreactivity in the aged ischemia-group was also significantly higher 1, 2 and 4 days post-ischemia, compared with the adult ischemia-group; however, the Prx3 immunoreactivity was significantly decreased 5 days post-ischemia. The western blot analyses revealed that the pattern of changes in the protein levels of Trx2 and Prx3 in the adult and aged hippocampal CA1 region following ischemic damage were similar to the results obtained in the immunohistochemical data. These findings indicated that cerebral ischemia lead to different protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils, and these differences may be associated with more delayed neuronal death in the aged

  9. 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.

  10. Oligomerization and Ca2+/calmodulin control binding of the ER Ca2+-sensors STIM1 and STIM2 to plasma membrane lipids

    PubMed Central

    Bhardwaj, Rajesh; Müller, Hans-Michael; Nickel, Walter; Seedorf, Matthias

    2013-01-01

    Ca2+ (calcium) homoeostasis and signalling rely on physical contacts between Ca2+ sensors in the ER (endoplasmic reticulum) and Ca2+ channels in the PM (plasma membrane). STIM1 (stromal interaction molecule 1) and STIM2 Ca2+ sensors oligomerize upon Ca2+ depletion in the ER lumen, contact phosphoinositides at the PM via their cytosolic lysine (K)-rich domains, and activate Ca2+ channels. Differential sensitivities of STIM1 and STIM2 towards ER luminal Ca2+ have been studied but responses towards elevated cytosolic Ca2+ concentration and the mechanism of lipid binding remain unclear. We found that tetramerization of the STIM1 K-rich domain is necessary for efficient binding to PI(4,5)P2-containing PM-like liposomes consistent with an oligomerization-driven STIM1 activation. In contrast, dimerization of STIM2 K-rich domain was sufficient for lipid binding. Furthermore, the K-rich domain of STIM2, but not of STIM1, forms an amphipathic α-helix. These distinct features of the STIM2 K-rich domain cause an increased affinity for PI(4,5)P2, consistent with the lower activation threshold of STIM2 and a function as regulator of basal Ca2+ levels. Concomitant with higher affinity for PM lipids, binding of CaM (calmodulin) inhibited the interaction of the STIM2 K-rich domain with liposomes in a Ca2+ and PI(4,5)P2 concentration-dependent manner. Therefore we suggest that elevated cytosolic Ca2+ concentration down-regulates STIM2-mediated ER–PM contacts via CaM binding. PMID:24044355

  11. Experienced Control in Pre-Adolescent and Adolescent Age Males and Females.

    ERIC Educational Resources Information Center

    Tiffany, Phyllis G.

    Adolescent determination of behavior can be viewed as the result of perceived locus of control. To investigate adolescent perceptions of control in terms of age, loci of control (internal or external), situations (community and home), and direction of control (from or over the environment), 909 adolescents (345 males, 564 females), aged 11-19,…

  12. Metabolic Control of Ca2+/Calmodulin-dependent Protein Kinase II (CaMKII)-mediated Caspase-2 Suppression by the B55β/Protein Phosphatase 2A (PP2A)*

    PubMed Central

    Huang, Bofu; Yang, Chih-Sheng; Wojton, Jeffrey; Huang, Nai-Jia; Chen, Chen; Soderblom, Erik J.; Zhang, Liguo; Kornbluth, Sally

    2014-01-01

    High levels of metabolic activity confer resistance to apoptosis. Caspase-2, an apoptotic initiator, can be suppressed by high levels of nutrient flux through the pentose phosphate pathway. This metabolic control is exerted via inhibitory phosphorylation of the caspase-2 prodomain by activated Ca2+/calmodulin-dependent protein kinase II (CaMKII). We show here that this activation of CaMKII depends, in part, on dephosphorylation of CaMKII at novel sites (Thr393/Ser395) and that this is mediated by metabolic activation of protein phosphatase 2A in complex with the B55β targeting subunit. This represents a novel locus of CaMKII control and also provides a mechanism contributing to metabolic control of apoptosis. These findings may have implications for metabolic control of the many CaMKII-controlled and protein phosphatase 2A-regulated physiological processes, because both enzymes appear to be responsive to alterations in glucose metabolized via the pentose phosphate pathway. PMID:25378403

  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. The Role of Ca and Mg in Controlling the Skeletal Composition of Scleractinian Corals

    NASA Astrophysics Data System (ADS)

    Swart, Peter; Giri, Sharmila; Devlin, Quinn; Adkins, Jess

    2015-04-01

    The concentrations of many trace and minor elements in aragonitic coral skeletons are widely used within the annual banding structure to provide information on a wide range of environmental factors. Such ratios are measured not only in recent corals, but also in well preserved corals collected from rocks as old as the Triassic where they have been interpreted as reflecting changes in the minor element and calcium concentrations of the oceans. In particular the changing Mg/Ca ratio of seawater throughout geological time. Most of these trace elements are believed to substitute for Ca within the skeleton and therefore a principal tenant of this approach is that the ratio of an element being measured relative to Ca responds directly the same ratio in seawater. In order to test the fundamental assumption in corals we have grown specimens of the coral Pocillopora damicornis in seawater spiked with combinations of elevated Ca and Mg for periods of ~ 10 weeks and measured the concentrations of a number of elements in the new skeletal growth. These elements include Ca, Sr, Mg, Ba, Mn, S, P, B, Li, and Fe. These experiments provide evidence that the minor and trace element incorporation is much more complicated than previously believed. For example, while the Sr/Ca ratio of coral skeletons is directly related to the same ratio in seawater over a wide range, is also influenced by the Mg content of the seawater. Hence raising the Mg content lowers the distribution coefficient for Sr in corals. The incorporation of other elements such as Ba, B, S, and P in the skeleton are influenced in other unexpected ways.

  15. 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

  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. A Chemical Controller of SNARE-Driven Membrane Fusion That Primes Vesicles for Ca(2+)-Triggered Millisecond Exocytosis.

    PubMed

    Heo, Paul; Yang, Yoosoo; Han, Kyu Young; Kong, Byoungjae; Shin, Jong-Hyeok; Jung, Younghoon; Jeong, Cherlhyun; Shin, Jaeil; Shin, Yeon-Kyun; Ha, Taekjip; Kweon, Dae-Hyuk

    2016-04-01

    Membrane fusion is mediated by the SNARE complex which is formed through a zippering process. Here, we developed a chemical controller for the progress of membrane fusion. A hemifusion state was arrested by a polyphenol myricetin which binds to the SNARE complex. The arrest of membrane fusion was rescued by an enzyme laccase that removes myricetin from the SNARE complex. The rescued hemifusion state was metastable and long-lived with a decay constant of 39 min. This membrane fusion controller was applied to delineate how Ca(2+) stimulates fusion-pore formation in a millisecond time scale. We found, using a single-vesicle fusion assay, that such myricetin-primed vesicles with synaptotagmin 1 respond synchronously to physiological concentrations of Ca(2+). When 10 μM Ca(2+) was added to the hemifused vesicles, the majority of vesicles rapidly advanced to fusion pores with a time constant of 16.2 ms. Thus, the results demonstrate that a minimal exocytotic membrane fusion machinery composed of SNAREs and synaptotagmin 1 is capable of driving membrane fusion in a millisecond time scale when a proper vesicle priming is established. The chemical controller of SNARE-driven membrane fusion should serve as a versatile tool for investigating the differential roles of various synaptic proteins in discrete fusion steps. PMID:26987363

  18. GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling.

    PubMed

    Hayama, Tatsuya; Noguchi, Jun; Watanabe, Satoshi; Takahashi, Noriko; Hayashi-Takagi, Akiko; Ellis-Davies, Graham C R; Matsuzaki, Masanori; Kasai, Haruo

    2013-10-01

    Activity-dependent competition of synapses plays a key role in neural organization and is often promoted by GABA; however, its cellular bases are poorly understood. Excitatory synapses of cortical pyramidal neurons are formed on small protrusions known as dendritic spines, which exhibit structural plasticity. We used two-color uncaging of glutamate and GABA in rat hippocampal CA1 pyramidal neurons and found that spine shrinkage and elimination were markedly promoted by the activation of GABAA receptors shortly before action potentials. GABAergic inhibition suppressed bulk increases in cytosolic Ca(2+) concentrations, whereas it preserved the Ca(2+) nanodomains generated by NMDA-type receptors, both of which were necessary for spine shrinkage. Unlike spine enlargement, spine shrinkage spread to neighboring spines (<15 μm) and competed with their enlargement, and this process involved the actin-depolymerizing factor ADF/cofilin. Thus, GABAergic inhibition directly suppresses local dendritic Ca(2+) transients and strongly promotes the competitive selection of dendritic spines. PMID:23974706

  19. Metabolic memory of ß-cells controls insulin secretion and is mediated by CaMKIIa

    PubMed Central

    Santos, Gustavo Jorge dos; Ferreira, Sandra Mara; Ortis, Fernanda; Rezende, Luiz Fernando; Li, Chengyang; Naji, Ali; Carneiro, Everardo Magalhães; Kaestner, Klaus H.; Boschero, Antonio Carlos

    2014-01-01

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators. Therefore, we hypothesized that pancreatic ß-cells acquire and store the information contained in calcium pulses as a form of “metabolic memory”, just as neurons store cognitive information. To test this hypothesis, we developed a novel paradigm of pulsed exposure of ß-cells to intervals of high glucose, followed by a 24-h consolidation period to eliminate any acute metabolic effects. Strikingly, ß-cells exposed to this high-glucose pulse paradigm exhibited significantly stronger insulin secretion. This metabolic memory was entirely dependent on CaMKII. Metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and Ca2+-dependent vesicle secretion, and by elevated levels of the key ß-cell transcription factor MAFA. In summary, like neurons, human and mouse ß-cells are able to acquire and retrieve information. PMID:24944908

  20. Unravelling how βCaMKII controls the direction of plasticity at parallel fibre-Purkinje cell synapses

    NASA Astrophysics Data System (ADS)

    Pinto, Thiago M.; Schilstra, Maria J.; Steuber, Volker; Roque, Antonio C.

    2015-12-01

    Long-term plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses is thought to mediate cerebellar motor learning. It is known that calcium-calmodulin dependent protein kinase II (CaMKII) is essential for plasticity in the cerebellum. Recently, Van Woerden et al. demonstrated that the β isoform of CaMKII regulates the bidirectional inversion of PF-PC plasticity. Because the cellular events that underlie these experimental findings are still poorly understood, our work aims at unravelling how β CaMKII controls the direction of plasticity at PF-PC synapses. We developed a bidirectional plasticity model that replicates the experimental observations by Van Woerden et al. Simulation results obtained from this model indicate the mechanisms that underlie the bidirectional inversion of cerebellar plasticity. As suggested by Van Woerden et al., the filamentous actin binding enables β CaMKII to regulate the bidirectional plasticity at PF-PC synapses. Our model suggests that the reversal of long-term plasticity in PCs is based on a combination of mechanisms that occur at different calcium concentrations.

  1. A Gq-Ca2+ Axis Controls Circuit-Level Encoding of Circadian Time in the Suprachiasmatic Nucleus

    PubMed Central

    Brancaccio, Marco; Maywood, Elizabeth S.; Chesham, Johanna E.; Loudon, Andrew S.I.; Hastings, Michael H.

    2013-01-01

    Summary The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) is well established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to the intercellular control of SCN pacemaking are poorly understood. We therefore combined viral transduction of SCN slices with fluorescence/bioluminescence imaging to visualize GCaMP3-reported circadian oscillations of intracellular calcium [Ca2+]i alongside activation of Ca2+/cAMP-responsive elements. We phase-mapped them to the TTFL, in time and SCN space, and demonstrated their dependence upon G-coupled vasoactive intestinal peptide (VIP) signaling. Pharmacogenetic manipulation revealed the individual contributions of Gq, Gs, and Gi to cytosolic and TTFL circadian rhythms. Importantly, activation of Gq-dependent (but not Gs or Gi) pathways in a minority of neurons reprogrammed [Ca2+]i and TTFL rhythms across the entire SCN. This reprogramming was mediated by intrinsic VIPergic signaling, thus revealing a Gq/[Ca2+]i-VIP leitmotif and unanticipated plasticity within network encoding of SCN circadian time. PMID:23623697

  2. 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. PMID:21878050

  3. 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.

  4. Innervation and neuromuscular control in ageing skeletal muscle.

    PubMed

    Hepple, Russell T; Rice, Charles L

    2016-04-15

    Changes in the neuromuscular system affecting the ageing motor unit manifest structurally as a reduction in motor unit number secondary to motor neuron loss; fibre type grouping due to repeating cycles of denervation-reinnervation; and instability of the neuromuscular junction that may be due to either or both of a gradual perturbation in postsynaptic signalling mechanisms necessary for maintenance of the endplate acetylcholine receptor clusters or a sudden process involving motor neuron death or traumatic injury to the muscle fibre. Functionally, these changes manifest as a reduction in strength and coordination that precedes a loss in muscle mass and contributes to impairments in fatigue. Regular muscle activation in postural muscles or through habitual physical activity can attenuate some of these structural and functional changes up to a point along the ageing continuum. On the other hand, regular muscle activation in advanced age (>75 years) loses its efficacy, and at least in rodents may exacerbate age-related motor neuron death. Transgenic mouse studies aimed at identifying potential mechanisms of motor unit disruptions in ageing muscle are not conclusive due to many different mechanisms converging on similar motor unit alterations, many of which phenocopy ageing muscle. Longitudinal studies of ageing models and humans will help clarify the cause and effect relationships and thus, identify relevant therapeutic targets to better preserve muscle function across the lifespan. PMID:26437581

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

    PubMed

    Jensen, Martin Borch; Jasper, Heinrich

    2014-08-01

    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. PMID:24930971

  6. 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. PMID:27093086

  7. 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.

  8. Electric Field-Controlled Crystallizing CaCO3 Nanostructures from Solution.

    PubMed

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

    2016-12-01

    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. PMID:26932759

  9. EPICS controlled sample mounting robots at the GM/CA CAT.

    SciTech Connect

    Makarov, O. A.; Benn, R.; Corcoran, S.; Devarapalli, S.; Fischetti, R.; Hilgart, M.; Smith, W. W.; Stepanov, S.; Xu, S.; Biosciences Division

    2007-11-11

    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 [R.F. Fischetti, et al., GM/CA canted undulator beamlines for protein crystallography, Acta Crystallogr. A 61 (2005) C139]. The facility consists of three beamlines; two based on canted undulators and one on a bending magnet. The scientific and technical goals of the CAT emphasize streamlined, efficient throughput for a variety of sample types, sizes and qualities, representing the cutting edge of structural biology research. For this purpose all three beamlines are equipped with the ALS-style robots [C.W.Cork, et al. Status of the BCSB automated sample mounting and alignment system for macromolecular crystallography at the Advanced Light Source, SRI-2003, San-Francisco, CA, USA, August 25-29, 2003] for an automated mounting of cryo-protected macromolecular crystals. This report summarizes software and technical solutions implemented with the first of the three operational robots at beamline 23-ID-B. The automounter's Dewar can hold up to 72 or 96 samples residing in six Rigaku ACTOR magazines or ALS-style pucks, respectively. Mounting of a crystal takes approximately 2 s, during which time the temperature of the crystal is maintained near that of liquid nitrogen.

  10. Factors controlling the rate of CaCO3 precipitation on Great Bahama Bank

    NASA Astrophysics Data System (ADS)

    Broecker, Wallace S.; Langdon, Chris; Takahashi, Taro; Peng, Tsung-Hung

    2001-09-01

    Measurements by Langdon et al. [2000] in the man-made mesocosm coral reef at Biosphere 2's ocean reveal a strong dependence of calcification rate on the degree of supersaturation of CaCO3 in seawater. A similar trend was previously encountered on the Bahama Banks, where Halimeda and other calcifiers are likely responsible for aragonite precipitation [Broecker and Takahashi, 1966]. In this paper we compare these two sets of results and conclude that the dependence on saturation state is significant but less strong in the Bahamas. However, it must be kept in mind that to some extent, the reduction in CaCO3 precipitation on the Bahama Banks may be due to impact of higher salinity on the growth of the calcifying algae. However, if, as many sedimentologists are convinced, the precipitation of CaCO3 on the Bahama Banks is inorganic [Macintyre and Reid, 1992; Milliman et al., 1993], then the comparison of the Bahamas and Biosphere 2 results for dependence of calcification rate on saturation state is telling us something quite different.

  11. 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.

  12. 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.

  13. Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α(1)-adrenoceptor stimulation of mouse aorta segments.

    PubMed

    Leloup, Arthur J; Van Hove, Cor E; De Meyer, Guido R Y; Schrijvers, Dorien M; Fransen, Paul

    2015-08-01

    α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K(+)) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with N(Ω)-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca(2+) store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. PMID:25913240

  14. Activation of the Ca{sup 2+}/calcineurin/NFAT{sub 2} pathway controls smooth muscle cell differentiation

    SciTech Connect

    Larrieu, Daniel; Thiebaud, Pierre; Duplaa, Cecile; Sibon, Igor; Theze, Nadine; Lamaziere, Jean-Marie Daniel . E-mail: jean-marie.d-lamaziere@bordeaux.inserm.fr

    2005-10-15

    Cellular mechanisms controlling smooth muscle cells (SMCs) phenotypic modulation are largely unknown. Intracellular Ca{sup 2+} movements are essential to ensure SMC functions; one of the roles of Ca{sup 2+} is to regulate calcineurin, which in turn induces nuclear localization of the nuclear factor of activated T-cell (NFAT). In order to investigate, during phenotypic differentiation of SMCs, the effect of calcineurin inhibition on NFAT{sub 2} nuclear translocation, we used a culture model of SMC differentiation in serum-free conditions. We show that the treatment of cultured SMC with the calcineurin inhibitor cyclosporine A induced their dedifferentiation while preventing their differentiation. These findings suggest that nuclear translocation of NFAT{sub 2} is dependent of calcineurin activity during the in vitro SMC differentiation kinetic and that the nuclear presence of NFAT{sub 2} is critical in the acquisition and maintenance of SMC differentiation.

  15. Locus of Control and Psychological Distress among the Aged.

    ERIC Educational Resources Information Center

    Hale, W. Daniel; And Others

    1986-01-01

    Examined relationship between locus of control and self-reported psychopathology in 139 residents of retirement complex. Correlation coefficients computed for locus of control and each of nine symptom dimensions of the Brief Symptom Inventory indicated that locus of control was correlated with self-reported psychopatholgoy for older women but not…

  16. Luminescent and aging characteristics of blue emitting (Ca 1- x,Mg x)Al 2Si 2O 8:Eu 2+ phosphor for PDPs application

    NASA Astrophysics Data System (ADS)

    Im, Won Bin; Kim, Yong-Il; Kang, Jong Hyuk; Jeon, Duk Young

    2005-06-01

    We have evaluated thermal stability and aging property of a blue color-emitting phosphor, CaAl 2Si 2O 8:Eu 2+ (CAS:Eu 2+), synthesized by conventional solid-state reaction method. When both CAS:Eu 2+ and BaMgAl 10O 19:Eu 2+ (BAM) were baked in air at 500 °C for 20 min, the decrease of photoluminescence (PL) intensity of CAS:Eu 2+ was lower than that of BAM. The aging property of CAS:Eu 2+ was also better than that of BAM. Due to its rigid structure and unlimited framework of silicon-oxygen and aluminum-oxygen around Eu 2+ ions, Eu 2+ ions were protected from outer oxidizing atmosphere and plasma discharge. After analysis of aging property and thermal stability, the differences of these thermal stability and aging property of CAS:Eu 2+ from those of BAM were ascribed to its crystal structure which plays a role of a shield for Eu 2+ ions against oxidation atmosphere and Xe ion bombardment.

  17. 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...

  18. 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…

  19. Air pollution control in an age of prevention

    SciTech Connect

    Smith, J.C.

    1996-01-01

    In the case of air pollution control technology, the case for pollution prevention is frequently cast as a case against pollution control technology. The errors in this argument are that pollution control technology is always the more expensive compliance option and that pollution prevention techniques exist to solve all or most of US air quality problems. A true market-based clean air policy would not contain these assumptions, would set a goal and appoint the market as the arbiter of final compliance decisions. This article discusses the market-based option and the balance needed between pollution prevention and pollution control technologies.

  20. Compliance and Self-Control across Situations at Age 4.

    ERIC Educational Resources Information Center

    Mulvihill, Beverly A.; Owen, Margaret Tresch

    This study investigated the relations between different measurements of 33 4-year-olds' compliance and self-control and the relation between the children's cognitive ability and compliance and self-control. The four compliance ratings involved the child's behavior with mother and father in separate puzzle tasks, free play in the child care…

  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. Controlling the Vaterite CaCO3 Crystal Pores. Design of Tailor-Made Polymer Based Microcapsules by Hard Templating.

    PubMed

    Feoktistova, Natalia; Rose, Juergen; Prokopović, Vladimir Z; Vikulina, Anna S; Skirtach, Andre; Volodkin, Dmitry

    2016-05-01

    The spherical vaterite CaCO3 microcrystals are nowadays widely used as sacrificial templates for fabrication of various microcarriers made of biopolymers (e.g., proteins, nucleic acids, enzymes) due to porous structure and mild template elimination conditions. Here, we demonstrated for the first time that polymer microcarriers with tuned internal nanoarchitecture can be designed by employing the CaCO3 crystals of controlled porosity. The layer-by-layer deposition has been utilized to assemble shell-like (hollow) and matrix-like (filled) polymer capsules due to restricted and free polymer diffusion through the crystal pores, respectively. The crystal pore size in the range of few tens of nanometers can be adjusted without any additives by variation of the crystal preparation temperature in the range 7-45 °C. The temperature-mediated growth mechanism is explained by the Ostwald ripening of nanocrystallites forming the crystal secondary structure. Various techniques including SEM, AFM, CLSM, Raman microscopy, nitrogen adsorption-desorption, and XRD have been employed for crystal and microcapsule analysis. A three-dimensional model is introduced to describe the crystal internal structure and predict the pore cutoff and available surface for the pore diffusing molecules. Inherent biocompatibility of CaCO3 and a possibility to scale the porosity in the size range of typical biomacromolecules make the CaCO3 crystals extremely attractive tools for template assisted designing tailor-made biopolymer-based architectures in 2D to 3D targeted at drug delivery and other bioapplications. PMID:27052835

  3. 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.

  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 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

  6. Injection control of an XeF (C-A) laser - A simple scheme

    NASA Astrophysics Data System (ADS)

    Hollins, R. C.; Jordan, D. J.; Feltman, A.

    1987-07-01

    Enhancement of the efficiency of a blue-green discharge laser is demonstrated using a simple dye laser which is excited by the UV output of the XeF medium itself. The 350-nm output is harnessed to excite a small dye laser which acts as an injection source. The occurrence of optical gain on the C-A transition (440-520 nm) is delayed with respect to the UV output due to the initial presence of visible absorbing species, resulting in the automatic injection of dye-laser radiation into the XeF laser cavity at the appropriate time. With selection of the oscillation wavelength by the choice of dye, improvement of the efficiency by a factor of 30 is possible with the present self-excited injection scheme.

  7. Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics.

    PubMed

    Arese, Marzia; Magnifico, Maria Chiara; Mastronicola, Daniela; Altieri, Fabio; Grillo, Caterina; Blanck, Thomas J J; Sarti, Paolo

    2012-03-01

    A novel role of melatonin was unveiled, using immortalized human keratinocyte cells (HaCaT) as a model system. Within a time window compatible with its circadian rhythm, melatonin at nanomolar concentration raised both the expression level of the neuronal nitric oxide synthase mRNA and the nitric oxide oxidation products, nitrite and nitrate. On the same time scale, a depression of the mitochondrial membrane potential was detected together with a decrease of the oxidative phosphorylation efficiency, compensated by glycolysis as testified by an increased production of lactate. The melatonin concentration, ∼ nmolar, inducing the bioenergetic effects and their time dependence, both suggest that the observed nitric oxide-induced mitochondrial changes might play a role in the metabolic pathways characterizing the circadian melatonin chemistry. PMID:22271455

  8. Aging.

    PubMed

    Park, Dong Choon; Yeo, Seung Geun

    2013-09-01

    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

  9. 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

  10. The Role of {Ca2+ / CO32-} Ratio in Calcite Dissolution and Growth: Implications for Mechanistic Control of Biomineralization

    NASA Astrophysics Data System (ADS)

    Arvidson, R. S.; Davis, K. J.; Luttge, A.

