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Sample records for age ca controls

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

    PubMed Central

    Weisleder, Noah; Ma, Jianjie

    2008-01-01

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

  2. Altered Network Timing in the CA3-CA1 Circuit of Hippocampal Slices from Aged Mice

    PubMed Central

    Kanak, Daniel J.; Rose, Gregory M.; Zaveri, Hitten P.; Patrylo, Peter R.

    2013-01-01

    Network patterns are believed to provide unique temporal contexts for coordinating neuronal activity within and across different regions of the brain. Some of the characteristics of network patterns modeled in vitro are altered in the CA3 or CA1 subregions of hippocampal slices from aged mice. CA3–CA1 network interactions have not been examined previously. We used slices from aged and adult mice to model spontaneous sharp wave ripples and carbachol-induced gamma oscillations, and compared measures of CA3–CA1 network timing between age groups. Coherent sharp wave ripples and gamma oscillations were evident in the CA3–CA1 circuit in both age groups, but the relative timing of activity in CA1 stratum pyramidale was delayed in the aged. In another sample of aged slices, evoked Schaffer collateral responses were attenuated in CA3 (antidromic spike amplitude) and CA1 (orthodromic field EPSP slope). However, the amplitude and timing of spontaneous sharp waves recorded in CA1 stratum radiatum were similar to adults. In both age groups unit activity recorded juxtacellularly from unidentified neurons in CA1 stratum pyramidale and stratum oriens was temporally modulated by CA3 ripples. However, aged neurons exhibited reduced spike probability during the early cycles of the CA3 ripple oscillation. These findings suggest that aging disrupts the coordination of patterned activity in the CA3–CA1 circuit. PMID:23593474

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

    PubMed

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

    2009-04-01

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

  4. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  7. 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

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

    PubMed

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

    2009-09-01

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

  9. Proteus DSA control room in Mojave, CA

    NASA Image and Video Library

    2003-04-03

    Proteus DSA control room in Mojave, CA (L to R) Jean-Pierre Soucy; Amphitech International Software engineer Craig Bomben; NASA Dryden Test Pilot Pete Siebold; (with headset, at computer controls) Scaled Composites pilot Bob Roehm; New Mexico State University (NMSU) UAV Technical Analysis Application Center (TAAC) Chuck Coleman; Scaled Composites Pilot Kari Sortland; NMSU TAAC Russell Wolfe; Modern Technology Solutions, Inc. Scaled Composites' unique tandem-wing Proteus was the testbed for a series of UAV collision-avoidance flight demonstrations. An Amphitech 35GHz radar unit installed below Proteus' nose was the primary sensor for the Detect, See and Avoid tests.

  10. Decreases in Plasma Membrane Ca2+-ATPase in Brain Synaptic Membrane Rafts from Aged Rats

    PubMed Central

    Jiang, Lei; Bechtel, Misty D.; Galeva, Nadezhda A.; Williams, Todd D.; Michaelis, Elias K.; Michaelis, Mary L.

    2012-01-01

    Precise regulation of free intracellular Ca2+ concentrations [Ca2+]i is critical for normal neuronal function, and alterations in Ca2+ homeostasis are associated with brain aging and neurodegenerative diseases. One of the most important proteins controlling [Ca2+]i is the plasma membrane Ca2+-ATPase (PMCA), the high affinity transporter that fine tunes the cytosolic nanomolar levels of Ca2+. We previously found that PMCA protein in synaptic plasma membranes (SPMs) is decreased with advancing age and the decrease in enzyme activity is much greater than that in protein levels. In the present study, we isolated raft and non-raft fractions from rat brain SPMs and used quantitative mass spectrometry to show that the specialized lipid microdomains in SPMs, the rafts, contain 60% of total PMCA, comprised of all four isoforms. The raft PMCA pool had the highest specific activity and this decreased progressively with age. The reduction in PMCA protein could not account for the dramatic activity loss. Addition of excess CaM to the assay did not restore PMCA activity to that in young brains. Analysis of the major raft lipids revealed a slight age-related increase in cholesterol levels and such increases might enhance membrane lipid order and prevent further loss of PMCA activity. PMID:22889001

  11. Overgeneral autobiographical memory in healthy young and older adults: Differential age effects on components of the capture and rumination, functional avoidance, and impaired executive control (CaRFAX) model.

    PubMed

    Ros, Laura; Latorre, Jose M; Serrano, Juan P; Ricarte, Jorge J

    2017-08-01

    The CaRFAX model (Williams et al., 2007) has been used to explain the causes of overgeneral autobiographical memory (OGM; the difficulty to retrieve specific autobiographical memories), a cognitive phenomenon generally related with different psychopathologies. This model proposes 3 different mechanisms to explain OGM: capture and rumination (CaR), functional avoidance (FA) and impaired executive functions (X). However, the complete CaRFAX model has not been tested in nonclinical populations. This study aims to assess the usefulness of the CaRFAX model to explain OGM in 2 healthy samples: a young sample and an older sample, to test for possible age-related differences in the underlying causes of OGM. A total of 175 young (age range: 19-36 years) and 175 older (age range: 53-88 years) participants completed measures of brooding rumination (CaR), functional avoidance (FA), and executive tasks (X). Using structural equation modeling, we found that memory specificity is mainly associated with lower functional avoidance and higher executive functions in the older group, but only with executive functions in young participants. We discuss the different roles of emotional regulation strategies used by young and older people and their relation to the CaRFAX model to explain OGM in healthy people. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Epigenetic Control of Aging

    PubMed Central

    Sedivy, John M.

    2011-01-01

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

  13. Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+ exchange to Ca2+ removal in rat left ventricular myocytes.

    PubMed

    Fowler, Mark R; Naz, James R; Graham, Mark D; Orchard, Clive H; Harrison, Simon M

    2007-03-01

    Age and hypertension contribute significantly to cardiac morbidity and mortality, however the importance of each during the progression of hypertrophy is unclear. This investigation examined the effect of age and hypertension on Ca(2+) handling in rat ventricular myocytes by comparing a genetic model of hypertension and cardiac hypertrophy (spontaneously hypertensive rat, SHR) with its normotensive control (Wistar-Kyoto rat, WKY) at 5 and 8 months of age. Experiments were performed on single left ventricular myocytes isolated from SHR or WKY hearts. Intracellular Ca(2+) was measured optically using fura-2 or fluo-3. SHR myocytes had a significantly larger cell width and volume and a significantly decreased cell length/width ratio at 5 and 8 months compared to normotensive controls. Age had no effect on cell length, width, volume or the length/width ratio. Ca(2+) transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) content and contraction amplitude were unaffected by age or hypertrophy. However at 8 months the contribution of the SR to Ca(2+) uptake during relaxation decreased, with a concomitant increase in the contribution of Na(+)/Ca(2+) exchanger (NCX) function to relaxation, in SHR and WKY myocytes. The incidence of non-synchronous SR Ca(2+) release decreased with age but not hypertrophy in SHR and WKY myocytes. These results show that the changes in Ca(2+) handling observed during progression of mild hypertrophy in SHR are the same as those that occur during ageing in normotensive control animals and can, therefore, be ascribed to maturation rather than hypertrophy.

  14. Controls on Sr/Ca in Scleractinian Corals: The Effects of Ca-ATPase and Ca channels on Skeletal Chemistry

    NASA Astrophysics Data System (ADS)

    Allison, N.; Cohen, I.; Finch, A. A.; Erez, J.

    2010-12-01

    Coral skeletal Sr/Ca is a commonly used palaeothermometer and has been used to estimate past sea surface temperatures. However the processes controlling Sr incorporation in coral aragonite are poorly understood. The Sr/Ca chemistry of the massive Porites spp. corals typically used for palaeoenvironmental reconstruction is dominated by short-term (weekly-monthly) oscillations of ~10% which do not reflect seawater temperature. This heterogeneity may reflect variations in the composition of the fluid used for calcification. Coral skeletons precipitate from an extracellular calcifying fluid enclosed in a semi-isolated space between the skeleton and the calicoblastic epithelium (the tissue layer at the base of the coral organism). Seawater diffuses directly to the calcification site and the calcification fluid has a composition derived from that of seawater but modified by other transport processes. In zooxanthellate corals, Ca2+ is transported transcellularly to the calcification site by both calcium channels and by the carrier protein Ca-ATPase. Sr2+ has a similar ionic radius to Ca2+, but it is not clear if Sr2+ can substitute for Ca2+ in these transport mechanisms. Variations in the relative contributions of each of the transport mechanisms to the calcification fluid and the efficiencies with which each process transports Sr2+ and Ca2+ could explain the Sr/Ca heterogeneity observed in coral skeletons. To test the impact of transcellular Ca transport processes on skeletal Sr/Ca and Mg/Ca we cultured Pocillopora damicornis corals in the presence of inhibitors of Ca-ATPase (ruthenium red) and Ca channels (verapamil). The photosynthesis, respiration and calcification rates of the colonies were monitored throughout the experiment. The skeleton subsequently deposited was identified (by 42Ca spike) and analysed by secondary ion mass spectrometry. The Sr/Ca and Mg/Ca of the aragonite deposited in the presence of either of the inhibitors was not significantly different from

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

    PubMed

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

    2012-08-01

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

  16. 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

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

    PubMed Central

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

    2017-01-01

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

  18. The other side of cardiac Ca2+ signaling: transcriptional control

    PubMed Central

    Domínguez-Rodríguez, Alejandro; Ruiz-Hurtado, Gema; Benitah, Jean-Pierre; Gómez, Ana M.

    2012-01-01

    Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling), but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling). ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII) and phosphatase calcineurin, both of which are activated by the complex Ca2+/Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n) or cytoplasmic ([Ca2+]c), and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs) in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs) in [Ca2+]c, needed to activate calcineurin (Cn). PMID:23226134

  19. Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.

    PubMed

    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

    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. 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. 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 signatures as novel therapeutic targets to counter effects of SD in young

  20. 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

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

    PubMed

    Hosseini-sharifabad, Mohammad; Esfandiari, Ebrahim

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-09-01

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

  4. Alterations of Ca2+ responsive proteins within cholinergic neurons in aging and AD

    PubMed Central

    Riascos, David; Nicholas, Alexander; Samaeekia, Ravand; Yukhnanov, Rustam; Mesulam, M.-Marsel; Bigio, Eileen H.; Weintraub, Sandra; Guo, Ling; Geula, Changiz

    2014-01-01

    The molecular basis of selective neuronal vulnerability in Alzheimer ’s disease (AD) remains poorly understood. Using basal forebrain cholinergic neurons (BFCN) as a model and immunohistochemistry, we have demonstrated significant age-related loss of the calcium binding protein calbindin-D28K (CB) from BFCN, which was associated with tangle formation and degeneration in AD. Here we determined alterations in RNA and protein for CB and other Ca2+ responsive proteins Ca2+/calmodulin-dependent protein kinase I (CaMKI), growth-associated protein-43 (GAP43), calpain in the basal forebrain. We observed progressive downregulation of CB and CaMKI RNA in laser-captured BFCN in the normal-aged-AD continuum. We also detected progressive loss of CB, CaMKI-Delta, and GAP43 proteins in BF homogenates in aging and AD. Activated μ-calpain, a calcium-sensitive protease that degrades CaMKI and GAP-43, was significantly increased in the normal aged BF and was 10-times higher in AD BF. Overactivation of μ-calpain was confirmed using proteolytic fragments of its substrate spectrin. Substantial age and AD related alterations in Ca2+-sensing proteins most likely contribute to selective vulnerability of BFCN to degeneration in AD. PMID:24461366

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

    PubMed

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

    2006-07-01

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

  6. 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.

  7. 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.

  8. In vitro aging promotes endoplasmic reticulum (ER)-mitochondria Ca(2+) cross talk and loss of store-operated Ca(2+) entry (SOCE) in rat hippocampal neurons.

    PubMed

    Calvo-Rodríguez, María; García-Durillo, Mónica; Villalobos, Carlos; Núñez, Lucía

    2016-11-01

    Aging is associated to cognitive decline and susceptibility to neuron death, two processes related recently to subcellular Ca(2+) homeostasis. Memory storage relies on mushroom spines stability that depends on store-operated Ca(2+) entry (SOCE). In addition, Ca(2+) transfer from endoplasmic reticulum (ER) to mitochondria sustains energy production but mitochondrial Ca(2+) overload promotes apoptosis. We have addressed whether SOCE and ER-mitochondria Ca(2+) transfer are influenced by culture time in long-term cultures of rat hippocampal neurons, a model of neuronal aging. We found that short-term cultured neurons show large SOCE, low Ca(2+) store content and no functional coupling between ER and mitochondria. In contrast, in long-term cultures reflecting aging neurons, SOCE is essentially lost, Stim1 and Orai1 are downregulated, Ca(2+) stores become overloaded, Ca(2+) release is enhanced, expression of the mitochondrial Ca(2+) uniporter (MCU) increases and most Ca(2+) released from the ER is transferred to mitochondria. These results suggest that neuronal aging is associated to increased ER-mitochondrial cross talking and loss of SOCE. This subcellular Ca(2+) remodeling might contribute to cognitive decline and susceptibility to neuron cell death in the elderly. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Ca2+ efflux from platelets. Control by protein kinase C and the filling state of the intracellular Ca2+ stores.

    PubMed

    Cavallini, L; Alexandre, A

    1994-06-01

    Large amounts of Ca2+ (almost 20 nmol/10(8) cells) are released from platelets by exocytosis. This secretory-granule-associated Ca2+ does not contribute to the cytosolic free Ca2+ ([Ca2+]i), which is controlled by the much smaller agonist-sensitive Ca2+ pool, unless high (1 microM), but not low (0.04 microM) concentrations of ionomycin are present. Low concentrations of ionomycin release Ca2+ almost exclusively from the agonist-sensitive stores. In aspirinated platelets incubated in the presence of 0.5 mM EGTA the extensive depletion of the agonist-sensitive stores is obtained by the combined action of low ionomycin and the endomembrane Ca(2+)-ATPase inhibitor thapsigargin (which individually promote only a partial depletion). The subsequent decay of [Ca2+]i is increased by phorbol-myristate acetate, confirming that Ca2+ efflux from platelets is potentiated by the activation of protein kinase C [Pollock, W. K., Sage, S. O. & Rink, T. J. (1987) FEBS Lett. 210, 132-140]. A novel type of control of Ca2+ efflux appears to be exerted by the filling state of the stores. Treatment with low ionomycin or thapsigargin determines the release of a fraction of the stores-associated Ca2+; the subsequent decay of [Ca2+]i is slow. The decay rate of [Ca2+]i accelerates after extensive depletion of the stores following the addition of thapsigargin or ionomycin. If the depletion of the stores is induced by thrombin, added alone or in combination with thapsigargin, the increases of [Ca2+]i are the same and the subsequent decay rates are largely superimposable; however a large fraction of [Ca2+]i is reaccumulated into the stores in the absence, but not in the presence of thapsigargin, indicating that Ca2+ efflux is activated when the stores are empty. Ca2+ efflux can proceed against a concentration gradient. In 45Ca-loaded platelets, the thrombin-promoted 45Ca efflux is potentiated by thapsigargin. The protein-kinase-C-dependent and store-depletion-dependent stimulations of 45Ca efflux

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

    PubMed Central

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

    2000-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Intracellular Ca(2+) signaling and Ca(2+) microdomains in the control of cell survival, apoptosis and autophagy.

    PubMed

    La Rovere, Rita M L; Roest, Gemma; Bultynck, Geert; Parys, Jan B

    2016-08-01

    The endoplasmic reticulum (ER), mitochondria and lysosomes are physically and/or functionally linked, establishing close contact sites between these organelles. As a consequence, Ca(2+) release events from the ER, the major intracellular Ca(2+)-storage organelle, have an immediate effect on the physiological function of mitochondria and lysosomes. Also, the lysosomes can act as a Ca(2+) source for Ca(2+) release into the cytosol, thereby influencing ER-based Ca(2+) signaling. Given the important role for mitochondria and lysosomes in cell survival, cell death and cell adaptation processes, it has become increasingly clear that Ca(2+) signals from or towards these organelles impact these processes. In this review, we discuss the most recent insights in the emerging role of Ca(2+) signaling in cellular survival by controlling basal mitochondrial bioenergetics and by regulating apoptosis, a mitochondrial process, and autophagy, a lysosomal process, in response to cell damage and cell stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Dahl, Ashley R.; Gagnon, Patricia M.

    2010-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-10-03

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

  16. K-Ca ages of authigenic sediments: examples from Paleozoic glauconite and applications to low-temperature thermochronometry

    NASA Astrophysics Data System (ADS)

    Cecil, M. Robinson; Ducea, Mihai N.

    2011-11-01

    K-Ca ages of Cambrian glauconites from the Llano uplift, central Texas, were determined in order to re-evaluate the ability of the K-Ca system to constrain the timing of deposition of sedimentary packages. All of the K-Ca ages presented here were found to be younger than their stratigraphic ages. In addition to being too young, the K-Ca ages are also highly variable, ranging in age from Silurian to Permian. The oldest subset of glauconite ages are in agreement with previously published Rb-Sr ages from the same outcrop and provide further evidence for there having been a post-depositional thermal or recrystallization event that reset both the Rb-Sr and K-Ca systems. The range of younger glauconite K-Ca ages is similar to the distribution of available apatite fission track ages for the Llano basement. K-Ca ages are interpreted as thermochronologic data reflecting partial retention of Ca in thermally fluctuating basin conditions. Estimates of the closure temperature of Ca in glauconite are found to be 60-90°C for cooling rates of ~0.5-1°C/My. The K-Ca system is potentially useful as a low-temperature thermochronometer with closure temperatures <100°C for glauconite.

  17. 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.

  18. 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

    2015-11-03

    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.

  19. Metformin and ageing: improving ageing outcomes beyond glycaemic control.

    PubMed

    Valencia, Willy Marcos; Palacio, Ana; Tamariz, Leonardo; Florez, Hermes

    2017-08-02

    In a world where the population is ageing, there is growing interest and demand for research evaluating strategies that address the ageing process. After 60 years of successful use of metformin in our pharmaceutical armamentarium, we are learning that, beyond improving glycaemic control, metformin may have additional mechanisms and pathways of action that need further study. Although, metformin's effect on clinical ageing outcomes may still be considered speculative, the findings from studies into cellular and animal models and from observational and pilot human studies support the existence of beneficial effects on ageing. At present, progress for human research, using randomised clinical trials to evaluate metformin's clinical impact, has just started. Here, we present a review on the ageing process and the mechanisms involved, and the role that metformin may have to counter these. We go on to discuss the upcoming large randomised clinical trials that may provide insight on the use of metformin for ageing outcomes beyond glycaemic control.

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

    PubMed

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

    2004-05-15

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

  1. 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

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

    PubMed

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

    2014-09-26

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

  3. Synaptic strength and postsynaptically silent synapses through advanced aging in rat hippocampal CA1 pyramidal neurons

    PubMed Central

    Sametsky, Evgeny A.; Disterhoft, John F.; Geinisman, Yuri; Nicholson, Daniel A.

    2009-01-01

    Synaptic dysfunction is thought to contribute to age-related learning impairments. Detailed information regarding the presence of silent synapses and the strength of functional ones through advanced aging, however, is lacking. Here we used paired-pulse minimal stimulation techniques in CA1 stratum radiatum to determine whether the amplitude of spontaneous and evoked miniature excitatory postsynaptic currents (sEPSCs and eEPSCs, respectively) changes over the lifespan of rats in hippocampal CA1 pyramidal neurons, and whether silent synapses are present in adult and aged rats. The amplitudes of both sEPSCs and eEPSCs at resting membrane potential (i.e., clamped at −65 mV) initially increased between 2 weeks and 3 months, but then remained constant through 36 months of age. The potency of the eEPSCs at depolarized membrane potentials (i.e., clamped at +40 mV), however, was highest among 36-month old rats. Additionally, presynaptically silent synapses in CA1 stratum radiatum disappeared between 2 weeks and 3 months, but postsynaptically silent synapses were present through advanced aging. The similarity of silent and functional synapses in CA1 hippocampus at resting membrane potentials throughout adulthood in rats may indicate that impairments in the mechanisms of synaptic plasticity and its subsequent stabilization, rather than deficient synaptic transmission, underlie age-related cognitive decline. Such a notion is consistent with the increased amplitude of synaptic currents at depolarized potentials, perhaps suggesting an upregulation in the expression of synaptic NMDA receptors once rats reach advanced age. PMID:18620783

  4. Spatial memory decline after masticatory deprivation and aging is associated with altered laminar distribution of CA1 astrocytes

    PubMed Central

    2012-01-01

    Background Chewing imbalances are associated with neurodegeneration and are risk factors for senile dementia in humans and memory deficits in experimental animals. We investigated the impact of long-term reduced mastication on spatial memory in young, mature and aged female albino Swiss mice by stereological analysis of the laminar distribution of CA1 astrocytes. A soft diet (SD) was used to reduce mastication in the experimental group, whereas the control group was fed a hard diet (HD). Assays were performed in 3-, 6- and 18-month-old SD and HD mice. Results Eating a SD variably affected the number of astrocytes in the CA1 hippocampal field, and SD mice performed worse on water maze memory tests than HD mice. Three-month-old mice in both groups could remember/find a hidden platform in the water maze. However, 6-month-old SD mice, but not HD mice, exhibited significant spatial memory dysfunction. Both SD and HD 18-month-old mice showed spatial memory decline. Older SD mice had astrocyte hyperplasia in the strata pyramidale and oriens compared to 6-month-old mice. Aging induced astrocyte hypoplasia at 18 months in the lacunosum-moleculare layer of HD mice. Conclusions Taken together, these results suggest that the impaired spatial learning and memory induced by masticatory deprivation and aging may be associated with altered astrocyte laminar distribution and number in the CA1 hippocampal field. The underlying molecular mechanisms are unknown and merit further investigation. PMID:22376223

  5. 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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2008-01-01

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

  9. Sex and Age Modify Biochemical and Skeletal Manifestations of Chronic Hyperparathyroidism by Altering Target Organ Responses to Ca2+ and PTH in Mice

    PubMed Central

    Cheng, Zhiqiang; Liang, Nathan; Chen, Tsui-Hua; Li, Alfred; Maria, Christian Santa; You, Michael; Ho, Hanson; Song, Fuqing; Bikle, Daniel; Tu, Chialing; Shoback, Dolores; Chang, Wenhan

    2012-01-01

    We studied mice with or without heterozygous deletion of the Casr in the parathyroid gland (PTG) [PTGCaSR(+/−)] to delineate effects of age and sex on manifestations of hyperparathyroidism (HPT). In control mice, aging induced a left-shift in the Ca2+/parathyroid hormone (PTH) set-point accompanied by increased PTG CaSR expression along with lowered serum Ca2+ and mildly increased PTH levels, suggesting adaptive responses of PTGs to aging-induced changes in mineral homeostasis. The aging effects on Ca2+/PTH set-point and CaSR expression were significantly blunted in PTGCaSR(+/−) mice who showed instead progressively elevated PTH levels with age, especially in 12-month-old females. These 12-month-old knockout mice demonstrated resistance to their high PTH levels in that serum 1,25-dihydroxyvitamin D (1,25-D) levels and RNA expression of renal Cyp27b1 and expression of genes involved in Ca2+ transport in kidney and intestine were unresponsive to the rising PTH levels. Such changes may promote negative Ca2+ balance, which further exacerbate the HPT. Skeletal responses to HPT were age-, sex-, and site-dependent. In control mice of either sex, trabecular bone in the distal femur decreased while cortical bone in the tibiofibular junction increased with age. In male PTGCaSR(+/−) mice, anabolic actions of the elevated PTH levels seemed to protect against trabecular bone loss at ≥3 months of age at the expense of cortical bone loss. In contrast, HPT produced catabolic effects on trabecular bone and anabolic effects on cortical bone in 3-month-old females; but these effects reversed by 12 months, preserving trabecular bone in aging mice. We demonstrate that the CaSR plays a central role in the adaptive responses of parathyroid function to age-induced changes in mineral metabolism and in target organ responses to calciotropic hormones. Restraining the ability of the PTG to upregulate CaSRs by heterozygous gene deletion contributes to biochemical and skeletal

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

    NASA Astrophysics Data System (ADS)

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

    2008-09-01

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

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

    PubMed

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

    2011-05-01

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

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

    PubMed

    Davey, Adam; Malmberg, Bo; Sundström, Gerdt

    2014-08-01

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

  13. 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

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

    PubMed Central

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

    2012-01-01

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

  15. 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.

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

    PubMed Central

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

    2006-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    Wang, Yue; Mattson, Mark P.

    2013-01-01

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

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

    PubMed

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

    2004-01-01

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

  20. 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

  1. 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.

  2. 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...

  3. Social inappropriateness, executive control, and aging.

    PubMed

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

    2009-03-01

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

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

    PubMed Central

    Verkhratsky, Alexei

    2016-01-01

    fascinating success story. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377729

  5. 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

  6. Increased GSNOR Expression during Aging Impairs Cognitive Function and Decreases S-Nitrosation of CaMKIIα.

    PubMed

    Zhang, Yuying; Wu, Kaiyuan; Su, Wenting; Zhang, Deng-Feng; Wang, Ping; Qiao, Xinhua; Yao, Qin; Yuan, Zengqiang; Yao, Yong-Gang; Liu, Guanghui; Zhang, Chen; Liu, Limin; Chen, Chang

    2017-10-04

    As the population ages, an increasing number of people suffer from age-related cognitive impairment. However, the mechanisms underlying this process remain unclear. Here, we found that S-nitrosoglutathione reductase (GSNOR), the key enzyme that metabolizes intracellular nitric oxide (NO) and regulates S-nitrosation, was significantly increased in the hippocampus of both aging humans and mice. Transgenic mice overexpressing GSNOR exclusively in neurons showed cognitive impairment in behavioral tests, including the Morris water maze, fear conditioning, and the Y-maze test. We also found that GSNOR transgenic mice have LTP defects and lower dendrite spine density, whereas GSNOR knock-out mice rescued the age-related cognitive impairment. Analysis of S-nitrosation showed significantly decreased hippocampal CaMKIIα S-nitrosation in naturally aged mice and GSNOR transgenic mice. Consistent with the change in CaMKIIα S-nitrosation, the accumulation of CaMKIIα in the hippocampal synaptosomal fraction, as well as its downstream signaling targets p(S831)-GLUR1, was also significantly decreased. All these effects could be rescued in the GSNOR knock-out mice. We further verified that the S-nitrosation of CaMKIIα was responsible for the CaMKIIα synaptosomal accumulation by mutating CaMKIIα S-nitrosated sites (C280/C289). Upregulation of the NO signaling pathway rescued the cognitive impairment in GSNOR transgenic mice. In summary, our research demonstrates that GSNOR impairs cognitive function in aging and it could serve as a new potential target for the treatment of age-related cognitive impairment. In contrast to the free radical theory of aging, NO signaling deficiency may be the main mediator of age-related cognitive impairment.SIGNIFICANCE STATEMENT This study indicated that S-nitrosoglutathione reductase (GSNOR), a key protein S-nitrosation metabolic enzyme, is a new potential target in age-related cognitive impairment; and in contrast to the free radical theory of

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

    PubMed

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

    2007-04-01

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

  8. Age-related Changes in Lateral Entorhinal and CA3 Neuron Allocation Predict Poor Performance on Object Discrimination

    PubMed Central

    Maurer, Andrew P.; Johnson, Sarah A.; Hernandez, Abbi R.; Reasor, Jordan; Cossio, Daniela M.; Fertal, Kaeli E.; Mizell, Jack M.; Lubke, Katelyn N.; Clark, Benjamin J.; Burke, Sara N.

    2017-01-01

    Age-related memory deficits correlate with dysfunction in the CA3 subregion of the hippocampus, which includes both hyperactivity and overly rigid activity patterns. While changes in intrinsic membrane currents and interneuron alterations are involved in this process, it is not known whether alterations in afferent input to CA3 also contribute. Neurons in layer II of the lateral entorhinal cortex (LEC) project directly to CA3 through the perforant path, but no data are available regarding the effects of advanced age on LEC activity and whether these activity patterns update in response to environmental change. Furthermore, it is not known the extent to which age-related deficits in sensory discrimination relate to the inability of aged CA3 neurons to update in response to new environments. Young and aged rats were pre-characterized on a LEGO© object discrimination task, comparable to behavioral tests in humans in which CA3 hyperactivity has been linked to impairments. The cellular compartment analysis of temporal activity with fluorescence in situ hybridization for the immediate-early gene Arc was then used to identify the principal cell populations that were active during two distinct epochs of random foraging in different environments. This approach enabled the extent to which rats could discriminate two similar objects to be related to the ability of CA3 neurons to update across different environments. In both young and aged rats, there were animals that performed poorly on the LEGO object discrimination task. In the aged rats only, however, the poor performers had a higher percent of CA3 neurons that were active during random foraging in a novel environment, but this is not related to the ability of CA3 neurons to remap when the environment changed. Afferent neurons to CA3 in LEC, as identified with the retrograde tracer choleratoxin B (CTB), also showed a higher percentage of cells that were positive for Arc mRNA in aged poor performing rats. This suggests

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

    PubMed

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

    2002-11-15

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

  10. The quality control theory of aging.

    PubMed

    Ladiges, Warren

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1991-10-01

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

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

    PubMed

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

    2015-01-01

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

  13. 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.

  14. 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.

  15. Long-term treatment with a Chinese herbal formula, Sheng-Mai-San, improves cardiac contractile function in aged rats: the role of Ca(2+) homeostasis.

    PubMed

    Zhang, Guang-Qin; Wang, Hui; Liu, Wen-Tao; Dong, Hang; Fong, Wang-Fun; Tang, Li-Min; Xiong, Yun-Hua; Yu, Zhi-Ling; Ko, Kam-Ming

    2008-12-01

    A Chinese herbal formula Sheng-Mai-Yin (SMY), the liquid dosage form of Sheng-Mai-San, has been used clinically for treating heart failure, particularly in aged patients. To investigate the effect of SMY treatment on the contractile function of aged hearts, we first examined cardiac hemodynamics in aged rats. To define the mechanism involved in the enhancement of cardiac function, we investigated the effect of SMY treatment on Ca(2+) homeostasis in ventricular cardiomyocytes isolated from aged rats. Ca(2+) release was assessed by measurements of changes in cardiac Ca(2+) transients and Ca(2+) sparks, using laser scanning confocal microscopy. The functional status of Ca(2+)-release regulators, including L-type Ca(2+) channels, sarcoplasmic reticulum (SR) Ca(2+)-adenosine triphosphatase (ATPase), and ryanodine receptors (RyRs), was also assessed. The results indicated that SMY treatment (2 g/kg per day for 30 doses within 6 weeks, intragastically) significantly improved hemodynamic parameters in aged rats. SMY treatment markedly increased the amplitude and shortened the duration of Ca(2+) transients in aged cardiomyocytes, and reversed the age-related increase in frequency, decrease in amplitude, and changes in spatiotemporal properties of Ca(2+) sparks in cardiomyocytes. In addition, SMY treatment increased the L-type Ca(2+) current density, SR Ca(2+) content, and SR Ca(2+)-ATPase expression, and decreased the sensitivity of RyRs to Ca(2+), all of which are causally related to increases in the amplitude of Ca(2+) transients and the size of Ca(2+) sparks. In conclusion, the improvement in cardiac contractile function afforded by SMY treatment in aged rats is likely mediated by an increase in Ca(2+) release from the SR through L-type Ca(2+) current-activated RyRs.

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-11-24

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

  20. 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.

  1. 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

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

    PubMed

    Tonkikh, A A; Carlen, P L

    2009-04-10

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

  3. Control of Ca2+ in rod outer segment disks by light and cyclic GMP.

    PubMed

    George, J S; Hagins, W A

    1983-05-26

    Photons absorbed in vertebrate rods and cones probably cause electrochemical changes at the photoreceptor plasma membrane by changing the cytoplasmic concentration of a diffusible transmitter substance, reducing the Na+ current flowing into the outer segment of the cell in the dark, to produce the observed membrane hyperpolarization that is the initial excitatory response. Cyclic GMP has been proposed as the transmitter because a light-activated cyclic GMP phosphodiesterase (PDE) has been found in rod disk membranes and because intracellularly injected cyclic GMP reduces rod membrane potentials. Free Ca2+ has also been proposed because increasing external [Ca2+] quickly and reversibly reduces the dark current and divalent cationophores increase the Ca2+ sensitivity. Ca2+ efflux from rod outer segments (ROS) of intact retinas occurs simultaneously with light responses. Vesicles prepared from ROS disk membranes become more permeable on illumination, releasing trapped ions or molecules, but intact outer segment disks have not previously been found to store sufficient Ca2+ in darkness and to release enough in light to meet the theoretical requirements for control of the dark current by varying cytoplasmic Ca2+ (refs 14-18). We now report experiments that show the required Ca2+ storage and release from rod disk membranes suspended in media containing high-energy phosphate esters and electrolytes approximating the cytoplasmic composition of live rod cells. Cyclic GMP stimulates Ca2+ uptake by ROS disks in such media.

  4. 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

  5. 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.

  6. 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.

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

    PubMed

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

    1998-05-01

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

  8. Urease activity in aged copper and zinc-spiked soils: relationship to CaCl2-extractable metals and Cu2+ activity.

    PubMed

    Kim, Bojeong; McBride, Murray B; Hay, Anthony G

    2008-12-01

    In the present study, the utilization of dilute CaCl2 extraction and free metal ion activity was tested for its ability to predict urease activity in soils that was measured by a simple and rapid urease assay. Two soil series (an Arkport sandy loam and a Hudson silty clay loam) were spiked with Cu and Zn, both singly and in combination, and then field aged for over a year prior to use. For both the metal-spiked Arkport and Hudson soils, much of the inhibition in measured urease activity was explained by increased CaCl2-extractable Cu, with a lesser effect from increased Zn extractability. A positive but weak interaction between Cu and Zn suggested by regression analysis indicates the toxicity of Cu-Zn mixtures to soil urease is slightly less than additive (antagonistic). Copper extractability using CaCl2 was able to predict urease activity in only one of the tested soils. By contrast, measurements of Cu2+ activity were predictive of reduced urease activity in both soils (R2adj = 0.726, p < 0.0001), indicating that Cu2+ activity is a more useful predictor of urease inhibition in soils than CaCl2-extractable Cu. The present study also highlighted the importance that clay mineral content had on controlling the availability of added metals in soils over time since a greater aging effect on Cu toxicity was found for the fine-textured Hudson than the coarse-textured Arkport soil.

  9. Alteration in temporal kinetics of Ca2+ signaling and control of growth and proliferation.

    PubMed

    Lipskaia, Larissa; Lompré, Anne-Marie

    2004-02-01

    Calcium is a ubiquitous second messenger controlling a broad range of cellular functions including growth and proliferation. Quiescent, hyperthrophic and proliferating cells have different types of calcium signal. In quiescent cells the calcium signal mostly involves elementary calcium events such as sparks and puffs, produced by localized Ca2+ release via a cluster of intracellular calcium channels, IP3 receptors and ryanodine receptors. This type of calcium signal promotes activation of the transcription factor CREB (cAMP response element binding protein) leading to cell cycle arrest in G1 phase via transactivation of p53/p21 signaling pathways. Proliferation is induced by phosphoinositide-coupled agonists and is associated with a sustained increase in cytosolic calcium due to 1.) enhanced excitability of IP3Rs after IP3 binding; 2.) enhanced activity of store-operated Ca2+ channels and T-type voltage-operated Ca2+ channels; 3.) decreased cytosolic Ca2+ removal due to inhibition of PMCA (plasma membrane Ca(2+)-ATPase) and SERCA (sarco/endoplasmic reticulum Ca(2+)-ATPase) calcium pumps. This type of calcium signal favors activation of the transcription factor NFAT (nuclear factor of activated T lymphocytes) that promotes hypertrophic growth and/or cell cycle progression. We suggest that the two main Ca(2+)-regulated transcription factors, CREB and NFAT, exert opposite control over cell growth and/or proliferation. Therapeutic strategies based on lowering intracellular Ca2+ or targeting of Ca(2+)-regulated transcription factors seems to be a promising approach to arrest growth and/or proliferation.