    2003-12-01

    The hypothesis that secular variations in the Mg/Ca ratio of seawater have exerted a fundamental control over the mineralogy and abundance of both skeletal and nonskeletal carbonates has received substantial support from both experimental and field data. In this context, ongoing efforts directed at understanding the mechanistic basis for interaction of Mg and Sr with carbonate mineral surfaces during growth (e.g., Davis et al. 2000) are of obvious importance. However, a growing body of experimental dissolution data records additional site-specific interactions between the surface and dissolved free carbon species and carbonate complexes. We suggest these data may provide additional insight into mechanisms by which organisms maintain skeletal integrity under variable conditions, including the possible development of surface precursors of mixed carbonate phases. For example, recent data have shown that kink dynamics along the fast, obtuse (+) step directions are highly sensitive to the ratio of magnesium to carbonate ion. We have used these observations as the basis for exploration of the relationship between the simple ratio of dissolved calcium to carbonate ion and surface dynamics. In sets of carefully designed experiments, we sought to maintain (1) a constant distance from equilibrium by varying {Ca2+ / CO32-} ratio at constant IAP, (2) constant {Ca2+ / CO32-} at variable IAP, (3) all under conditions of both over- and undersaturation ranging from far to close to equilibrium. Using an integrated approach, observations were made over a wide range of space and time scales using both AFM and VSI (vertical scanning interferometry). These coupled observations provide resolution of the relationship between the overall rate of reaction (total change in surface topography) and detailed observations of characteristic step dynamics developed during both dissolution and growth. Our preliminary results confirm a strong sensitivity of the conventional fast step direction to

  11. 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

  12. Control of cortical axon elongation by a GABA-driven Ca2+/calmodulin-dependent protein kinase cascade

    PubMed Central

    Ageta-Ishihara, Natsumi; Takemoto-Kimura, Sayaka; Nonaka, Mio; Adachi-Morishima, Aki; Suzuki, Kanzo; Kamijo, Satoshi; Fujii, Hajime; Mano, Tatsuo; Blaeser, Frank; Chatila, Talal A.; Mizuno, Hidenobu; Hirano, Tomoo; Tagawa, Yoshiaki; Okuno, Hiroyuki; Bito, Haruhiko

    2009-01-01

    Ca2+ signaling plays important roles during both axonal and dendritic growth. Yet, whether and how Ca2+ rises may trigger and contribute to the development of long range cortical connections remains largely unknown. Here we demonstrate that two separate limbs of CaMK kinase (CaMKK) - CaMKI cascades, CaMKK-CaMKIα and CaMKK-CaMKIγ, critically coordinate axonal and dendritic morphogenesis of cortical neurons, respectively. The axon-specific morphological phenotype required a diffuse cytoplasmic localization and a strikingly α-isoform-specific kinase activity of CaMKI. Unexpectedly, treatment with muscimol, a GABAA receptor agonist, selectively stimulated elongation of axons but not of dendrites, and the CaMKK-CaMKIα cascade critically mediated this axonogenic effect. Consistent with these findings, during early brain development, in vivo knockdown of CaMKIα significantly impaired the terminal axonal extension, and thereby perturbed the refinement of the interhemispheric callosal projections into the contralateral cortices. Our findings thus indicate a novel role for the GABA-driven CaMKK-CaMKIα cascade as a mechanism critical for accurate cortical axon pathfinding, an essential process which may contribute to fine-tuning the formation of interhemispheric connectivity during the perinatal development of the central nervous system. PMID:19864584

  13. 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.

  14. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  15. 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…

  16. Sustained Attention and Age Predict Inhibitory Control during Early Childhood

    ERIC Educational Resources Information Center

    Reck, Sarah G.; Hund, Alycia M.

    2011-01-01

    Executive functioning skills develop rapidly during early childhood. Recent research has focused on specifying this development, particularly predictors of executive functioning skills. Here we focus on sustained attention as a predictor of inhibitory control, one key executive functioning component. Although sustained attention and inhibitory…

  17. 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…

  18. 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…

  19. Evaluating controlling factors to Al(i)/(Ca + Mg) molar ratio in acidic soil water, southern and southwestern China: multivariate approach.

    PubMed

    Guo, Jing-Heng; Zhang, Xiao-Shan; Vogt, Rolf D; Xiao, Jin-Song; Zhao, Da-Wei; Xiang, Ren-Jun; Luo, Jia-Hai

    2007-06-01

    Al(i)/(Ca + Mg) molar ratio in soil water has been used as an indicator to the effects of acid deposition on terrestrial ecosystems. However, the main factors controlling this ratio have not been well documented in southern and southwestern China. In this study, we presented the variation in inorganic aluminum (Al(i)) and Al(i)/(Ca + Mg) molar ratio in different sites and soil horizons based on two to three years monitoring data, and evaluated the main factors controlling Al(i)/(Ca + Mg) molar ratio using principle component analysis (PCA) and partial least square (PLS) regression. Monitoring data showed although Al(i)/(Ca + Mg) molar ratios in most soil water were lower than assumed critical 1.0, higher molar ratios were found in some soil water at TSP and LXH site. Besides acid loading, both soil properties and soil water chemistry affected the value of Al(i)/(Ca + Mg) molar ratio in soil water. Partial least square (PLS) indicated that they had different relative importance in different soil horizons. In A-horizon, soil aluminum saturation (AlS) had higher influence on Al(i)/(Ca + Mg) molar ratio than soil water chemistry did; higher soil aluminum saturation (AlS) led to higher Al(i)/(Ca + Mg) molar ratio in soil water. In the deeper horizons (i.e., B(1)-, B(2)- and BC-horizon), inorganic aluminum (Al(i)) in soil water had more and more important role in regulating Al(i)/(Ca + Mg) molar ratio. On regional scale, soil aluminum saturation (AlS) as well as cation exchange capacity (CEC) was the dominant factor controlling Al(i)/(Ca + Mg) molar ratio. This should be paid enough attention on when making regional acid rain control policy in China. PMID:17057971

  20. 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

  1. 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.

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

    USGS Publications Warehouse

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

    2005-01-01

    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. Copyright 2005 by the American Geophysical Union.

  3. CALSITES, ANNUAL WORK PLAN (AWP), CA DEPARTMENT OF TOXIC SUBSTANCE CONTROL(DTSC)

    EPA Science Inventory

    The California Department of Toxic Substances Control (DTSC) has developed an electronic database system with information about sites that are known to be contaminated with hazardous substances as well as information on uncharacterized properties where further studies may reveal...

  4. Ca2+-activated K+ channels of small and intermediate conductance control eNOS activation through NAD(P)H oxidase.

    PubMed

    Gaete, Pablo S; Lillo, Mauricio A; Ardiles, Nicolás M; Pérez, Francisco R; Figueroa, Xavier F

    2012-03-01

    Ca(2+)-activated K(+) channels (K(Ca)) and NO play a central role in the endothelium-dependent control of vasomotor tone. We evaluated the interaction of K(Ca) with NO production in isolated arterial mesenteric beds of the rat. In phenylephrine-contracted mesenteries, acetylcholine (ACh)-induced vasodilation was reduced by NO synthase (NOS) inhibition with N(ω)-nitro-L-arginine (L-NA), but in the presence of tetraethylammonium, L-NA did not further affect the response. In KCl-contracted mesenteries, the relaxation elicited by 100 nM ACh or 1 μM ionomycin was abolished by L-NA, tetraethylammonium, or simultaneous blockade of small-conductance K(Ca) (SK(Ca)) channels with apamin and intermediate-conductance K(Ca) (IK(Ca)) channels with triarylmethane-34 (TRAM-34). Apamin-TRAM-34 treatment also abolished 100 nM ACh-activated NO production, which was associated with an increase in superoxide formation. Endothelial cell Ca(2+) buffering with BAPTA elicited a similar increment in superoxide. Apamin-TRAM-34 treatment increased endothelial NOS phosphorylation at threonine 495 (P-eNOS(Thr495)). Blockade of NAD(P)H oxidase with apocynin or superoxide dismutation with PEG-SOD prevented the increment in superoxide and changes in P-eNOS(Thr495) observed during apamin and TRAM-34 application. Our results indicate that blockade of SK(Ca) and IK(Ca) activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOS(Thr495). These findings disclose a novel mechanism involved in the control of NO production. PMID:22210378

  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. Solvent controlled synthesis of CaO-MgO nanocomposites and their application in the photodegradation of organic pollutants of industrial waste

    NASA Astrophysics Data System (ADS)

    Shahid, Muhammad; Farrukh, Muhammad Akhyar; Umar, Akrajas Ali; Khaleeq-ur-Rahman, Muhammad

    2014-05-01

    Conventional heating method and hydrothermal method were used for the synthesis of CaO nanoparticles and CaO/MgO nanocomposites under solvent control conditions. Ca(NO3)2 and Mg(NO3)2 were used as precursors, amyl alcohol as surface directing agent and NaOH as source of OH-. Different samples of CaO were prepared by conventional heating method in order to investigate the effect of calcination temperature and stirring time. Similarly two different kinds of sets of CaO as well as of CaO/MgO were synthesized under hydrothermal conditions for the investigation of effect of solvent and temperature on catalytic efficiency. Characterizations of these samples were carried out by Powder X-ray Diffractions (XRD), Thermo Gravimetric Analysis (TGA), Field Emission Scanning Electron Microscope (FESEM) Energy dispersive X-ray (EDX) and Fourier Transformed Infrared spectroscopy (FTIR). The synthesized samples of CaO and CaO/MgO were used to degrade methylene blue under UV-Visible conditions, which is an organic pollutant of waste from industries and causing serious health problems. First order data for degradation for methylene blue at λmax = 665 nm was used to quantify the degradation. Effect of solvent was found to be prominent in all samples. Similarly effect of temperature variation was also pronounced on catalytic efficiency as indicated by value of k.

  7. Reactor control system upgrade for the McClellan Nuclear Radiation Center Sacramento, CA.

    SciTech Connect

    Power, M. A.

    1999-03-10

    Argonne National Laboratory is currently developing a new reactor control system for the McClellan Nuclear Radiation Facility. This new control system not only provides the same functionality as the existing control system in terms of graphic displays of reactor process variables, data archival capability, and manual, automatic, pulse and square-wave modes of operation, but adds to the functionality of the previous control system by incorporating signal processing algorithms for the validation of sensors and automatic calibration and verification of control rod worth curves. With the inclusion of these automated features, the intent of this control system is not to replace the operator but to make the process of controlling the reactor easier and safer for the operator. For instance, an automatic control rod calibration method reduces the amount of time to calibrate control rods from days to minutes, increasing overall reactor utilization. The control rod calibration curve, determined using the automatic calibration system, can be validated anytime after the calibration, as long as the reactor power is between 50W and 500W. This is done by banking all of the rods simultaneously and comparing the tabulated rod worth curves with a reactivity computer estimate. As long as the deviation between the tabulated values and the reactivity estimate is within a prescribed error band, then the system is in calibration. In order to minimize the amount of information displayed, only the essential flux-related data are displayed in graphical format on the control screen. Information from the sensor validation methods is communicated to the operators via messages, which appear in a message window. The messages inform the operators that the actual process variables do not correlate within the allowed uncertainty in the reactor system. These warnings, however, cannot cause the reactor to shutdown automatically. The reactor operator has the ultimate responsibility of using this

  8. 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…

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

    DOE PAGESBeta

    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.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

  10. 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

  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. The crucial role of physiological Ca2+ concentrations in the production of endothelial nitric oxide and the control of vascular tone.

    PubMed Central

    Lopez-Jaramillo, P.; Gonzalez, M. C.; Palmer, R. M.; Moncada, S.

    1990-01-01

    1. The effect of varying the extracellular Ca2+ concentration on the basal and acetylcholine (ACh)-induced release of nitric oxide (NO) from the rabbit aorta was investigated by use of a superfusion bioassay system. 2. Changes between 0.5 and 2.0 mM in the concentration of Ca2+ superfusing the detector bioassay tissues or perfusing endothelium-denuded donor aortae had no effect on the tone of these tissues. 3. Increasing the concentration of Ca2+ perfusing endothelium-containing donor aortae from zero to 1.25 mM caused a transient (24 +/- 9 min), concentration-dependent basal release of NO, which was attenuated at higher concentrations of Ca2+ (1.5-2.0 mM). 4. The duration of the effect of Ca2+ on the basal release of NO was increased by a concomitant infusion of L-arginine (100 microM) through the donor aorta. 5. Changes in the concentration of Ca2+ between 0.5 and 2.0 mM had a similar biphasic effect on the release of NO induced by ACh, which was also maximal at 1.25 mM Ca2+. 6. When Ca2+ was removed from the Krebs buffer perfusing the donor aorta, the basal release of NO declined within 2 min. In contrast, the release of NO induced by ACh declined progressively over 60 min. 7. Thus changes in the concentration of Ca2+ around the physiological range modulate the synthesis of NO by the vascular endothelium and consequently, vascular tone. This may account for the effects of dietary Ca2+ supplements on the control of some hypertensive states. PMID:2257446

  13. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

    PubMed Central

    Foster, Thomas C.

    2012-01-01

    In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D-aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate-term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging. PMID:22307057

  14. Age differences in coping and locus of control: a study of managerial stress in Hong Kong.

    PubMed

    Siu, O; Cooper, C L; Spector, P E; Donald, I

    2001-12-01

    The present study involved data collection from 3 samples of Hong Kong managers to examine mechanisms by which age would relate to work well-being. A total of 634 managers was drawn by random sampling and purposive sampling methods. The results showed that age was positively related to well-being (job satisfaction and mental well-being). Furthermore, older managers reported fewer sources of stress, better coping, and a more internal locus of control. Multiple regression analyses suggested that the relations of age with 2 well-being indicators can be attributed to various combinations of coping, work locus of control, sources of stress, managerial level, and organizational tenure. PMID:11766923

  15. Effects of aging on interference control in selective attention and working memory.

    PubMed

    Cansino, Selene; Guzzon, Daniela; Martinelli, Massimiliano; Barollo, Michele; Casco, Clara

    2011-11-01

    Working memory decay in advanced age has been attributed to a concurrent decrease in the ability to control interference. The present study contrasted a form of interference control in selective attention that acts upon the perception of external stimuli (access) with another form that operates on internal representations in working memory (deletion), in order to determine both of their effects on working memory efficiency in younger and older adults. Additionally, we compared memory performance under these access and deletion functions to performance in their respective control conditions. The results indicated that memory accuracy improved in both age groups from the access functions, but that only young adults benefited from the deletion functions. In addition, intrusion effects in the deletion condition were larger in older than in younger adults. The ability to control the irrelevant perception- and memory-elicited interference did not decline in general with advancing age; rather, the control mechanisms that operate on internal memory representations declined specifically. PMID:21557003

  16. Open-Loop Control of Oxidative Phosphorylation in Skeletal and Cardiac Muscle Mitochondria by Ca(2.).

    PubMed

    Vinnakota, Kalyan C; Singhal, Abhishek; Van den Bergh, Françoise; Bagher-Oskouei, Masoumeh; Wiseman, Robert W; Beard, Daniel A

    2016-02-23

    In cardiac muscle, mitochondrial ATP synthesis is driven by demand for ATP through feedback from the products of ATP hydrolysis. However, in skeletal muscle at higher workloads there is an apparent contribution of open-loop stimulation of ATP synthesis. Open-loop control is defined as modulation of flux through a biochemical pathway by a moiety, which is not a reactant or a product of the biochemical reactions in the pathway. The role of calcium, which is known to stimulate the activity of mitochondrial dehydrogenases, as an open-loop controller, was investigated in isolated cardiac and skeletal muscle mitochondria. The kinetics of NADH synthesis and respiration, feedback from ATP hydrolysis products, and stimulation by calcium were characterized in isolated mitochondria to test the hypothesis that calcium has a stimulatory role in skeletal muscle mitochondria not apparent in cardiac mitochondria. A range of respiratory states were obtained in cardiac and skeletal muscle mitochondria utilizing physiologically relevant concentrations of pyruvate and malate, and flux of respiration, NAD(P)H fluorescence, and rhodamine 123 fluorescence were measured over a range of extra mitochondrial calcium concentrations. We found that under these conditions calcium stimulates NADH synthesis in skeletal muscle mitochondria but not in cardiac mitochondria. PMID:26910432

  17. 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

  18. 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. PMID:26359527

  19. 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

  20. Age and Cohort Patterns of Medical and Nonmedical Use of Controlled Medication Among Adolescents

    PubMed Central

    Austic, Elizabeth; McCabe, Sean Esteban; Stoddard, Sarah; Ngo, Quyen Epstein; Boyd, Carol

    2015-01-01

    Objectives We identified peak annual incidence rates for medical and nonmedical use of prescription opioid analgesics, stimulants, sedatives and anxiolytics (controlled medication), and explored cohort effects on age of initiation. Methods Data were gathered retrospectively between 2009–2012 from Detroit area students (n=5185). Modal age at last assessment was 17 years. A meta-analytic approach produced age-, year-, and cohort-specific risk estimates of first-time use of controlled medication. Cox regression models examined cohort patterns in age of initiation for medical and nonmedical use with any of four classes of controlled medication (opioid analgesics, stimulants, sedatives or anxiolytics). Results Peak annual incidence rates were observed at age 16, when 11.3% started medical use, and 3.4% started using another person’s prescription for a controlled medication (i.e., engaged in nonmedical use). In the more recent birth cohort group (1996–2000), 82% of medical users and 76% of nonmedical users reported initiating such use by age 12. In contrast, in the less recent birth cohort group (1991–1995), 42% of medical users and 35% of nonmedical users initiated such use by age 12. Time to initiation was 2.6 times less in the more recent birth cohort group (medical use: adjusted hazard ratio [aHR]=2.57 [95% confidence interval (CI)= 2.32, 2.85]; nonmedical use: aHR=2.57 [95% CI=2.17, 3.03]). Conclusions Peak annual incidence rates were observed at age 16 for medical and nonmedical use. More recent cohorts reported initiating both types of use at younger ages. Earlier interventions may be needed to prevent adolescent nonmedical use of controlled medication. PMID:26291544

  1. 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

  2. P300 EVENT RELATED POTENTIAL IN NORMAL HEALTHY CONTROLS OF DIFFERENT AGE GROUPS

    PubMed Central

    Shukla, R.; Trivedi, J.K.; Singh, R.; Singh, Y.; Chakravorty, P.

    2000-01-01

    P300 event related potential was recorded in 115 healthy controls with a mean age of35.9±14.81 years and a male : female ratio of 72 : 43. There was significant difference in the P300 latency in < 40 years as compared to ≥ 40 years group (p< 0.001). There was no significant difference between males and females. There was a strong positive correlation between age and P300 latency (p< 0.001). The regression equation for P300 latency was Y=287.9+1.492x with an SEE of 20.2 (where Y is the P300 latency in ms, x is the age in years, SEE is the standard error of estimate). There was a negative correlation between age and P300 amplitude which was significant in ≥ 40 years age group while in > 40 years age group it was not significant. PMID:21407977

  3. [Aging and the control of the insulin-FOXO signaling pathway].

    PubMed

    Brunet, Anne

    2012-03-01

    Aging is a complex process that is accompanied by the onset of a series of age-related diseases, including Alzheimer's disease. Aging is controlled by a combination of genetic and environmental factors. Among the genes that regulate aging, the insulin-FOXO signaling pathway plays a central role, as this pathway regulates lifespan in multiple species, such as worms, flies, and mice. In humans, exceptional longevity - being a centenarian - is also associated with genetic variation in this insulin-FOXO pathway. Recent evidence indicates that the FOXO family of transcription factors plays a key role in the self-renewal of adult and embryonic stem cells, which could contribute to tissue regeneration. Understanding the mechanisms underlying aging should help better prevent and treat age-dependent diseases. PMID:22480657

  4. 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

  5. Disseminating the Positively Aging[R] Teaching Materials: Results of a Controlled Trial

    ERIC Educational Resources Information Center

    Lichtenstein, Michael J.; Pruski, Linda A.; Marshall, Carolyn E.; Blalock, Cheryl L.; Liu, Yan; Plaetke, Rosemarie

    2005-01-01

    This study tested the effectiveness of 2 dissemination methods for the Positively Aging teaching materials. In San Antonio, Texas, 4 middle schools participated in a 3-year controlled trial of dissemination via distance electronic support alone (control) compared to distance electronic support plus in-school support from study staff…

  6. Childhood physical neglect promotes development of mild cognitive impairment in old age - A case-control study.

    PubMed

    Wang, Lan; Yang, Linlin; Yu, Lulu; Song, Mei; Zhao, Xiaochuan; Gao, Yuanyuan; Han, Keyan; An, Cuixia; Xu, Shunjiang; Wang, Xueyi

    2016-08-30

    This study aimed to investigate the role of early traumatic experiences in development of mild cognitive impairment (MCI) in Chinese elderly people. Seventy six patients and 61 controls were selected and assigned into two study groups, MCI and control, respectively. Childhood Trauma Questionnaire-Short Form (CTQ-SF) was used for assessment of early trauma, episodic memory and association learning scales for memory evaluation. In addition, event-related potentials (ERPs) were measured using electroencephalography (EEG) to indicate brain electrical activity of subjects during memory/cognitive tests. MCI patients showed higher scores of physical neglect and lower scores of emotional abuse in childhood than control group. Physical neglect score was negatively correlated with scores of MMSE, MoCA, episodic memory, calculation, and the amplitude of CzP300, FzP300 and PzP300, while a positive correlation was seen between the score of physical neglect and the latency of PzN200, FzN200, CzN200, CzP300, FzP300 and PzP300. The score of emotional abuse was weakly correlated with FzP300 amplitude, but not with any other ERP components. Our results suggested that early childhood exposure to physical neglect may lead to impairment in learning and memory, particularly in the associative learning and episodic memory, in old age. PMID:27236588

  7. Inter- and intra-specimen variability masks reliable temperature control on shell Mg/Ca ratios in laboratory- and field-cultured Mytilus edulis and Pecten maximus (bivalvia)

    NASA Astrophysics Data System (ADS)

    Freitas, P. S.; Clarke, L. J.; Kennedy, H. A.; Richardson, C. A.

    2008-09-01

    The Mg/Ca ratios of biogenic calcite is commonly seen as a valuable palaeo-proxy for reconstructing past ocean temperatures. The temperature dependence of Mg/Ca ratios in bivalve calcite has been the subject of contradictory observations. The palaeoceanographic use of a geochemical proxy is dependent on initial, rigorous calibration and validation of relationships between the proxy and the ambient environmental variable to be reconstructed. Shell Mg/Ca ratio data are reported for the calcite of two bivalve species, Mytilus edulis (common mussel) and Pecten maximus (king scallop), which were grown in laboratory culturing experiments at controlled and constant aquarium seawater temperatures over a range from ~10 to ~20°C. Furthermore, Mg/Ca ratio data of laboratory- and field-grown M. edulis specimens were compared. Only a weak, albeit significant, shell Mg/Ca ratio temperature relationship was observed in the two bivalve species: M. edulis (r2=0.37, p<0.001 for laboratory-cultured specimens and r2=0.50, p<0.001 for field-cultured specimens) and P. maximus (r2=0.21, p<0.001 for laboratory-cultured specimens only). In the two species, shell Mg/Ca ratios were not found to be controlled by shell growth rate or salinity. The Mg/Ca ratios in the shells exhibited a large degree of variability among and within species and individuals. The results suggest that the use of bivalve calcite Mg/Ca ratios as a temperature proxy is limited, at least in the species studied to date. Such limitations are most likely due to the presence of physiological effects on Mg incorporation in bivalve calcite. The utilization is further limited by the great variability both within and among shells of the same species that were precipitated under the same ambient conditions.

  8. 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

  9. 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. PMID:24587224

  10. The Effect of Paternal Age on Offspring Intelligence and Personality when Controlling for Parental Trait Levels

    PubMed Central

    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. PMID:24587224

  11. The STIM1-Orai1 pathway of store-operated Ca2+ entry controls the checkpoint in cell cycle G1/S transition

    PubMed Central

    Chen, Yun-Wen; Chen, Yih-Fung; Chen, Ying-Ting; Chiu, Wen-Tai; Shen, Meng-Ru

    2016-01-01

    Ca2+ signaling is important to trigger the cell cycle progression, while it remains elusive in the regulatory mechanisms. Here we show that store-operated Ca2+ entry (SOCE), mediated by the interaction between STIM1 (an endoplasmic reticulum Ca2+ sensor) and Orai1 (a cell membrane pore structure), controls the specific checkpoint of cell cycle. The fluctuating SOCE activity during cell cycle progression is universal in different cell types, in which SOCE is upregulated in G1/S transition and downregulated from S to G2/M transition. Pharmacological or siRNA inhibition of STIM1-Orai1 pathway of SOCE inhibits the phosphorylation of CDK2 and upregulates the expression of cyclin E, resulting in autophagy accompanied with cell cycle arrest in G1/S transition. The subsequently transient expression of STIM1 cDNA in STIM1−/− MEF rescues the phosphorylation and nuclear translocation of CDK2, suggesting that STIM1-mediated SOCE activation directly regulates CDK2 activity. Opposite to the important role of SOCE in controlling G1/S transition, the downregulated SOCE is a passive phenomenon from S to G2/M transition. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for the Ca2+ sensitivity controlling G1/S transition. PMID:26917047

  12. 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

  13. 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. PMID:26413894

  14. 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

  15. 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

  16. 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.

  17. Hf W mineral isochron for Ca,Al-rich inclusions: Age of the solar system and the timing of core formation in planetesimals

    NASA Astrophysics Data System (ADS)

    Burkhardt, Christoph; Kleine, Thorsten; Bourdon, Bernard; Palme, Herbert; Zipfel, Jutta; Friedrich, Jon M.; Ebel, Denton S.