  10. Paeonol attenuates aging MRC-5 cells and inhibits epithelial-mesenchymal transition of premalignant HaCaT cells induced by aging MRC-5 cell-conditioned medium.

    PubMed

    Yang, Lihua; Xing, Shangping; Wang, Kun; Yi, Hua; Du, Biaoyan

    2017-08-12

    Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear. In this study, we first established a senescent human fetal lung fibroblast MRC-5 cell model using hydrogen peroxide evaluated by senescence-associated β-galactosidase assay. Upon paeonol treatment, intracellular reactive oxygen species levels in aging MRC-5 cells were significantly decreased via regulation of nuclear translocation of Nrf2. Then we curiously studied whether the aging MRC-5 cell-conditioned medium could induce EMT in premalignant HaCaT cells, and the results showed that paeonol significantly reduced the clonogenic, migratory, and invasive capacities of premalignant HaCaT cells potentially induced by IL-6 and IL-8. Moreover, we found that paeonol notably altered pluripotency of EMT-associated markers via the modulation of ERK and TGF-β1/Smad pathway in premalignant HaCaT cells. These findings suggest that paeonol may be used as an adjuvant therapy for SASP factor-mediated EMT in premalignant lesion.

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

    PubMed

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

    2005-10-18

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

  12. 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

  13. Bidirectional NMDA receptor plasticity controls CA3 output and heterosynaptic metaplasticity

    PubMed Central

    Hunt, David L.; Puente, Nagore; Grandes, Pedro; Castillo, Pablo E.

    2013-01-01

    N–methyl–d–aspartate glutamate receptors (NMDARs) are classically known as coincidence detectors for the induction of long–term synaptic plasticity, and have been implicated in hippocampal CA3–dependent spatial memory functions that likely rely on dynamic cellular ensemble encoding of space. The unique functional properties of both NMDARs and mossy fiber (MF) projections to CA3 pyramidal cells place MF–NMDARs in a prime position to influence CA3 ensemble dynamics. By mimicking pre and postsynaptic activity patterns observed in–vivo, we report a burst timing–dependent paradigm for bidirectional long–term NMDAR plasticity at MF–CA3 synapses in rat hippocampal slices. This form of plasticity imparts bimodal control of MF–driven CA3 burst–firing and spike temporal fidelity. Moreover, we show that MF–NMDARs mediate heterosynaptic metaplasticity between MF and associational/commissural synapses. Thus, bidirectional NMDAR plasticity at MF–CA3 synapses could significantly contribute to the formation, storage, and recall of CA3 cell assembly patterns. PMID:23852115

  14. Degradation of postural control with aging.

    PubMed

    Baltich, Jennifer; von Tscharner, Vinzenz; Nigg, Benno M

    2015-09-01

    Aging negatively impacts the ability to maintain postural stability due to degraded control systems. The entropic half-life, a non-linear variable that quantifies the transition of sample entropy with increasing time scales, quantifies the time that elapses before old positional information no longer influences, or is no longer related to, the control mechanisms that regulate the movement at the current center of pressure location. The entropic half-life provides a more representative and comprehendible way of detecting changes in complexity using measurement units of time. The purpose of this study was to determine the effects of aging on the magnitude and temporal structure of the center of pressure movement during quiet single-limb stance. Center of pressure data of 24 older and 24 younger subjects were analyzed. The complexity of the temporal structure of the center of pressure signal was quantified by calculating the entropic half-life of the center of pressure in the medio-lateral and anterior-posterior directions. The magnitude of movement was quantified using excursion of the center of pressure in the medio-lateral and anterior-posterior directions, the path length, and the 95% ellipse area of the center of pressure. The older subjects demonstrated a significantly shorter entropic half-life for the center of pressure in the anterior-posterior direction (p < 0.001), longer excursions of the center of pressure in the medio-lateral (p < 0.001) and anterior-posterior (p = 0.001) directions, increased center of pressure path lengths (p < 0.001), and increased 95% ellipse areas of the center of pressure (p < 0.001). The results from this study showed that even though older subjects demonstrated more frequent postural adjustments (shorter entropic half-life), this did not help to reduce the magnitude of movement of their center of pressure during quiet stance, thus indicating an impaired peripheral and/or central neuromuscular control mechanism. © IMechE 2015.

  15. Activity-Dependent IGF-1 Exocytosis is Controlled by the Ca2+-Sensor Synaptotagmin-10

    PubMed Central

    Cao, Peng; Maximov, Anton; Südhof, Thomas C.

    2011-01-01

    Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca2+-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown. Here, we show that olfactory bulb neurons secrete IGF-1 by an activity-dependent pathway of exocytosis, and that Syt10 functions as the Ca2+-sensor that triggers IGF-1 exocytosis in these neurons. Deletion of Syt10 impaired activity-dependent IGF-1 secretion in olfactory bulb neurons, resulting in smaller neurons and an overall decrease in synapse numbers. Exogenous IGF-1 completely reversed the Syt10 knockout phenotype. Syt10 co-localized with IGF-1 in somatodendritic vesicles of olfactory bulb neurons, and Ca2+-binding to Syt10 caused these vesicles to undergo exocytosis, thereby secreting IGF-1. Thus, Syt10 controls a previously unrecognized pathway of Ca2+-dependent exocytosis that is spatially and temporally distinct from Ca2+-dependent synaptic vesicle exocytosis controlled by Syt1 in the same neurons, and two different synaptotagmins regulate distinct Ca2+-dependent membrane fusion reactions during exocytosis in the same neuron. PMID:21496647

  16. Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10.

    PubMed

    Cao, Peng; Maximov, Anton; Südhof, Thomas C

    2011-04-15

    Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca(2+)-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown. Here, we show that olfactory bulb neurons secrete IGF-1 by an activity-dependent pathway of exocytosis, and that Syt10 functions as the Ca(2+)-sensor that triggers IGF-1 exocytosis in these neurons. Deletion of Syt10 impaired activity-dependent IGF-1 secretion in olfactory bulb neurons, resulting in smaller neurons and an overall decrease in synapse numbers. Exogenous IGF-1 completely reversed the Syt10 knockout phenotype. Syt10 colocalized with IGF-1 in somatodendritic vesicles of olfactory bulb neurons, and Ca(2+)-binding to Syt10 caused these vesicles to undergo exocytosis, thereby secreting IGF-1. Thus, Syt10 controls a previously unrecognized pathway of Ca(2+)-dependent exocytosis that is spatially and temporally distinct from Ca(2+)-dependent synaptic vesicle exocytosis controlled by Syt1. Our findings thereby reveal that two different synaptotagmins can regulate functionally distinct Ca(2+)-dependent membrane fusion reactions in the same neuron. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca(2+)/calmodulin (CaM) dependence of Ca(2+)/CaM-dependent protein kinase kinase β.

    PubMed

    Nakanishi, Akihiro; Hatano, Naoya; Fujiwara, Yuya; Bin Shari, Arian; Takabatake, Shota; Akano, Hiroki; Kanayama, Naoki; Magari, Masaki; Nozaki, Naohito; Tokumitsu, Hiroshi

    2017-10-03

    The Ca(2+)/calmodulin-dependent protein kinase kinase β(CaMKKβ)/5'AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca(2+)-dependent metabolic pathways and cancer growth. Unlike recombinant CaMKKβ that exhibits higher basal activity (autonomous activity), activation of the CaMKKβ/AMPK signaling pathway requires increased intracellular Ca(2+) concentrations. Moreover, the Ca(2+)/CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases. However, the effects of proximal downstream kinases on CaMKKβ activity have not yet been evaluated. Here, we demonstrate feedback phosphorylation of CaMKKβ at multiple residues by CaMKKβ-activated AMPK in addition to autophosphorylation in vitro, leading to reduced autonomous, but not Ca(2+)/CaM-activated, CaMKKβ activity. MS analysis and site-directed mutagenesis of AMPK phosphorylation sites in CaMKKβ indicated that Thr144 phosphorylation by activated AMPK converts CaMKKβ into a Ca(2+)/CaM-dependent enzyme, as shown by completely Ca(2+)/CaM-dependent CaMKK activity of a phosphomimetic Thr144Glu CaMKKβ mutant. CaMKKβ mutant analysis indicated that the C-terminal domain (residues 471-587) including the autoinhibitory region plays an important role in stabilizing an inactive conformation in a Thr144 phosphorylation-dependent manner. Furthermore, immunoblot analysis with antiphospho-Thr144 antibody revealed phosphorylation of Thr144 in CaMKKβ in transfected COS-7 cells that was further enhanced by exogenous expression of AMPKα. These results indicate that AMPK-mediated feedback phosphorylation of CaMKKβ regulates the CaMKKβ/AMPK signaling cascade and may be physiologically important for intracellular maintenance of Ca(2+)-dependent AMPK activation by CaMKKβ. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  18. Androgenetic Alopecia at Various Ages and Prostate Cancer Risk in an Equal Access Multiethnic Case Control Series of Veterans

    PubMed Central

    Thomas, Jean-Alfred; Antonelli, Jodi A.; Banez, Lionel L.; Hoyo, Catherine; Grant, Delores; Demark-Wahnefried, Wendy; Platz, Elizabeth A.; Gerber, Leah; Shuler, Kathryn; Eyoh, Enwono; Calloway, Elizabeth; Freedland, Stephen J.

    2013-01-01

    Purpose Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. Materials and Methods We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30, 40 and at study enrollment. We tested the association between hair pattern (overall, vertex or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. Results Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p=0.008). Similar patterns were noted for frontal (p=0.005) and not vertex balding (p=0.22). When compared to biopsy negative men, a similar pattern was seen with younger age of AA onset having higher risk for CaP, though this was not significant (p=0.07). A suggestion for younger age of AA onset for frontal (p=0.07) being associated with CaP vs. biopsy negative men was also observed. Overall balding (yes/no) was associated with > 2-fold increase of high-grade disease (p=0.02). Conclusions Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology. PMID:23529469

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

    PubMed Central

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

    2004-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. 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…

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

    PubMed

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

    2012-08-24

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

  5. 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.

  6. 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

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

    PubMed

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

    2013-02-15

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

  8. Impaired TNF-α Control of IP3R-mediated Ca2+ Release in Alzheimer's Disease Mouse Neurons

    PubMed Central

    Park, Keigan M.; Yule, David I.; Bowers, William J.

    2009-01-01

    The misguided control of inflammatory signaling has been previously implicated in the pathogenesis of several neurological disorders, including Alzheimer's disease (AD). Induction of tumor necrosis factor-alpha (TNF-α), a central mediator of neuroinflammation, occurs commensurate with the onset of early disease in 3xTg-AD mice, which develop both amyloid plaque and neurofibrillary tangle pathologies in an age- and region-dependent pattern. Herein, we describe regulation inherent to 3xTg-AD neurons, which results in the loss of TNF-α mediated enhancement of inositol 1,4,5 trisphosphate (IP3R)-mediated Ca2+ release. This modulation also leads to significant down regulation of IP3R signaling following protracted cytokine exposure. Through the experimental isolation of each AD-related transgene, it was determined that expression of the PS1M146V transgene product is responsible for the loss of the TNF-α effect on IP3R-mediated Ca2+ release. Furthermore, it was determined that the suppression of TNF-α receptor expression occurred in the presence of the presenilin transgene. Our findings attribute this familial AD mutation to suppressing a Ca2+-regulated signal cascade potentially intended to “inform” neurons of proximal neuroinflammatory events and trigger compensatory responses for protection of neural transmission. PMID:19922794

  9. The relationship between age-stereotypes and health locus of control across adult age-groups.

    PubMed

    Sargent-Cox, Kerry; Anstey, Kaarin J

    2015-01-01

    This study integrates healthy ageing and health psychology theories to explore the mechanisms underlying the relationship between health control expectancies and age-attitudes on the process of ageing well. Specifically, the aim of this study is to investigate the relationship between age-stereotypes and health locus of control. A population-based survey of 739 adults aged 20-97 years (mean = 57.3 years, SD = 13.66; 42% female) explored attitudes towards ageing and health attitudes. A path-analytical approach was used to investigate moderating effects of age and gender. Higher age-stereotype endorsement was associated with higher chance (β = 2.91, p < .001) and powerful other (β = 1.07, p = .012) health expectancies, after controlling for age, gender, education and self-rated health. Significant age and gender interactions were found to influence the relationship between age-stereotypes and internal health locus of control. Our findings suggest that the relationship between age-stereotypes and health locus of control dimensions must be considered within the context of age and gender. The findings point to the importance of targeting health promotion and interventions through addressing negative age-attitudes.

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

    PubMed

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

    2014-01-01

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

  12. 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

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

    PubMed

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

    2011-08-01

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

  14. A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster

    PubMed Central

    Hoff, Max; Balfanz, Sabine; Ehling, Petra; Gensch, Thomas; Baumann, Arnd

    2011-01-01

    Rhythmic activity of cells and cellular networks plays an important role in physiology. In the nervous system oscillations of electrical activity and/or second messenger concentrations are important to synchronize neuronal activity. At the molecular level, rhythmic activity can be initiated by different routes. We have recently shown that an octopamine-activated G-protein-coupled receptor (GPCR; DmOctα1Rb, CG3856) from Drosophila initiates Ca2+ oscillations. Here, we have unraveled the molecular basis of cellular Ca2+ signaling controlled by the DmOctα1Rb receptor using a combination of pharmacological intervention, site-directed mutagenesis, and functional cellular Ca2+ imaging on heterologously expressed receptors. Phosphorylation of a single amino acid residue in the third intracellular loop of the GPCR by PKC is necessary and sufficient to desensitize the receptor. From its desensitized state, DmOctα1Rb is resensitized by dephosphorylation, and a new Ca2+ signal occurs on octopamine stimulation. Our findings show that transient changes of the receptor's surface profile have a strong effect on its physiological signaling properties. We expect that the detailed knowledge of DmOctα1Rb-dependent signal transduction fosters the identification of specific drugs that can be used for GPCR-mediated pest control, since octopamine serves important physiological and behavioral functions in arthropods.—Hoff M., Balfanz, S., Ehling, P., Gensch, T., Baumann, A. A single amino acid residue controls Ca2+ signaling by an octopamine receptor from Drosophila melanogaster. PMID:21478261

  15. Reduction in Sensorimotor Control with Age.

    ERIC Educational Resources Information Center

    Seidler, Rachael D.; Stelmach, George E.

    1995-01-01

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

  16. Reduction in Sensorimotor Control with Age.

    ERIC Educational Resources Information Center

    Seidler, Rachael D.; Stelmach, George E.

    1995-01-01

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

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

    PubMed

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

    2005-05-01

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

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

    PubMed

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

    2017-05-01

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

  19. Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport

    PubMed Central

    Lambers, Tim T; Mahieu, Frank; Oancea, Elena; Hoofd, Louis; de Lange, Frank; Mensenkamp, Arjen R; Voets, Thomas; Nilius, Bernd; Clapham, David E; Hoenderop, Joost G; Bindels, René J

    2006-01-01

    In Ca2+-transporting epithelia, calbindin-D28K (CaBP28K) facilitates Ca2+ diffusion from the luminal Ca2+ entry side of the cell to the basolateral side, where Ca2+ is extruded into the extracellular compartment. Simultaneously, CaBP28K provides protection against toxic high Ca2+ levels by buffering the cytosolic Ca2+ concentration ([Ca2+]i) during high Ca2+ influx. CaBP28K consistently colocalizes with the epithelial Ca2+ channel TRPV5, which constitutes the apical entry step in renal Ca2+-transporting epithelial cells. Here, we demonstrate using protein-binding analysis, subcellular fractionation and evanescent-field microscopy that CaBP28K translocates towards the plasma membrane and directly associates with TRPV5 at a low [Ca2+]i. 45Ca2+ uptake measurements, electrophysiological recordings and transcellular Ca2+ transport assays of lentivirus-infected primary rabbit connecting tubule/distal convolute tubule cells revealed that associated CaBP28K tightly buffers the flux of Ca2+ entering the cell via TRPV5, facilitating high Ca2+ transport rates by preventing channel inactivation. In summary, CaBP28K acts in Ca2+-transporting epithelia as a dynamic Ca2+ buffer, regulating [Ca2+] in close vicinity to the TRPV5 pore by direct association with the channel. PMID:16763551

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. Hypothalamic control of sleep in aging.

    PubMed

    Rolls, Asya

    2012-09-01

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

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

    SciTech Connect

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

    2014-10-03

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

  5. 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

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

    PubMed

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

    2017-02-01

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

  7. Sr/Ca and Mg/Ca in Glycymeris glycymeris (Bivalvia) shells from the Iberian upwelling system: Ontogeny and environmental control

    NASA Astrophysics Data System (ADS)

    Freitas, Pedro; Richardson, Christopher; Chenery, Simon; Monteiro, Carlos; Butler, Paul; Reynolds, David; Scourse, James; Gaspar, Miguel

    2017-04-01

    Bivalve shells have a great potential as high-resolution geochemical proxy archives of marine environmental conditions. In addition, sclerochronology of long-lived bivalve species (e.g. Arctica islandica) provides a timeline of absolutely dated shell material for geochemical analysis that can extend into the past beyond the lifetime of single individuals through the use of replicated crossmatched centennial to millennial chronologies. However, the interpretation of such records remains extremely challenging and complex, with multiple environmental and biological processes affecting element incorporation in the shell (e.g. crystal fabrics, organic matrix, biomineralization mechanisms and physiological processes). As a result, the effective use of bivalve shell elemental/Ca ratios as palaeoenvironmental proxies has been limited, often to species-specific applications or applications restricted to particular environmental settings. The dog-cockle, Glycymeris glycymeris, is a relatively long-lived bivalve (up to 200 years) that occurs in coarse-grained subtidal sediments of coastal shelf seas of Europe and North West Africa. Glycymeris glycymeris shells provide a valuable, albeit not fully explored, archive to reconstruct past environmental variability in an area lacking sclerochronological studies due to the rarity of long-lived bivalves and lack of coral reefs. In this study, we evaluate the potential of Sr/Ca and Mg/Ca ratios in G. glycymeris shells as geochemical proxies of upwelling conditions in the Iberian Upwelling System, the northern section of the Canary Current Eastern Boundary Upwelling System. Sr/Ca and Mg/Ca generally co-varied significantly and a clear ontogenetic, non-environmental related change in Sr/Ca and Ba/Ca variability was observed. High Sr/Ca and Mg/Ca ratios in older shells (> 10 years old) were found to be associated with the occurrence of growth lines deposited during the winter reduction in shell growth. Nevertheless, Sr/Ca and Mg/Ca

  8. 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…

  9. 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…

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

    PubMed

    Chen, Shmuel; Benninger, Felix; Yaari, Yoel

    2014-06-11

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

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    1994-10-24

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

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

    PubMed

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

    2011-06-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. /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.

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

    PubMed Central

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

    2010-01-01

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

  17. An alien divalent ion reveals a major role for Ca²⁺ buffering in controlling slow transmitter release.

    PubMed

    Babai, Norbert; Kochubey, Olexiy; Keller, Daniel; Schneggenburger, Ralf

    2014-09-17

    Ca(2+)-dependent transmitter release occurs in a fast and in a slow phase, but the differential roles of Ca(2+) buffers and Ca(2+) sensors in shaping release kinetics are still controversial. Replacing extracellular Ca(2+) by Sr(2+) causes decreased fast release but enhanced slow release at many synapses. Here, we established presynaptic Sr(2+) uncaging and made quantitative Sr(2+)- and Ca(2+)-imaging experiments at the mouse calyx of Held synapse, to reveal the interplay between Ca(2+) sensors and Ca(2+) buffers in the control of fast and slow release. We show that Sr(2+) activates the fast, Synaptotagmin-2 (Syt2) sensor for vesicle fusion with sixfold lower affinity but unchanged high cooperativity. Surprisingly, Sr(2+) also activates the slow sensor that remains in Syt2 knock-out synapses with a lower efficiency, and Sr(2+) was less efficient than Ca(2+) in the limit of low concentrations in wild-type synapses. Quantitative imaging experiments show that the buffering capacity of the nerve terminal is markedly lower for Sr(2+) than for Ca(2+) (~5-fold). This, together with an enhanced Sr(2+) permeation through presynaptic Ca(2+) channels (~2-fold), admits a drastically higher spatially averaged Sr(2+) transient compared with Ca(2+). Together, despite the lower affinity of Sr(2+) at the fast and slow sensors, the massively higher amplitudes of spatially averaged Sr(2+) transients explain the enhanced late release. This also allows us to conclude that Ca(2+) buffering normally controls late release and prevents the activation of the fast release sensor by residual Ca(2+). Copyright © 2014 the authors 0270-6474/14/3412622-14$15.00/0.

  18. 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.

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

    PubMed Central

    Zhang, Qiuhong; Ren, Zhaohui

    2016-01-01

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

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

    PubMed

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

    1997-10-23

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

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

    PubMed

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

    2017-03-22

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

  2. 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

  3. Age-structured optimal control in population economics.

    PubMed

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

    2004-06-01

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

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

    PubMed

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

    2017-03-08

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

  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. Differential Control of Calcium Homeostasis and Vascular Reactivity by CaMKII

    PubMed Central

    Prasad, Anand M.; Nuno, Daniel W.; Koval, Olha M.; Ketsawatsomkron, Pimonrat; Li, Weiwei; Li, Hui; Shen, Fred Y.; Joiner, Mei-ling A.; Kutschke, William; Weiss, Robert M.; Sigmund, Curt D.; Anderson, Mark E.; Lamping, Kathryn G.; Grumbach, Isabella M.

    2013-01-01

    The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by vasoconstrictors in vascular smooth muscle cells (VSMC), but its impact on vasoconstriction remains unknown. We hypothesized that CaMKII inhibition in VSMC decreases vasoconstriction. Using novel transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), we investigated the effect of CaMKII inhibition on L-type Ca2+ channel (LTCC) current (ICa), cytoplasmic and sarcoplasmic reticulum (SR) Ca2+ and vasoconstriction in mesenteric arteries. In mesenteric VSMC, CaMKII inhibition significantly reduced action potential duration and the residual ICa 50 ms after peak amplitude, indicative of loss of LTCC-dependent ICa facilitation. Treatment with angiotensin-II or phenylephrine increased the intracellular Ca2+ concentration ([Ca2+]i) in WT but not TG SM-CaMKIIN VSMC. The difference in [Ca2+]i was abolished by pretreatment with nifedipine, an LTCC antagonist. In TG SM-CaMKIIN VSMC, the total SR Ca2+ content was reduced as a result of diminished SR Ca2+ ATPase (SERCA) activity via impaired derepression of the SERCA inhibitor phospholamban. Despite the differences in [Ca2+]i, CaMKII inhibition did not alter myogenic tone or vasoconstriction of mesenteric arteries in response to KCl, angiotensin-II and phenylephrine. However, it increased myosin light chain kinase activity. These data suggest that CaMKII activity maintains intracellular calcium homeostasis but is not required for vasoconstriction of mesenteric arteries. PMID:23753415

  7. 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

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

    PubMed Central

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

    2011-01-01

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

  9. Novel STIM1-dependent control of Ca2+ clearance regulates NFAT activity during T-cell activation.

    PubMed

    Samakai, Elsie; Hooper, Robert; Martin, Kayla A; Shmurak, Maya; Zhang, Yi; Kappes, Dietmar J; Tempera, Italo; Soboloff, Jonathan

    2016-11-01

    Antigen presentation to the T-cell receptor leads to sustained cytosolic Ca(2+) elevation, which is critical for T-cell activation. We previously showed that in activated T cells, Ca(2+) clearance is inhibited by the endoplasmic reticulum Ca(2+) sensor stromal interacting molecule 1 (STIM1) via association with the plasma membrane Ca(2+)/ATPase 4 (PMCA4) Ca(2+) pump. Having further observed that expression of both proteins is increased in activated T cells, the current study focused on mechanisms regulating both up-regulation of STIM1 and PMCA4 and assessing how this up-regulation contributes to control of Ca(2+) clearance. Using a STIM1 promoter luciferase vector, we found that the zinc finger transcription factors early growth response (EGR) 1 and EGR4, but not EGR2 or EGR3, drive luciferase activity. We further found that neither STIM1 nor PMCA4 is up-regulated when both EGR1 and EGR4 are knocked down using RNA interference. Further, under these conditions, activation-induced Ca(2+) clearance inhibition was eliminated with little effect on Ca(2+) entry. Finally, we found that nuclear factor of activated T-cell (NFAT) activity is profoundly attenuated if Ca(2+) clearance is not inhibited by STIM1. These findings reveal a critical role for STIM1-mediated control of Ca(2+) clearance in NFAT induction during T-cell activation.-Samakai, E., Hooper, R., Martin, K. A., Shmurak, M., Zhang, Y., Kappes, D. J., Tempera, I., Soboloff, J. Novel STIM1-dependent control of Ca(2+) clearance regulates NFAT activity during T-cell activation. © FASEB.

  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.

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

    PubMed Central

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

    2015-01-01

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

  12. 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.

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

    PubMed

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

    2005-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. p53, ROS and senescence in the control of aging.

    PubMed

    Vigneron, Arnaud; Vousden, Karen H

    2010-08-01

    In addition to its function as a tumour suppressor, p53 is also involved in an increasing number of pathology associated with aging. Several activities of p53 appear contribute to its role in aging; one function that might be particularly relevant in this context is the regulation of senescence. The control of ROS and senescence by p53 may help to explain how p53 can function to both restrain and promote aging.

  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. 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

  19. Managing threats against control in old age: a narrative inquiry.

    PubMed

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

    2013-01-01

    The desire to retain personal control over self and life circumstances continues into old age; it exists in tension with late-life vulnerabilities. This article investigates how older adults respond to threats against control in light of changes surrounding health and identity. Community-dwelling African American (n = 10) and European-American older adults (n = 10), aged 70 years and older, with varied self-reported health statuses were qualitatively interviewed. Open-ended interviews explored older adults' perceptions of control and threats to control in older age. Three themes linked older adults' responses to threats to control. Older adults (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. This study shows that the construct of control is not abstract; it is interpreted and applied by older adults in the contexts of everyday life. Respondents used personal resources honed throughout the life course to respond to threats to control. Older adults 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 older adults with the cognitive and emotional tasks required to deal with threats to personal control surrounding health and identity.

  20. Concise Whole-Cell Modeling of BKCa-CaV Activity Controlled by Local Coupling and Stoichiometry.

    PubMed

    Montefusco, Francesco; Tagliavini, Alessia; Ferrante, Marco; Pedersen, Morten Gram

    2017-06-06

    Large-conductance Ca(2+)-dependent K(+) (BKCa) channels are important regulators of electrical activity. These channels colocalize and form ion channel complexes with voltage-dependent Ca(2+) (CaV) channels. Recent stochastic simulations of the BKCa-CaV complex with 1:1 stoichiometry have given important insight into the local control of BKCa channels by fluctuating nanodomains of Ca(2+). However, such Monte Carlo simulations are computationally expensive, and are therefore not suitable for large-scale simulations of cellular electrical activity. In this work we extend the stochastic model to more realistic BKCa-CaV complexes with 1:n stoichiometry, and analyze the single-complex model with Markov chain theory. From the description of a single BKCa-CaV complex, using arguments based on timescale analysis, we derive a concise model of whole-cell BKCa currents, which can readily be analyzed and inserted into models of cellular electrical activity. We illustrate the usefulness of our results by inserting our BKCa description into previously published whole-cell models, and perform simulations of electrical activity in various cell types, which show that BKCa-CaV stoichiometry can affect whole-cell behavior substantially. Our work provides a simple formulation for the whole-cell BKCa current that respects local interactions in BKCa-CaV complexes, and indicates how local-global coupling of ion channels may affect cell behavior. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Control of InsP3-induced Ca2+ oscillations in permeabilized blowfly salivary gland cells: contribution of mitochondria

    PubMed Central

    Zimmermann, Bernhard

    2000-01-01

    Many agonists linked to the generation of inositol 1,4,5-trisphosphate (InsP3) and release of Ca2+ from intracellular stores induce repetitive transients in cytosolic Ca2+ whose frequency increases over a certain range of agonist concentrations.In order to investigate the mechanisms underlying this frequency modulation, the fluorescent Ca2+ sensor mag-fura-2 was loaded into intracellular calcium stores and used to monitor InsP3-induced dynamics of the intraluminal calcium concentration ([Ca2+]L) in secretory cells of permeabilized blowfly Calliphora vicina salivary glands.In this preparation, increasing concentrations of InsP3 induced graded decreases in [Ca2+]L that were often superimposed with repetitive [Ca2+]L transients produced by sequential Ca2+ release and re-uptake. These [Ca2+]L oscillations developed at frequencies of 3–11 min−1 unrelated to the concentration of InsP3 present.In contrast, incremental concentrations of InsP3 applied in the presence of the oxidizable mitochondrial substrates citrate, succinate, or pyruvate-malate induced repetitive [Ca2+]L transients whose frequency increased with the concentration of InsP3.This InsP3 concentration-dependent modulation of oscillation frequency was abolished after dissipating the mitochondrial membrane potential (Δψm) by combined treatment with carbonyl cyanide p-trifluoromethoxyphenyl hydrazone + oligomycin or after application of Ruthenium Red, an inhibitor of mitochondrial Ca2+ uptake.Taken together, the data indicate that energized mitochondria exert negative control over the frequency of InsP3-induced Ca2+ oscillations. It is concluded that mitochondria play a crucial role in determining the duration of the interspike period and, therefore, for the encoding of amplitude-modulated, InsP3-liberating stimuli into the frequency of cytosolic Ca2+ oscillations. PMID:10856123

  2. 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.

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

    PubMed Central

    Hatch, Robert John; Leinenga, Gerhard

    2016-01-01

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

  4. Augmented neuronal death in CA3 hippocampus following hyperventilation early after controlled cortical impact.

    PubMed

    Forbes, M L; Clark, R S; Dixon, C E; Graham, S H; Marion, D W; DeKosky, S T; Schiding, J K; Kochanek, P M

    1998-03-01

    Minimizing secondary injury after severe traumatic brain injury (TBI) is the primary goal of cerebral resuscitation. For more than two decades, hyperventilation has been one of the most often used strategies in the management of TBI. Laboratory and clinical studies, however, have verified a post-TBI state of reduced cerebral perfusion that may increase the brain's vulnerability to secondary injury. In addition, it has been suggested in a clinical study that hyperventilation may worsen outcome after TBI. Using the controlled cortical impact model in rats, the authors tested the hypothesis that aggressive hyperventilation applied immediately after TBI would worsen functional outcome, expand the contusion, and promote neuronal death in selectively vulnerable hippocampal neurons. Twenty-six intubated, mechanically ventilated, isoflurane-anesthetized male Sprague-Dawley rats were subjected to controlled cortical impact (4 m/second, 2.5-mm depth of deformation) and randomized after 10 minutes to either hyperventilation (PaCO2 = 20.3 +/- 0.7 mm Hg) or normal ventilation groups (PaCO2 = 34.9 +/- 0.3 mm Hg) containing 13 rats apiece and were treated for 5 hours. Beam balance and Morris water maze (MWM) performance latencies were measured in eight rats from each group on Days 1 to 5 and 7 to 11, respectively, after controlled cortical impact. The rats were killed at 14 days postinjury, and serial coronal sections of their brains were studied for contusion volume and hippocampal neuron counting (CA1, CA3) by an observer who was blinded to their treatment group. Mortality rates were similar in both groups (two of 13 in the normal ventilation compared with three of 13 in the hyperventilation group, not significant [NS]). There were no differences between the groups in mean arterial blood pressure, brain temperature, and serum glucose concentration. There were no differences between groups in performance latencies for both beam balance and MWM or contusion volume (27.8 +/- 5

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2004-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  8. Optimal birth control of age-dependent competitive species

    NASA Astrophysics Data System (ADS)

    He, Ze-Rong

    2005-05-01

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

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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.

  14. Aging and amyloid β oligomers enhance TLR4 expression, LPS-induced Ca(2+) responses, and neuron cell death in cultured rat hippocampal neurons.

    PubMed

    Calvo-Rodríguez, María; de la Fuente, Carmen; García-Durillo, Mónica; García-Rodríguez, Carmen; Villalobos, Carlos; Núñez, Lucía

    2017-01-31

    Toll-like receptors (TLRs) are transmembrane pattern-recognition receptors of the innate immune system recognizing diverse pathogen-derived and tissue damage-related ligands. It has been suggested that TLR signaling contributes to the pathogenesis of age-related, neurodegenerative diseases, including Alzheimer's disease (AD). AD is associated to oligomers of the amyloid β peptide (Aβo) that cause intracellular Ca(2+) dishomeostasis and neuron cell death in rat hippocampal neurons. Here we assessed the interplay between inflammation and Aβo in long-term cultures of rat hippocampal neurons, an in vitro model of neuron aging and/or senescence. Ca(2+) imaging and immunofluorescence against annexin V and TLR4 were applied in short- and long-term cultures of rat hippocampal neurons to test the effects of TLR4-agonist LPS and Aβo on cytosolic [Ca(2+)] and on apoptosis as well as on expression of TLR4. LPS increases cytosolic [Ca(2+)] and promotes apoptosis in rat hippocampal neurons in long-term culture considered aged and/or senescent neurons, but not in short-term cultured neurons considered young neurons. TLR4 antagonist CAY10614 prevents both effects. TLR4 expression in rat hippocampal neurons is significantly larger in aged hippocampal cultures. Treatment of aged hippocampal cultures with Aβo increases TLR4 expression and enhances LPS-induced Ca(2+) responses and neuron cell death. Aging and amyloid β oligomers, the neurotoxin involved in Alzheimer's disease, enhance TLR4 expression as well as LPS-induced Ca(2+) responses and neuron cell death in rat hippocampal neurons aged in vitro.

  15. Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case-control series of veterans.

    PubMed

    Thomas, Jean-Alfred; Antonelli, Jodi A; Banez, Lionel L; Hoyo, Catherine; Grant, Delores; Demark-Wahnefried, Wendy; Platz, Elizabeth A; Gerber, Leah; Shuler, Kathryn; Eyoh, Enwono; Calloway, Elizabeth; Freedland, Stephen J

    2013-05-01

    Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.

  16. 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.

  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. 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.

  19. 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

  20. 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.

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

    PubMed

    Tremblay, Pascale; Sato, Marc; Deschamps, Isabelle

    2017-03-06

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

  2. Expression profile analysis of vulnerable CA1 pyramidal neurons in young-middle aged Ts65Dn mice

    PubMed Central

    Alldred, Melissa J.; Lee, Sang Han; Petkova, Eva; Ginsberg, Stephen D.

    2014-01-01

    Down syndrome (DS) is the most prevalent cause of intellectual disability (ID). Individuals with DS show a variety of cognitive deficits, most notably in hippocampal learning and memory, and display pathological hallmarks of Alzheimer's disease (AD), with neurodegeneration of cholinergic basal forebrain (CBF) neurons. Elucidation of the molecular and cellular underpinnings of neuropathology has been assessed via gene expression analysis in a relevant animal model, termed the Ts65Dn mouse. The Ts65Dn mouse is a segmental trisomy model of DS which mimics DS/AD pathology, notably age-related cognitive dysfunction and degeneration of basal forebrain cholinergic neurons (BFCNs). To determine expression level changes, molecular fingerprinting of Cornu Ammonis 1 (CA1) pyramidal neurons was performed in adult (4-9 month old) Ts65Dn mice, at the initiation of BFCN degeneration. To quantitate transcriptomic changes during this early time period, laser capture microdissection (LCM), terminal continuation (TC) RNA amplification, custom-designed microarray analysis, and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting was performed. Results indicate significant alterations within CA1 pyramidal neurons of Ts65Dn mice compared to normal disomic (2N) littermates, notably in the downregulation of neurotrophins and their cognate neurotrophin receptors among other classes of transcripts relevant to neurodegeneration. These results of this single population gene expression analysis at the time of septohippocampal deficits in a trisomic mouse model shed light on a vulnerable circuit that may cause the AD-like pathology invariably seen in DS that could help to identify mechanisms of degeneration, and provide novel gene targets for therapeutic interventions. PMID:25131634

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2015-09-01

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

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

    PubMed

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

    2015-07-16

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

  6. Color Control of Pr(3+) Luminescence by Electron-Hole Recombination Energy Transfer in CaTiO3 and CaZrO3.

    PubMed

    Barandiarán, Zoila; Bettinelli, Marco; Seijo, Luis

    2017-07-06

    Controlling luminescence in phosphors able to produce several emissions from different stable excited states determines their use in optical devices. We investigate the color control mechanism that quenches the greenish-blue emission in favor of the red one in the archetype phosphor CaTiO3:Pr(3+). State-of-the-art ab initio calculations indicate that direct host-to-dopant energy transfer (released by electron-hole recombination following the interband excitation and structural reorganization) selectively populates the (1)D2 red luminescent state of Pr(3+) and bypasses the (3)P0 greenish-blue emitter. Local defects can modulate the electron-hole recombination energy and therefore increase the red emission efficiency, as experimentally observed. The selection of red emission does not happen in CaZrO3:Pr(3+) because the electron-hole recombination energy is much higher. The calculations could not support the widely accepted color control mechanism based on metal-to-metal charge transfer states. The conclusion sets new points of view for the color control of lanthanide activated inorganic phosphors.