    2008-12-01

    Application of 182Hf- 182W chronometry to constrain the duration of early solar system processes requires the precise knowledge of the initial Hf and W isotope compositions of the solar system. To determine these values, we investigated the Hf-W isotopic systematics of bulk samples and mineral separates from several Ca,Al-rich inclusions (CAIs) from the CV3 chondrites Allende and NWA 2364. Most of the investigated CAIs have relative proportions of 183W, 184W, and 186W that are indistinguishable from those of bulk chondrites and the terrestrial standard. In contrast, one of the investigated Allende CAIs has a lower 184W/ 183W ratio, most likely reflecting an overabundance of r-process relative to s-process isotopes of W. All other bulk CAIs have similar 180Hf/ 184W and 182W/ 184W ratios that are elevated relative to average carbonaceous chondrites, probably reflecting Hf-W fractionation in the solar nebula within the first ˜3 Myr. The limited spread in 180Hf/ 184W ratios among the bulk CAIs precludes determination of a CAI whole-rock isochron but the fassaites have high 180Hf/ 184W and radiogenic 182W/ 184W ratios up to ˜14 ɛ units higher than the bulk rock. This makes it possible to obtain precise internal Hf-W isochrons for CAIs. There is evidence of disturbed Hf-W systematics in one of the CAIs but all other investigated CAIs show no detectable effects of parent body processes such as alteration and thermal metamorphism. Except for two fractions from one Allende CAI, all fractions from the investigated CAIs plot on a single well-defined isochron, which defines the initial ɛ 182W = -3.28 ± 0.12 and 182Hf/ 180Hf = (9.72 ± 0.44) × 10 -5 at the time of CAI formation. The initial 182Hf/ 180Hf and 26Al/ 27Al ratios of the angrites D'Orbigny and Sahara 99555 are consistent with the decay from initial abundances of 182Hf and 26Al as measured in CAIs, suggesting that these two nuclides were homogeneously distributed throughout the solar system. However, the

  18. 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.

  19. 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

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

    2016-01-01

    Several neuropsychiatric disorders are associated with cognitive and social dysfunction. Postmortem studies of patients with schizophrenia have revealed specific changes in area CA2, a long-overlooked 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-expressing interneurons, a reduction in the amount of feedforward 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

  20. PKC-mediated inhibitory feedback of the cholecystokinin 1 receptor controls the shape of oscillatory Ca²⁺ signals.

    PubMed

    Willems, Peter H G M; Pahle, Jürgen; Stalpers, Xenia L; Mugahid, Douaa; Nikolaew, Alexander; Koopman, Werner J H; Kummer, Ursula

    2015-06-01

    Translation of extracellular hormonal input into cellular responses is often mediated by repetitive increases in cytosolic free Ca(2+) concentration ([Ca(2+) ]c ). Amplitude, duration and frequency of these so-called [Ca(2+) ]c oscillations then carry information about the nature and concentration of the extracellular signalling molecule. At present, there are different hypotheses concerning the induction and control of these oscillations. Here, we investigated the role of agonist-induced receptor phosphorylation in this process using Chinese hamster ovary cells stably expressing a variant of the cholecystokinin 1 receptor (CCK1R) lacking the four consensus sites for protein kinase C (PKC) phosphorylation and deficient in CCK-induced receptor phosphorylation (CCK1R-mt cells). In the presence of cholecystokinin-(26-33)-peptide amide (CCK-8), these cells displayed Ca(2+) oscillations with a much more pronounced bursting dynamics rather than the dominant spiking dynamics observed in Chinese hamster ovary cells stably expressing the wild-type CCK1R. The bursting behaviour returned to predominantly spiking behaviour following removal of extracellular Ca(2+) , suggesting that CCK-8-induced, PKC-mediated CCK1R phosphorylation inhibits Ca(2+) influx across the plasma membrane. To gain mechanistic insight into the underlying mechanism we developed a mathematical model able to reproduce the experimental observations. From the model we conclude that binding of CCK-8 to the CCK1R leads to activation of PKC which subsequently phosphorylates the receptor to inhibit the receptor-mediated influx of Ca(2+) across the plasma membrane. Receptor-specific differences in this feedback mechanism may, at least in part, explain the observation that different agonists evoke [Ca(2+) ]c oscillations with different kinetics in the same cell type. PMID:25779353

  1. The effect of aging on fronto-striatal reactive and proactive inhibitory control.

    PubMed

    Kleerekooper, Iris; van Rooij, Sanne J H; van den Wildenberg, Wery P M; de Leeuw, Max; Kahn, Rene S; Vink, Matthijs

    2016-05-15

    Inhibitory control, like most cognitive processes, is subject to an age-related decline. The effect of age on neurofunctional inhibition processing remains uncertain, with age-related increases as well as decreases in activation being reported. This is possibly because reactive (i.e., outright stopping) and proactive inhibition (i.e., anticipation of stopping) have not been evaluated separately. Here, we investigate the effects of aging on reactive as well as proactive inhibition, using functional MRI in 73 healthy subjects aged 30-70years. We found reactive inhibition to slow down with advancing age, which was paralleled by increased activation in the motor cortex. Behaviorally, older adults did not exercise increased proactive inhibition strategies compared to younger adults. However, the pattern of activation in the right inferior frontal gyrus (rIFG) showed a clear age-effect on proactive inhibition: rather than flexibly engaging the rIFG in response to varying stop-signal probabilities, older subjects showed an overall hyperactivation. Whole-brain analyses revealed similar hyperactivations in various other frontal and parietal brain regions. These results are in line with the neural compensation hypothesis of aging: processing becomes less flexible and efficient with advancing age, which is compensated for by overall enhanced activation. Moreover, by disentangling reactive and proactive inhibition, we can show for the first time that the age-related increase in activation during inhibition that is reported generally by prior studies may be the result of compensation for reduced neural flexibility related to proactive control strategies. PMID:26899783

  2. Age-related changes in executive control and their relationships with activity performance in handwriting.

    PubMed

    Rosenblum, Sara; Engel-Yeger, Batya; Fogel, Yael

    2013-04-01

    Deterioration in the frontal and prefrontal cortex associated with executive functions (EF) occurs with age and may be associated with changes in daily performance. The aim of the present study was to describe changes occurring with age in Executive Functions (EF) and handwriting activity, as well as to analyze relationships between age, EF and handwriting performance. The study population included 80 healthy participants (aged 31 to 76+) living in the community. After answering five questions about their writing habits, the participants completed the Behavioral Assessment of the Dysexecutive Syndrome (BADS). In addition, they performed a handwriting task on a digitizer included in the Computerized Penmanship Evaluation Tool (ComPET), which provides kinematic measures of the handwriting process. Significant differences were found between the four age groups for both EF and temporal and spatial handwriting measures. A series of regressions indicated that age predicted 35% of the variance of the BADS profile score (EF control) and 32% of the variance of in-air time while writing. The results of this study indicated age effect on both EF control and handwriting performance. Possible implications for further research and clinical evaluation and intervention are discussed. PMID:23558056

  3. αCaMKII autophosphorylation controls the establishment of alcohol-induced conditioned place preference in mice.

    PubMed

    Easton, Alanna C; Lucchesi, Walter; Mizuno, Keiko; Fernandes, Cathy; Schumann, Gunter; Giese, K Peter; Müller, Christian P

    2013-09-01

    The autophosphorylation of alpha Ca2+ /calmodulin dependent protein kinase II (αCaMKII) is important for memory formation and is becoming increasingly implicated in the development of drug addiction. Previous work suggests that αCaMKII acts via the monoaminergic systems to facilitate the establishment of alcohol drinking behaviour. The present study aims to investigate whether αCaMKII autophosphorylation deficient αCaMKII(T286A) mice show a difference in the rewarding properties of alcohol (2 g/kg, i.p.), as measured by conditioned place preference (CPP). We found that alcohol-induced CPP could be established at an accelerated rate in αCaMKII(T286A) compared to wild type (WT) mice. Hyperactivity/hyper-arousal induced by the test environment was normalised by alcohol in the αCaMKII(T286A), but not WT mice. This effect could be conditioned to the test environment and may suggest enhanced negative reinforcing action of alcohol in αCaMKII autophosphorylation deficient mice. PMID:23732653

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

    PubMed

    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

    2011-04-01

    In blood vessels, tone is maintained by agonist-induced cytosolic Ca(2+) 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 Ca(2+) 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 Ca(2+) transient and the resulting down-stream signaling pathway. Indeed, restoring SERCA2a expression by gene transfer in synthetic hCASMCs 1) increased Ca(2+) storage capacity; 2) modified agonist-induced IP(3)R Ca(2+) release from steady-state to oscillatory mode (the frequency of agonist-induced IP(3)R Ca(2+) signal was 11.66 ± 1.40/100 s in SERCA2a-expressing cells (n=39) vs 1.37 ± 0.20/100 s in control cells (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 Ca(2+) transients have different effects on calcium-dependent physiological functions in smooth muscle cells. PMID:21195084

  5. 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

  6. Evaluation of the biogeochemical controls on B/Ca of Globigerinoides ruber white from the Oceanic Flux Program, Bermuda

    NASA Astrophysics Data System (ADS)

    Babila, Tali L.; Rosenthal, Yair; Conte, Maureen H.

    2014-10-01

    Boron to calcium (B/Ca) ratios in planktonic foraminifera is suggested to be a proxy for the surface oceanic carbonate system. The reliability of the proxy has been questioned due to conflicting reports from culture and sediment calibrations on the influence of temperature on B/Ca. To assess this issue, B/Ca and Mg/Ca ratios and δO18 were measured in tests of the symbiont-bearing surface dwelling planktonic foraminifer Globigerinoides ruber white collected by the Oceanic Flux Program (OFP) time series sediment traps, located approximately 75 km SE of Bermuda. B/Ca ratios in the 300-400 μm size fraction of G. ruber were approximately 10-20% higher than those in the 200-300 μm size fraction. In contrast, Mg/Ca ratios and δO18 values do not exhibit any relationship to test size, which indicates that the size effect observed for B/Ca is not due to differences in depth habitat but to vital effects. Seasonal variation in the B/Ca ratio was similar in both size fractions and ranged by ∼20-30 μmol/mol. This range is larger than that predicted by seasonal variations in seawater [B(OH)-4/HCO-3], the proposed boron species incorporated into planktonic foraminiferal calcite, and indicates that B/Ca in G. ruber is influenced by an additional variable (s). The seasonal cycle of B/Ca in G. ruber white was more strongly correlated with light intensity than with temperature. Both observations suggest that the presence of symbionts in G. ruber and seasonal variability in their photosynthetic activity act to modify the internal pH during calcification, by up to ∼0.2 units relative to ambient seawater.

  7. 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

  8. 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. PMID:24252727

  9. 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

  10. The Role of Neuromuscular Changes in Aging and Knee Osteoarthritis on Dynamic Postural Control

    PubMed Central

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

    2013-01-01

    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. PMID:23696951

  11. Inhibitory Control in Pediatric Trichotillomania (Hair Pulling Disorder): The Importance of Controlling for Age and Symptoms of Inattention and Hyperactivity.

    PubMed

    Brennan, Elle; Francazio, Sarah; Gunstad, John; Flessner, Christopher

    2016-04-01

    Trichotillomania (hair pulling disorder, HPD) is characterized by significant psychological distress, childhood-onset, and, in adults, certain cognitive deficits such as inhibitory control. A total absence of such literature exists within pediatric HPD samples, including research investigating neurocognitive aspects of disparate pulling-styles. The present study aims to address these gaps in the literature. Youth with HPD and healthy controls (N = 45) were compared on an automated neurocognitive task-stop-signal task (SST)-assessing inhibitory control. Youth with HPD (n = 17), controlling for age and attention issues, were found to perform better on the stop-signal reaction time compared to controls (n = 28). No significant relationships between performance on the SST and HPD severity, distress/impairment, or pulling-styles were noted. Findings from the current study suggest that children with HPD may not exhibit deficits in motor inhibition as compared to controls when the effects of age and attentional problems are controlled. PMID:26001984

  12. Controllable synthesis and luminescent properties of three-dimensional nanostructured CaWO4:Tb3+ microspheres.

    PubMed

    Tian, Yue; Chen, Baojiu; Yu, Hongquan; Hua, Ruinian; Li, Xiangping; Sun, Jiashi; Cheng, Lihong; Zhong, Haiyang; Zhang, Jinsu; Zheng, Yanfeng; Yu, Tingting; Huang, Libo

    2011-08-15

    Three-dimensional (3D) nanostructured CaWO(4):Tb(3+)microspheres assembled by submicrospindles were synthesized via a mild sonochemical route from an aqueous solution of CaCl(2), TbCl(3) and Na(2)WO(4) with the aid of surfactant Polyglycol 600 (PEG-600). The crystal structure and morphology of the as-prepared products were characterized by using X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM). Rietveld refinement was carried out on the XRD data. The results showed that the CaWO(4):Tb(3+)nanoparticles can be formed without ultrasonic irradiation or addition of PEG-600. With continuously increasing irradiation time the submicrospindles and microspheres could be self-assembled. The central diameter and length of the submicrospindles are around 190 and 500 nm, respectively. The 3D CaWO(4):Tb(3+)nanostructured microspheres with diameter of 2-4 μm were assembled by the submicrospindles. A possible formation mechanism for the 3D-structured CaWO(4):Tb(3+)microspheres was proposed. The Photoluminescent (PL) properties of Tb(3+) ions in the nanostructured CaWO(4) microspheres were studied. The energy transfer processes in CaWO(4):Tb(3+)microspheres were analyzed. The electric dipole-dipole energy transfers related to (5)D(3) level were studied by inspecting the fluorescence decay of (5)D(3) level. The energy transfer critical distance was estimated. PMID:21621217

  13. Structure of a Ca2+-Myristoyl Switch Protein That Controls Activation of a Phosphatidylinositol 4-Kinase in Fission Yeast*

    PubMed Central

    Lim, Sunghyuk; Strahl, Thomas; Thorner, Jeremy; Ames, James B.

    2011-01-01

    Neuronal calcium sensor (NCS) proteins transduce Ca2+ signals and are highly conserved from yeast to humans. We determined NMR structures of the NCS-1 homolog from fission yeast (Ncs1), which activates a phosphatidylinositol 4-kinase. Ncs1 contains an α-NH2-linked myristoyl group on a long N-terminal arm and four EF-hand motifs, three of which bind Ca2+, assembled into a compact structure. In Ca2+-free Ncs1, the N-terminal arm positions the fatty acyl chain inside a cavity near the C terminus. The C14 end of the myristate is surrounded by residues in the protein core, whereas its amide-linked (C1) end is flanked by residues at the protein surface. In Ca2+-bound Ncs1, the myristoyl group is extruded (Ca2+-myristoyl switch), exposing a prominent patch of hydrophobic residues that specifically contact phosphatidylinositol 4-kinase. The location of the buried myristate and structure of Ca2+-free Ncs1 are quite different from those in other NCS proteins. Thus, a unique remodeling of each NCS protein by its myristoyl group, and Ca2+-dependent unmasking of different residues, may explain how each family member recognizes distinct target proteins. PMID:21288895

  14. 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

  15. Self-control forecasts better psychosocial outcomes but faster epigenetic aging in low-SES youth.

    PubMed

    Miller, Gregory E; Yu, Tianyi; Chen, Edith; Brody, Gene H

    2015-08-18

    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

  16. 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

  17. Effect of aging upon CE and B and W control rod drives

    SciTech Connect

    Grove, E.; Gunther, W.

    1992-01-01

    The effect of aging upon the Babcock Wilcox (B W) and Combustion Engineering (CE) Control Rod Drive (CRD) systems has been evaluated as part of the US NRC Nuclear Plant Aging Research (NPAR) program. Operating experience data for the 1980--1990 time period was reviewed to identify predominant failure modes, causes, and effects. These results, in conjunction with an assessment of component materials and operating environment, conclude that both systems are susceptible to age degradation. System failures have resulted in significant plant effects, including power reductions, plant shutdowns, scrams, and Engineered Safety Feature (ESF) actuation. Current industry inspection and maintenance practices were assessed. Some of these practices effectively address aging, while others do not.

  18. Effect of aging upon CE and B and W control rod drives

    SciTech Connect

    Grove, E.; Gunther, W.

    1992-05-01

    The effect of aging upon the Babcock & Wilcox (B&W) and Combustion Engineering (CE) Control Rod Drive (CRD) systems has been evaluated as part of the US NRC Nuclear Plant Aging Research (NPAR) program. Operating experience data for the 1980--1990 time period was reviewed to identify predominant failure modes, causes, and effects. These results, in conjunction with an assessment of component materials and operating environment, conclude that both systems are susceptible to age degradation. System failures have resulted in significant plant effects, including power reductions, plant shutdowns, scrams, and Engineered Safety Feature (ESF) actuation. Current industry inspection and maintenance practices were assessed. Some of these practices effectively address aging, while others do not.

  19. 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. PMID:25105541

  20. 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.

  1. Exposure age and climate controls on weathering in deglaciated watersheds of western Greenland

    NASA Astrophysics Data System (ADS)

    Scribner, C. A.; Martin, E. E.; Martin, J. B.; Deuerling, K. M.; Collazo, D. F.; Marshall, A. T.

    2015-12-01

    Fine-grained sediments deposited by retreating glaciers weather faster than the global average and this weathering can impact the global carbon cycle and oceanic fluxes of nutrients and radiogenic isotopes. Much work has focused on subglacial and proglacial weathering of continental ice sheets, but little is known about weathering and resulting fluxes from deglacial watersheds, which are disconnected from the ice sheets and discharge only annual precipitation and permafrost melt. We investigate the effects of exposure age and precipitation on weathering intensity in four deglacial watersheds on Greenland that form a transect from the coast near Sisimiut toward the Greenland Ice Sheet (GrIS) near Kangerlussuaq based on evaluations of major ion compositions, Sr isotope ratios, and mineral saturation states of waters and sediments. The transect is underlain by Archean orthogneiss and is characterized by gradients in moraine ages (∼7.5-8.0 ky inland to ∼10 ky at the coast) and water balance (-150 mm/yr inland to +150 mm/yr at the coast). Anion compositions are generally dominated by HCO3, but SO4 becomes increasingly important toward the coast, reflecting a switch from trace carbonate dissolution to sulfide mineral oxidation. Coastal watersheds have a higher proportion of dissolved silica, higher Na/Cl, Si/Ca, and lower Ca/Sr ratios than inland watersheds, indicating an increase in the relative proportion of silicate weathering and an increase in the extent of weathering toward the coast. More extensive weathering near the coast is also apparent in differences in the 87Sr/86Sr ratios of stream water and bedload (Δ87Sr/86Sr), which decreases from 0.017 inland to 0.005 at the coast, and in increased saturation states relative to amorphous SiO2 and quartz. The steep weathering gradient from inland to coastal watersheds reflects enhanced weathering compared to that expected from the 2 to 3 ky difference in exposure age caused by elevated coastal precipitation. The

  2. 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)

  3. 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…

  4. 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,…

  5. Controlled sumoylation of the mevalonate pathway enzyme HMGS-1 regulates metabolism during aging

    PubMed Central

    Sapir, Amir; Tsur, Assaf; Koorman, Thijs; Ching, Kaitlin; Mishra, Prashant; Bardenheier, Annabelle; Podolsky, Lisa; Bening-Abu-Shach, Ulrike; Boxem, Mike; Chou, Tsui-Fen; Broday, Limor; Sternberg, Paul W.

    2014-01-01

    Many metabolic pathways are critically regulated during development and aging but little is known about the molecular mechanisms underlying this regulation. One key metabolic cascade in eukaryotes is the mevalonate pathway. It catalyzes the synthesis of sterol and nonsterol isoprenoids, such as cholesterol and ubiquinone, as well as other metabolites. In humans, an age-dependent decrease in ubiquinone levels and changes in cholesterol homeostasis suggest that mevalonate pathway activity changes with age. However, our knowledge of the mechanistic basis of these changes remains rudimentary. We have identified a regulatory circuit controlling the sumoylation state of Caenorhabditis elegans HMG-CoA synthase (HMGS-1). This protein is the ortholog of human HMGCS1 enzyme, which mediates the first committed step of the mevalonate pathway. In vivo, HMGS-1 undergoes an age-dependent sumoylation that is balanced by the activity of ULP-4 small ubiquitin-like modifier protease. ULP-4 exhibits an age-regulated expression pattern and a dynamic cytoplasm-to-mitochondria translocation. Thus, spatiotemporal ULP-4 activity controls the HMGS-1 sumoylation state in a mechanism that orchestrates mevalonate pathway activity with the age of the organism. To expand the HMGS-1 regulatory network, we combined proteomic analyses with knockout studies and found that the HMGS-1 level is also governed by the ubiquitin–proteasome pathway. We propose that these conserved molecular circuits have evolved to govern the level of mevalonate pathway flux during aging, a flux whose dysregulation is associated with numerous age-dependent cardiovascular and cancer pathologies. PMID:25187565

  6. 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

  7. 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.

  8. Inhibitory Motor Control in Old Age: Evidence for De-Automatization?

    PubMed Central

    Maylor, Elizabeth Ann; Birak, Kulbir Singh; Schlaghecken, Friederike

    2011-01-01

    To examine age-related effects on high-level consciously controlled and low-level automatically controlled inhibitory processes, the Simon task was combined with the masked prime task in a hybrid procedure. Young and older adults responded to the identity of targets (left/right key-press to left-/right-pointing arrows) that appeared on the left/right of the screen and were preceded by left-/right-pointing backward-masked arrow primes at fixation. Responses were faster and more accurate when the target was congruent with its location than incongruent (Simon effect), and when the target was incompatible with the prime than compatible (negative compatibility effect; NCE). The Simon effect was disproportionately larger, and the NCE disproportionately delayed, in older adults compared to young adults, indicating both high- and low-level inhibitory control deficits with aging. Moreover, the two effects were additive in young adults, but interactive in older adults, providing support for the dedifferentiation hypothesis of aging. Specifically, older adults’ prime-related inhibitory control appeared improved on incongruent relative to congruent trials, suggesting that impaired automatic control was substituted by high-level, non-automatic processes. PMID:21734899

  9. 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…

  10. 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…

  11. Parental Negative Control Moderates the Shyness–Emotion Regulation Pathway to School-Age Internalizing Symptoms

    PubMed Central

    Shaw, Daniel S.; Moilanen, Kristin L.

    2011-01-01

    Models of developmental psychopathology emphasize both mediation and moderation processes among child and caregiving attributes; however, little research has examined both these processes simultaneously on the development of internalizing problems. This study tested a moderated mediation model that related early childhood shyness, emotion regulation and maternal negative control to school-age internalizing problems among 257 boys from low-income families. Shyness and maternal negative control was assessed at ages 1.5–2, emotion regulation was observed at age 3.5, and internalizing symptoms were assessed by mothers and teachers at age 6 or 7. Results indicated that 1) the active distraction regulation strategy mediated the relations between early shyness and maternal report of internalizing symptoms; 2) the passive/dependent regulation strategy mediated the relations between shyness and teacher report of internalizing symptoms; and 3) both mediation processes were moderated by maternal negative control. The results are discussed in relation to implications for early prevention and intervention. PMID:21107676

  12. Age effects on transfer index performance and executive control in baboons (Papio papio)

    PubMed Central

    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. PMID:24624114

  13. The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria.

    PubMed

    Azarashvili, Tamara; Grachev, Dmitry; Krestinina, Olga; Evtodienko, Youri; Yurkov, Igor; Papadopoulos, Vassilios; Reiser, Georg

    2007-07-01

    involvement in PTP opening, controlling the Ca2+-induced Ca2+ efflux, and AIF release from mitochondria, important stages of initiation of programmed cell death. PMID:17174393

  14. Store-Operated Ca2+ Entry Is Remodelled and Controls In Vitro Angiogenesis in Endothelial Progenitor Cells Isolated from Tumoral Patients

    PubMed Central

    Dragoni, Silvia; Bottino, Cinzia; Ong, Hwei Ling; Guerra, Germano; Ganini, Carlo; Massa, Margherita; Manzoni, Mariangela; Ambudkar, Indu S.; Genazzani, Armando A.; Rosti, Vittorio; Pedrazzoli, Paolo; Tanzi, Franco; Moccia, Francesco

    2012-01-01

    Background Endothelial progenitor cells (EPCs) may be recruited from bone marrow to sustain tumor vascularisation and promote the metastatic switch. Understanding the molecular mechanisms driving EPC proliferation and tubulogenesis could outline novel targets for alternative anti-angiogenic treatments. Store-operated Ca2+ entry (SOCE), which is activated by a depletion of the intracellular Ca2+ pool, regulates the growth of human EPCs, where is mediated by the interaction between the endoplasmic reticulum Ca2+-sensor, Stim1, and the plasmalemmal Ca2+ channel, Orai1. As oncogenesis may be associated to the capability of tumor cells to grow independently on Ca2+ influx, it is important to assess whether SOCE regulates EPC-dependent angiogenesis also in tumor patients. Methodology/Principal Findings The present study employed Ca2+ imaging, recombinant sub-membranal and mitochondrial aequorin, real-time polymerase chain reaction, gene silencing techniques and western blot analysis to investigate the expression and the role of SOCE in EPCs isolated from peripheral blood of patients affected by renal cellular carcinoma (RCC; RCC-EPCs) as compared to control EPCs (N-EPCs). SOCE, activated by either pharmacological (i.e. cyclopiazonic acid) or physiological (i.e. ATP) stimulation, was significantly higher in RCC-EPCs and was selectively sensitive to BTP-2, and to the trivalent cations, La3+ and Gd3+. Furthermore, 2-APB enhanced thapsigargin-evoked SOCE at low concentrations, whereas higher doses caused SOCE inhibition. Conversely, the anti-angiogenic drug, carboxyamidotriazole (CAI), blocked both SOCE and the intracellular Ca2+ release. SOCE was associated to the over-expression of Orai1, Stim1, and transient receptor potential channel 1 (TRPC1) at both mRNA and protein level The intracellular Ca2+ buffer, BAPTA, BTP-2, and CAI inhibited RCC-EPC proliferation and tubulogenesis. The genetic suppression of Stim1, Orai1, and TRPC1 blocked CPA-evoked SOCE in RCC

  15. Effects of aging on whole body and segmental control while obstacle crossing under impaired sensory conditions.

    PubMed

    Novak, Alison C; Deshpande, Nandini

    2014-06-01

    The ability to safely negotiate obstacles is an important component of independent mobility, requiring adaptive locomotor responses to maintain dynamic balance. This study examined the effects of aging and visual-vestibular interactions on whole-body and segmental control during obstacle crossing. Twelve young and 15 older adults walked along a straight pathway and stepped over one obstacle placed in their path. The task was completed under 4 conditions which included intact or blurred vision, and intact or perturbed vestibular information using galvanic vestibular stimulation (GVS). Global task performance significantly increased under suboptimal vision conditions. Vision also significantly influenced medial-lateral center of mass displacement, irrespective of age and GVS. Older adults demonstrated significantly greater trunk pitch and head roll angles under suboptimal vision conditions. Similar to whole-body control, no GVS effect was found for any measures of segmental control. The results indicate a significant reliance on visual but not vestibular information for locomotor control during obstacle crossing. The lack of differences in GVS effects suggests that vestibular information is not up-regulated for obstacle avoidance. This is not differentially affected by aging. In older adults, insufficient visual input appears to affect ability to minimize anterior-posterior trunk movement despite a slower obstacle crossing time and walking speed. Combined with larger medial-lateral deviation of the body COM with insufficient visual information, the older adults may be at a greater risk for imbalance or inability to recover from a possible trip when stepping over an obstacle. PMID:24746603

  16. Initiation of metamorphosis and control of ecdysteroid biosynthesis in insects: The interplay of absence of Juvenile hormone, PTTH, and Ca(2+)-homeostasis.