  7. Ca isotopes reveal weak control of tectonic uplift on long-term climate change

    NASA Astrophysics Data System (ADS)

    Moore, J.; Jacobson, A. D.; Holmden, C. E.; Craw, D.

    2010-12-01

    Ca-Mg silicate weathering consumes atmospheric CO2 over geological timescales (≥106 yr) whereas carbonate weathering has no effect. High Ca fluxes from active orogens have been used to argue that mountain uplift is a disproportionately large CO2 sink. To test this hypothesis, it is essential to determine proportions of Ca from silicate versus carbonate weathering. High precision measurement of Ca isotopes (δ44/40Ca) provides a novel method to directly quantify Ca sources. To this end, we examined δ44/40Ca in rivers draining the Southern Alps of New Zealand. The Southern Alps have large tectonic and climatic gradients but nearly constant bedrock chemistry. West of the main topographic divide, uplift and precipitation rates are high, and steep, fast-flowing rivers drain schist. East of the divide, uplift and precipitation rates are low, and low-gradient, braided rivers drain either schist or greywacke. Both schist and greywacke contain up to 3% hydrothermal and metamorphic calcite. Glaciers feed several schist and greywacke catchments. Examined as δ44/40Ca versus Sr/Ca, values measured for carbonate and silicate end-members define two-component mixing envelopes. Rivers west of the divide plot within the envelope, ruling out isotopic fractionation as a factor for these streams. Several rivers east of the divide are 40Ca enriched relative to the envelope. In-situ fractionation of stream water Ca cannot explain this pattern because fractionation is expected to preferentially remove 40Ca. We measured δ42/44Ca ratios to test if chemical weathering preferentially releases 40Ca. When examined as δ40/44Ca versus δ42/44Ca, the data only display mass-dependent isotope effects. Ca in grass and the exchangeable pool of shallow soils is enriched in 40Ca relative to waters and bedrock. This Ca defines a third mixing end-member that contributes 15-30% of the Ca in rivers east of the divide. Evidence of the plant-fractionated signal likely reflects water residence times

  8. 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

  9. Human aging compromises attentional control of auditory perception.

    PubMed

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

    2012-03-01

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

  10. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter

    PubMed Central

    Csordás, György; Golenár, Tünde; Seifert, Erin L.; Kamer, Kimberli J.; Sancak, Yasemin; Perocchi, Fabiana; Moffat, Cynthia; Weaver, David; Perez, Sergio de la Fuente; Bogorad, Roman; Koteliansky, Victor; Adijanto, Jeffrey; Mootha, Vamsi K.; Hajnóczky, György

    2013-01-01

    Summary Mitochondrial Ca2+ uptake via the uniporter is central to cell metabolism, signaling and survival. Recent studies identified MCU as the uniporter’s likely pore and MICU1, an EF-hand protein, as its critical regulator. How this complex decodes dynamic cytoplasmic [Ca2+] ([Ca2+]c) signals, to tune out small [Ca2+]c increases yet permit pulse transmission, remains unknown. We report that loss of MICU1 in mouse liver and cultured cells causes mitochondrial Ca2+ accumulation during small [Ca2+]c elevations, yet an attenuated response to agonist-induced [Ca2+]c pulses. The latter reflects loss of positive cooperativity, likely via the EF-hands. MICU1 faces the intermembrane space and responds to [Ca2+]c changes. Prolonged MICU1 loss leads to an adaptive increase in matrix Ca2+ binding, yet cells show impaired oxidative metabolism and sensitization to Ca2+ overload. Collectively, the data indicate that MICU1 senses the [Ca2+]c to establish the uniporter’s threshold and gain, thereby allowing mitochondria to properly decode different inputs. PMID:23747253

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Adult Age Differences in Functional Connectivity during Executive Control

    PubMed Central

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

    2010-01-01

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

  16. The influence of toothbrush age on plaque control and gingivitis.

    PubMed

    Pochapski, Márcia Thaís; Canever, Tatiana; Wambier, Denise Stadler; Pilatti, Gibson Luiz; Santos, Fábio André

    2011-01-01

    The purpose of this single-blind randomised controlled clinical trial was to verify the impact of progressive toothbrush age on clinical variables of dental plaque and gingival conditions. A total of 110 undergraduates were randomly assigned to one of four groups according to toothbrush age, as measured at 4, 8, 12, and 16 weeks. Clinical parameters (plaque and gingival indices) were assessed at 1 week (initial) and final periods. The wear of toothbrushes was evaluated by the wear index. Despite progressive toothbrush age, plaque and gingival indices were similar after the toothbrushing periods (p > 0.05, ANOVA). Significantly more plaque and gingivitis were present on lingual/palatal surfaces as compared with facial surfaces for all weeks, including the baseline (P < 0.001, paired t test.). The wear index increased from 4 weeks to 16 weeks. Plaque and gingival indices did not show statistical differences among 'lowest wear', 'moderate wear' and 'highest wear' (P > 0.05, ANOVA). Under the experimental conditions of this study, progressive toothbrush age did not lead to a decrease in plaque control. It was concluded that toothbrush age may not be critical in ensuring optimal plaque control.

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

    PubMed

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

    2013-01-09

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

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

    PubMed Central

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

    2013-01-01

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

  19. Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA receptors and L-type Ca2+ channels.

    PubMed

    Kouvaros, S; Kotzadimitriou, D; Papatheodoropoulos, C

    2015-07-09

    Aging is accompanied by a complicated pattern of changes in the brain organization and often by alterations in specific memory functions. One of the brain activities with important role in the process of memory consolidation is thought to be the hippocampus activity of sharp waves and ripple oscillation (SWRs). Using field recordings from the CA1 area of hippocampal slices we compared SWRs as well as single pyramidal cell activity between adult (3-6-month old) and old (24-34-month old) Wistar rats. The slices from old rats displayed ripple oscillation with a significantly less number of ripples and lower frequency compared with those from adult animals. However, the hippocampus from old rats had significantly higher propensity to organized SWRs in long sequences. Furthermore, the bursts recorded from complex spike cells in slices from old compared with adult rats displayed higher number of spikes and longer mean inter-spike interval. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) increased the amplitude of both sharp waves and ripples and increased the interval between events of SWRs in both age groups. On the contrary, CPP reduced the probability of occurrence of sequences of SWRs more strongly in slices from adult than old rats. Blockade of L-type voltage-dependent calcium channels by nifedipine only enhanced the amplitude of sharp waves in slices from adult rats. CPP increased the postsynaptic excitability and the paired-pulse inhibition in slices from both adult and old rats similarly while nifedipine increased the postsynaptic excitability only in slices from adult rats. We propose that the tendency of the aged hippocampus to generate long sequences of SWR events might represent the consequence of homeostatic mechanisms that adaptively try to compensate the impairment in the ripple oscillation in order to maintain the behavioral outcome efficient in the old individuals. The age

  20. 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

  1. Serum CA 19-9 and risk of incident diabetes in middle-aged and elderly Chinese: a prospective cohort study.

    PubMed

    Du, Rui; Sun, Wanwan; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Li, Donghui; Lu, Jieli

    2017-02-01

    Carbohydrate antigen (CA) 19-9 is a tumor marker for gastrointestinal and pancreatic cancers. Previous studies found that CA 19-9 was elevated in patients with diabetes, but little is known about its relationship with diabetes risk in prospective studies. Our objective was to evaluate the association between serum CA 19-9 and the risk of incident diabetes in Chinese population. Data were obtained from a prospective cohort study among 2391 middle-aged and elderly Chinese with a median follow-up of 3.8 years. The measurement for the study outcome was incident diabetes. Compared with individuals in the lowest quartile, those in the highest quartile of CA 19-9 had significantly higher incidence of diabetes (12.54 vs. 8.86%, P = 0.04). In the fully adjusted logistic regression model, compared with the lowest quartile, the highest quartile of CA 19-9 was significantly associated with 58% increased risk of incident diabetes [odds ratio (OR), 95% confidence interval (CI) 1.58, 1.02-2.44]. Stratified analysis suggested that the increased risk was seen only in women (OR, 95% CI 1.96, 1.10-3.48), or participants aged ≥65 (OR, 95% CI 2.32, 1.03-5.19), or those with body mass index ≥24 (OR, 95% CI 2.09, 1.20-3.63), or current nondrinkers (OR, 95% CI 1.79, 1.09-2.92), or those with impaired glucose regulation (IGR) (OR, 95% CI 2.49, 1.33-4.67). Significant interaction was detected between IGR and serum CA 19-9 (P for interaction <0.0001). Serum CA 19-9 is associated with a significantly increased risk of diabetes among the middle-aged and elderly Chinese population. Further investigations are needed to confirm this association and disclose potential mechanisms.

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

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  3. Assessing sedimentation issues within aging flood-control reservoirs

    USDA-ARS?s Scientific Manuscript database

    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. ...

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

    ERIC Educational Resources Information Center

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

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

  5. 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

  6. 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.

  7. Case-control analysis of paternal age and trisomic anomalies.

    PubMed

    De Souza, E; Morris, J K

    2010-11-01

    To determine whether older paternal age increases the risk of fathering a pregnancy with Patau (trisomy 13), Edwards (trisomy 18), Klinefelter (XXY) or XYY syndrome. Case-control: cases with each of these syndromes were matched to four controls with Down syndrome from within the same congenital anomaly register and with maternal age within 6 months. Data from 22 EUROCAT congenital anomaly registers in 12 European countries. Diagnoses with observed or (for terminations) predicted year of birth from 1980 to 2005, comprising live births, fetal deaths with gestational age ≥ 20 weeks and terminations after prenatal diagnosis of the anomaly. Data include 374 cases of Patau syndrome, 929 of Edwards syndrome, 295 of Klinefelter syndrome, 28 of XYY syndrome and 5627 controls with Down syndrome. Odds ratio (OR) associated with a 10-year increase in paternal age for each anomaly was estimated using conditional logistic regression. Results were adjusted to take account of the estimated association of paternal age with Down syndrome (1.11; 95% CI 1.01 to 1.23). The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26). There was a statistically significant increase in the odds of Klinefelter syndrome with increasing paternal age. The larger positive associations of Klinefelter and XYY syndromes with paternal age compared with Patau and Edwards syndromes are consistent with the greater percentage of these sex chromosome anomalies being of paternal origin.

  8. Men, bodily control, and health behaviors: the importance of age.

    PubMed

    Calasanti, Toni; Pietilä, Ilkka; Ojala, Hanna; King, Neal

    2013-01-01

    To conduct an intersectional analysis of relations between gender and age in the health behaviors of middle-aged men, informed by cross-national comparison between Finland and the United States. Thematic and discourse analysis of data from interviews conducted among professional and working-class, middle-aged men in the U.S. and Finland. Respondents report that middle age inspires them to regard many bodily changes as more than transitory; and they assume a sense of responsibility that can lead to greater self-care. Men reported using such strategies as discipline, routine, and monitoring in their attempts to forestall aging. The men face contradictions: While they may adopt ideologies of masculinity and control and accept responsibility for influencing their health, their bodies may also present them with age-based limitations to their abilities to do so. How men respond to these changes varies by context, including their aging and these nations' different systems of health care. PsycINFO Database Record (c) 2013 APA, all rights reserved.

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

    PubMed Central

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

    2011-01-01

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

  10. 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

  11. 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.

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

    PubMed

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

    2012-02-01

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

  13. Cortisol response to challenge involving low controllability: the role of control beliefs and age.

    PubMed

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

    2013-04-01

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 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

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

    PubMed

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

    2014-01-07

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

  16. Optogenetic Control of Ca(2+) and Voltage-Dependent Large Conductance (BK) Potassium Channels.

    PubMed

    Mager, Thomas; Wood, Phillip G; Bamberg, Ernst

    2017-03-24

    Ca(2+) concentration jumps for the activation of Ca(2+)-dependent ion channels or transporters can be obtained either by fast solution exchange or by the use of caged Ca(2+). Here, we report on an alternate optogenetic method for the activation of Ca(2+) and voltage-dependent large conductance (BK) potassium channels. This was achieved through the use of the light-gated channelrhodopsin 2 variant, CatCh(Calcium translocating Channelrhodopsin) with enhanced Ca, which produces locally [Ca(2+)] in the μM range on the inner side of the membrane, without significant [Ca(2+)] increase in the cytosol. BK channel subunits α and β1 were expressed together with CatCh in HEK293 cells, and voltage and Ca(2+) dependence were analyzed. Light activation of endogenous BK channels under native conditions in astrocytes and glioma cells was also investigated. Additionally, BK channels were used as sensors for the calibration of the [Ca(2+)] on the inner surface of the cell membrane. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. 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

  18. Sympathetic control of reflex cutaneous vasoconstriction in human aging

    PubMed Central

    Alexander, Lacy M.; Kenney, W. Larry

    2015-01-01

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

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

    PubMed

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

    2015-10-01

    This Synthesis highlights a series of recent studies that has systematically interrogated age-related deficits in cold-induced skin vasoconstriction. In response to cold stress, a reflex increase in sympathetic nervous system activity mediates reductions in skin blood flow. Reflex vasoconstriction during cold exposure is markedly impaired in aged skin, contributing to the relative inability of healthy older adults to maintain core temperature during mild cold stress in the absence of appropriate behavioral thermoregulation. This compromised reflex cutaneous vasoconstriction in healthy aging can occur as a result of functional deficits at multiple points along the efferent sympathetic reflex axis, including blunted sympathetic outflow directed to the skin vasculature, reduced presynaptic neurotransmitter synthesis and/or release, and altered end-organ responsiveness at several loci, in addition to potential alterations in afferent thermoreceptor function. Arguments have been made that the relative inability of aged skin to appropriately constrict is due to the aging cutaneous arterioles themselves, whereas other data point to the neural circuitry controlling those vessels. The argument presented herein provides strong evidence for impaired efferent sympathetic control of the peripheral cutaneous vasculature during whole body cold exposure as the primary mechanism responsible for attenuated vasoconstriction. Copyright © 2015 the American Physiological Society.

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

    PubMed

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

    2014-09-01

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

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

    SciTech Connect

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

    2011-10-15

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

  2. Does Bilingual Language Control Decline in Older Age?

    PubMed Central

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

    2016-01-01

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

  3. Control of mitochondrial integrity in ageing and disease.

    PubMed

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

    2014-07-05

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

  4. Record of Little Ice Age sea surface temperatures at Bermuda using a growth-dependent calibration of coral Sr/Ca

    NASA Astrophysics Data System (ADS)

    Goodkin, Nathalie F.; Hughen, Konrad A.; Cohen, Anne L.; Smith, Struan R.

    2005-12-01

    Strontium to calcium ratios (Sr/Ca) are reported for a massive brain coral Diploria labyrinthiformis collected from the south shore of Bermuda and are strongly correlated with both sea surface temperature (SST) and mean annual skeletal growth rate. High Sr/Ca ratios correspond with cold SSTs and slow skeletal growth rate and vice versa. We provide a quantitative calibration of Sr/Ca to extension rate and SST along the axis of maximum growth and derive a growth-dependent Sr/Ca-SST calibration equation to reconstruct western subtropical North Atlantic SSTs for the past 223 years. When the influence of growth rate is excluded from the calibration, Sr/Ca ratios yield SSTs that are too cold during cool anomalies and too warm during warm anomalies. Toward the end of the Little Ice Age (˜1850), SST changes derived using a calibration that is not growth-dependent are exaggerated by a factor of 2 relative to those from the growth-corrected model that yields SSTs ˜1.5°C cooler than today. Our results indicate that incorporation of growth rate effects into coral Sr/Ca calibrations may improve the accuracy of SSTs derived from living and fossil corals.

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

    SciTech Connect

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

    1992-01-01

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

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

    SciTech Connect

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

    1992-06-01

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

  7. CRAC channels drive digital activation and provide analog control and synergy to Ca(2+)-dependent gene regulation.

    PubMed

    Kar, Pulak; Nelson, Charmaine; Parekh, Anant B

    2012-02-07

    Ca(2+)-dependent gene expression is critical for cell growth, proliferation, plasticity, and adaptation [1-3]. Because a common mechanism in vertebrates linking cytoplasmic Ca(2+) signals with activation of protein synthesis involves the nuclear factor of activated T cells (NFAT) family of transcription factors [4, 5], we have quantified protein expression in single cells following physiological Ca(2+) signals by using NFAT-driven expression of a genetically encoded fluorescent protein. We find that gene expression following CRAC channel activation is an all-or-nothing event over a range of stimulus intensities. Increasing agonist concentration recruits more cells but each responding cell does so in an essentially digital manner. Furthermore, Ca(2+)-dependent gene expression shows both short-term memory and strong synergy, where two pulses of agonist, which are ineffectual individually, robustly activate gene expression provided that the time interval between them is short. Such temporal filtering imparts coincidence detection to Ca(2+)-dependent gene activation. The underlying molecular basis mapped to time-dependent, nonlinear accumulation of nuclear NFAT. Local Ca(2+) near CRAC channels has to rise above a threshold level to drive gene expression, providing analog control to the digital activation process and a means to filter out fluctuations in background noise from activating transcription while ensuring robustness and high fidelity in the excitation-transcription coupling mechanism. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2011-01-01

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

  9. The cytoplasmic loop located between transmembrane segments 6 and 7 controls activation by Ca2+ of sarcoplasmic reticulum Ca2+-ATPase.

    PubMed

    Menguy, T; Corre, F; Bouneau, L; Deschamps, S; Møller, J V; Champeil, P; le Maire, M; Falson, P

    1998-08-07

    During active cation transport, sarcoplasmic reticulum Ca2+-ATPase, like other P-type ATPases, undergoes major conformational changes, some of which are dependent on Ca2+ binding to high affinity transport sites. We here report that, in addition to previously described residues of the transmembrane region (Clarke, D. M., Loo, T. W., Inesi, G., and MacLennan, D. H. (1989) Nature 339, 476-478), the region located in the cytosolic L6-7 loop connecting transmembrane segments M6 and M7 has a definite influence on the sensitivity of the Ca2+-ATPase to Ca2+, i.e. on the affinity of the ATPase for Ca2+. Cluster mutation of aspartic residues in this loop results in a strong reduction of the affinity for Ca2+, as shown by the Ca2+ dependence of ATPase phosphorylation from either ATP or Pi. The reduction in Ca2+ affinity for phosphorylation from Pi is observed both at acidic and neutral pH, suggesting that these mutations interfere with binding of the first Ca2+, as proposed for some of the intramembranous residues essential for Ca2+ binding (Andersen, J. P. (1995) Biosci. Rep. 15, 243-261). Treatment of the mutated Ca2+-ATPase with proteinase K, in the absence or presence of various Ca2+ concentrations, leads to Ca2+-dependent changes in the proteolytic degradation pattern similar to those in the wild type but observed only at higher Ca2+ concentrations. This implies that these effects are not due to changes in the conformational state of Ca2+-free ATPase but that changes affecting the proteolytic digestion pattern require higher Ca2+ concentrations. We conclude that aspartic residues in the L6-7 loop might interact with Ca2+ during the initial steps of Ca2+ binding.

  10. Pathogen-inducible CaUGT1 is involved in resistance response against TMV infection by controlling salicylic acid accumulation.

    PubMed

    Lee, Boo-Ja; Kim, Sung-Kyu; Choi, Soo Bok; Bae, Jungdon; Kim, Ki-Jeong; Kim, Young-Jin; Paek, Kyung-Hee

    2009-07-07

    Capsicum annuum L. Bugang exhibits a hypersensitive response against Tobacco mosaic virus (TMV) P(0) infection. The C. annuumUDP-glucosyltransferase 1 (CaUGT1) gene was upregulated during resistance response to TMV and by salicylic acid, ethephon, methyl viologen, and sodium nitroprusside treatment. When the gene was downregulated by virus-induced gene silencing, a delayed HR was observed. In addition, free and total SA concentrations in the CaUGT1-downregulated hot pepper were decreased by 52% and 48% compared to that of the control plants, respectively. This suggested that the CaUGT1 gene was involved in resistance response against TMV infection by controlling the accumulation of SA.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-10-24

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

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

    PubMed

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

    2012-03-05

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

  14. Exercise-trained young men have higher calcium absorption rates and plasma calcitriol levels compared with age-matched sedentary controls.

    PubMed

    Zittermann, A; Sabatschus, O; Jantzen, S; Platen, P; Danz, A; Dimitriou, T; Scheld, K; Klein, K; Stehle, P

    2000-09-01

    The effect of physical activity on human calcium (Ca) metabolism is still not completely understood. Thus, we investigated fractional Ca absorption using a stable strontium test (Fc(240)), calciotropic hormones, and renal Ca excretion in 31 young men with a high activity level (GH) and in 26 age-matched sedentary control subjects (GL). Weekly hours spent on physical activity, obtained with a questionnaire were 15.0 +/- 6.6 (GH) and 1.0 +/- 1.4 (GL), respectively. Serum testosterone levels were significantly lower in GH compared with GL (P < 0.005). Dietary Ca intake (4-day food record) was twice as high in GH compared with GL men (P < 0.001). GH had significantly higher serum calcitriol levels and Fc(240) values than GL (P < 0.001 and P < 0.01, respectively). In a stepwise multiple regression analysis including serum levels of 25-hydroxyvitamin D, calcitriol, testosterone, and dietary Ca intake, only calcitriol was significantly correlated with Fc(240) (P = 0. 017). Twenty-four hour renal Ca excretion was only slightly higher in GH compared with GL (P < 0.05). However, additional Ca losses might have occurred through the extensive sweating of GH, as indicated by a difference of 1.7 liter between fluid intake and renal fluid excretion (P < 0.001). In summary, we observed a higher fractional Ca absorption rate in physically active young men compared with sedentary controls which is probably mediated by calcitriol. The low testosterone serum levels of the athletes were obviously not a limiting factor in Ca absorption efficiency. An additional Ca retention might, however, only be obtained if absorbed Ca exceeded total obligatory Ca losses.

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

    PubMed

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

    2017-03-01

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

  16. Receptors and aging: structural selectivity of the rhamnose-receptor on fibroblasts as shown by Ca(2+)-mobilization and gene-expression profiles.

    PubMed

    Faury, G; Molinari, J; Rusova, E; Mariko, B; Raveaud, S; Huber, P; Velebny, V; Robert, A M; Robert, L

    2011-01-01

    Qualitative and quantitative modifications of receptors were shown to play a key role in cell and tissue aging. We recently described the properties of a rhamnose-recognizing receptor on fibroblasts involved in the mediation of age-dependent functions of these cells. Using Ca(2+)-mobilization and DNA-microarrays we could show in the presence of rhamnose-rich oligo- and polysaccharides (RROPs) Ca(2+)-mobilization and changes in gene regulation. Here, we compared the effects of several RROPs, differing in their carbohydrate sequence and molecular weights, in normal human dermal fibroblasts (NHDFs). It appeared that different structural features were required for maximal effects on Ca(2+)-mobilization and gene-expression profiles. Maximal effect on Ca(2+) influx and intracellular free calcium regulation was exhibited by RROP-1, a 50 kDa average molecular weight polysaccharide, and RROP-3, a 5 kDa average molecular weight oligosaccharide with a different carbohydrate sequence. Maximal effect on gene-expression profiles was obtained with RROP-3. These results suggest the possibility of several different transmission pathways from the rhamnose-receptor to intracellular targets, differentially affecting these two intracellular functions, with potential consequences on aging. Although of only relative specificity, this receptor site exhibits a high affinity for rhamnose, absent from vertebrate glycoconjugates. The rhamnose-receptor might well represent an evolutionary conserved conformation of a prokaryote lectin. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2011-01-01

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

  18. 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

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

    PubMed

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

    1984-01-01

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

  20. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. 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

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

    PubMed

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

    2013-09-09

    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 and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry 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 Ca(2+)/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. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. 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

  4. 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

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

    DTIC Science & Technology

    2007-11-02

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

  6. 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.

  7. Myoplasmic resting Ca2+ regulation by ryanodine receptors is under the control of a novel Ca2+-binding region of the receptor

    PubMed Central

    Chen, Yanyi; Xue, Shenghui; Zou, Juan; Lopez, Jose R.; Yang, Jenny J.; Perez, Claudio F.

    2014-01-01

    Passive SR (sarcoplasmic reticulum) Ca2+ leak through the RyR (ryanodine receptor) plays a critical role in the mechanisms that regulate [Ca2+]rest (intracellular resting myoplasmic free Ca2+ concentration) in muscle. This process appears to be isoform-specific as expression of either RyR1 or RyR3 confers on myotubes different [Ca2+]rest. Using chimaeric RyR3–RyR1 receptors expressed in dyspedic myotubes, we show that isoform-dependent regulation of [Ca2+]rest is primarily defined by a small region of the receptor encompassing amino acids 3770–4007 of RyR1 (amino acids 3620–3859 of RyR3) named as the CLR (Ca2+ leak regulatory) region. [Ca2+]rest regulation by the CLR region was associated with alteration of RyRs’ Ca2+-activation profile and changes in SR Ca2+-leak rates. Biochemical analysis using Tb3+-binding assays and intrinsic tryptophan fluorescence spectroscopy of purified CLR domains revealed that this determinant of RyRs holds a novel Ca2+-binding domain with conformational properties that are distinctive to each isoform. Our data suggest that the CLR region provides channels with unique functional properties that modulate the rate of passive SR Ca2+ leak and confer on RyR1 and RyR3 distinctive [Ca2+]rest regulatory properties. The identification of a new Ca2+-binding domain of RyRs with a key modulatory role in [Ca2+]rest regulation provides new insights into Ca2+-mediated regulation of RyRs. PMID:24635445

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

    PubMed

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

    2014-04-01

    In holometabolous insects the fall to zero of the titer of Juvenile Hormone ends its still poorly understood "status quo" mode of action in larvae. Concurrently it initiates metamorphosis of which the programmed cell death of all internal tissues that actively secrete proteins, such as the fat body, midgut, salivary glands, prothoracic glands, etc. is the most drastic aspect. These tissues have a very well developed rough endoplasmic reticulum, a known storage site of intracellular Ca(2+). A persistent high [Ca(2+)]i is toxic, lethal and causal to apoptosis. Metamorphosis becomes a logical phenomenon if analyzed from: (1) the causal link between calcium toxicity and apoptosis; (2) the largely overlooked fact that at least some isoforms of Ca(2+)-ATPases have a binding site for farnesol-like endogenous sesquiterpenoids (FRS). The Ca(2+)-ATPase blocker thapsigargin, like JH a sesquiterpenoid derivative, illustrates how absence of JH might work. The Ca(2+)-homeostasis system is concurrently extremely well conserved in evolution and highly variable, enabling tissue-, developmental-, and species specificity. As long as JH succeeds in keeping [Ca(2+)]i low by keeping the Ca(2+)-ATPases pumping, it acts as "the status quo" hormone. When it disappears, its various inhibitory effects are lifted. The electrical wiring system of cells, in particular in the regenerating tissues, is subject to change during metamorphosis. The possibility is discussed that in vertebrates an endogenous farnesol-like sesquiterpenoid, probably farnesol itself, acts as a functional, but hitherto completely overlooked Juvenile anti-aging "Inbrome", a novel concept in signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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.

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

    PubMed

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

    2015-01-01

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

  11. 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

  12. Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

    PubMed

    Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

    2015-03-01

    To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

  13. A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

    PubMed

    Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

    2016-10-01

    Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

  14. Protein Homeostasis and Aging: the importance of exquisite quality control

    PubMed Central

    Koga, Hiroshi; Kaushik, Susmita; Cuervo, Ana Maria

    2010-01-01

    All cells count on precise mechanisms that regulate protein homeostasis to maintain a stable and functional proteome. A progressive deterioration in the ability of cells to preserve the stability of their proteome occurs with age and contributes to the functional loss characteristic of old organisms. Molecular chaperones and the proteolytic systems are responsible for this cellular quality control by assuring continuous renewal of intracellular proteins. When protein damage occurs, such as during cellular stress, the coordinated action of these cellular surveillance systems allows detection and repair of the damaged structures or, in many instances, leads to the complete elimination of the altered proteins from inside cells. Dysfunction of the quality control mechanisms and intracellular accumulation of abnormal proteins in the form of protein inclusions and aggregates occur in almost all tissues of an aged organism. Preservation or enhancement of the activity of these surveillance systems until late in life improves their resistance to stress and is sufficient to slow down aging. In this work, we review recent advances on our understanding of the contribution of chaperones and proteolytic systems to the maintenance of cellular homeostasis, the cellular response to stress and ultimately to longevity. PMID:20152936

  15. 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.

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

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. 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

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

    PubMed

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

    2007-01-01

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

  20. The effect of aging on anticipatory postural control

    PubMed Central

    Kanekar, Neeta; Aruin, Alexander S.

    2014-01-01

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

  1. The effect of aging on anticipatory postural control.

    PubMed

    Kanekar, Neeta; Aruin, Alexander S

    2014-04-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2014-01-01

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

  4. PAA-PAMPS copolymers as an efficient tool to control CaCO3 scale formation.

    PubMed

    Dietzsch, Michael; Barz, Matthias; Schüler, Timo; Klassen, Stefanie; Schreiber, Martin; Susewind, Moritz; Loges, Niklas; Lang, Michael; Hellmann, Nadja; Fritz, Monika; Fischer, Karl; Theato, Patrick; Kühnle, Angelika; Schmidt, Manfred; Zentel, Rudolf; Tremel, Wolfgang

    2013-03-05

    Scale formation, the deposition of certain minerals such as CaCO3, MgCO3, and CaSO4·2H2O in industrial facilities and household devices, leads to reduced efficiency or severe damage. Therefore, incrustation is a major problem in everyday life. In recent years, double hydrophilic block copolymers (DHBCs) have been the focus of interest in academia with regard to their antiscaling potential. In this work, we synthesized well-defined blocklike PAA-PAMPS copolymers consisting of acrylic acid (AA) and 2-acrylamido-2-methyl-propane sulfonate (AMPS) units in a one-step reaction by RAFT polymerization. The derived copolymers had dispersities of 1.3 and below. The copolymers have then been investigated in detail regarding their impact on the different stages of the crystallization process of CaCO3. Ca(2+) complexation, the first step of a precipitation process, and polyelectrolyte stability in aqueous solution have been investigated by potentiometric measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). A weak Ca(2+) induced copolymer aggregation without concomitant precipitation was observed. Nucleation, early particle growth, and colloidal stability have been monitored in situ with DLS. The copolymers retard or even completely suppress nucleation, most probably by complexation of solution aggregates. In addition, they stabilize existing CaCO3 particles in the nanometer regime. In situ AFM was used as a tool to verify the coordination of the copolymer to the calcite (104) crystal surface and to estimate its potential as a growth inhibitor in a supersaturated CaCO3 environment. All investigated copolymers instantly stopped further crystal growth. The carboxylate richest copolymer as the most promising antiscaling candidate proved its enormous potential in scale inhibition as well in an industrial-filming test (Fresenius standard method).

  5. 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.

  6. 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

  7. 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

  8. Molecular Interactions in the Voltage Sensor Controlling Gating Properties of CaV Calcium Channels.

    PubMed

    Tuluc, Petronel; Yarov-Yarovoy, Vladimir; Benedetti, Bruno; Flucher, Bernhard E

    2016-02-02

    Voltage-gated calcium channels (CaV) regulate numerous vital functions in nerve and muscle cells. To fulfill their diverse functions, the multiple members of the CaV channel family are activated over a wide range of voltages. Voltage sensing in potassium and sodium channels involves the sequential transition of positively charged amino acids across a ring of residues comprising the charge transfer center. In CaV channels, the precise molecular mechanism underlying voltage sensing remains elusive. Here we combined Rosetta structural modeling with site-directed mutagenesis to identify the molecular mechanism responsible for the specific gating properties of two CaV1.1 splice variants. Our data reveal previously unnoticed interactions of S4 arginines with an aspartate (D1196) outside the charge transfer center of the fourth voltage-sensing domain that are regulated by alternative splicing of the S3-S4 linker. These interactions facilitate the final transition into the activated state and critically determine the voltage sensitivity and current amplitude of these CaV channels. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  11. Computer-aided control of electrolysis of solid Nb2O5 in molten CaCl2.

    PubMed

    Wu, Tian; Xiao, Wei; Jin, Xianbo; Liu, Chao; Wang, Dihua; Chen, George Z

    2008-04-07

    Low energy production of Nb powders via computer-aided control (CAC) of two-electrode electrolysis of porous Nb2O5 pellets (ca. 1.0 g) has been successfully demonstrated in molten CaCl2 at 1123 K. It was observed that potentiostatic electrolysis of the oxide in a three-electrode cell led to a cell voltage, i.e. the potential difference between the working (cathode) and counter (anode) electrodes, that decreased to a low and stable value within 1-2 h of the potential application until the end of the electrolysis (up to 12 h in this work). The cell voltage varied closely according to the current change. The stabilised cell voltage was below 2.5 V when the cathode potential was more positive than that for the reduction of Ca2+, leading to much lower energy consumption than that of constant voltage (>3.0 V) two-electrode electrolysis, as previously reported. Using a computer to program the variation of the cell voltage of two-electrode electrolysis according to that observed in the potentiostatic three-electrode electrolysis (0.05 V vs. Ca/Ca2+), a Nb powder with ca. 3900 ppm oxygen was produced in 12 h, with the energy consumption being 37.4% less than that of constant voltage two-electrode electrolysis at 3.0 V. Transmission electron microscopy revealed thin oxide layers (4-6 nm) on individual nodular particles (1-5 microm) of the obtained Nb powder. The oxide layer was likely formed in post-electrolysis processing operations, including washing in water, and contributed largely to the oxygen content in the obtained Nb powder.