    PubMed

    De Loof, Arnold; Vandersmissen, Tim; Marchal, Elisabeth; Schoofs, Liliane

    2015-06-01

    The paradigm saying that release of the brain neuropeptide big prothoracicotropic hormone (PTTH) initiates metamorphosis by activating the Torso-receptor/ERK pathway in larval prothoracic glands (PGs) is widely accepted nowadays. Upon ligand-receptor interaction Ca(2+) enters the PG cells and acts as a secondary messenger. Ecdysteroidogenesis results, later followed by apoptosis. Yet, some data do not fit in this model. In some species decapitated animals can still molt, even repeatedly, and metamorphose. PTTH does not universally occur in all insect species. PGs may also have other functions; PGs as counterpart of the vertebrate thymus? There are also small PTTHs. Finally, PTTH remains abundantly present in adults and plays a role in control of ecdysteroidogenesis (=sex steroid production) in gonads. This is currently documented only in males. This urges a rethinking of the PTTH-PG paradigm. The key question is: Why does PTTH-induced Ca(2+) entry only result in ecdysteroidogenesis and apoptosis in specific cells/tissues, namely the PGs and gonads? Indeed, numerous other neuropeptides also use Ca(2+) as secondary messenger. The recent rediscovery that in both invertebrates and vertebrates at least some isoforms of Ca(2+)-ATPase need the presence of an endogenous farnesol/juvenile hormone(JH)-like sesquiterpenoid for keeping cytosolic [Ca(2+)]i below the limit of apoptosis-induction, triggered the idea that it is not primarily PTTH, but rather the drop to zero of the JH titer that acts as the primordial initiator of metamorphosis by increasing [Ca(2+)]i. PTTH likely potentiates this effect but only in cells expressing Torso. PTTH: an evolutionarily ancient gonadotropin? PMID:25102449

  17. 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

  18. Visual working memory capacity increases between ages 3 and 8 years, controlling for gains in attention, perception, and executive control.

    PubMed

    Pailian, Hrag; Libertus, Melissa E; Feigenson, Lisa; Halberda, Justin

    2016-08-01

    Research in adults has aimed to characterize constraints on the capacity of Visual Working Memory (VWM), in part because of the system's broader impacts throughout cognition. However, less is known about how VWM develops in childhood. Existing work has reached conflicting conclusions as to whether VWM storage capacity increases after infancy, and if so, when and by how much. One challenge is that previous studies did not control for developmental changes in attention and executive processing, which also may undergo improvement. We investigated the development of VWM storage capacity in children from 3 to 8 years of age, and in adults, while controlling for developmental change in exogenous and endogenous attention and executive control. Our results reveal that, when controlling for improvements in these abilities, VWM storage capacity increases across development and approaches adult-like levels between ages 6 and 8 years. More generally, this work highlights the value of estimating working memory, attention, perception, and decision-making components together. PMID:27225467

  19. 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.

  20. 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.

  1. Prioritization of reactor control components susceptible to fire damage as a consequence of aging

    SciTech Connect

    Lowry, W.; Vigil, R.; Nowlen, S.

    1994-01-01

    The Fire Vulnerability of Aged Electrical Components Test Program is to identify and assess issues of plant aging that could lead to an increase in nuclear power plant risk because of fires. Historical component data and prior analyses are used to prioritize a list of components with respect to aging and fire vulnerability and the consequences of their failure on plant safety systems. The component list emphasizes safety system control components, but excludes cables, large equipment, and devices encompassed in the Equipment Qualification (EQ) program. The test program selected components identified in a utility survey and developed test and fire conditions necessary to maximize the effectiveness of the test program. Fire damage considerations were limited to purely thermal effects.

  2. 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. PMID:25819172

  3. 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.

  4. 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

  5. Age at diagnosis predicts deterioration in glycaemic control among children and adolescents with type 1 diabetes

    PubMed Central

    Clements, Mark A; Lind, Marcus; Raman, Sripriya; Patton, Susana R; Lipska, Kasia J; Fridlington, Amanda G; Tang, Fengming; Jones, Phil G; Wu, Yue; Spertus, John A; Kosiborod, Mikhail

    2014-01-01

    Background Poor glycemic control early in the course of type 1 diabetes mellitus (T1DM) increases the risk for microvascular complications. However, predictors of deteriorating control after diagnosis have not been described, making it difficult to identify high-risk patients and proactively provide aggressive interventions. Objective We examined whether diagnostic age, gender, and race were associated with deteriorating glycemic control during the first 5 years after diagnosis. Participants 2218 pediatric patients with T1DM. Methods We conducted a longitudinal cohort study of pediatric patients with T1DM from the Midwest USA, 1993–2009, evaluating within-patient glycated hemoglobin (HbA1c) trajectories constructed from all available HbA1c values within 5 years of diagnosis. Results 52.6% of patients were male; 86.1% were non-Hispanic Caucasian. The mean diagnostic age was 9.0±4.1 years. The mean number of HbA1c values/year/participant was 2.4±0.9. HbA1c trajectories differed markedly across age groups, with older patients experiencing greater deterioration than their younger counterparts (p<0.001). HbA1c trajectories, stratified by age, varied markedly by race (p for race×diagnostic age <0.001). Non-Hispanic African-American patients experienced higher initial HbA1c (8.7% vs 7.6% (71.6 vs 59.6 mmol/mol); p<0.001), and greater deterioration in HbA1c than non-Hispanic Caucasian patients across diagnostic ages (rise of 2.04% vs 0.99% per year (22.3 vs 10.8 mmol/mol/year); p<0.0001). Conclusions Older diagnostic age and black race are major risk factors for deterioration in glycemic control early in the course of T1DM. These findings can inform efforts to explore the reasons behind these differences and develop preventive interventions for high-risk patients. PMID:25452876

  6. Early psychological intervention in accidentally injured children ages 2–16: a randomized controlled trial

    PubMed Central

    Kramer, Didier N.; Landolt, Markus A.

    2014-01-01

    Background Road traffic accidents (RTA) and burns are frequent events in children. Although many children recover spontaneously, a considerable number develop long-term psychological sequelae. Evidence on early psychological interventions to prevent such long-term problems is still scarce for school-age children and completely lacking for pre-school children. Objectives To evaluate the efficacy of an early two-session cognitive-behavioral intervention in 108 children ages 2–16 after RTAs and burns. Methods Children assessed at risk for the development of posttraumatic stress disorder (PTSD) were randomly assigned to either a control group offered treatment as usual or an intervention group. Primary outcomes were PTSD, behavioral problems, and depression symptoms. Baseline and blinded 3- and 6-month follow-up assessments were conducted. Results In pre-school children, no intervention effects were found. School-age children in the intervention group exhibited significantly fewer internalizing problems at 3-month follow-up relative to controls and a borderline significant time-by-group effect for PTSD intrusion symptoms was found (p=0.06). Conclusions This is the first study examining the efficacy of an indicated, early psychological intervention among both school-age and pre-school-age children. Because the intervention was ineffective for young children, no evidence-based practice can currently be suggested. Given that parents of pre-school children perceived the intervention as helpful, brief counseling of parents in terms of psychoeducation and training in coping skills still should be provided by clinicians, despite the current lack of evidence. To prevent trauma-related disorders in school-age children, the intervention might be used in a step-wise manner, where only children at risk for long-term psychological maladjustment are provided with psychological support. PMID:24987498

  7. WormFarm: a quantitative control and measurement device toward automated Caenorhabditis elegans aging analysis.

    PubMed

    Xian, Bo; Shen, Jie; Chen, Weiyang; Sun, Na; Qiao, Nan; Jiang, Dongqing; Yu, Tao; Men, Yongfan; Han, Zhijun; Pang, Yuhong; Kaeberlein, Matt; Huang, Yanyi; Han, Jing-Dong J

    2013-06-01

    Caenorhabditis elegans is a leading model organism for studying the basic mechanisms of aging. Progress has been limited, however, by the lack of an automated system for quantitative analysis of longevity and mean lifespan. To address this barrier, we developed 'WormFarm', an integrated microfluidic device for culturing nematodes. Cohorts of 30-50 animals are maintained throughout their lifespan in each of eight separate chambers on a single WormFarm polydimethylsiloxane chip. Design features allow for automated removal of progeny and efficient control of environmental conditions. In addition, we have developed computational algorithms for automated analysis of video footage to quantitate survival and other phenotypes, such as body size and motility. As proof-of-principle, we show here that WormFarm successfully recapitulates survival data obtained from a standard plate-based assay for both RNAi-mediated and dietary-induced changes in lifespan. Further, using a fluorescent reporter in conjunction with WormFarm, we report an age-associated decrease in fluorescent intensity of GFP in transgenic worms expressing GFP tagged with a mitochondrial import signal under the control of the myo-3 promoter. This marker may therefore serve as a useful biomarker of biological age and aging rate. PMID:23442149

  8. Antifatigue Effects of Panax ginseng C.A. Meyer: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Yoo, Sa-Ra; Lee, Jin-Seok; Han, Jong-Min; Lee, Nam-Hun; Ahn, Yo-Chan; Son, Chang-Gue

    2013-01-01

    The present study investigated the antifatigue effects of Panax ginseng C.A. Meyer in 90 subjects (21 men and 69 women) with idiopathic chronic fatigue (ICF) in a randomised, double-blind, placebo-controlled and parallel designed trial. A bespoke 20% ethanol extract of P. ginseng (1 g or 2 g day–1) or a placebo was administered to each group for 4 weeks, and then fatigue severity was monitored using a self-rating numeric scale (NRS) and a visual analogue scale (VAS) as a primary endpoint. Serum levels of reactive oxygen species (ROS), malondialdehyde (MDA), total glutathione (GSH) contents and glutathione reductase (GSH-Rd) activity were determined. After 4-week, P. ginseng administration decreased the total NRS score, but they were not statistically significant compared with placebo (P>0.05). Mental NRS score was significantly improved by P. ginseng administrations as 20.4±5.0 to 15.1±6.5 [95% CI 2.3∼8.2] for 1 g and 20.7±6.3 to 13.8±6.2 [95% CI −0.1∼4.2] for 2 g compared with placebo 20.9±4.5 to 18.8±2.9 [95% CI 4.1∼9.9, P<0.01]. Only 2 g P. ginseng significantly reduced the VAS score from 7.3±1.3 to 4.4±1.8 [95% CI 0.7∼1.8] compared with the placebo 7.1±1.0 to 5.8±1.3 [95% CI 2.2 ∼3.7, P<0.01]. ROS and MDA levels were lowered by P. ginseng compared to placebo. P. ginseng 1 g increased GSH concentration and GSH-Rd activity. Our results provide the first evidence of the antifatigue effects of P. ginseng in patients with ICF, and we submit that these changes in antioxidant properties contribute in part to its mechanism. Trial Registration Clinical Research Information Service (CRIS) KCT0000048 PMID:23613825

  9. Optimal control for an age-structured model for the transmission of hepatitis B.

    PubMed

    Djidjou Demasse, Ramses; Tewa, Jean-Jules; Bowong, Samuel; Emvudu, Yves

    2016-08-01

    One of the characteristics of HBV transmission is the age structure of the host population and the vertical transmission of the disease. That is the infection is transmitted directly from infected mother to an embryo, fetus, or baby during pregnancy or childbirth (the perinatal infection). We formulated an age-structured model for the transmission dynamics of HBV with differential infectivity: symptomatic and asymptomatic infections. The model without intervention strategies is completely analyzed. We compute the basic reproduction number which determines the outcome of the disease. We also compute equilibria and study their stability. The sensitivity analysis of the initial model parameters is performed (to determine the impact of control-related parameters on outbreak severity). Using optimal control theory, we determine the cost-effective balance of three interventions methods which minimizes HBV-related deaths as well as the costs associated with intervention. PMID:26676356

  10. 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. PMID:18462745

  11. 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).

  12. Effects of incentives, age, and behavior on brain activation during inhibitory control: A longitudinal fMRI study

    PubMed Central

    Paulsen, David J.; Hallquist, Michael N.; Geier, Charles F.; Luna, Beatriz

    2014-01-01

    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 × 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. PMID:25284272

  13. 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. PMID:25902870

  14. 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

  15. 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. PMID:26020580

  16. 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…

  17. 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

  18. Theory of mind, inhibitory control, and preschool-age children's suggestibility in different interviewing contexts.

    PubMed

    Scullin, Matthew H; Bonner, Karri

    2006-02-01

    The current study examined the relations among 3- to 5-year-olds' theory of mind, inhibitory control, and three measures of suggestibility: yielding to suggestive questions (yield), shifting answers in response to negative feedback (shift), and accuracy in response to misleading questions during a pressured interview about a live event. Theory of mind aided in the prediction of suggestibility about the live event, and inhibitory control was a moderator variable affecting the consistency of children's sensitivity to social pressure across situations. The findings indicate that theory of mind and inhibitory control predict children's suggestibility about a live event above and beyond yield, shift, and age and that the construct validity of shift may improve as children's inhibitory control develops. PMID:16236306

  19. Age differences in the functional interactions among the default, frontoparietal control, and dorsal attention networks.

    PubMed

    Grady, Cheryl; Sarraf, Saman; Saverino, Cristina; Campbell, Karen

    2016-05-01

    Older adults typically show weaker functional connectivity (FC) within brain networks compared with young adults, but stronger functional connections between networks. Our primary aim here was to use a graph theoretical approach to identify age differences in the FC of 3 networks-default mode network (DMN), dorsal attention network, and frontoparietal control (FPC)-during rest and task conditions and test the hypothesis that age differences in the FPC would influence age differences in the other networks, consistent with its role as a cognitive "switch." At rest, older adults showed lower clustering values compared with the young, and both groups showed more between-network connections involving the FPC than the other 2 networks, but this difference was greater in the older adults. Connectivity within the DMN was reduced in older compared with younger adults. Consistent with our hypothesis, between-network connections of the FPC at rest predicted the age-related reduction in connectivity within the DMN. There was no age difference in within-network FC during the task (after removing the specific task effect), but between-network connections were greater in older adults than in young adults for the FPC and dorsal attention network. In addition, age reductions were found in almost all the graph metrics during the task condition, including clustering and modularity. Finally, age differences in between-network connectivity of the FPC during both rest and task predicted cognitive performance. These findings provide additional evidence of less within-network but greater between-network FC in older adults during rest but also show that these age differences can be altered by the residual influence of task demands on background connectivity. Our results also support a role for the FPC as the regulator of other brain networks in the service of cognition. Critically, the link between age differences in inter-network connections of the FPC and DMN connectivity, and the link

  20. 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...

  1. Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling.

    PubMed

    Reilly, Louise; Howie, Jacqueline; Wypijewski, Krzysztof; Ashford, Michael L J; Hilgemann, Donald W; Fuller, William

    2015-11-01

    The electrogenic Na/Ca exchanger (NCX) mediates bidirectional Ca movements that are highly sensitive to changes of Na gradients in many cells. NCX1 is implicated in the pathogenesis of heart failure and a number of cardiac arrhythmias. We measured NCX1 palmitoylation using resin-assisted capture, the subcellular location of yellow fluorescent protein-NCX1 fusion proteins, and NCX1 currents using whole-cell voltage clamping. Rat NCX1 is substantially palmitoylated in all tissues examined. Cysteine 739 in the NCX1 large intracellular loop is necessary and sufficient for NCX1 palmitoylation. Palmitoylation of NCX1 occurs in the Golgi and anchors the NCX1 large regulatory intracellular loop to membranes. Surprisingly, palmitoylation does not influence trafficking or localization of NCX1 to surface membranes, nor does it strongly affect the normal forward or reverse transport modes of NCX1. However, exchangers that cannot be palmitoylated do not inactivate normally (leading to substantial activity in conditions when wild-type exchangers are inactive) and do not promote cargo-dependent endocytosis that internalizes 50% of the cell surface following strong G-protein activation or large Ca transients. The palmitoylated cysteine in NCX1 is found in all vertebrate and some invertebrate NCX homologs. Thus, NCX palmitoylation ubiquitously modulates Ca homeostasis and membrane domain function in cells that express NCX proteins. PMID:26174834

  2. 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. PMID:25231503

  3. Controls on the Flux, Age, and Composition of Terrestrial Organic Carbon Exported by Rivers to the Ocean

    NASA Astrophysics Data System (ADS)

    Galy, Valier; Peucker-Ehrenbrink, Bernhard; Eglinton, Timothy; Holmes, Robert; Soule, Adam; Goetz, Scott; Laporte, Nadine; Wollheim, Wilfred

    2010-05-01

    Export of organic carbon, alkalinity and silicate-derived Ca and Mg ions to the ocean exerts critical controls on the sequestration of atmospheric carbon. As this export is mediated to a significant extent by river systems, understanding processes that control transport of land-derived matter to the coastal ocean is of fundamental importance to successful models of past and future climates. Scientists from the Woods Hole Oceanographic Institution, the Woods Hole Research Center and the University of New Hampshire have formed a river research consortium that aims at investigating large river systems with a holistic approach. The National Science Foundation is funding this initiative through its Emerging Topics in Biogeochemical Cycles (ETBC) program. Our project focuses on the biogeochemistries of the Lena and Kolyma rivers in the Russian Arctic, the Yangtze river in China, the Ganges and Brahmaputra rivers in India and Bangladesh, the Congo river in central Africa as well as the Fraser river basin in western Canada. Campaign-style sampling using a uniform sampling strategy is complemented by time-series sampling that is accomplished through collaborations with scientists at local institutions such as the East China Normal University in Shanghai (Yangtze), the University of the Fraser Valley in Abbotsford (Fraser), schools and research institutions in eastern Russia (Lena and Kolyma) and the University of Nancy, France (Ganges, Brahmaputra). We combine a standardized sampling approach for organic and inorganic constituents with spatial analyzes of digital, mostly satellite-based data products with the aim of obtaining an integrated understanding of the response of river ecosystems to past, ongoing and future environmental changes. We will present first results with a special emphasis on the age of terrestrial organic carbon exported by the Ganges-Brahmaputra river system.

  4. The prevalence of lacunar infarct decreases with aging in the elderly: a case-controlled analysis

    PubMed Central

    Cai, Zhiyou; He, Wenbo; Peng, Chuan-yong; Zhou, Jin; Xu, Qi-lan; Wu, Zong-shan

    2016-01-01

    Background and purpose Lacunar infarct (LI) is well known as a heterogeneous primary disorder of cerebral small vessel. Compelling results have demonstrated that age is a risk factor to the prevalence of LI. However, the relationship between age and the prevalence of LI remains obscure. It is essential to note the relationship between age and the prevalence of LI through more clinical data. Methods A total of 3,500 patients were included in the case-controlled study. All data were collected from the Examination Center of Magnetic Resonance Imaging, Lu’an People’s Hospital from January 2014 to December 2015. A primary discharge diagnosis of LI was done, and all subjects were evaluated as retrospective data. The relationship between the risk factors and the prevalence of diabetes and the relationship between age and the prevalence of diabetes was analyzed. A chi-square test was used to analyze the associations between different variables. A one-way analysis of variance was used to test the equality of three or more means at one time by using variances. Statistical significance was defined as a P-value of <0.05. Results The one-way analysis of variance demonstrated that the prevalence of LI increased with age before 60 years and decreased with age after 69 years. The same results were found in both the male and the female subjects. These results showed that the age-related risk factors (hypertension, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking) have no relationship with the prevalence of LI on the basis of age. There is a significant difference among the different age ranges (P=0.0006). Two-tailed P-value (unpaired t-test) showed the mean significant difference between 30–39 years and 40–49 years (P=0.009) and between 70–79 years and 80–100 years (P=0.0196). F-test (to compare variances) demonstrated that the variances of the different age ranges are significantly different between 30–39 years and 40–49 years (P=0

  5. Age at marriage and fertility in Java-Bali, a question of natural or controlled fertility.

    PubMed

    Adioetomo, S M

    1983-12-01

    Controlled fertility, as defined by Henry (1961), is fertility achieved in a stituation where the behavior of couples is bound to parity, that is the number of children they aim to have, while natural fertility is a fertility achieved under the absence of deliberate birth control practices. Based on this definition, the fertility of women in Java-Bali aged 40 years and over in 1976 was examined. Age at 1st marriage of the Java-Bali women was examined in relation to their subsequent fertility following their 1st marriage, namely, their 1st birth interval, their ages at the birth of their 1st child, intervals between births (up to the 4th birth), and their estimated age at completion of childbearing. The data used were derived from the 1976 Indonesia Fertility Survey. This examination of the impact of age at marriage on fertility produced evidence of a natural fertility situation. Women who married before their 15th birthday had, on the average, twice as many children as those who married at age 25 years or older. The differences in the mean number of children ever born between women who married at ages 15-17, 18-19, 20-21, and 20-24 were small. A marked decline was shown among the women who married at age 25 or older. Women who married before their 15th birthday had the longest 1st birth interval of 44.1 months. The interval then decreased with increasing age at marriage with the lowest birth interval reached by the women married at ages 22-24 years old. The interval rose again for women married at 25 years or older. Examination of the subsequent births yielded the impression that women who married older tended to have their children in rapid succession and thus reached the 4th birth quicker than those who married younger. This evidence is not indicative of Henry's catching up effect but rather an indication of peak level of fecundity in the early years of marriage for those who married older. The examination of the estimated age at completion of childbearing and

  6. 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.

  7. SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-evoked granule recruitment.

    PubMed

    Iezzi, Mariella; Theander, Sten; Janz, Roger; Loze, Chantal; Wollheim, Claes B

    2005-12-01

    Synaptic vesicle protein 2 (SV2) is expressed in neuroendocrine cells as three homologous isoforms, SV2A, SV2B and SV2C. Ca2+-dependent function in exocytosis has been attributed to SV2A and SV2B, without elucidation of the mechanism. The role of SV2C has not yet been addressed. Here we characterize the three SV2 isoforms and define their involvement in regulated insulin secretion. SV2A and SV2C are associated with insulin-containing granules and synaptic-like-microvesicles (SLM) in INS-1E insulinoma and primary beta-cells, whereas SV2B is only present on SLM. Neither overexpression nor isoform-specific silencing of SV2A or SV2C by RNA interference modifies depolarization-triggered cytosolic [Ca2+] rises or secretory granule [Ca2+], measured with a VAMP-2 aequorin chimera. This strongly argues against any Ca2+ transport function of SV2. Moreover, up- or downregulation of these isoforms has no influence on K+-induced insulin release suggesting that SV2 does not affect the Ca2+-dependent step(s) of exocytosis. By contrast, glucose-elicited secretion is inhibited during the sustained rather than the early phase, placing the action of SV2 on the recruitment of granules from the reserve pool to the plasma membrane. This conclusion is reinforced by capacitance measurements in glucose-stimulated SV2C-deficient cells. Like capacitance, evoked and basal hormone release are attenuated more by silencing of SV2C compared with SV2A. This indicates only partial redundancy and highlights a key role for SV2C in the secretory process. PMID:16306227

  8. Locus of Control, Social Interdependence, Academic Preparation, Age, Study Time, and the Study Skills of College Students.

    ERIC Educational Resources Information Center

    Jones, Craig H.; Slate, John R.; Marini, Irmo

    1995-01-01

    The relationship of students' study skills to their locus of control, social interdependence, academic preparation, age, and study time was studied with 266 college students. Study skills were related to locus of control, age, expected course grade, and study time. The need to address attitudinal and motivational variables in study skills programs…

  9. 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…

  10. Manual control age and sex differences in 4 to 11 year old children.

    PubMed

    Flatters, Ian; Hill, Liam J B; Williams, Justin H G; Barber, Sally E; Mon-Williams, Mark

    2014-01-01

    To what degree does being male or female influence the development of manual skills in pre-pubescent children? This question is important because of the emphasis placed on developing important new manual skills during this period of a child's education (e.g. writing, drawing, using computers). We investigated age and sex-differences in the ability of 422 children to control a handheld stylus. A task battery deployed using tablet PC technology presented interactive visual targets on a computer screen whilst simultaneously recording participant's objective kinematic responses, via their interactions with the on-screen stimuli using the handheld stylus. The battery required children use the stylus to: (i) make a series of aiming movements, (ii) trace a series of abstract shapes and (iii) track a moving object. The tasks were not familiar to the children, allowing measurement of a general ability that might be meaningfully labelled 'manual control', whilst minimising culturally determined differences in experience (as much as possible). A reliable interaction between sex and age was found on the aiming task, with girls' movement times being faster than boys in younger age groups (e.g. 4-5 years) but with this pattern reversing in older children (10-11 years). The improved performance in older boys on the aiming task is consistent with prior evidence of a male advantage for gross-motor aiming tasks, which begins to emerge during adolescence. A small but reliable sex difference was found in tracing skill, with girls showing a slightly higher level of performance than boys irrespective of age. There were no reliable sex differences between boys and girls on the tracking task. Overall, the findings suggest that prepubescent girls are more likely to have superior manual control abilities for performing novel tasks. However, these small population differences do not suggest that the sexes require different educational support whilst developing their manual skills. PMID

  11. Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging.