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

    PubMed

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

    2002-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

  14. Synaptic vesicles control the time course of neurotransmitter secretion via a Ca2+/H+ antiport

    PubMed Central

    Cordeiro, J Miguel; Gonçalves, Paula P; Dunant, Yves

    2011-01-01

    We investigated the physiological role of the vesicular Ca2+/H+ antiport in rapid synaptic transmission using the Torpedo electric organ (a modified neuromuscular system). By inhibiting V-type H+-transporting ATPase (V-ATPase), bafilomycin A1 dissipates the H+ gradient of synaptic vesicles, thereby abolishing the Ca2+/H+ antiport driving force. In electrophysiology experiments, bafilomycin A1 significantly prolonged the duration of the evoked electroplaque potential. A biochemical assay for acetylcholine (ACh) release showed that the effect of bafilomycin A1 was presynaptic. Indeed, bafilomycin A1 increased the amount of radio-labelled ACh released in response to paired-pulse stimulation. Bafilomycin A1 also enhanced Ca2+-dependent ACh release from isolated nerve terminals (synaptosomes). The bafilomycin-induced electroplaque potential lengthening did not arise from cholinesterase inhibition, since eserine (which also prolonged the electroplaque potential) strongly decreased evoked ACh release. Bafilomycin A1 augmented the amount of calcium accumulating in nerve terminals following a short tetanic stimulation and delayed subsequent calcium extrusion. By reducing stimulation-dependent calcium accumulation in synaptic vesicles, bafilomycin A1 diminished the corresponding depletion of vesicular ACh, as tested using both intact tissue and isolated synaptic vesicles. Strontium ions inhibit the vesicular Ca2+/H+ antiport, while activating transmitter release at concentrations one order of magnitude higher than Ca2+ does. In the presence of Sr2+ the time course of the electroplaque potential was also prolonged but, unlike bafilomycin A1, Sr2+ enhanced facilitation in paired-pulse experiments. It is therefore proposed that the vesicular Ca2+/H+ antiport function is to shorten ‘phasic’ transmitter release, allowing the synapse to transmit briefer impulses and so to work at higher frequencies. PMID:21059764

  15. Search and the Aging Mind: The Promise and Limits of the Cognitive Control Hypothesis of Age Differences in Search.

    PubMed

    Mata, Rui; von Helversen, Bettina

    2015-07-01

    Search is a prerequisite for successful performance in a broad range of tasks ranging from making decisions between consumer goods to memory retrieval. How does aging impact search processes in such disparate situations? Aging is associated with structural and neuromodulatory brain changes that underlie cognitive control processes, which in turn have been proposed as a domain-general mechanism controlling search in external environments as well as memory. We review the aging literature to evaluate the cognitive control hypothesis that suggests that age-related change in cognitive control underlies age differences in both external and internal search. We also consider the limits of the cognitive control hypothesis and propose additional mechanisms such as changes in strategy use and affect that may be necessary to understand how aging affects search. Copyright © 2015 Cognitive Science Society, Inc.

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  17. 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

  18. 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.

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

    PubMed Central

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

    2017-01-01

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

  20. 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

  1. Metabolic memory of ß-cells controls insulin secretion and is mediated by CaMKII.

    PubMed

    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

    2014-07-01

    Ca(2+)/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 Ca(2+)-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.

  2. 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.

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

    PubMed

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

    2016-03-08

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

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

    PubMed Central

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

    2015-01-01

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

  5. 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.

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

    PubMed

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

    2014-06-01

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

  7. Low-dose radiation accelerates aging of the T-cell receptor repertoire in CBA/Ca mice.

    PubMed

    Candéias, Serge M; Mika, Justyna; Finnon, Paul; Verbiest, Tom; Finnon, Rosemary; Brown, Natalie; Bouffler, Simon; Polanska, Joanna; Badie, Christophe

    2017-06-30

    While the biological effects of high-dose-ionizing radiation on human health are well characterized, the consequences of low-dose radiation exposure remain poorly defined, even though they are of major importance for radiological protection. Lymphocytes are very radiosensitive, and radiation-induced health effects may result from immune cell loss and/or immune system impairment. To decipher the mechanisms of effects of low doses, we analyzed the modulation of the T-cell receptor gene repertoire in mice exposed to a single low (0.1 Gy) or high (1 Gy) dose of radiation. High-throughput T-cell receptor gene profiling was used to visualize T-lymphocyte dynamics over time in control and irradiated mice. Radiation exposure induces "aging-like" effects on the T-cell receptor gene repertoire, detectable as early as 1 month post-exposure and for at least 6 months. Surprisingly, these effects are more pronounced in animals exposed to 0.1 Gy than to 1 Gy, where partial correction occurs over time. Importantly, we found that low-dose radiation effects are partially due to the hematopoietic stem cell impairment. Collectively, our findings show that acute low-dose radiation exposure specifically results in long-term alterations of the T-lymphocyte repertoire.

  8. 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.

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

    PubMed Central

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

    2015-01-01

    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.—Reilly, L., Howie, J., Wypijewski, K., Ashford, M. L. J., Hilgemann, D. W., Fuller, W. Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling. PMID:26174834

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  12. 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.

  13. 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.

  14. 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.

  15. Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors

    PubMed Central

    2010-01-01

    The time scale of the photoresponse in photoreceptor cells is set by the slowest of the steps that quench the light-induced activity of the phototransduction cascade. In vertebrate photoreceptor cells, this rate-limiting reaction is thought to be either shutoff of catalytic activity in the photopigment or shutoff of the pigment's effector, the transducin-GTP–phosphodiesterase complex. In suction pipette recordings from isolated salamander L-cones, we found that preventing changes in internal [Ca2+] delayed the recovery of the light response and prolonged the dominant time constant for recovery. Evidence that the Ca2+-sensitive step involved the pigment itself was provided by the observation that removal of Cl− from the pigment's anion-binding site accelerated the dominant time constant for response recovery. Collectively, these observations indicate that in L-cones, unlike amphibian rods where the dominant time constant is insensitive to [Ca2+], pigment quenching rate limits recovery and provides an additional mechanism for modulating the cone response during light adaptation. PMID:20231373

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

    PubMed

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

    2001-01-01

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

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

    PubMed

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

    2012-03-01

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

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

    PubMed

    Geiger, J R; Jonas, P

    2000-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2002-10-01

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed

    Saito, Yasuhiko; Yanagawa, Yuchio

    2013-01-01

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

  2. Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer's disease (AD).

    PubMed

    Alldred, Melissa J; Lee, Sang Han; Petkova, Eva; Ginsberg, Stephen D

    2015-09-01

    Down syndrome (DS) is caused by the triplication of human chromosome 21 (HSA21) and is the most common genetic cause of intellectual disability, with individuals having deficits in cognitive function including hippocampal learning and memory and neurodegeneration of cholinergic basal forebrain neurons, a pathological hallmark of Alzheimer's disease (AD). To date, the molecular underpinnings driving this pathology have not been elucidated. The Ts65Dn mouse is a segmental trisomy model of DS and like DS/AD pathology, displays age-related cognitive dysfunction and basal forebrain cholinergic neuron (BFCN) degeneration. To determine molecular and cellular changes important for elucidating mechanisms of neurodegeneration in DS/AD pathology, expression profiling studies were performed. Molecular fingerprinting of homogeneous populations of Cornu Ammonis 1 (CA1) pyramidal neurons was performed via laser capture microdissection followed by Terminal Continuation RNA amplification combined with custom-designed microarray analysis and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting. Significant alterations were observed within CA1 pyramidal neurons of aged Ts65Dn mice compared to normal disomic (2N) littermates, notably in excitatory and inhibitory neurotransmission receptor families and neurotrophins, including brain-derived neurotrophic factor as well as several cognate neurotrophin receptors. Examining gene and protein expression levels after the onset of BFCN degeneration elucidated transcriptional and translational changes in neurons within a vulnerable circuit that may cause the AD-like pathology seen in DS as these individuals age, and provide rational targets for therapeutic interventions.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  5. Age-Related Differences in Locus of Control Orientation in Three Behavior Domains

    ERIC Educational Resources Information Center

    Bradley, Robert H.; Webb, Roger

    1976-01-01

    Age correlated differences in locus of control orientation were examined for 306 persons aged 13 to 90 in three areas of activity: intellectual, social and physical. The Locus of Control Inventory for Three Achievement Domains was administered. (MS)

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

    PubMed Central

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

    1993-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  9. Local Control of Postinhibitory Rebound Spiking in CA1 Pyramidal Neuron Dendrites

    PubMed Central

    Ascoli, Giorgio A.; Gasparini, Sonia; Medinilla, Virginia; Migliore, Michele

    2012-01-01

    Postinhibitory rebound spiking is characteristic of several neuron types and brain regions, where it sustains spontaneous activity and central pattern generation. However, rebound spikes are rarely observed in the principal cells of the hippocampus under physiological conditions. We report that CA1 pyramidal neurons support rebound spikes mediated by hyperpolarization-activated inward current (Ih), and normally masked by A-type potassium channels (KA). In both experiments and computational models, KA blockage or reduction consistently resulted in a somatic action potential upon release from hyperpolarizing injections in the soma or main apical dendrite. Rebound spiking was systematically abolished by the additional blockage or reduction of Ih. Since the density of both KA and Ih increases in these cells with the distance from the soma, such “latent” mechanism may be most effective in the distal dendrites, which are targeted by a variety of GABAergic interneurons. Detailed computer simulations, validated against the experimental data, demonstrate that rebound spiking can result from activation of distal inhibitory synapses. In particular, partial KA reduction confined to one or few branches of the apical tuft may be sufficient to elicit a local spike following a train of synaptic inhibition. Moreover, the spatial extent and amount of KA reduction determines whether the dendritic spike propagates to the soma. These data suggest that the plastic regulation of KA can provide a dynamic switch to unmask postinhibitory spiking in CA1 pyramidal neurons. This newly discovered local modulation of postinhibitory spiking further increases the signal processing power of the CA1 synaptic microcircuitry. PMID:20445069

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-05-01

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

  12. Morphology control and high critical currents in superconducting thin films in the Tl-Ca-Ba-Cu-O system

    NASA Astrophysics Data System (ADS)

    Ginley, D. S.; Kwak, J. F.; Venturini, E. L.; Morosin, B.; Baughman, R. J.

    1989-08-01

    Superconducting polycrystalline thin films in the Tl-Ca-Ba-Cu-O system have been prepared by electron beam evaporation followed by appropriate sintering and annealing. The configuration employed (free or confined surface) to sinter the films determines the morphology varying from random to highly oriented, respectively. These films are predominantly the Tl 2Ca 2Ba 2Cu 3O 10 phase, but some contain up to 50 at % Tl 2CaBa 2Cu 2O 8, demonstrating a toleration of variable stoichiometry. The key to obtaining high quality materials with short air sintering times is precise control of the Tl and oxygen partial pressures. Transition temperatures to 110 K and transport critical current densities to 600 000 A/cm 2 at 76 K have been attained. The best films (room temperature resistance p < 1 mΩcm) show no evidence of weak links, but do exhibit weak flux pinning at 77 K. On the other hand, films with p > 1 mΩcm show a definite correlation between critical current and p, consistent with the presence of weak links.

  13. Young runoff fractions control streamwater age and solute concentration dynamics

    Treesearch

    Paolo Benettin; Scott W. Bailey; Andrea Rinaldo; Gene E. Likens; Kevin J. McGuire; Gianluca Botter

    2017-01-01

    We introduce a new representation of coupled solute and water age dynamics at the catchment scale, which shows how the contributions of young runoff waters can be directly referenced to observed water quality patterns. The methodology stems from recent trends in hydrologic transport that acknowledge the dynamic nature of streamflow age and explores the use of water age...

  14. 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.

  15. 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.

  16. 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.

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

    PubMed

    Heckhausen, J; Baltes, P B

    1991-07-01

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

  18. 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

  19. 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

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  2. Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases.

    PubMed

    Cunningham, K W; Fink, G R

    1994-02-01

    Ca2+ ATPases deplete the cytosol of Ca2+ ions and are crucial to cellular Ca2+ homeostasis. The PMC1 gene of Saccharomyces cerevisiae encodes a vacuole membrane protein that is 40% identical to the plasma membrane Ca2+ ATPases (PMCAs) of mammalian cells. Mutants lacking PMC1 grow well in standard media, but sequester Ca2+ into the vacuole at 20% of the wild-type levels. pmc1 null mutants fail to grow in media containing high levels of Ca2+, suggesting a role of PMC1 in Ca2+ tolerance. The growth inhibitory effect of added Ca2+ requires activation of calcineurin, a Ca2+ and calmodulin-dependent protein phosphatase. Mutations in calcineurin A or B subunits or the inhibitory compounds FK506 and cyclosporin A restore growth of pmc1 mutants in high Ca2+ media. Also, growth is restored by recessive mutations that inactivate the high-affinity Ca(2+)-binding sites in calmodulin. This mutant calmodulin has apparently lost the ability to activate calcineurin in vivo. These results suggest that activation of calcineurin by Ca2+ and calmodulin can negatively affect yeast growth. A second Ca2+ ATPase homolog encoded by the PMR1 gene acts together with PMC1 to prevent lethal activation of calcineurin even in standard (low Ca2+) conditions. We propose that these Ca2+ ATPase homologs are essential in yeast to deplete the cytosol of Ca2+ ions which, at elevated concentrations, inhibits yeast growth through inappropriate activation of calcineurin.

  3. Endoplasmic reticulum-mitochondria Ca(2+) crosstalk in the control of the tumor cell fate.

    PubMed

    Missiroli, Sonia; Danese, Alberto; Iannitti, Tommaso; Patergnani, Simone; Perrone, Mariasole; Previati, Maurizio; Giorgi, Carlotta; Pinton, Paolo

    2017-06-01

    Mitochondria-associated membranes are juxtaposed between the endoplasmic reticulum and mitochondria and have been identified as a critical hub in the regulation of apoptosis and tumor growth. One key function of mitochondria-associated membranes is to provide asylum to a number of proteins with tumor suppressor and oncogenic properties. In this review, we discuss how Ca(2+) flux manipulation represents the primary mechanism underlying the action of several oncogenes and tumor-suppressor genes and how these networks might be manipulated to provide novel therapies for cancer. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 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.

  5. Autophagy Controls Acquisition of Aging Features in Macrophages.

    PubMed

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

    2015-01-01

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

  6. 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

  7. 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,…

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

    PubMed

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

    2001-08-01

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

  9. Study of Chardonnay and Sauvignon blanc wines from D.O.Ca Rioja (Spain) aged in different French oak wood barrels: Chemical and aroma quality aspects.

    PubMed

    Herrero, Paula; Sáenz-Navajas, María Pilar; Avizcuri, José Miguel; Culleré, Laura; Balda, Pedro; Antón, Elena C; Ferreira, Vicente; Escudero, Ana

    2016-11-01

    This study discusses chemical data corresponding to the analysis of twenty-one wood-extractable aromatic compounds in twenty-four different barrels varying in the toasting level at three sampling times: at the end of the alcoholic fermentation and after 5 and 12months of aging. Twelve barrels contained monovarietal Chardonnay wine while the other twelve barrels contained Sauvignon blanc wine. The levels of nearly all the analyzed compounds increased with the aging time, with the exception of vinylphenols and methyl vanillate, which decreased. These latter compounds had significantly higher levels in the Chardonnay wines than in the Sauvignon blanc. Furfural, guaiacol and vanillin derivatives increased with the toasting level. ANOVA study showed significant interactions between the toasting level and aging time as well as between the variety and aging time, which revealed significant differences in the levels of the compounds studied in the wines dependent on the toasting level, variety and aging time. Quality perception based exclusively on orthonasal aroma stimuli was evaluated by a panel of Spanish wine professionals in 12-month aged wines belonging to both grape varieties. Experts from D.O.Ca Rioja aroma did not share a common aroma quality concept for aged Chardonnay and Sauvignon blanc wines. Considering the cluster formed by the majority of experts (76%) for the Chardonnay and cluster 1 (56%) for Sauvignon blanc, quality scores were negatively correlated with the concentration level of 4-vinylphenol and positively with the concentration level of (E)-isoeugenol. The opposite was observed for cluster 2 (44%) identified for Sauvignon blanc wines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Autophagy Controls Acquisition of Aging Features in Macrophages

    PubMed Central

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

    2015-01-01

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

  11. Promoting work ability and well-being in hospital nursing: the interplay of age, job control, and successful ageing strategies.

    PubMed

    Müller, Andreas; Weigl, Matthias; Heiden, Barbara; Glaser, Jürgen; Angerer, Peter

    2012-01-01

    Previous research shows that work ability of nurses decreases with age. In our study we therefore addressed the following questions: Do successful ageing strategies at work in terms of selection, optimization, and compensation (SOC) support the work ability of nurses? Does SOC mediate the relationship between job control (i.e., decision opportunities at work) and work ability? Does the mediation differ between age-groups? 438 nurses (Age Range 21-63 years) completed a questionnaire in the course of an employee survey. Results show that SOC is positively related with work ability. The positive effect of job control on work ability is significantly mediated by SOC. There are stronger mediating effects for elder nurses than for younger nurses. Results indicate that the interplay of job control and SOC at work helps to maintain the work ability of nurses in nursing care.

  12. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Jensen, Martin Borch; Jasper, Heinrich

    2014-08-05

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

  16. All for One But Not One for All: Excitatory Synaptic Scaling and Intrinsic Excitability Are Coregulated by CaMKIV, Whereas Inhibitory Synaptic Scaling Is Under Independent Control.

    PubMed

    Joseph, Annelise; Turrigiano, Gina G

    2017-07-12

    Neocortical circuits use a family of homeostatic plasticity mechanisms to stabilize firing, including excitatory and inhibitory synaptic scaling and homeostatic intrinsic plasticity (Turrigiano and Nelson, 2004). All three mechanisms can be induced in tandem in cultured rat neocortical pyramidal neurons by chronic manipulations of firing, but it is unknown whether they are coinduced by the same activity-sensors and signaling pathways, or whether they are under independent control. Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) is a key sensory/effector in excitatory synaptic scaling that senses perturbations in firing through changes in calcium influx, and translates this into compensatory changes in excitatory quantal amplitude (Ibata et al., 2008; Goold and Nicoll, 2010). Whether CaMKIV also controls inhibitory synaptic scaling and intrinsic homeostatic plasticity was unknown. To test this we manipulated CaMKIV signaling in individual neurons using dominant-negative (dn) or constitutively-active (ca) forms of nuclear-localized CaMKIV and measured the induction of all three forms of homeostatic plasticity. We found that excitatory synaptic scaling and intrinsic plasticity were bidirectionally coinduced by these manipulations. In contrast, these cell-autonomous manipulations had no impact on inhibitory quantal amplitude. Finally, we found that spontaneous firing rates were shifted up or down by dnCaMKIV or caCaMKIV, respectively, suggesting that uncoupling CaMKIV activation from activity generates an error signal in the negative feedback mechanism that controls firing rates. Together, our data show that excitatory synaptic scaling and intrinsic excitability are tightly coordinated through bidirectional changes in the same signaling pathway, whereas inhibitory synaptic scaling is sensed and regulated through an independent control mechanism.SIGNIFICANCE STATEMENT Maintaining stable function in highly interconnected neural circuits is essential for

  17. 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.

  18. Persistent fine-scale fault structures control rupture development in Parkfield, CA.

    NASA Astrophysics Data System (ADS)

    Perrin, C.; Waldhauser, F.; Scholz, C. H.