    PubMed

    Joseph, Anna-Maria; Adhihetty, Peter J; Wawrzyniak, Nicholas R; Wohlgemuth, Stephanie E; Picca, Anna; Kujoth, Gregory C; Prolla, Tomas A; Leeuwenburgh, Christiaan

    2013-01-01

    Mitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in skeletal muscle from animals (young; 3-6 months and older; 8-15 months) expressing a proofreading-deficient version of mtDNA polymerase gamma (PolG). This progeroid aging model exhibits elevated mtDNA mutation rates, mitochondrial dysfunction, and a premature aging phenotype that includes sarcopenia. We found increased expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its target proteins, nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam) in PolG animals compared to wild-type (WT) (P<0.05). Muscle from older PolG animals displayed higher mitochondrial fission protein 1 (Fis1) concurrent with greater induction of autophagy, as indicated by changes in Atg5 and p62 protein content (P<0.05). Additionally, levels of the Tom22 import protein were higher in PolG animals when compared to WT (P<0.05). In contrast, muscle from normally-aged animals exhibited a distinctly different expression profile compared to PolG animals. Older WT animals appeared to have higher fusion (greater Mfn1/Mfn2, and lower Fis1) and lower autophagy (Beclin-1 and p62) compared to young WT suggesting that autophagy is impaired in aging muscle. In conclusion, muscle from mtDNA mutator mice display higher mitochondrial fission and autophagy levels that likely contribute to the sarcopenic phenotype observed in premature aging and this differs from the response observed in normally-aged muscle. PMID:23935986

  12. 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

  13. In vitro controlled release of vitamin C from Ca/Al layered double hydroxide drug delivery system.

    PubMed

    Gao, Xiaorui; Chen, Le; Xie, Juan; Yin, Yaobing; Chang, Tao; Duan, Yancong; Jiang, Nan

    2014-06-01

    A new drug delivery system for vitamin C (VC), Ca/Al layered double hydroxide (LDH), is demonstrated in this work. VC anions were intercalated successfully in the Ca/Al LDH gallery by a coprecipitation method. The interlayer space of 9.8Å suggests that VC anions are vertical to the LDH layers in the form of interdigitated bilayer. The loading of VC in LDH is 36.4wt.%. The thermal stability of VC is significantly enhanced after intercalation. In vitro VC release results show that the release time of VC in a phosphate buffer at pH7.4 was significantly extended, and the maximal percentage of VC released is 80% of the total. The Avrami-Erofe'ev equation most satisfactorily explains the release kinetics of VC, which is that the release of VC is mainly dominated by the ion-exchange reaction. PMID:24863197

  14. The genetic impact (C957T-DRD2) on inhibitory control is magnified by aging.

    PubMed

    Colzato, Lorenza S; van den Wildenberg, Wery P M; Hommel, Bernhard

    2013-06-01

    Healthy aging beyond the age of 65 is characterized by a general decrease in cognitive control over actions: old adults have more difficulty than young adults in stopping overt responses. Responsible for this cognitive decrement is the continuous decline of striatal and extrastriatal dopamine (DA). The resource-modulation hypothesis assumes that genetic variability is more likely to result in performance differences when brain resources move away from close-to-optimal levels, as in aging. To test this hypothesis we investigated, first, whether individual differences in the C957T polymorphism at DRD2 gene (rs6277) contribute to individual differences in the proficiency to inhibit behavioral responses in a stop-signal task. Second, we assessed whether this genetic effect is magnified in older adults, due to the considerable decline in dopamine function. Our findings show that individuals carrying genotype associated with higher density of extrastriatal D2 receptors (C957T CC) were more efficient in inhibiting unwanted action tendencies, but not in term of response execution. This effect was stronger in older than in younger adults. Our findings support the idea that aging-related decline in dopamine availability alters the balance between genotypes and cognitive functions. PMID:23376770

  15. 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.

  16. 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

  17. 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. PMID:26548366

  18. Multi-rule quality control for the age-related eye disease study.

    PubMed

    Caudill, Samuel P; Schleicher, Rosemary L; Pirkle, James L

    2008-09-10

    The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, was designed to study the natural history and risk factors of age-related macular degeneration (AMD) and cataract, and to evaluate the effect of high doses of antioxidants and zinc on eye disease progression. AMD and cataract are leading causes of visual impairment and blindness in the U.S., with frequency of both diseases increasing dramatically after age 65. Participants were randomly chosen to receive antioxidant or placebo tablets. Blood was drawn annually from a subset of patients, and serum concentrations of 17 different nutritional indicators were measured. Because of the complexity of the analytical methods, and possibility of instrument error due to failure of any one of many component parts, several different instruments were used for most analytes. In addition, to assure that the measurement systems were performing adequately across a wide range of concentrations, multiple control pools were monitored with analyte concentrations at low, medium, and high concentrations. We report here the multi-rule quality control system (MRQCS) used during the later part of the trial (AREDS Phase III). This system was designed to monitor systematic error and random within- and among-run error for analytical runs using 1-3 different quality control pools per run and 1-2 measurements of each pool per run. We demonstrate the features of the MRQCS using quality control (QC) data associated with vitamin C measurements. We also provide operating characteristics to demonstrate how the MRQCS responds to increases in systematic and/or random error. PMID:18344178

  19. CA1 Long-Term Potentiation Is Diminished but Present in Hippocampal Slices from α-CaMKII Mutant Mice

    PubMed Central

    Hinds, Heather L.; Tonegawa, Susumu; Malinow, Roberto

    1998-01-01

    Previous work has shown that mice missing the α-isoform of calcium–calmodulin-dependent protein kinase II (α-CaMKII) have a deficiency in CA1 hippocampal long-term potentiation (LTP). Follow-up studies on subsequent generations of these mutant mice in a novel inbred background by our laboratories have shown that whereas a deficiency in CA1 LTP is still present in α-CaMKII mutant mice, it is different both quantitatively and qualitatively from the deficiency first described. Mice of a mixed 129SvOla/SvJ;BALB/c;C57Bl/6 background derived from brother/sister mating of the α-CaMKII mutant line through multiple generations (>10) were produced by use of in vitro fertilization. Although LTP at 60 min post-tetanus was clearly deficient in these (−/−) α-CaMKII mice (42.6%, n = 33) compared with (+/+) α-CaMKII control animals (81.7%, n = 17), α-CaMKII mutant mice did show a significant level of LTP. The amount of LTP observed in α-CaMKII mutants was normally distributed, blocked by APV (2.7%, n = 8), and did not correlate with age. Although this supports a role for α-CaMKII in CA1 LTP, it also suggests that a form of α-CaMKII-independent LTP is present in mice that could be dependent on another kinase, such as the β-isoform of CaMKII. A significant difference in input/output curves was also observed between (−/−) α-CaMKII and (+/+) α-CaMKII animals, suggesting that differences in synaptic transmission may be contributing to the LTP deficit in mutant mice. However, tetani of increasing frequency (50, 100, and 200 Hz) did not reveal a higher threshold for potentiation in (−/−) α-CaMKII mice compared with (+/+) α-CaMKII controls. PMID:10454359

  20. The Ca2+-activated Cl- channel Ano1 controls microvilli length and membrane surface area in the oocyte.

    PubMed

    Courjaret, Raphael; Hodeify, Rawad; Hubrack, Satanay; Ibrahim, Awab; Dib, Maya; Daas, Sahar; Machaca, Khaled

    2016-07-01

    Ca(2+)-activated Cl(-) channels (CaCCs) play important physiological functions in epithelia and other tissues. In frog oocytes the CaCC Ano1 regulates resting membrane potential and the block to polyspermy. Here, we show that Ano1 expression increases the oocyte surface, revealing a novel function for Ano1 in regulating cell morphology. Confocal imaging shows that Ano1 increases microvilli length, which requires ERM-protein-dependent linkage to the cytoskeleton. A dominant-negative form of the ERM protein moesin precludes the Ano1-dependent increase in membrane area. Furthermore, both full-length and the truncated dominant-negative forms of moesin co-localize with Ano1 to the microvilli, and the two proteins co-immunoprecipitate. The Ano1-moesin interaction limits Ano1 lateral membrane mobility and contributes to microvilli scaffolding, therefore stabilizing larger membrane structures. Collectively, these results reveal a newly identified role for Ano1 in shaping the plasma membrane during oogenesis, with broad implications for the regulation of microvilli in epithelia. PMID:27173493

  1. Odor control in evaporation ponds treating olive mill wastewater through the use of Ca(OH)2.

    PubMed

    Lagoudianaki, E; Manios, T; Geniatakis, M; Frantzeskaki, N; Manios, V

    2003-01-01

    Different amounts of Ca(OH)2 were added in 2 L beakers containing 1 L of olive mill wastewater (OMW). The mixture was stirred for 45 min and left to settle. Wastewater analysis was used in order to determine the effect of the different amounts of calcium hydroxide in the treating process, three days after the application. The Odor Detection Threshold was used for determining the effect of the treatment in the odors produced in the beakers, three and 30 days after. Both sets of measurements indicated an important reduction in wastewater pollutants and odor emission when 10 g/L of Ca(OH)2 were added. In order to evaluate these results in more realistic conditions. 10 L plastic containers were filled with 6 L of OMW, relevant amounts of Ca(OH)2 were added, the mixture was stirred manually and left to settle in the open. Again, 10 g/L of calcium hydroxide produced the best results in odor reduction and wastewater treatment. PMID:14533921

  2. 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.

  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. 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

  5. Fitness level moderates executive control disruption during exercise regardless of age.

    PubMed

    Labelle, Veronique; Bosquet, Laurent; Mekary, Said; Vu, Thien Tuong Minh; Smilovitch, Mark; Bherer, Louis

    2014-06-01

    The purpose of this study was to assess the effects of exercise intensity, age, and fitness levels on executive and nonexecutive cognitive tasks during exercise. Participants completed a computerized modified-Stroop task (including denomination, inhibition, and switching conditions) while pedaling on a cycle ergometer at 40%, 60%, and 80% of peak power output (PPO). We showed that a bout of moderate-intensity (60% PPO) to high-intensity (80% PPO) exercise was associated with deleterious performance in the executive component of the computerized modified-Stroop task (i.e., switching condition), especially in lower-fit individuals (p < .01). Age did not have an effect on the relationship between acute cardiovascular exercise and cognition. Acute exercise can momentarily impair executive control equivalently in younger and older adults, but individual's fitness level moderates this relation. PMID:24918309

  6. Single stance stability and proprioceptive control in older adults living at home: gender and age differences.

    PubMed

    Riva, Dario; Mamo, Carlo; Fanì, Mara; Saccavino, Patrizia; Rocca, Flavio; Momenté, Manuel; Fratta, Marianna

    2013-01-01

    In developed countries, falls in older people represent a rising problem. As effective prevention should start before the risk becomes evident, an early predictor is needed. Single stance instability would appear as a major risk factor. Aims of the study were to describe single stance stability, its sensory components, and their correlation with age and gender. A random sample of 597 older adults (319 men, 278 women) living at home, aged 65-84, was studied. Stability tests were performed with an electronic postural station. The single stance test showed the impairment of single stance stability in older individuals (75-84 yrs). The significant decline of stability in the older subjects may be explained by the impairment of proprioceptive control together with the decrease in compensatory visual stabilization and emergency responses. Younger subjects (65-74 yrs) exhibited better, but still inadequate, proprioceptive control with compensatory visual stabilization. Gender differences appeared in older subjects: women were significantly less stable than men. The measurement of the sensory components of single stance stability could aid in the early detection of a decay in antigravity movements many years before the risk of falling becomes evident. Adequate proprioceptive control could mitigate the effects of all other risks of falling. PMID:23984068

  7. 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. PMID:24532389

  8. Diabetes and Age-Related Demographic Differences in Risk Factor Control

    PubMed Central

    Egan, Brent M.; Li, Jiexiang; Wolfman, Tamara E.; Sinopoli, Angelo

    2014-01-01

    Background Disparate vascular outcomes in diabetes by race/ethnicity may reflect differential risk factor control, especially pre-Medicare. Methods Assess concurrent target attainment for glycohemoglobin <7%, non-HDL-cholesterol <130 mg/dL, and blood pressure <140/<90 mmHg in white, black, and Hispanic diabetics <65 (younger) and ≥65 (older) years. NHANES 1999–2010 data were analyzed on diagnosed and undiagnosed diabetics ≥18 years. Results Concurrent target attainment was higher in whites (18.7%) than blacks (13.4% [p=0.02] and Hispanics (10.3%, p<0.001) <65 but not ≥65 years (20.0% vs. 15.9% [p=0.13], 19.5% [p=0.88]). Disparities in healthcare insurance among younger whites, blacks, and Hispanics, respectively, (87.4% vs. 81.1% (p<0.01), 68.0% (p<0.001) and infrequent healthcare (0–1 visits/year; 14.3% vs. 15.0% (p=NS), 32.0% (p<0.001) declined with age. Cholesterol treatment predicted concurrent control in both age groups (multivariable odds ratio >2, p<0.001). Risk factor awareness and treatment were lower in Hispanics than whites. When treated, diabetes and hypertension control were greater in whites than blacks or Hispanics. Conclusions Concurrent risk factor control is low in all diabetics and could improve with greater statin use. Insuring younger adults, especially Hispanic, could raise risk factor awareness and treatment. Improving treatment effectiveness in younger black and Hispanic diabetics could promote equitable risk factor control. PMID:24952652

  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. Biotic Control of Surface pH and Evidence of Light-Induced H+ Pumping and Ca2+-H+ Exchange in a Tropical Crustose Coralline Alga.

    PubMed

    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

  11. Do fertility control policies affect health in old age? Evidence from China's one-child experiment.

    PubMed

    Islam, Asadul; Smyth, Russell

    2015-05-01

    How do fertility control policies contribute to the welfare of women, and their husbands, particularly as they get older? We consider whether the reduction in fertility resulting from population control policies has had any effect on the health of elderly parents in China. In particular, we examine the influence of this fertility decline, experienced due to China's one-child policy, on several measures of the health of parents in middle and old age. Overall, our results suggest that having fewer children has a positive effect on self-reported parental health but generally no effect on other measures of health. The results also suggest that upstream financial transfers have a positive effect on several measures of parental health. PMID:24692342

  12. Age-related differences in control of a visuomotor coordination task: a preliminary study

    PubMed Central

    Ryu, Young Uk; Lee, Kyu-Ho; Lee, Hocheol; Park, Jungsik

    2016-01-01

    [Purpose] The purpose of the current study was to examine age-related differences in control of a perception-action coordination skill. We adapted a visuomotor tracking experiment requiring various coordination patterns between a limb’s motion and an external signal. [Subjects and Methods] A total of 12 subjects (6 elderly and 6 young) voluntarily participated in the study. The experimental session consisted of 3 trials for 3 different relative phase patterns: 0°, 90°, and 180°, defined by the relationship between the online visual feedback of the joystick motion and the white dot signal. [Results] The 0° and 180° tracking patterns were stable compared with the 90° tracking pattern for both age groups. The present results also showed that the elderly subjects were less stable than were young subjects for all tracking patterns. [Conclusion] The intrinsic coordination dynamics predicted by the Haken-Kelso-Bunz (HKB) mathematical model did not change with age, whereas utilization of visual feedback information declined overall. Further research is needed regarding methods for increasing utilization of visual feedback information from the perspective of rehabilitation. PMID:27190463

  13. Age-related differences in control of a visuomotor coordination task: a preliminary study.

    PubMed

    Ryu, Young Uk; Lee, Kyu-Ho; Lee, Hocheol; Park, Jungsik

    2016-04-01

    [Purpose] The purpose of the current study was to examine age-related differences in control of a perception-action coordination skill. We adapted a visuomotor tracking experiment requiring various coordination patterns between a limb's motion and an external signal. [Subjects and Methods] A total of 12 subjects (6 elderly and 6 young) voluntarily participated in the study. The experimental session consisted of 3 trials for 3 different relative phase patterns: 0°, 90°, and 180°, defined by the relationship between the online visual feedback of the joystick motion and the white dot signal. [Results] The 0° and 180° tracking patterns were stable compared with the 90° tracking pattern for both age groups. The present results also showed that the elderly subjects were less stable than were young subjects for all tracking patterns. [Conclusion] The intrinsic coordination dynamics predicted by the Haken-Kelso-Bunz (HKB) mathematical model did not change with age, whereas utilization of visual feedback information declined overall. Further research is needed regarding methods for increasing utilization of visual feedback information from the perspective of rehabilitation. PMID:27190463

  14. Online games training aging brains: limited transfer to cognitive control functions

    PubMed Central

    van Muijden, Jesse; Band, Guido P. H.; Hommel, Bernhard

    2011-01-01

    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. PMID:22912609

  15. 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. PMID:20820629

  16. Trapping control of phase development in zone melting of Bi-Sr-Ca-Cu-O superconducting fibres

    NASA Astrophysics Data System (ADS)

    Costa, F. M.; Carrasco, M. F.; Silva, R. F.; Vieira, J. M.

    2003-03-01

    Highly-texturized polycrystalline fibres of the Bi-Sr-Ca-Cu-O system have been grown by the laser floating zone technique at seven different pulling rates: (1.1, 2.2, 4.17, 8.3, 16.7, 33.3, 60.5) × 10-6 m s-1. The assessment of the cation segregation at the solid/liquid interface allowed us to calculate their equilibrium and effective distribution coefficients. The equilibrium distribution coefficients (k0,Bi = 0.55, k0,Sr = 0.97, k0,Ca = 1.67, k0,Cu = 1.10) were estimated using the Burton, Primm and Slichter (BPS) theory by taking into account the determined effective values. The effective distribution coefficients tend to unity as long as the pulling rate increases. The composition profiles along the initial transient region of the solidified fibres show a fast approach to the nominal composition as the pulling rate increases. The outstanding effect of the growth speed on superconducting phase type development is explained based on the solute trapping phenomena. The sequence of crystallization for superconducting phases ('2212' rightarrow '4413' rightarrow '2201') with pulling rate is a spontaneous effect of the system thermodynamics in order to balance the Bi trapping. This phase sequence corresponds to the smallest change of Bi chemical potential from the liquid phase to the solid phase. A diagram of free energy curves of the interdendritic superconducting phases illustrates the partitionless solidification phenomena at the highest growth speed.

  17. Evaluation of the ovarian reserve function in patients with metabolic syndrome in relation to healthy controls and different age groups

    PubMed Central

    2014-01-01

    Objective To evaluate the ovarian reserve function in female patients with metabolic syndrome (MetS). Methods This study evaluated 136 subjects, 67 with MetS and 69 controls. Subjects were divided into three age groups. Group I included 49 subjects aged 20–29 years, 22 with MetS and 27 controls; group II included 45 subjects aged 30–39 years, 22 with MetS and 23 controls; and group III included 42 subjects aged 40–49 years, 23 with MetS and 19 controls. Demographic characteristics, anthropometrics, blood biochemistry, and gonadotrophic hormones were compared as total ovarian volume and antral follicle count on ovarian transvaginal ultrasonography. Results Serum levels of FSH, LH, E2 and progesterone were similar in the MetS and control groups, while testosterone levels were significantly higher in MetS patients than controls, both in the overall population (p = 0.024) and in those aged 20–29 years (p = 0.018). Total ovarian volume was significantly lower in MetS patients than controls, in both the overall population (p = 0.003) and those aged 20–29 years (p = 0.018), while antral follicle counts were similar. Ovarian volume correlated positively with antral follicle count (AFC) (r = 0.37; p < 0.001) and negatively with age (r = 0.34; p < 0.001) and FSH concentration (r = 0.21; p = 0.013). AFC was negatively correlated with age (r = 0.36; p < 0.001). Conclusion Ovarian reserve function is significantly lower in MetS patients than in healthy control subjects, particularly in women aged 20–29 years. PMID:24955131

  18. Reconfiguration of brain network architecture to support executive control in aging.

    PubMed

    Gallen, Courtney L; Turner, Gary R; Adnan, Areeba; D'Esposito, Mark

    2016-08-01

    Aging is accompanied by declines in executive control abilities and changes in underlying brain network architecture. Here, we examined brain networks in young and older adults during a task-free resting state and an N-back task and investigated age-related changes in the modular network organization of the brain. Compared with young adults, older adults showed larger changes in network organization between resting state and task. Although young adults exhibited increased connectivity between lateral frontal regions and other network modules during the most difficult task condition, older adults also exhibited this pattern of increased connectivity during less-demanding task conditions. Moreover, the increase in between-module connectivity in older adults was related to faster task performance and greater fractional anisotropy of the superior longitudinal fasciculus. These results demonstrate that older adults who exhibit more pronounced network changes between a resting state and task have better executive control performance and greater structural connectivity of a core frontal-posterior white matter pathway. PMID:27318132

  19. Age-related deficits in low-level inhibitory motor control.

    PubMed

    Schlaghecken, Friederike; Birak, Kulbir S; Maylor, Elizabeth A

    2011-12-01

    Inhibitory control functions in old age were investigated with the "masked prime" paradigm in which participants executed speeded manual choice responses to simple visual targets. These were preceded--either immediately or at some earlier time--by a backward-masked prime. Young adults produced positive compatibility effects (PCEs)--faster and more accurate responses for matching than for nonmatching prime-target pairs--when prime and target immediately followed each other, and the reverse effect (negative compatibility effect, NCE) for targets that followed the prime after a short interval. Older adults produced similar PCEs to young adults, indicating intact low-level motor activation, but failed to produce normal NCEs even with longer delays (Experiment 1), increased opportunity for prime processing (Experiment 2), and prolonged learning (Experiment 3). However, a fine-grained analysis of each individual's time course of masked priming effects revealed NCEs in the majority of older adults, of the same magnitude as those of young adults. These were significantly delayed (even more than expected on the basis of general slowing), indicating a disproportionate impairment of low-level inhibitory motor control in old age. PMID:21604886

  20. Age-related changes in the control of finger force vectors.

    PubMed

    Kapur, Shweta; Zatsiorsky, Vladimir M; Latash, Mark L

    2010-12-01

    We explored changes in finger interaction in the process of healthy aging as a window into neural control strategies of natural movements. In particular, we quantified the amount of force produced by noninstructed fingers in different directions, the amount of force produced by the instructed finger orthogonally to the task direction, and the strength of multifinger synergies stabilizing the total force magnitude and direction during accurate force production. Healthy elderly participants performed accurate isometric force production tasks in five directions by individual fingers and by all four fingers acting together. Their data were compared with a dataset obtained in a similar earlier study of young subjects. Finger force vectors were measured using six-component force/torque sensors. Multifinger synergies were quantified using the framework of the uncontrolled manifold hypothesis. The elderly participants produced lower force magnitudes by noninstructed fingers and higher force magnitudes by instructed fingers in nontask directions. They showed strong synergies stabilizing the magnitude and direction of the total force vector. However, the synergy indexes were significantly lower than those observed in the earlier study of young subjects. The results are consistent with an earlier hypothesis of preferential weakening of intrinsic hand muscles with age. We interpret the findings as a shift in motor control from synergic to element-based, which may be causally linked to the documented progressive neuronal death at different levels of the neural axis. PMID:20829494

  1. Age effects on the control of dynamic balance during step adjustments under temporal constraints.

    PubMed

    Nakano, Wataru; Fukaya, Takashi; Kobayashi, Satomi; Ohashi, Yukari

    2016-06-01

    This study investigated the age effects on the control of dynamic balance during step adjustments under temporal constraints. Fifteen young adults and 14 older adults avoided a virtual white planar obstacle by lengthening or shortening their steps under free or constrained conditions. In the anterior-posterior direction, older adults demonstrated significantly decreased center of mass velocity at the swing foot contact under temporal constraints. Additionally, the distances between the 'extrapolated center of mass' position and base of support at the swing foot contact were greater in older adults than young adults. In the mediolateral direction, center of mass displacement was significantly increased in older adults compared with young adults. Consequently, older adults showed a significantly increased step width at the swing foot contact in the constraint condition. Overall, these data suggest that older adults demonstrate a conservative strategy to maintain anterior-posterior stability. By contrast, although older adults are able to modulate their step width to maintain mediolateral dynamic balance, age-related changes in mediolateral balance control under temporal constraints may increase the risk of falls in the lateral direction during obstacle negotiation. PMID:26852293

  2. Eating habits and appetite control in the elderly: the anorexia of aging.

    PubMed

    Donini, Lorenzo M; Savina, Claudia; Cannella, Carlo

    2003-03-01

    Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a

  3. Internal versus external controls on age variability: Definitions, origins and implications in a changing climate

    NASA Astrophysics Data System (ADS)

    Helton, A. M.; Poole, G. C.; Payn, R. A.; Izurieta, C.; Wright, M.; Bernhardt, E. S.; Stanford, J. A.

    2014-12-01

    The unsteadiness of stream water age is now well established, but the controls on the age dynamics, and the adequate representation and prediction of those dynamics, are not. A basic distinction can be made between internal variability that arises from changes in the proportions of flow moving through the diverse flow pathways of a hydrologic system, and external variability that arises from the stochasticity of inputs and outputs (such as precipitation and streamflow). In this talk I will show how these two types of age variability can be formally defined and distinguished within the framework of rank StorAge Selection (rSAS) functions. Internal variability implies variations in time in the rSAS function, while external variability does not. This leads naturally to the definition of several modes of internal variability, reflecting generic ways that system flowpaths may be rearranged. This rearrangement may be induced by fluctuations in the system state (such as catchment wetness), or by longer-term changes in catchment structure (such as land use change). One type of change, the 'inverse storage effect' is characterized by an increase in the release of young water from the system in response to an increase in overall system storage. This effect can be seen in many hydrologic settings, and has important implications for the effect of altered hydroclimatic conditions on solute transport through a landscape. External variability, such as increased precipitation, can induce a decrease in mean transit time (and vice versa), but this effect is greatly enhanced if accompanied by an internal shift in flow pathways that increases the relative importance of younger water. These effects will be illustrated using data from field and experimental studies.

  4. Pathology of aging female SENCAR mice used as controls in skin two-stage carcinogenesis studies.

    PubMed Central

    Ward, J M; Quander, R; Devor, D; Wenk, M L; Spangler, E F

    1986-01-01

    The pathology of 60 aged female SENCAR mice used as acetone controls in skin painting studies was studied. Fifty percent of the mice survived past 96 weeks of age. The major contributing causes of death identified in 42 mice were glomerulonephritis (8 mice), histiocytic sarcoma (7 mice), and other tumors (8 mice). Glomerulonephritis was found in the majority of mice and was associated with thymic hyperplasia, focal vasculitis, and lymphoid hyperplasia. Necropsy of 58 mice surviving past 50 weeks of age revealed that 41 had an average of 1.36 tumors per mouse. The most common tumors included histiocytic sarcoma (13 mice), pulmonary adenoma or adenocarcinoma (11 mice), mammary tumors (11 mice), follicular center cell lymphoma (4 mice), and hepatocellular adenoma (4 mice). The 13 histiocytic sarcomas appeared to arise in the uterus and metastasized to liver (9 mice), lung (4 mice), kidney (3 mice), and other tissues. Lung tumors were of the solid and papillary types, and tumor cells frequently contained surfactant apoprotein (SAP) but did not contain Clara cell antigens, suggesting their origin from alveolar Type II cells. A variety of nonneoplastic lesions, similar to those observed in other mouse strains, were seen in other tissues of these mice. Amyloid-like material was seen only in nasal turbinates and thyroid gland. In a group of 28 mice exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA) for up to 88 weeks, as a control for other treatment groups, 7 (25%) had papillomas and 5 (17.8%) had squamous cell carcinomas of the skin at necropsy, although many other induced papillomas regressed during the study. Images FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 13. FIGURE 14. PMID:3780636

  5. 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.

  6. Controlling Factors of Soil CO2 Efflux in Pinus yunnanensis across Different Stand Ages

    PubMed Central

    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. PMID:25996943

  7. Antecedents and outcomes of level and rates of change in perceived control: The moderating role of age.

    PubMed

    Infurna, Frank J; Okun, Morris A

    2015-10-01

    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 symptoms, and emotional support as antecedents of level and rates of change in perceived control and whether level and rates of change in perceived control buffer the relations between high functional limitations and depressive symptoms and lack of emotional support and mortality risk. In addition, age was investigated as a moderator of these associations. To do so, we used 16-year longitudinal data from participants in the Americans' Changing Lives (ACL) Study who were at least 40 years old at Wave 1 (N = 2,540; mean age = 62.85, SD = 12.15; 65% women). With respect to the antecedents of perceived control, results indicated that more functional limitations and depressive symptoms, as well as having less emotional support, were each associated with lower levels of and stronger declines in perceived control over time. Additionally, more functional limitations and less emotional support were more detrimental to levels of perceived control in midlife compared to old age. Focusing on outcomes of perceived control, more positive rates of change in perceived control protected against mortality risk for those with fewer functional limitations and depressive symptoms and more emotional support, and this was more pronounced for functional limitations and depressive symptoms in old age as compared to midlife. Our discussion focuses on the complex interplay among perceived control, functional limitations, depressive symptoms, and emotional support; how they vary with age; and the implications of our findings for interventions. PMID:26214226

  8. Investigating Age-Related Changes in Fine Motor Control Across Different Effectors and the Impact of White Matter Integrity

    PubMed Central

    Holtrop, Joseph L.; Loucks, Torrey M; Sosnoff, Jacob J; Sutton, Bradley P

    2014-01-01

    Changes in fine motor control that eventually compromise dexterity accompany advanced age; however there is evidence that age-related decline in motor control may not be uniform across effectors. Particularly, the role of central mechanisms in effector-specific decline has not been examined but is relevant for placing age-related motor declines into the growing literature of age-related changes in brain function. We examined sub-maximal force control across three different effectors (fingers, lips, and tongue) in 18 young and 14 older adults. In parallel with the force variability measures we examined changes in white matter structural integrity in effector-specific pathways in the brain with diffusion tensor imaging (DTI). Motor pathways for each effector were identified by using an fMRI localizer task followed by tractography to identify the fiber tracts propagating to the midbrain. Increases in force control variability were found with age in all three effectors but the effectors showed different degrees of age-related variability. Motor control changes were accompanied by a decline in white matter structural integrity with age shown by measures of fractional anisotropy and radial diffusivity. The DTI metrics appear to mediate some of the age-related declines in motor control. Our findings indicate that the structural integrity of descending motor systems may play a significant role in age-related increases in motor performance variability, but that differential age-related declines in oral and manual effectors are not likely due to structural integrity of descending motor pathways in the brain. PMID:24657352

  9. Aging and the mechanisms underlying head and postural control during voluntary motion.

    PubMed

    Di Fabio, R P; Emasithi, A

    1997-05-01

    The quality of sensory information that is necessary for balance and postural stability will depend to a great extent on head stability as the body moves. How older persons coordinate head and body motion for balance during volitional activities is not known. The purposes of this article are to present a basis for understanding the influence of aging on head control during voluntary motion and to discuss some data that demonstrate how elderly people might control head movement to improve gaze and the quality of vestibular inputs. A "top-down" or "head-first" control scheme is proposed as the mechanism that elderly people without disabilities use to maintain head position during self-initiated motion. This type of control ensures that the angular position of the head in space remains relatively constant--through the use of a head-stabilization-in-space (HSS) strategy--regardless of the magnitude or direction of displacements in the body's center of force. The HSS strategy is thought to reduce potential ambiguities in the interpretation of sensory inputs for balance and is derived primarily from a geocentric (orientation to the vertical) frame of reference. Egocentric (orientation of the head with respect to the body) or exocentric (orientation to objects in the environment) frames of reference, however, refine the control of head stabilization. Preliminary research suggests that elderly people use the HSS strategy to control head pitch during difficult balance tasks. These findings, if supported by more definitive studies, may be useful in the treatment of patients with balance disorders. The treatment of patients with balance dysfunction is discussed within the conceptual framework of a "head-first" organization scheme. PMID:9149758

  10. Reliability of Selected Measures of Movement Control and Force Production on Children Four Through Ten Years of Age.

    ERIC Educational Resources Information Center

    Heston, Melissa; And Others

    1986-01-01

    The purpose of this study was to establish tentative reliability estimates for movement control and force production tasks as the initial phase of a cross-cultural motor-performance study. Ten boys and ten girls for each of seven age groups (ages four through ten) performed four specific tasks. Results are discussed. (MT)

  11. Effects of Age, Intelligence and Executive Control Function on Saccadic Reaction Time in Persons with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Haishi, Koichi; Okuzumi, Hideyuki; Kokubun, Mitsuru

    2011-01-01

    The current research aimed to clarify the influence of age, intelligence and executive control function on the central tendency and intraindividual variability of saccadic reaction time in persons with intellectual disabilities. Participants were 44 persons with intellectual disabilities aged between 13 and 57 years whose IQs were between 14 and…

  12. 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

  13. Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing

    PubMed Central

    White, Ryan R.; Milholland, Brandon; de Bruin, Alain; Curran, Samuel; Laberge, Remi-Martin; van Steeg, Harry; Campisi, Judith; Maslov, Alexander Y.; Vijg, Jan

    2015-01-01

    DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing. PMID:25858675

  14. 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

  15. 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…

  16. 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. PMID:27103518

  17. Higher Education is an Age-Independent Predictor of White Matter Integrity and Cognitive Control in Late Adolescence

    PubMed Central

    Korgaonkar, Mayuresh S.; Grieve, Stuart M.; Brickman, Adam M.

    2013-01-01

    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. PMID:24033571

  18. Analgesics use and ESRD in younger age: a case-control study

    PubMed Central

    van der Woude, Fokke J; Heinemann, Lothar AJ; Graf, Helmut; Lewis, Michael; Moehner, Sabine; Assmann, Anita; Kühl-Habich, Doerthe

    2007-01-01

    Background An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design. Methods We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed. Results The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a

  19. 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. PMID:26386110

  20. 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. PMID:9731194

  1. 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

  2. Mitochondria-Ros Crosstalk in the Control of Cell Death and Aging

    PubMed Central

    Marchi, Saverio; Giorgi, Carlotta; Suski, Jan M.; Agnoletto, Chiara; Bononi, Angela; Bonora, Massimo; De Marchi, Elena; Missiroli, Sonia; Patergnani, Simone; Poletti, Federica; Rimessi, Alessandro; Duszynski, Jerzy; Wieckowski, Mariusz R.; Pinton, Paolo

    2012-01-01

    Reactive oxygen species (ROS) are highly reactive molecules, mainly generated inside mitochondria that can oxidize DNA, proteins, and lipids. At physiological levels, ROS function as “redox messengers” in intracellular signalling and regulation, whereas excess ROS induce cell death by promoting the intrinsic apoptotic pathway. Recent work has pointed to a further role of ROS in activation of autophagy and their importance in the regulation of aging. This review will focus on mitochondria as producers and targets of ROS and will summarize different proteins that modulate the redox state of the cell. Moreover, the involvement of ROS and mitochondria in different molecular pathways controlling lifespan will be reported, pointing out the role of ROS as a “balance of power,” directing the cell towards life or death. PMID:22175013

  3. The sources and manifestations of stress amongst school-aged dyslexics, compared with sibling controls.

    PubMed

    Alexander-Passe, Neil

    2008-11-01

    All school children experience stress at some point in their school careers. This study investigates whether dyslexic children, by way of their educational and social difficulties, experience higher levels of stress at school. The School Situation Survey was used to investigate both the sources and manifestations of stress amongst dyslexic children and non-dyslexic sibling controls. Samples were broken down by gender, age and the size of families. Results suggest significant differences between the groups, with dyslexics in academic years 3-5 experiencing the highest stress levels, specifically in interactions with teachers, worries over academic examinations (SATs) and performance testing, causing emotional (fear, shyness and loneliness) and physiological (nausea, tremors or rapid heart beat) manifestations. Results also suggest that dyslexics in larger families (3-4 sibling families) experience greater stress in interactions with their peers, than those in smaller families (two sibling families)--possibly from unfair sibling comparison. PMID:17910007

  4. 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

  5. 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

  6. 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

  7. 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...

  8. 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…

  9. Examining Dynamic Links between Perceived Control and Health: Longitudinal Evidence for Differential Effects in Midlife and Old Age

    ERIC Educational Resources Information Center

    Infurna, Frank J.; Gerstorf, Denis; Zarit, Steven H.

    2011-01-01

    Perceived control and health are often closely linked in adulthood and old age. Little is known, however, about their time-ordered interplay at various phases of adult life. By applying dynamic models to four waves of data over 15.5 years from the Americans' Changing Lives Study, we examined time-ordered relations between perceived control and…

  10. Effects of Korean White Ginseng (Panax Ginseng C.A. Meyer) on Vascular and Glycemic Health in Type 2 Diabetes: Results of a Randomized, Double Blind, Placebo-controlled, Multiple-crossover, Acute Dose Escalation Trial

    PubMed Central

    Shishtar, Esra'; Jovanovski, Elena; Jenkins, Alexandra

    2014-01-01

    Korean red ginseng (steam treated Panax ginseng C.A. Meyer), among most prized traditional herbal remedies, has been clinically shown to improve cardiovascular disease (CVD) risk factors. Whether this holds true for the dried non-steamed variety, known as Korean white ginseng (KWG) is unclear. This study therefore, investigated the efficacy and safety of escalating doses of KWG on vascular and glycemic parameters in type 2 diabetes (T2DM). Using an acute, randomized, placebo-controlled, double-blind, crossover design, 25 participants with well-controlled T2DM (12-males: 13-females, age: 63 ± 9 years, A1c: 6.9 ± 0.7%, BMI: 29.3 ± 4.3 kg/m2) underwent five visits during which they received 1 g, 3 g, or 6 g KWG or 3 g wheat-bran control (twice) together with 50 g-glucose load. For the duration of 240 minutes, augmentation index (AI), and central blood pressure were measured at baseline and at 60 min-intervals, and ambulatory blood pressure was assessed at baseline and at 10 min-intervals. Additionally, capillary blood was collected at time zero and at 15, 30, 45, 60, 90, 120, and 180 minutes post-treatment. A symptoms questionnaire was used to assess safety and adverse events. Two-way ANOVA demonstrated a significant time-treatment interaction effect on AI (p = 0.01) with one-way ANOVA showing significant reductions in AI with 3 g KWG relative to control (p = 0.04). Compared to control, acute administration of KWG appeared to be safe, but did not affect any other postprandial, vascular or glycemic parameters. KWG might have a beneficial effect on AI, a cumulative indicator of arterial health. However, these results are preliminary and highlight the need for long-term investigation with a focus on its accountable components. Clinical Trial Registration: NCT01699074 PMID:25136536

  11. Chinese Eye Exercises and Myopia Development in School Age Children: A Nested Case-control Study.

    PubMed

    Kang, Meng-Tian; Li, Shi-Ming; Peng, Xiaoxia; Li, Lei; Ran, Anran; Meng, Bo; Sun, Yunyun; Liu, Luo-Ru; Li, He; Millodot, Michel; Wang, Ningli

    2016-01-01

    Chinese eye exercises have been implemented in China as an intervention for controlling children's myopia for over 50 years. This nested case-control study investigated Chinese eye exercises and their association with myopia development in junior middle school children. Outcome measures were the onset and progression of myopia over a two-year period. Cases were defined as 1. Myopia onset (cycloplegic spherical equivalent ≤ -0.5 diopter in non-myopic children). 2. Myopia progression (myopia shift of ≥1.0 diopter in those who were myopic at baseline). Two independent investigators assessed the quality of Chinese eye exercises performance at the end of the follow-up period. Of 260 children at baseline (mean age was 12.7 ± 0.5 years), 201 were eligible for this study. There was no association between eye exercises and the risk of myopia-onset (OR = 0.73, 95%CI: 0.24-2.21), nor myopia progression (OR = 0.79, 95%CI: 0.41-1.53). The group who performed high quality exercises had a slightly lower myopia progression of 0.15 D than the children who did not perform the exercise over a period of 2 years. However, the limited sample size, low dosage and performance quality of Chinese eye exercises in children did not result in statistical significance and require further studies. PMID:27329615

  12. Chinese Eye Exercises and Myopia Development in School Age Children: A Nested Case-control Study

    PubMed Central

    Kang, Meng-Tian; Li, Shi-Ming; Peng, Xiaoxia; Li, Lei; Ran, Anran; Meng, Bo; Sun, Yunyun; Liu, Luo-Ru; Li, He; Millodot, Michel; Wang, Ningli

    2016-01-01

    Chinese eye exercises have been implemented in China as an intervention for controlling children’s myopia for over 50 years. This nested case-control study investigated Chinese eye exercises and their association with myopia development in junior middle school children. Outcome measures were the onset and progression of myopia over a two-year period. Cases were defined as 1. Myopia onset (cycloplegic spherical equivalent ≤ −0.5 diopter in non-myopic children). 2. Myopia progression (myopia shift of ≥1.0 diopter in those who were myopic at baseline). Two independent investigators assessed the quality of Chinese eye exercises performance at the end of the follow-up period. Of 260 children at baseline (mean age was 12.7 ± 0.5 years), 201 were eligible for this study. There was no association between eye exercises and the risk of myopia-onset (OR = 0.73, 95%CI: 0.24–2.21), nor myopia progression (OR = 0.79, 95%CI: 0.41–1.53). The group who performed high quality exercises had a slightly lower myopia progression of 0.15 D than the children who did not perform the exercise over a period of 2 years. However, the limited sample size, low dosage and performance quality of Chinese eye exercises in children did not result in statistical significance and require further studies. PMID:27329615

  13. 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. PMID:25260219

  14. Evidence of a Ca(2+)-(*)NO-cGMP signaling pathway controlling zoospore biogenesis in the aquatic fungus Blastocladiella emersonii.

    PubMed

    Vieira, André L G; Linares, Edlaine; Augusto, Ohara; Gomes, Suely L

    2009-08-01

    The sporulation stage of the aquatic fungus Blastocladiella emersonii culminates with the formation and release to the medium of a number of zoospores, which are motile cells responsible for the dispersal of the fungus. The presence in the sporulation solution of 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a potent and selective inhibitor of nitric oxide-sensitive guanylyl cyclases, completely prevented biogenesis of the zoospores. In addition, this compound was able to significantly reduce cGMP levels, which increase drastically during late sporulation, suggesting the existence of a nitric oxide-dependent mechanism for cGMP synthesis. Furthermore, increased levels of nitric oxide-derived products were detected during sporulation by fluorescence assays using DAF-2 DA, whose signal was drastically reduced in the presence of the nitric oxide synthase inhibitor Nomega-Nitro-L-arginine methyl ester (L-NAME). These results were confirmed by quantitative chemiluminescent determination of the intracellular levels of nitric oxide-derived products. A putative nitric oxide synthase (NOS) activity was detected throughout sporulation, and this enzyme activity decreased significantly when L-NAME and 1-[2-(Trifluoromethyl)phenyl]imidazole (TRIM) were added to the assays. NOS assays carried out in the presence of EGTA showed decreased enzyme activity, suggesting the involvement of calcium ions in enzyme activation. Additionally, expressed sequence tags (ESTs) encoding putative guanylyl cyclases and a cGMP-phosphodiesterase were found in B. emersonii EST database (http://blasto.iq.usp.br), and the mRNA levels of the corresponding genes were observed to increase during sporulation. Altogether, data presented here revealed the presence and expression of guanylyl cyclase and cGMP phosphodiesterase genes in B. emersonii and provided evidence of a Ca(2+)-(*)NO-cGMP signaling pathway playing a role in zoospore biogenesis. PMID:19393757

  15. 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.

  16. 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.

  17. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo.

    PubMed

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke; Mathiesen, Claus; Thomsen, Kirsten; Jensen, Kimmo; Lauritzen, Martin

    2015-09-01

    Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate of oxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect of GABA is incompletely understood. Here we performed in vivo studies in mice to investigate how THIP (which tonically activates extrasynaptic GABAARs) and Zolpidem (a positive allosteric modulator of synaptic GABAARs) impact stimulation-induced ΔCBF, ΔCMRO2, local field potentials (LFPs), and fluorescent cytosolic Ca(2+) transients in neurons and astrocytes. Low concentrations of THIP increased ΔCBF and ΔCMRO2 at low stimulation frequencies. These responses were coupled to increased synaptic activity as indicated by LFP responses, and to Ca(2+) activities in neurons and astrocytes. Intermediate and high concentrations of THIP suppressed ΔCBF and ΔCMRO2 at high stimulation frequencies. Zolpidem had similar but less-pronounced effects, with similar dependence on drug concentration and stimulation frequency. Our present findings suggest that slight increases in both synaptic and extrasynaptic GABAAR activity might selectively gate and amplify transient low-frequency somatosensory inputs, filter out high-frequency inputs, and enhance vascular and metabolic responses that are likely to be reflected in BOLD functional neuroimaging signals. PMID:24692513

  18. Mitochondrial Ca(2+) Processing by a Unit of Mitochondrial Ca(2+) Uniporter and Na(+)/Ca(2+) Exchanger Supports the Neuronal Ca(2+) Influx via Activated Glutamate Receptors.

    PubMed

    Strokin, Mikhail; Reiser, Georg

    2016-06-01

    The current study demonstrates that in hippocampal neurons mitochondrial Ca(2+) processing supports Ca(2+) influx via ionotropic glutamate (Glu) receptors. We define mitochondrial Ca(2+) processing as Ca(2+) uptake via mitochondrial Ca(2+) uniporter (MCU) combined with subsequent Ca(2+) release via mitochondrial Na(+)/Ca(2+) exchanger (NCX). Our tool is to measure the Ca(2+) influx rate in primary hippocampal co-cultures, i.e. neurons and astrocytes, by fluorescent digital microscopy, using a Fura-2-quenching method where we add small amounts of Mn(2+) in the superfusion medium. Thus, Ca(2+) influx is measured with Mn(2+) in the bath. Ru360 as inhibitor of mitochondrial Ca(2+) uptake through MCU strongly reduces the rate of Ca(2+) influx in Glu-stimulated primary hippocampal neurons. Similarly, the Ca(2+) influx rate in Glu-stimulated neurons declines after suppression of potential-dependent MCU, when we depolarize mitochondria with rotenone. With inhibition of Ca(2+) release from mitochondria via NCX using CGP-37157 the Ca(2+) influx via N-methyl-D-aspartate (NMDA)- and kainate-sensitive receptors is slowed down. Working jointly as mitochondrial Ca(2+) processing unit, MCU and NCX, apparently sustain the Ca(2+) throughput of activated Glu-sensitive receptors. Our results revise the role frequently attributed to mitochondria in neuronal Ca(2+) homeostasis, where mitochondria function mainly as Ca(2+) buffer, and prevent excessively high cytosolic Ca(2+) concentration increase during neuronal activity. The mechanism to control Ca(2+) influx in neurons, as discovered in this study, highlights mitochondrial Ca(2+) processing as a promising pharmacological target. We discuss this pathway in relation to the endoplasmic reticulum-related mechanisms of Ca(2+) processing. PMID:26842930

  19. 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. PMID:21875900

  20. Controlled on-chip stimulation of quantal catecholamine release from chromaffin cells using photolysis of caged Ca2+ on transparent indium-tin-oxide microchip electrodes.

    PubMed

    Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D

    2008-01-01

    Photorelease of caged Ca(2+) is a uniquely powerful tool to study the dynamics of Ca(2+)-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca(2+), together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm thick transparent indium-tin-oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (approximately 20 microm by 20 microm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca(2+) cage NP-EGTA and Ca(2+) indicator dye fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca(2+), a uniform rise of [Ca(2+)](i) within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca(2+)](i) and a "priming" effect of sub-stimulatory [Ca(2+)](i) on the response of cells to subsequent [Ca(2+)](i) elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca(2+) is a suitable stimulation technique for higher-throughput studies of Ca(2+)-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

  1. Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

    PubMed Central

    Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

    2008-01-01

    Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

  2. Control system for the 2nd generation Berkeley AutoMounters (BAM2) at GM/CA CAT macromolecular crystallography beamlines

    PubMed Central

    Makarov, O.; Hilgart, M.; Ogata, C.; Pothineni, S.; Cork, C.

    2011-01-01

    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. PMID:21822343

  3. Floating-Zone Growth and Characterization of Large High Quality Single Crystals of Bi_2Sr_2CaCu_2Ox and Control of Oxygen Stoichiometry

    NASA Astrophysics Data System (ADS)

    Guptasarma, P.; Hinks, D. G.

    1997-03-01

    High quality single crystals of Bi_2Sr_2CaCu_2Ox (BSCCO) of sizes upto 8mm x 4mm x 0.2mm were grown from a travelling solvent floating melt-zone (TSFZ) without crucible contact. Polycrystalline rods were consecutively passed twice at growth-rates of 10mm/hr and 0.15-0.25 mm/hr respectively through a mirror-focussed image of two infra-red lamps. Flowing a high-purity mixture of 20% O2 in Ar instead of static air during growth yielded crystals with high as-grown Tc (92 K; ΔT_c<=1K). Oxygen content x of the crystals was varied by annealing in thermodynamically controlled P(O_2) until equilibrium was reached, as evidenced by a sharp superconducting transition.

  4. 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.

  5. Ca2+ controls gating of voltage-gated calcium channels by releasing the β2e subunit from the plasma membrane.

    PubMed

    Kim, Dong-Il; Kweon, Hae-Jin; Park, Yongsoo; Jang, Deok-Jin; Suh, Byung-Chang

    2016-01-01

    Voltage-gated calcium (Cav) channels, which are regulated by membrane potential, cytosolic Ca(2+), phosphorylation, and membrane phospholipids, govern Ca(2+) entry into excitable cells. Cav channels contain a pore-forming α1 subunit, an auxiliary α2δ subunit, and a regulatory β subunit, each encoded by several genes in mammals. In addition to a domain that interacts with the α1 subunit, β2e and β2a also interact with the cytoplasmic face of the plasma membrane through an electrostatic interaction for β2e and posttranslational acylation for β2a. We found that an increase in cytosolic Ca(2+) promoted the release of β2e from the membrane without requiring substantial depletion of the anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane. Experiments with liposomes indicated that Ca(2+) disrupted the interaction of the β2e amino-terminal peptide with membranes containing PIP2 Ca(2+) binding to calmodulin (CaM) leads to CaM-mediated inactivation of Cav currents. Although Cav2.2 coexpressed with β2a required Ca(2+)-dependent activation of CaM for Ca(2+)-mediated reduction in channel activity, Cav2.2 coexpressed with β2e exhibited Ca(2+)-dependent inactivation of the channel even in the presence of Ca(2+)-insensitive CaM. Inducible depletion of PIP2 reduced Cav2.2 currents, and in cells coexpressing β2e, but not a form that lacks the polybasic region, increased intracellular Ca(2+) further reduced Cav2.2 currents. Many hormone- or neurotransmitter-activated receptors stimulate PIP2 hydrolysis and increase cytosolic Ca(2+); thus, our findings suggest that β2e may integrate such receptor-mediated signals to limit Cav activity. PMID:27382026

  6. Biogeochemical controls on seasonal variations of the stable isotopes of dissolved oxygen and dissolved inorganic carbon in Castle Lake, CA

    NASA Astrophysics Data System (ADS)

    Brown, J. M.; Poulson, S. R.

    2010-12-01

    The purpose of this project is to perform a seasonal dissolved oxygen (DO) and dissolved inorganic carbon (DIC) stable isotope (δ18O, δ13C) study to assess the fluctuations in biogeochemical processes with depth in a lake. DO and DIC concentrations and stable isotope compositions (δ18O-DO, δ13C-DIC) have been used as a technique to study the systematics of diurnal freshwater biogeochemical processes, primarily photosynthesis, respiration, and gas-exchange (e.g. Quay et al. 1995, Trojanowska et al. 2008). For example, photosynthesis produces DO isotopically identical to the host water, typically light relative to atmospheric oxygen (+23.5‰), while respiration preferentially consumes isotopically light DO. Diel δ18O-DO and δ13C-DIC studies in rivers (e.g. Parker et al. 2005, Parker et al. 2010, Poulson & Sullivan 2010) have been used to determine the rates of biogeochemical processes over a 24h time scale. However, similar studies in lakes are rare, for either diel or seasonal time scales. The focus of this project is Castle Lake, 12km southwest of Mt. Shasta, CA, at an elevation of 1660m. Castle Lake is an alpine, meso-oligotrophic lake with a 19ha surface area and a maximum depth of up to 35m. This project consists of sampling profiles, 2-3 weeks apart, throughout the 2010 field season for monitoring seasonal depth trends, with measurements of DO concentration, temperature, pH, alkalinity, specific conductivity, PAR, chlorophyll concentration, δ18O-DO, δ13C-DIC, δ18O-H2O, and δD-H2O. Diel measurements of DO concentration, temperature, pH, specific conductivity, PAR, and chlorophyll concentration have also been performed at various depths. To date, the profile data collected at Castle Lake show various seasonal changes, starting after ice-out (late June 2010) through mid-August 2010. DO profiles display a positive heterograde trend with a maximum of 11.33mg/L at 12m in mid-August and minima of ≤0.12mg/L near the lake bottom. DIC concentrations increase

  7. Biological Fe oxidation controlled deposition of banded iron formation in the ca. 3770 Ma Isua Supracrustal Belt (West Greenland)

    NASA Astrophysics Data System (ADS)

    Czaja, Andrew D.; Johnson, Clark M.; Beard, Brian L.; Roden, Eric E.; Li, Weiqiang; Moorbath, Stephen

    2013-02-01

    The redox balance of the Archean atmosphere-ocean system is among the most significant uncertainties in our understanding of the earliest history of Earth's surface zone. Most workers agree that oxygen did not constitute a significant proportion of the atmosphere until after ca. 2.45 Ga, after the Great Oxidation Event, but there is less agreement on when O2 production began, and how this may have been consumed by reduced species such as Fe(II) in the oceans. The Fe redox cycle through time has been traced using banded iron formations (BIFs), and Fe isotopes are increasingly used to constrain the conditions of Earth's paleoenvironments, including the pathways of formation of BIFs. Iron isotope analyses of BIFs from the 3.7 to 3.8 Ga Isua Supracrustal Belt (ISB), obtained by micro-sampling of magnetite-rich layers and conventional analysis, as well as by in situ femtosecond laser ablation (fs-LA-ICP-MS), indicate a consistently narrow range of non-zero δ56Fe values. Analysis of magnetite by fs-LA-ICP-MS allows for precise and accurate micron-scale analyses without the problems of orientation effects that are associated with secondary ion mass spectrometry (SIMS) analyses. Magnetite δ56Fe values range from +0.4‰ to +1.1‰ among different bands, but within individual layers magnetite grains are mostly homogeneous. Although these BIFs have been metamorphosed to amphibolite-facies, the metamorphism can neither explain the range in Fe isotope compositions across bands, nor that between hand samples. The isotopic compositions therefore reflect “primary”, low-temperature sedimentary values. The positive δ56Fe values measured from the ISB magnetites are best explained by deposition of Fe(III)-oxides produced by partial oxidation of Fe(II)-rich ocean water. A dispersion/reaction model, which accounts for rates of hydrothermal Fe(II)aq input, rates of oxidation, and rates of Fe(OH)3 settling suggests exceptionally low O2 contents, <0.001% of modern O2 contents in

  8. 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. PMID:26682607

  9. Thermoelectric properties of metallic antiperovskites AXD3 (A=Ge, Sn, Pb, Al, Zn, Ga; X=N, C; D=Ca, Fe, Co)

    NASA Astrophysics Data System (ADS)

    Bilal, Muhammad; Ahmad, Iftikhar; Asadabadi, Saeid Jalali; Ahmad, Rashid; Maqbool, Muhammad

    2015-05-01

    In this paper we communicate the thermoelectric properties of carbon and nitrogen based metallic antiperovskites ANCa3 (A=Ge, Sn, Pb), BCFe3 (B=Al, Zn, Ga) and SnCD3 (D=Co and Fe) using the ab-initio calculations to explore efficient metallic thermoelectric materials. The consistency of the calculated results of SnCCo3 and SnCFe3 with the experimental results confirms the reliability of our theoretical calculations for the other investigated metallic antiperovskites. The results indicate that the thermopower of these materials can be enhanced by changing the chemical potential. The dimensionless figure of merit for the three nitrides approaches 0.96 at room temperature, which proves the usefulness of these materials in thermoelectric generators. Furthermore, the thermal conductivity is minimum at room temperature for chemical potential values between -0.25 μ(eV) and 0.25 μ(eV), and provides the maximum values of dimensionless figure of merit in this range. The striking feature of these studies is identifying a metallic compound, SnNCa3, with the highest value of Seebeck coefficient at room temperature out of all metals. The results anticipate that these materials could be efficient in thermoelectric generators; however, this needs experimental verification.[Figure not available: see fulltext.

  10. 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

  11. The effects of dynamic changes of malonyl ginsenosides on evaluation and quality control of Panax ginseng C.A. Meyer.

    PubMed

    Liu, Zhi; Li, Yu; Li, Xiang; Ruan, Chang-Chun; Wang, Li-Juan; Sun, Guang-Zhi

    2012-05-01

    To clarify the effects of malonyl ginsenosides (MGR) on evaluation and quality control of Panax ginseng, the contents of neutral and malonyl ginsenosides from P. ginseng were examined by high-performance liquid chromatography equipped with UV-VIS detector (HPLC-UV) during extraction, processing and storage. Several solvents, including water, ethanol, methanol, and n-butanol were used in the cold-soaked extraction (CSE). Among the four extraction solvents, methanol was found to be the most efficient. CSE was compared with other extraction methods such as Soxhlet extraction (SE), heat reflux extraction (HRE), ultrasonic-assisted extraction (UAE), and microwave-assisted extraction (MAE). The content of MGR showed significant differences, higher in CSE and UAE; lower in MAE and HRE; no MGR could be detected after SE. However, the total contents of neutral and malonyl ginsenosides were not different. Meanwhile, white ginseng, stored at 25°C in air of low humidity, showed a marked decrease in the concentration of MGR from 1.19% to 0.63% but with an increase in the neutral ginsenosides from 1.12% to 1.53% after 0-9-month storage. The results indicated that MGR changed dynamically in P. ginseng with different extraction solvents, extraction methods and increasing storage time. The total ginsenosides was not only underestimated but also determined imprecisely by ignoring malonyl ginsenosides. On the basis of our results, we suggest that malonyl ginsenosides should be transformed into the corresponding neutral ginsenosides during sample preparation for quality control and evaluation of P. ginseng. Then the content of six neutral ginsenosides in samples was used as the true level of total ginsenosides. The results reported here might provide useful information for accurate evaluation and quality control of P. ginseng. PMID:22387101

  12. 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.

  13. Depression and the Sense of Control: Aging Vectors, Trajectories and Trends*

    PubMed Central

    Mirowsky, John

    2013-01-01

    Adulthood trajectories of outcomes such as depression and the sense of control measure aspects of the human condition that Americans may view as objects of change. Social science should provide information on that progress, or its absence. Whether these trajectories change their shape, and how and why if they do, is important theoretically too. A range of birth cohorts coexist in time, place, and social relationship. Each cohort, as it goes through adulthood, follows in aggregate a path left by older ones, reshaping that path as it goes. The shapes of the trajectories, and the trends reshaping them, represent two inseparable aspects of the same phenomenon. This report describes methods for mapping aging trajectories and inter-cohort trends, using linear latent-growth models of relatively brief followup data (six years in the examples). It reviews shared research ideals that led to the model: put theory into modeling, go where the data lead, use what you have, go beyond where you have been, and risk being precisely wrong. PMID:24311752

  14. Depression and the sense of control: aging vectors, trajectories, and trends.

    PubMed

    Mirowsky, John

    2013-01-01

    Adulthood trajectories of outcomes such as depression and the sense of control measure aspects of the human condition that Americans may view as objects of change. Social science should provide information on that progress, or its absence. Whether these trajectories change their shape, and how and why if they do, is important theoretically too. A range of birth cohorts coexist in time, place, and social relationship. Each cohort, as it goes through adulthood, follows in aggregate a path left by older ones, reshaping that path as it goes. The shapes of the trajectories, and the trends reshaping them, represent two inseparable aspects of the same phenomenon. This report describes methods for mapping aging trajectories and intercohort trends, using linear latent-growth models of relatively brief follow-up data (six years in the examples). The author reviews shared research ideals that led to the model: put theory into modeling, go where the data lead, use what you have, go beyond where you have been, and risk being precisely wrong. PMID:24311752

  15. 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…

  16. 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

  17. 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. PMID:25253079

  18. Understanding the climate science policy nexus: Lessons from modeling climate impacts to temperature control regimes on Lake Shasta, CA

    NASA Astrophysics Data System (ADS)

    Kauneckis, D. L.; Saito, L.; Sapin, J. R.; Rajagopalan, B.; Hanna, R. B.

    2014-12-01

    Investigators in the natural sciences have long been frustrated by the slow diffusion of increasing knowledge about the potential impacts of climate change into policy and decision making about the management of those system most likely to be affected. This presentation uses information based on the case study of a recent project that worked closely with water managers to incorporate stochastic climate conditions into two-dimensional hydrodynamic model (CE-QUAL-W2) in order to examine the downstream impacts of reservoir operations at Shasta Lake in northern California. The inclusion of reservoir operational rules was incorporated into the coupled model in order to better represent the operating conditions under which management decisions are made. Shasta Dam utilizes a unique temperature control device (TCD) that allows water releases from multiple levels of the reservoir in order to control downstream temperatures and meet management guidelines for Chinook salmon. The case study illustrates how three characteristics of a decision system influence the use of climate science: (i) the built structural components of ecosystem service delivery, (ii) institutional rule structures that include regulatory systems, operational rules, and informal decision criteria, (iii) decision systems used to manage competing demands on a natural resource. Additional cases are used to develop a general framework for understanding under what conditions climate science can provide information useful to decision makers.

  19. Prospective Control Abilities during Visuo-Manual Tracking in Children with 22q11.2 Deletion Syndrome Compared to Age- and IQ-Matched Controls

    ERIC Educational Resources Information Center

    Van Aken, Katrijn; Swillen, Ann; Beirinckx, Marc; Janssens, Luc; Caeyenberghs, Karen; Smits-Engelsman, Bouwien

    2010-01-01

    To examine whether children with a 22q11.2 Deletion syndrome (22q11.2DS) are able to use prospective control, 21 children with 22q11.2DS (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.05 [plus or minus] 10.2) and 21 control children (mean age=9.6 [plus or minus] 1.9; mean FSIQ=73.38 [plus or minus] 12.0) were asked to perform a visuo-manual…

  20. 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

  1. 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. PMID:26201656

  2. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    PubMed Central

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    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. PMID:26046761

  3. The Effect of Aging in Inhibitory Control of Major Depressive Disorder Revealed by Event-Related Potentials

    PubMed Central

    Zhang, Bing-Wei; Xu, Jing; Chang, Yi

    2016-01-01

    Elderly depressed patients manifest pronounced executive dysfunction compared with younger subjects with depressive disorder. Aging-related brain changes may result in executive dysfunction in geriatric depression. We investigated the neural correlates of inhibitory control processing in depressed subjects at different ages using event-related potentials (ERPs). A equiprobable visual Go/Nogo task was used in 19 young (27.4 ± 5.0 years) and 18 elderly (70.8 ± 6.9 years) depressed subjects and their age-matched healthy controls (20 young subjects, 26.2 ± 3.7 years, and 18 elderly subjects, 68.1 ± 4.8 years). The responses were based on two types of equilateral triangular figures of upright (Go) and inverted triangle (Nogo). The elderly subjects exhibited later N2 and P3 latencies, and larger Go-N2 and P3 amplitudes, compared with the younger subjects. Further, the elderly controls displayed smaller P3 in the central and parietal regions, and yielded larger Nogo-P3 amplitude in the frontal region compared with younger controls. While the young depressed patients yielded smaller P3 amplitude than the controls across frontal, central and parietal regions, elderly depressed patients yielded smaller P3 than the elderly controls only in the frontal region. Our results suggest that the inhibitory control subprocesses are differentially affected by depression and aging. The stimulus response speed and the effort intensity of inhibition control are specifically impaired in the elderly depressed patients. And the diminished amplitudes of frontal P3 in the elderly depression imply a frontal dysfunction mechanism. PMID:27065830

  4. Age-Dependent Decline of Endogenous Pain Control: Exploring the Effect of Expectation and Depression

    PubMed Central

    Grashorn, Wiebke; Sprenger, Christian; Forkmann, Katarina; Wrobel, Nathalie; Bingel, Ulrike

    2013-01-01

    Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20–40 years, middle-aged = 41–60 years, old = 61–80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age. PMID:24086595

  5. 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,…

  6. 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…

  7. Basement control on thermochronometer cooling ages: an example from the Andean fold-thrust belt in Bolivia

    NASA Astrophysics Data System (ADS)

    McQuarrie, N.; Ehlers, T. A.; Rak, A. J.

    2015-12-01

    Understanding the style, geometry and kinematics of basement deformation where it is not exposed is an ongoing challenge in orogenic belts. Basement deformation must be inferred based on the resulting surface observables. Geologic map patterns, thermochronometer cooling signals, and synorogenic sediment distribution in the northern Bolivian Andes strongly argue for displacement on large-scale basement thrust sheets. To show the relationship between basement deformation and surface observables such as mapped geology and thermochronometer cooling ages, we link a forward modeled balanced cross section to a 2-D thermokinematic model to compare predicted to measured cooling ages. Applying isostasy and erosion to sequentially deformed balanced cross sections links the growth of hinterland structures to the developing foreland basins and highlights subsurface controls on surface geology. The cross section kinematics become velocity vectors by assigning ages to displacement amounts. A range of potential velocity vectors is then used to calculate heat transport, erosion, and rock cooling. Predicted cooling ages highlight that large basement ramps impart a significant and tractable cooling signal. This signal is the most visible in the across strike pattern of cooling ages for each system (zircon fission track, apatite fission track and apatite (U-Th)/ He). The pronounced, predicted cooling age pattern generated by large basement thrust sheets match measured ages across the northern Bolivian Andes strongly suggesting basement deformation similar to that show in balanced cross sections.

  8. 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.

  9. The effect of intensity controlled aerobic dance exercise on aerobic capacity of middle-aged, overweight women.

    PubMed

    Gillett, P A; Eisenman, P A

    1987-12-01

    The purpose of this study was to determine the effect of intensity controlled exercise on the aerobic capacity of overweight, middle-aged women. Thirty-eight moderately overweight women, ages 35-57, participated in a 16-week dance-exercise program. Random assignment was made to an experimental group (n = 20) in which intensity of exercise was controlled and prescribed, and a control group (n = 18) in which exercise was of an intensity typical to commercial aerobic classes. Prior to the onset of training, and at the completion of 16 weeks, the following fitness tests were administered: Aerobic capacity expressed as VO2 max, body composition analysis, blood chemistry, blood pressure, resting heart rate, muscular endurance, and flexibility. T-tests, ANCOVA, and gain-score analyses were utilized to evaluate data. Both groups showed small changes in weight, percent fat, resting systolic and diastolic blood pressure, resting heart rate, high density lipoprotein-cholesterol (HDL-C), muscular endurance, and flexibility, but these changes were statistically nonsignificant. The VO2 max for the experimental group increased 41%, while the VO2 max for the control group increased 22% (p less than 0.05). The results suggest that the cardiovascular fitness changes for overweight, middle-aged women are greater when exercise intensity and progression are tailored to their age and fitness level. PMID:3423310

  10. Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

    ERIC Educational Resources Information Center

    Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

    2011-01-01

    Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

  11. A Randomized Controlled Trial of a Parent Training and Emotion Socialization Program for Families of Hyperactive Preschool-Aged Children

    ERIC Educational Resources Information Center

    Herbert, Sharonne D.; Harvey, Elizabeth A.; Roberts, Jasmin L.; Wichowski, Kayla; Lugo-Candelas, Claudia I.

    2013-01-01

    The present study evaluated the effectiveness of a parent training and emotion socialization program designed specifically for hyperactive preschoolers. Participants were 31 preschool-aged children whose parents were randomly assigned to a parent training (PT) or waitlist (WL) control group. PT parents took part in a 14-week parenting program that…

  12. 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…

  13. Age-related changes in the attentional control of visual cortex: A selective problem in the left visual hemifield

    PubMed Central

    Nagamatsu, Lindsay S.; Carolan, Patrick; Liu-Ambrose, Teresa Y.L.; Handy, Todd C.

    2012-01-01

    To what extent does our visual-spatial attention change with age? In this regard, it has been previously reported that relative to young controls, seniors show delays in attention-related sensory facilitation. Given this finding, our study was designed to examine two key questions regarding age-related changes in the effect of spatial attention on sensory-evoked responses in visual cortex –– are there visual field differences in the age-related impairments in sensory processing, and do these impairments co-occur with changes in the executive control signals associated with visual spatial orienting? Therefore, our study examined both attentional control and attentional facilitation in seniors (aged 66 to 74 years) and young adults (aged 18 to 25 years) using a canonical spatial orienting task. Participants responded to attended and unattended peripheral targets while we recorded event-related potentials (ERPs) to both targets and attention-directing spatial cues. We found that not only were sensory-evoked responses delayed in seniors specifically for unattended events in the left visual field as measured via latency shifts in the lateral occipital P1 elicited by visual targets, but seniors also showed amplitude reductions in the anterior directing attentional negativity (ADAN) component elicited by cues directing attention to the left visual field. At the same time, seniors also had significantly higher error rates for targets presented in the left vs. right visual field. Taken together, our data thus converge on the conclusion that age-related changes in visual spatial attention involve both sensory-level and executive attentional control processes, and that these effects appear to be strongly associated with the left visual field. PMID:21356222

  14. Effect of age of feed restriction and microelement supplementation to control ascites on production and carcass characteristics of broilers.

    PubMed

    Camacho, M A; Suárez, M E; Herrera, J G; Cuca, J M; García-Bojalil, C M

    2004-04-01

    Three experiments were conducted, from January until September 2001, to estimate the optimized age to apply feed restriction to control mortality from ascites, with no negative effects on production and carcass characteristics of broilers. For each experiment, 1,200 1-d-old mixed Ross x Peterson chicks were reared in floor pens (50 chicks in each) and fed commercial feed. Feed restriction was applied for 8 h/d for 14 d at 21 or 28 d of age in experiment 1, 14 or 21 d in experiment 2, and 7 or 14 d in experiment 3. In experiments 2 and 3, a microelement supplement (without or with) was tested; the control groups received feed ad libitum and no supplement. Body weight gain, feed conversion, total mortality, and mortality from ascites, leg problems, and carcass characteristics were considered at the end of each experiment. The data were analyzed as a completely randomized design, or as a 2 x 2 factorial to estimate main and interaction effects (experiments 2 and 3). Additional analyses, including the control, were done; means comparisons were by orthogonal contrasts. The production and carcass characteristics of the restricted groups were lower than the control but were not statistically different in experiments 2 and 3, although the optimized age for feed restriction was at 7 d. Total mortality and mortality from ascites decreased by restriction, but leg problems increased without supplement. The results indicated that quantitative feed restriction and microelement supplementation at 7 d of age reduced mortality from ascites and leg problems and permitted compensatory growth sufficient to equal the production characteristics of the control group at 49 d of age. However, it is necessary to determine the specific microelements to be supplemented and to estimate the effects of season and genetic line. PMID:15109050

  15. 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. PMID:25143549

  16. 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

  17. Age at Virologic Control Influences Peripheral Blood HIV Reservoir Size and Serostatus in Perinatally-Infected Adolescents

    PubMed Central

    Persaud, Deborah; Patel, Kunjal; Karalius, Brad; Rainwater-Lovett, Kaitlin; Ziemniak, Carrie; Ellis, Angela; Chen, Ya Hui; Richman, Douglas; Siberry, George K.; Van Dyke, Russell B.; Burchett, Sandra; Seage, George R.; Luzuriaga, Katherine

    2014-01-01

    Importance Combination antiretroviral therapy (cART) initiated within several weeks of HIV infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure. Objectives To quantify peripheral blood proviral reservoir size in perinatally HIV-infected adolescents and to identify correlates of limited proviral reservoirs. Design, Setting, and Participants A cross-sectional study including 144 perinatally HIV-infected (PHIV+) youth (median age: 14.3 years), enrolled in the US-based Pediatric HIV/AIDS Cohort Study, on durable (median: 10.2 years) cART, stratified by age at virologic control. Main Outcome and Measures The primary endpoint was peripheral blood mononuclear cell (PBMC) proviral load following virologic control at different ages. Correlations between proviral load and markers of active HIV production (HIV-specific antibodies, 2-long terminal repeat (2-LTR) circles), and markers of immune activation and inflammation were also assessed. Results Proviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control by age 1 year (4.2 [interquartile range, 2.6-8 6] copies per 1 million PBMCs) compared to those who achieved virologic control between 1-5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after age 5 years (−(70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P < .00l). A proviral burden <10 copies/million PBMCs was measured in 11 (79%), 20 (40%), and 13 (18%) participants with virologic control at ages <1 year, 1-5 years, and >5 years, respectively (p<0.001). Lower proviral load was associated with undetectable 2-LTR circles (p<0.001) and HIV negative or indeterminate serostatus (p<0.001), but not with concentrations of soluble immune activation markers CD14 and CD163. Conclusions and Relevance Early effective cART along with prolonged virologic suppression after perinatal HIV

  18. New Neurons in Aging Brains: Molecular Control by Small Non-Coding RNAs

    PubMed Central

    Schouten, Marijn; Buijink, M. Renate; Lucassen, Paul J.; Fitzsimons, Carlos P.

    2012-01-01

    Adult neurogenesis generates functional neurons from neural stem cells present in specific brain regions. It is largely confined to two main regions: the subventricular zone of the lateral ventricle, and the subgranular zone of the dentate gyrus (DG), in the hippocampus. With age, the function of the hippocampus and particularly the DG is impaired. For instance, adult neurogenesis is decreased with aging, in both proliferating and differentiation of newborn cells, while in parallel an age-associated decline in cognitive performance is often seen. Surprisingly, the synaptogenic potential of adult-born neurons is only marginally influenced by aging. Therefore, although proliferation, differentiation, and synaptogenesis of adult-born new neurons in the DG are closely related to each other, they are differentially affected by aging. In this review we discuss the crucial roles of a novel class of recently discovered modulators of gene expression, the small non-coding RNAs, in the regulation of adult neurogenesis. Multiple small non-coding RNAs are differentially expressed in the hippocampus. In particular a subgroup of the small non-coding RNAs, the microRNAs, fine-tune the progression of adult neurogenesis. This makes small non-coding RNAs appealing candidates to orchestrate the functional alterations in adult neurogenesis and cognition associated with aging. Finally, we summarize observations that link changes in circulating levels of steroid hormones with alterations in adult neurogenesis, cognitive decline, and vulnerability to psychopathology in advanced age, and discuss a potential interplay between steroid hormone receptors and microRNAs in cognitive decline in aging individuals. PMID:22363255

  19. A Comparison of Measures of Endothelial Function in Patients with Peripheral Arterial Disease and Age and Gender Matched Controls

    PubMed Central

    Allan, Richard B.; Vun, Simon V.; Spark, J. Ian

    2016-01-01

    This study compared flow-mediated dilatation (FMD), peripheral artery tonometry (PAT), and serum nitric oxide (NO) measures of endothelial function in patients with peripheral artery disease (PAD) against age/gender matched controls. 25 patients (mean age: 72.4 years, M : F 18 : 7) with established PAD and an age/gender matched group of 25 healthy controls (mean age: 72.4 years, M : F 18 : 7) were studied. Endothelial function was measured using the % FMD, reactive hyperemia index (RHI) using PAT and serum NO (μmol). Difference for each method between PAD and control patients and correlation between the methods were investigated. FMD and RHI were lower in patients with PAD (median FMD for PAD = 2.16% versus control = 3.77%, p = 0.034 and median RHI in PAD = 1.64 versus control = 1.92, p = 0.005). NO levels were not significantly different between the groups (PAD median = 7.70 μmol, control median = 13.05 μmol, p = 0.662). These results were obtained in elderly patients and cannot be extrapolated to younger individuals. FMD and PAT both demonstrated a lower hyperaemic response in patients with PAD; however, FMD results in PAD patients were unequivocally reduced whereas half the PAD patients had RHI values above the established threshold for endothelial dysfunction. This suggests that FMD is a more appropriate method for the measurement of NO-mediated endothelial function. PMID:26942010

  20. Coherent THz-wave emission from voltage- and number-controlled intrinsic Josephson junctions in Bi2 Sr 2 CaCu 2 O 8+δ

    NASA Astrophysics Data System (ADS)

    Tsujimoto, Manabu; Nakayama, Ryo; Orita, Naoki; Koike, Takashi; Deguchi, Kota; Delfanazari, Kaveh; Yamamoto, Takashi; Kashiwagi, Takanari; Minami, Hidetoshi; Tachiki, Masashi; Kadowaki, Kazuo

    2011-03-01

    Intense and coherent terahertz electromagnetic wave (THz-wave) emission from the intrinsic Josephson junctions (IJJs) in single crystalline high-Tc superconductor Bi 2 Sr 2 CaCu 2 O8 + δ (Bi-2212) was reported in 2007 [L. Ozyuzer et al., Science 318, (2007) 1291.]. In the present work, we demonstrate the relationship between the bias condition and the resonance state by controlling both the applied voltage, V , and the number of resistive junctions, N . We directly observed that if N junctions are in resistive state, the resonance frequency, fJ , varies in accordance with the ac-Josephson relation; fJ = (2 | e | / h) V / N , although frequency fJ has previously been thought to be uniquely determined by the geometrical condition due to the cavity resonance effect [M. Tsujimoto et al., Phys. Rev. Lett. 105, (2010) 037005.]. We also found that the emission intensity varies as a function of both fJ and N . CREST-JST, WPI-MANA, Strategic Initiative A (University of Tsukuba).

  1. Climate control of decadal-scale increases in apparent ages of eogenetic karst spring water

    NASA Astrophysics Data System (ADS)

    Martin, Jonathan B.; Kurz, Marie J.; Khadka, Mitra B.

    2016-09-01

    Water quantity and quality in karst aquifers may depend on decadal-scale variations in recharge or withdrawal, which we hypothesize could be assessed through time-series measurements of apparent ages of spring water. We tested this hypothesis with analyses of various age tracers (3H/3He, SF6, CFC-11, CFC-12, CFC-113) and selected solute concentrations [dissolved oxygen (DO), NO3, Mg, and SO4] from 6 springs in a single spring complex (Ichetucknee springs) in northern Florida over a 16-yr period. These springs fall into two groups that reflect shallow short (Group 1) and deep long (Group 2) flow paths. Some tracer concentrations are altered, with CFC-12 and CFC-113 concentrations yielding the most robust apparent ages. These tracers show a 10-20-yr monotonic increase in apparent age from 1997 to 2013, including the flood recession that followed Tropical Storm Debby in mid-2012. This increase in age indicates most water discharged during the study period recharged the aquifer within a few years of 1973 for Group 2 springs and 1980 for Group 1 springs. Inverse correlations between apparent age and DO and NO3 concentrations reflect reduced redox state in older water. Positive correlations between apparent age and Mg and SO4 concentrations reflect increased water-rock reactions. Concentrated recharge in the decade around 1975 resulted from nearly 2 m of rain in excess of the monthly average that fell between 1960 and 2014, followed by a nearly 4 m deficit to 2014. This excess rain coincided with two major El Niño events during the maximum cool phase in the Atlantic Multidecadal Oscillation. Although regional water withdrawal increased nearly 5-fold between 1980 and 2005, withdrawals represent only 2-5% of Ichetucknee River flow and are less important than decadal-long variations in precipitation. These results suggest that groundwater management should consider climate cycles as predictive tools for future water resources.

  2. The Relationship Between Postural Control and Self-Reported Engagement in Physical Activity in Young and Older Age.

    PubMed

    Wojciechowska-Maszkowska, Bozena; Borzucka, Dorota; Rogowska, Aleksandra Maria; Kuczynski, Michal

    2016-04-01

    Physical activity is known to have beneficial effects on a host of factors related to physical and mental health, and positively affects postural control. However, there is no agreement on which measures of postural control and to what extent they are dependent on the past and present physical activity in older adults. To answer this question we compared the postural performance in a 20-s quiet stance with eyes open on a Kistler force plate in 38 subjects, aged 60-92, who were formerly and are currently physically active (AA) with those who were always inactive (II) and those who were either formerly (AI) or are currently (IA) active. Results indicated that only current activity promoted better postural control while former activity was ineffective. Postural control in AA and IA was very similar and much better than in II and AI who, in contrast, displayed similarly deteriorated postural control. PMID:26252835

  3. Prevalence, awareness, treatment, and control of hypertension in the older population: results from the multiple national studies on ageing.

    PubMed

    Yang, Fan; Qian, Dongfu; Hu, Dan

    2016-02-01

    The international comparisons that provided useful epidemiologic information of hypertension in the elderly people is still sparse; we aim to provide the latest international estimates on the burden of hypertension. These sampling methods of the selection of surveys mainly used multistage population registry; this cross-national study of 63,014 adults aged ≥50 years was from in four high-income countries, four upper-middle-income countries (UMICs), and three low-middle-income countries (LMICs). Overall, the age-standardized prevalence of hypertension among the adult population aged ≥50 years was 53.2% (51.9% of men and 54.3% of women). The high-income countries and UMICs had more or less twice the prevalence of hypertension compare with LMICs. The rates of awareness, treatment, and control of hypertension were 55.6%, 44.1%, and 17.1%, respectively, and awareness and control of hypertension were lowest in UMICs and treatment of hypertension was lowest in LMICs. Among this multiple national study population, hypertension was very common among elderly population. Even more worrisome is that the rates of awareness, treatment, and control of hypertension were relatively low in UMICs and IMICs. These results indicate that improving the ability to control and prevention of hypertension in resource-limited settings is needed. PMID:26778770

  4. Age, Education, and the Gender Gap in the Sense of Control

    ERIC Educational Resources Information Center

    Slagsvold, Britt; Sorensen, 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…

  5. Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue

    PubMed Central

    Remaud, Anthony; Thuong-Cong, Cécile; Bilodeau, Martin

    2016-01-01

    Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n = 15; healthy seniors: n = 13) performed a dynamic postural task along the antero-posterior (AP) and the medio-lateral (ML) axes, with and without the addition of a simple reaction time (RT) task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP). This protocol was repeated before and after a fatigue task where ankle plantar flexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. RTs were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, RT increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system (CNS) functions. Finally, plantar flexor muscle fatigue and dual-tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks. PMID:26834626

  6. Understanding controls on organic (Uk’37 and TEX86) and inorganic (Mg/Ca) SST proxies: insights from a long term Mozambique Channel sediment trap study

    NASA Astrophysics Data System (ADS)

    Castañeda, I. S.; Fallet, U.; Brummer, G. A.; Sinninghe Damsté, J. S.; Schouten, S.

    2009-12-01

    In 2003, an array of moorings equipped with instruments to measure temperature, salinity and water mass transport was placed across the Mozambique Channel as part of the Long-term Ocean Currents Observation (LOCO) Project. In addition, a sediment trap in the deep channel at 2011 m collected material at 21 day intervals from November 2003 until the present. These sediment trap samples, in combination with in situ and satellite-derived SST measurements, provide a unique opportunity to examine and directly compare organic and inorganic SST proxies. In this study we measured two organic SST proxies, the Uk’37 Index, which is based on the ratio of long-chain di- and triunsaturated ketones produced by haptophyte algae, and the more recently developed TEX86 proxy, which is based on glycerol dialkyl glycerol tetraethers (GDGTs) produced by Marine Group 1 Crenarchaeota. We also analyzed Mg/Ca ratios from two species of surface-dwelling foraminifera, G. ruber and G. trilobus, which provide an inorganic SST proxy. The results obtained up to now show that TEX86-based SST reconstructions capture the mean annual temperature of the study location accurately (mean annual SST is 28.1°C and TEX86 mean annual SST is 28.3°C); however, seasonal variability is not reflected by the TEX86 measurements. In contrast, the Mg/Ca records of G. ruber and G. trilobus, capture the seasonal variability in SST but display a slight offset relative to each other, with G. ruber typically 2 to 3°C warmer than G. trilobus. The Uk’37 Index was nearly always near unity due to the absence of the C37:3 alkenone, showing that this proxy is unable to capture SST at this tropical location. The differences between the organic and inorganic proxies might be due to the different sinking rates and lateral transport effects. To further investigate controls on the TEX86 proxy, we are currently examining intact polar lipids (IPLs) of GDGTs from the most recent year of sediment trap material. IPLs are more

  7. Changes in frontal EEG coherence across infancy predict cognitive abilities at age 3: The mediating role of attentional control.

    PubMed

    Whedon, Margaret; Perry, Nicole B; Calkins, Susan D; Bell, Martha Ann

    2016-09-01

    Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the second half of the first year predicted observed cognitive performance in early childhood 1 year prior indirectly through observed attentional control (N = 300). Results indicated that greater change in left-but not right-frontal EEG coherence between 5 and 10 months was positively associated with attentional control, cognitive flexibility, receptive language, and behavioral inhibitory control. Specifically, a larger increase in coherence between left frontal regions was positively associated with accuracy on a visual search task at Age 2, and visual search accuracy was positively associated with receptive vocabulary, performance on a set-shifting task (DCCS), and delay of gratification at Age 3. Finally, the indirect effects from the change in left frontal EEG coherence to 3-year cognitive flexibility, receptive language, and behavioral inhibitory control were significant, suggesting that internally controlled attention is a mechanism through which early neural maturation influences children's cognitive development. (PsycINFO Database Record PMID:27441486

  8. Stable Schizophrenia Patients Learn Equally Well as Age-Matched Controls and Better than Elderly Controls in Two Sensorimotor Rotary Pursuit Tasks

    PubMed Central

    De Picker, Livia J.; Cornelis, Claudia; Hulstijn, Wouter; Dumont, Glenn; Fransen, Erik; Timmers, Maarten; Janssens, Luc; Morrens, Manuel; Sabbe, Bernard G. C.

    2014-01-01

    Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. Results: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls. Conclusion: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study. PMID:25505425

  9. Fine tuning of cytosolic Ca 2+ oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent

    2016-01-01

    Ca 2+ oscillations, a widespread mode of cell signaling, were reported in non-excitable cells for the first time more than 25 years ago. Their fundamental mechanism, based on the periodic Ca 2+ exchange between the endoplasmic reticulum and the cytoplasm, has been well characterized. However, how the kinetics of cytosolic Ca 2+ changes are related to the extent of a physiological response remains poorly understood. Here, we review data suggesting that the downstream targets of Ca 2+ are controlled not only by the frequency of Ca 2+ oscillations but also by the detailed characteristics of the oscillations, such as their duration, shape, or baseline level. Involvement of non-endoplasmic reticulum Ca 2+ stores, mainly mitochondria and the extracellular medium, participates in this fine tuning of Ca 2+ oscillations. The main characteristics of the Ca 2+ exchange fluxes with these compartments are also reviewed.

  10. Increased calcium deposits and decreased Ca2+ -ATPase in erythrocytes of ascitic broiler chickens.

    PubMed

    Li, Kai; Zhao, Lihong; Geng, Guangrui; Ma, Liqin; Dong, Shishan; Xu, Tong; Wang, Jianlin; Wang, Huiyu; Tian, Yong; Qiao, Jian

    2011-06-01

    The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca2+ and Ca2+ -ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca2+ -ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca2+ -ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers. PMID:20728193

  11. Chromosome painting and the accumulation of stable cytogenetic damage with age in healthy controls

    SciTech Connect

    Tucker, J.D.; Ramsey, M.J.; Lee, D.A.

    1995-11-01

    Chromosome painting is now routinely used to identify induced stable chromosomal rearrangements, which are difficult and expensive to analyze with classical cytogenetic methods. Theoretically the inherent stability of translocations, in contrast to unstable dicentrics, enables their use as a biodosimeter for chronic and temporally-displaced exposure. To quantify the effects of adverse exposure, it is important that the baseline frequency of stable aberrations be well understood. Recently we have used chromosome painting to show that translocations accumulate with age. We have now extended this study to nearly 100 subjects ranging in age from newborns (umbilical cord bloods, n=14) to adults aged 19-79 years. All subjects were healthy, had not received chemo- or radiotherapy, and had not been occupationally or accidentally exposed to radiation or chemicals. We scored the equivalent of 1000 metaphase cells for each subject, and observed an overall average of 1.36 stable aberrations per 100 cells. Stable aberrations increased significantly with age, and were observed at frequencies of 0.19{plus_minus}0.04, 0.77{plus_minus}0.07, and 2.39{plus_minus}0.24 per 100 cells in cord blood, adults aged 19 to 49, and adults over age 50, respectively. To understand the extent that lifestyle factors influence the frequency of stable aberrations, each subject (or one parent of each newborn) completed a comprehensive questionnaire inquiring about lifestyle factors such as smoking, alcohol consumption, and dietary habits. No smoking effect is apparent in adults, however newborns whose mothers smoked during pregnancy had a 2.6-fold increase in stable aberration frequencies (p=0.033). Repeat samples from a subset of the adults suggest that individual translocation frequencies change little over a period of -3 years.

  12. Individual differences in aging and cognitive control modulate the neural indexes of context updating and maintenance during task switching.

    PubMed

    Adrover-Roig, Daniel; Barceló, Francisco

    2010-04-01

    This study aimed to explore the combined influence of age and cognitive control on the behavioural and electrophysiological indicators of local, restart and mixing costs. Two groups of middle-aged (49-60 y.o., N=40) and older (61-80 y.o., N=40) adults were split according to their overall z-score in a composite of six neuropsychological measures of executive function. All participants performed a task-cueing version of the Wisconsin Card Sorting Test (WCST) adapted for measuring event-related potentials, whereby tonal cues instructed to switch or repeat the task rule. A single-task condition with identical sensory and motor response demands was used to aid interpretation of behavioural and brain responses to cues and target events. Working memory updating of stimulus-response mappings, as putatively indexed by local switch costs and cue-locked P3 activity (350-460 msec post-cue onset), was preserved in both older and low control adults. In turn, low control adults showed larger restart costs and enhanced cue-locked P2 amplitudes (190-250 msec) in the task-switching condition only, suggesting lesser preparatory control in the presence of interference. Low control adults showed comparatively larger mixing costs and smaller cue-locked fronto-central slow negativities (500-700 msec), suggesting an inefficient online maintenance of task-set information over time. In contrast, target-locked brain responses were mostly sensitive to age-related effects, with older adults showing two well-known effects: (1) an "anterior shift" in target P3 activity (350-460 msec), and (2) an attenuation of fronto-central slow negativities in single-task and task-switching conditions, respectively. The additive association found between age and cognitive control for different behavioural indexes of task-switch costs suggests a differential influence of these factors upon two successive information processing stages: individual differences in cognitive control mainly influenced the neural

  13. Exploring the Glycosylation of Serum CA125

    PubMed Central

    Saldova, Radka; Struwe, Weston B.; Wynne, Kieran; Elia, Giuliano; Duffy, Michael J.; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecologic cancer affecting women. The most widely used biomarker for ovarian cancer, CA125, lacks sensitivity and specificity. Here, we explored differences in glycosylation of CA125 between serum from patients with ovarian cancer and healthy controls. We found differences between CA125 N-glycans from patient sera compared to controls. These include increases in core-fucosylated bi-antennary monosialylated glycans, as well as decreases in mostly bisecting bi-antennary and non-fucosylated glycans in patients compared to controls. Measurement of the glycosylated state of CA125 may therefore provide a more specific biomarker for patients with ovarian cancer. PMID:23896595

  14. Effects of stretching on menopausal and depressive symptoms in middle-aged women: a randomized controlled trial

    PubMed Central

    Kai, Yuko; Nagamatsu, Toshiya; Kitabatake, Yoshinori; Sensui, Hiroomi

    2016-01-01

    Abstract Objective: Exercise may help alleviate menopausal and depressive symptoms in middle-aged women, but sufficient evidence does not currently exist to fully support this theory. Whereas frequent moderate- to vigorous-intensity exercise may be associated with the risk of menopausal hot flashes, light-intensity exercise, such as stretching, is not likely to increase the occurrence of hot flashes. Little is, however, known about the effects of light-intensity exercise on menopausal and depressive symptoms. We examined the effects of a 3-week stretching program on the menopausal and depressive symptoms in middle-aged, Japanese women. Methods: Forty Japanese women, aged 40 to 61 years, were recruited (mean age, 51.1 ± 7.3 y). The participants were randomly assigned to either a stretching or a control group. The stretching group (n = 20) participated in a 3-week intervention program that involved 10 minutes of daily stretching, just before bedtime. The control group (n = 20) was assigned to a waiting list. Menopausal symptoms were evaluated using the Simplified Menopausal Index, which measures vasomotor, psychological, and somatic symptoms. Depressive symptoms were assessed using the Self-Rating Depression Scale. Results: The compliance rate was 75.8% during the 3-week intervention program. The total Simplified Menopausal Index scores, including the vasomotor, psychological, and somatic symptoms, and the Self-Rating Depression Scale scores significantly decreased in the stretching group compared with that in the control group. No adverse events, including increased hot flashes, were reported by the participants during the study period. Conclusions: These findings suggest that 10 minutes of stretching before bedtime decreases menopausal and depressive symptoms in middle-aged, Japanese women. PMID:27300113

  15. Pitch Characteristics Before Ulnar Collateral Ligament Reconstruction in Major League Pitchers Compared With Age-Matched Controls

    PubMed Central

    Prodromo, John; Patel, Nimit; Kumar, Neil; Denehy, Kevin; Tabb, Loni Philip; Tom, James

    2016-01-01

    Background: Ulnar collateral ligament reconstruction (UCLR) is commonly performed in Major League Baseball (MLB) pitchers, but little is known about the preoperative pitch type and velocity characteristics of pitchers who go on to undergo UCLR. Hypothesis: Pitchers who required UCLR have thrown a greater percentage of fastballs and have greater pitch velocities compared with age-matched controls in the season before injury. Study Design: Case-control study; Level of evidence, 3. Methods: MLB pitchers active during the 2002 to 2015 seasons were included. The UCLR group consisted of MLB pitchers who received UCLR between 2003 and 2015, utilizing the season before surgery (2002-2014) for analysis. The control group comprised age-matched controls of the same season. Players who pitched less than 20 innings in the season before surgery were excluded. Pitch types were recorded as percentage of total pitches thrown. Pitch velocities were recorded for each pitch type. Pitch type and pitch velocities during preoperative seasons for UCLR pitchers were compared with age-matched controls using univariate and multivariate models. Results: A total of 114 cases that went on to UCLR and 3780 controls were included in the study. Pitchers who went on to UCLR appear to have greater fastball, slider, curveball, changeup, and split-fingered fastball velocities; there were no significant differences in pitch selection between the 2 groups. Conclusion: In the season before surgery, MLB pitchers who underwent UCLR demonstrated greater fastball, slider, curveball, changeup, and split-fingered fastball velocities, with no significant difference in pitch type. PMID:27350954

  16. Protein aggregates are associated with replicative aging without compromising protein quality control

    PubMed Central

    Saarikangas, Juha; Barral, Yves

    2015-01-01

    Differentiation of cellular lineages is facilitated by asymmetric segregation of fate determinants between dividing cells. In budding yeast, various aging factors segregate to the aging (mother)-lineage, with poorly understood consequences. In this study, we show that yeast mother cells form a protein aggregate during early replicative aging that is maintained as a single, asymmetrically inherited deposit over the remaining lifespan. Surprisingly, deposit formation was not associated with stress or general decline in proteostasis. Rather, the deposit-containing cells displayed enhanced degradation of cytosolic proteasome substrates and unimpaired clearance of stress-induced protein aggregates. Deposit formation was dependent on Hsp42, which collected non-random client proteins of the Hsp104/Hsp70-refolding machinery, including the prion Sup35. Importantly, loss of Hsp42 resulted in symmetric inheritance of its constituents and prolonged the lifespan of the mother cell. Together, these data suggest that protein aggregation is an early aging-associated differentiation event in yeast, having a two-faceted role in organismal fitness. DOI: http://dx.doi.org/10.7554/eLife.06197.001 PMID:26544680

  17. The development of dental alloys conserving precious metals: improving corrosion resistance by controlled ageing.

    PubMed

    Yasuda, K; Hisatsune, K; Ohta, M

    1983-03-01

    To determine the conditions which confer desirable mechanical properties and corrosion resistance upon dental alloys, age-hardening mechanism and the associated structural changes were studied by means of resistometric measurements, hardness tests, electron microscope observations and electron diffraction studies. Five commercial dental alloys, a high-gold content alloy, a low-gold alloy and three Au-Ag-Pd silver-based alloys and two experimental gold alloys, were examined. The structural and morphological changes which gave rise to age-hardening were classified into five types of phase transformation, i.e., (1) the formation of the AuCu I type superlattice and its twinning characterized by a stair-step mode, (2) the formation of the AuCu II type super-lattice with periodic antiphase domain structure, (3) the precipitation of the CuPd superlattice with fct structure analogous to the AuCu I type, (4) spinodal decomposition giving rise to a modulated structure and (5) the formation of the lamellar structure developed from grain boundaries by discontinuous precipitations. (1), (2) and (3) made a contribution to corrosion resistance superior to (4) and (5). A lamellar structure was prone to a high corrosion rate. The results obtained in this study are useful in predicting age-hardening characteristics and structural changes associated with corrosion, because the microstructural variation induced by ageing as well as nobility of alloys affects greatly their corrosion resistance. PMID:6574108

  18. Is There a Relation between Onset Age of Bilingualism and Enhancement of Cognitive Control?

    ERIC Educational Resources Information Center

    Luk, Gigi; de Sa, Eric; Bialystok, Ellen

    2011-01-01

    Young English-speaking monolingual and bilingual adults were examined for English proficiency, language use history, and performance on a flanker task. The bilinguals, who were about twenty years old, were divided into two groups (early bilinguals and late bilinguals) according to whether they became actively bilingual before or after the age of…

  19. Risk and Resilience Factors in Coping with Daily Stress in Adulthood: The Role of Age, Self-Concept Incoherence, and Personal Control

    ERIC Educational Resources Information Center

    Diehl, Manfred; Hay, Elizabeth L.

    2010-01-01

    This study observed young, middle-aged, and older adults (N = 239; M[subscript age] = 49.6 years; range = 18-89 years) for 30 consecutive days to examine the association between daily stress and negative affect, taking into account potential risk (i.e., self-concept incoherence) and resilience (i.e., age, perceived personal control) factors.…

  20. EPIFIL: the development of an age-structured model for describing the transmission dynamics and control of lymphatic filariasis.

    PubMed Central

    Norman, R. A.; Chan, M. S.; Srividya, A.; Pani, S. P.; Ramaiah, K. D.; Vanamail, P.; Michael, E.; Das, P. K.; Bundy, D. A.

    2000-01-01

    Mathematical models of transmission dynamics of infectious diseases provide a useful tool for investigating the impact of community based control measures. Previously, we used a dynamic (constant force-of-infection) model for lymphatic filariasis to describe observed patterns of infection and disease in endemic communities. In this paper, we expand the model to examine the effects of control options against filariasis by incorporating the impact of age structure of the human community and by addressing explicitly the dynamics of parasite transmission from and to the vector population. This model is tested using data for Wuchereria bancrofti transmitted by Culex quinquefasciatus in Pondicherry, South India. The results show that chemotherapy has a larger short-term impact than vector control but that the effects of vector control can last beyond the treatment period. In addition we compare rates of recrudescence for drugs with different macrofilaricidal effects. PMID:10982078

  1. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2015-02-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  2. Kinetic Study on Desulfurization of Hot Metal Using CaO and CaC2

    NASA Astrophysics Data System (ADS)

    Lindström, David; Sichen, Du

    2014-09-01

    The kinetics and reaction mechanisms of hot metal desulfurization using CaO and CaC2 were studied in a well-controlled atmosphere with a lab scale high temperature furnace. The growths of CaS around CaO and CaC2 were measured and compared at 1773 K (1500 °C). The parabolic rate constant was evaluated to be 5 × 10-7 (cm s-1) on CaO particles, and 2.4 × 10-7 (cm s-1) on CaC2. The bigger parabolic constant of CaO resulted in more efficient desulfurization. Agglomerates and big CaO particles led to 2CaO·SiO2 formation which hindered further utilization of CaO for desulfurization. The 2CaO·SiO2 formation was favoured by a high oxygen potential. Since the desulfurization reaction of CaO not only produced CaS but also oxygen, the local oxygen concentration around big CaO particles was higher than around small particles.

  3. Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

    PubMed Central

    Leung, Kim Hung; Yip, Shea Ping; Wong, Wa Sang; Yiu, Lap San; Chan, Kam Keung; Lai, Wai Man; Chow, Eudora YD; Lin, Che Kit; Yam, Wing Cheong; Chan, Kin Sang

    2007-01-01

    Background Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. Methods A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. Results Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older