    2016-12-01

    We investigate the fine-scale geometry and structure of the San Andreas Fault (SAF) near Parkfield, CA, and their role in the development of the 1966 and 2004 M6 earthquakes. Both events broke the fault mainly unilaterally with similar length ( 30 km) but in opposite directions. Seismic slip occurred in a narrow zone between 5 and 10 km depth, as outlined by the concentration of aftershocks along the edge of the slip area. Across fault distribution of the 2004 aftershocks show a rapid decrease of event density away from the fault core. The damage zone is narrower in the Parkfield section (few 100 meters) than in the creeping section ( 1 km). We observe a similar but broader distribution during the interseismic periods. This implies that stress accumulates in a volume around the fault during interseismic periods, whereas coseismic deformation is more localized on the mature SAF. Large aftershocks are concentrated at both rupture tips, characterized by strong heterogeneities in the fault structure at the surface and at depth: i) in the south near Gold Hill-Cholame, a large releasing bend (>25°) separates the Parkfield section from the southern section of the SAF; ii) in the north at Middle Mountain, the surface fault trace goes through an ancient restraining step-over connecting the Parkfield and creeping sections. Fine-scale analysis of the 2004 aftershocks reveals a change in the fault dip and local variations of the fault strike (up to 25°) beneath Middle Mountain, in good agreement with focal mechanisms, which show oblique normal and reverse faulting. We observe these variations during the interseismic periods before and after the 2004 event, suggesting that the structural heterogeneities persisted through at least two earthquake cycles. These heterogeneities act as barriers to rupture propagation of moderate size earthquakes at Parkfield, but also as stress concentrations where rupture initiates.

  19. Are Middle-Aged Men with Chronic Kidney Disease at Higher Risk of Having Nocturia than Age-Matched Controls.

    PubMed

    Hsu, Chun-Kai; Wu, Mei-Yi; Chiang, I-Ni; Yang, Stephen S-D; Chang, Shang-Jen

    2015-09-01

    We compared the lower urinary tract symptoms between middle-aged men with and without chronic kidney disease (CKD) under 50 years of age. Between October 2010 and July 2013, patients with CKD aged below 50 who received regular follow-ups at the nephrology outpatient clinics were enrolled. We also enrolled men aged below 50 years with estimated glomerular filtration rates (eGFR) higher than 60 mL/min per 1.73 m(2) and without history of kidney diseases from the health examination department as the control group. Clinical parameters and laboratory parameters were collected for analysis and comparison. The lower urinary tract symptoms were evaluated using the International Prostate Symptom Score (IPSS). Metabolic syndromes were defined according to the ATP III guidelines. Overall, 50 men with CKD and 187 age-matched men without CKD were enrolled in the study (age: 44.9 ± 6.9 vs. 43.7.0 ± 4.3, P = 0.11). When compared with the age-matched control group, the occurrences of lower urinary tract symptoms were fewer in CKD patients, though not statistically significant. CKD Patients had significantly higher scores of nocturia (1.3 vs. 0.8, P = 0.02) but had significantly less urinary frequency and relatively fewer urgency score. Nocturia was significantly associated with eGFR. Multivariate analysis showed that lower eGFR and overweight were the only two independent risk factors for nocturia (P < 0.01), but was not the case for metabolic syndromes. Middle-aged men with CKD had significantly more nocturia episodes than the age-matched control group, but had lower urinary frequency scores. Lower eGFR and overweight are independent risk factors for nocturia in middle-aged men. © 2014 Wiley Publishing Asia Pty Ltd.

  20. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2005-06-01

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

  2. 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

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

    PubMed Central

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

    2009-01-01

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

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

    DOE PAGES

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

    2012-06-22

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

  5. Synaptic correlates of increased cognitive vulnerability with aging: peripheral immune challenge and aging interact to disrupt theta-burst late-phase long-term potentiation in hippocampal area CA1.

    PubMed

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

    2010-06-02

    Variability in cognitive functioning increases markedly with age, as does cognitive vulnerability to physiological and psychological challenges. Exploring the basis of this vulnerability may provide important insights into the mechanisms underlying aging-associated cognitive decline. As we have previously reported, the cognitive abilities of aging (24-month-old) F344 x BN rats are generally good, but are more vulnerable to the consequences of a peripheral immune challenge (an intraperitoneal injection of live Escherichia coli) than those of their younger (3-month-old) counterparts. Four days after the injection, the aging, but not the young rats show profound memory deficits, specific to the consolidation of hippocampus-dependent memory processes. Here, we have extended these observations, using hippocampal slices to examine for the first time the combined effects of aging and a recent infection on several forms of synaptic plasticity. We have found that the specific deficit in long-lasting memory observed in the aged animals after infection is mirrored by a specific deficit in a form of long-lasting synaptic plasticity. The late-phase long-term potentiation induced in area CA1 using theta-burst stimulation is particularly compromised by the combined effects of aging and infection-a deficit that can be ameliorated by intra-cisterna magna administration of the naturally occurring antiinflammatory cytokine IL-1Ra (interleukin-1 receptor antagonist). These data support the idea that the combination of aging and a negative life event such as an infection might produce selective, early-stage failures of synaptic plasticity in the hippocampus, with corresponding selective deficits in memory.

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

    PubMed

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

    2016-01-01

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

  7. 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

  8. Osmotic dehydration of apple slices using a sucrose/CaCl2 combination to control spoilage caused by Botrytis cinerea, Colletotrichum acutatum, and Penicillium expansum.

    PubMed

    Chardonnet, C O; Sams, C E; Conway, W S; Mount, J R; Draughon, F A

    2001-09-01

    The efficacy of sucrose combined with CaCl2 during osmotic dehydration (OD) was tested for the control of Botrytis cinerea, Colletotrichum acutatum, and Penicillium expansum growth on lightly processed apple slices. The objective of this work was to determine whether the addition of CaCl2 in the osmotic solutions would limit the proliferation of fungal decay organisms. Slices were submitted to OD for 1 h at 25 degrees C in solutions containing 5 to 65% sucrose. Calcium chloride was added to a similar set of sucrose solutions at 0 to 8%. Control slices were made of untreated slices, and slices were processed in water. The mass ratio of the slices did not vary when fruit pieces were processed in solutions containing 5 to 65% sucrose. These slices showed a high susceptibility to spoilage compared to the control slices not submitted to OD: a significant twofold and 60% increase in decay area caused by B. cinerea and P. expansum, respectively, was observed when slices were processed in 50% sucrose/0% CaCl2; C. acutatum showed a significant 50% increase in decay area when slices were processed in 20% sucrose/0% CaCl2. Calcium uptake was significantly increased when slices were processed in CaCl2 solutions, and the highest Ca content was observed when processed in 8% CaCl2, reaching 40 times that of the control slices processed in water. Calcium-treated slices were less susceptible to spoilage by all three pathogens, and the most effective combination in reducing apple slice spoilage was 20 to 30% sucrose combined with 2% CaCl2.

  9. TEMPERATURE AND MOISTURE CONTROL OF SEED AGING IN RYE

    USDA-ARS?s Scientific Manuscript database

    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...

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

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

    GM/CA-CAT at Sector 23 of the Advanced Photon Source (APS) is an NIH funded facility for crystallographic structure determination of biological macromolecules by X-ray diffraction. A second-generation Berkeley automounter is being integrated into the beamline control system at the 23BM 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.

  11. 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…

  12. Reevaluation of the Crooked Ridge River- Early Pleistocene (ca. 2 Ma) age and origin of the White Mesa Alluvium, northeastern Arizona

    USGS Publications Warehouse

    Hereford, Richard; Beard, Sue; Dickinson, William R.; Karlstrom, Karl E.; Heizler, Matthew T.; Crossey, Laura J.; Amoroso, Lee; House, Kyle; Pecha, Mark

    2016-01-01

    Essential features of the previously named and described Miocene Crooked Ridge River in northeastern Arizona (USA) are reexamined using new geologic and geochronologic data. Previously it was proposed that Cenozoic alluvium at Crooked Ridge and southern White Mesa was pre–early Miocene, the product of a large, vigorous late Paleogene river draining the 35–23 Ma San Juan Mountains volcanic field of southwestern Colorado. The paleoriver probably breeched the Kaibab uplift and was considered important in the early evolution of the Colorado River and Grand Canyon. In this paper, we reexamine the character and age of these Cenozoic deposits. The alluvial record originally used to propose the hypothetical paleoriver is best exposed on White Mesa, providing the informal name White Mesa alluvium. The alluvium is 20–50 m thick and is in the bedrock-bound White Mesa paleovalley system, which comprises 5 tributary paleochannels. Gravel composition, detrital zircon data, and paleochannel orientation indicate that sediment originated mainly from local Cretaceous bedrock north, northeast, and south of White Mesa. Sedimentologic and fossil evidence imply alluviation in a low-energy suspended sediment fluvial system with abundant fine-grained overbank deposits, indicating a local channel system rather than a vigorous braided river with distant headwaters. The alluvium contains exotic gravel clasts of Proterozoic basement and rare Oligocene volcanic clasts as well as Oligocene–Miocene detrital sanidine related to multiple caldera eruptions of the San Juan Mountains and elsewhere. These exotic clasts and sanidine likely came from ancient rivers draining the San Juan Mountains. However, in this paper we show that the White Mesa alluvium is early Pleistocene (ca. 2 Ma) rather than pre–early Miocene. Combined 40Ar/39Ar dating of an interbedded tuff and detrital sanidine ages show that the basal White Mesa alluvium was deposited at 1.993 ± 0.002 Ma, consistent with a detrital

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

    PubMed

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

    2007-09-01

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

  14. Control of growth rate on Li/Ca values during the growth of calcite - An experimental approach

    NASA Astrophysics Data System (ADS)

    Füger, Anja; Mavromatis, Vasileios; Leis, Albrecht; Dietzel, Martin

    2017-04-01

    Lithium in seawater essentially originates from chemical weathering of continental silicate rocks. Dissolved Li ions in seawater are incorporated into marine carbonates, e.g. brachiopod shells, corals, authigenic carbonates, and Li incorporation and its isotope variations in the precipitated carbonates can be used to study the evolution of environmental conditions in seawater over geological timescales. In order to understand the Li incorporation during carbonate mineral formation, constrained inorganic precipitation experiments are necessary to identify the influence of parameters controlling fractionation (e.g. temperature, pH, calcification rate). In this study we performed Li co-precipitation experiments with calcite at 25 ˚ C using a mixed flow reactor. Therefore two separate solutions (CaCl2 with LiCl and Na2CO3) are mixed together using a peristaltic pump, at controlled flowrate. The pH is adjusted to be constant by bubbling continuous air or CO2 gas in the reactor during the experiment. In the present study we aim to quantify the dependence of precipitation rate, pH, calcification rate and Mg impact on Li/Ca values during the growth of calcium carbonate, in order to understand the incorporation behavior of Li into the calcite structure as well as the isotopic fractionation mechanisms. Preliminary results show that the distribution coefficient of Li into calcite, DLi (i.e. ˜10-3.56), does not depend on the precipitation rate. The pH seems to play a crucial role during the incorporation of Li in calcium carbonate. In the pH range between 6.3 and 8.5, the distribution coefficient DLi decreases with increasing pH from 10-3.56 to 10-2.18. Experiments with respect to calcification rate and the impact of aqueous Mg on the incorporation are ongoing as well as Li isotope measurements are planned.

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

    PubMed

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

    2013-12-01

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

  16. Facile and controllable synthesis of monodisperse CaF2 and CaF2:Ce3+/Tb3+ hollow spheres as efficient luminescent materials and smart drug carriers.

    PubMed

    Zhang, Cuimiao; Li, Chunxia; Peng, Chong; Chai, Ruitao; Huang, Shanshan; Yang, Dongmei; Cheng, Ziyong; Lin, Jun

    2010-05-17

    Highly uniform and well-dispersed CaF(2) hollow spheres with tunable particle size (300-930 nm) have been synthesized by a facile hydrothermal process. Their shells are composed of numerous nanocrystals (about 40 nm in diameter). The morphology and size of the CaF(2) products are strongly dependent on experimental parameters such as reaction time, pH value, and organic additives. The size of the CaF(2) hollow spheres can be controlled from 300 to 930 nm by adjusting the pH value. Nitrogen adsorption-desorption measurements suggest that mesopores (av 24.6 nm) exist in these hollow spheres. In addition, Ce(3+)/Tb(3+)-codoped CaF(2) hollow spheres can be prepared similarly, and show efficient energy transfer from Ce(3+) to Tb(3+) and strong green photoluminescence of Tb(3+) (541 nm, (5)D(4)-->(7)F(5) transition of Tb(3+), the highest quantum efficiency reaches 77%). The monodisperse CaF(2):Ce(3+)/Tb(3+) hollow spheres also have desirable properties as drug carriers. Ibuprofen-loaded CaF(2):Ce(3+)/Tb(3+) samples still show green luminescence of Tb(3+) under UV irradiation, and the emission intensity of Tb(3+) in the drug-carrier system varies with the released amount of ibuprofen, so that drug release can be easily tracked and monitored by means of the change in luminescence intensity. The formation mechanism and luminescent and drug-release properties were studied in detail.

  17. CaAP2 transcription factor is a candidate gene for a flowering repressor and a candidate for controlling natural variation of flowering time in Capsicum annuum.

    PubMed

    Borovsky, Yelena; Sharma, Vinod K; Verbakel, Henk; Paran, Ilan

    2015-06-01

    The APETALA2 transcription factor homolog CaAP2 is a candidate gene for a flowering repressor in pepper, as revealed by induced-mutation phenotype, and a candidate underlying a major QTL controlling natural variation in flowering time. To decipher the genetic control of transition to flowering in pepper (Capsicum spp.) and determine the extent of gene function conservation compared to model species, we isolated and characterized several ethyl methanesulfonate (EMS)-induced mutants that vary in their flowering time compared to the wild type. In the present study, we report on the isolation of an early-flowering mutant that flowers after four leaves on the primary stem compared to nine leaves in the wild-type 'Maor'. By genetic mapping and sequencing of putative candidate genes linked to the mutant phenotype, we identified a member of the APETALA2 (AP2) transcription factor family, CaAP2, which was disrupted in the early-flowering mutant. CaAP2 is a likely ortholog of AP2 that functions as a repressor of flowering in Arabidopsis. To test whether CaAP2 has an effect on controlling natural variation in the transition to flowering in pepper, we performed QTL mapping for flowering time in a cross between early and late-flowering C. annuum accessions. We identified a major QTL in a region of chromosome 2 in which CaAP2 was the most significant marker, explaining 52 % of the phenotypic variation of the trait. Sequence comparison of the CaAP2 open reading frames in the two parents used for QTL mapping did not reveal significant variation. In contrast, significant differences in expression level of CaAP2 were detected between near-isogenic lines that differ for the flowering time QTL, supporting the putative function of CaAP2 as a major repressor of flowering in pepper.

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

    PubMed Central

    Brown-Borg, Holly M.

    2015-01-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-12

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

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

    USGS Publications Warehouse

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

    2017-01-01

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

  2. Identification of residues that control Li(+) versus Na(+) dependent Ca(2+) exchange at the transport site of the mitochondrial NCLX.

    PubMed

    Roy, Soumitra; Dey, Kuntal; Hershfinkel, Michal; Ohana, Ehud; Sekler, Israel

    2017-06-01

    The Na(+)/Ca(2+)/Li(+) exchanger (NCLX) is a member of the Na(+)/Ca(2+) exchanger family. NCLX is unique in its capacity to transport both Na(+) and Li(+), unlike other members, which are Na(+) selective. The major aim of this study was twofold, i.e., to identify NCLX residues that confer Li(+) or Na(+) selective Ca(2+) transport and map their putative location on NCLX cation transport site. We combined molecular modeling to map transport site of NCLX with euryarchaeal H(+)/Ca(2+) exchanger, CAX_Af, and fluorescence analysis to monitor Li(+) versus Na(+) dependent mitochondrial Ca(2+) efflux of transport site mutants of NCLX in permeabilized cells. Mutation of Asn149, Pro152, Asp153, Gly176, Asn467, Ser468, Gly494 and Asn498 partially or strongly abolished mitochondrial Ca(2+) exchange activity in intact cells. In permeabilized cells, N149A, P152A, D153A, N467Q, S468T and G494S demonstrated normal Li(+)/Ca(2+) exchange activity but a reduced Na(+)/Ca(2+) exchange activity. On the other hand, D471A showed dramatically reduced Li(+)/Ca(2+) exchange, but Na(+)/Ca(2+) exchange activity was unaffected. Finally, simultaneous mutation of four putative Ca(2+) binding residues was required to completely abolish both Na(+)/Ca(2+) and Li(+)/Ca(2+) exchange activities. We identified distinct Na(+) and Li(+) selective residues in the NCLX transport site. We propose that functional segregation in Li(+) and Na(+) sites reflects the functional properties of NCLX required for Ca(2+) exchange under the unique membrane potential and ion gradient across the inner mitochondrial membrane. The results of this study provide functional insights into the unique Li(+) and Na(+) selectivity of the mitochondrial exchanger. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Open-Loop Control of Oxidative Phosphorylation in Skeletal and Cardiac Muscle Mitochondria by Ca2+

    PubMed Central

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

    2016-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  6. Endothelium-dependent control of cerebrovascular functions through age: exercise for healthy cerebrovascular aging.

    PubMed

    Bolduc, Virginie; Thorin-Trescases, Nathalie; Thorin, Eric

    2013-09-01

    Cognitive performances are tightly associated with the maximal aerobic exercise capacity, both of which decline with age. The benefits on mental health of regular exercise, which slows the age-dependent decline in maximal aerobic exercise capacity, have been established for centuries. In addition, the maintenance of an optimal cerebrovascular endothelial function through regular exercise, part of a healthy lifestyle, emerges as one of the key and primary elements of successful brain aging. Physical exercise requires the activation of specific brain areas that trigger a local increase in cerebral blood flow to match neuronal metabolic needs. In this review, we propose three ways by which exercise could maintain the cerebrovascular endothelial function, a premise to a healthy cerebrovascular function and an optimal regulation of cerebral blood flow. First, exercise increases blood flow locally and increases shear stress temporarily, a known stimulus for endothelial cell maintenance of Akt-dependent expression of endothelial nitric oxide synthase, nitric oxide generation, and the expression of antioxidant defenses. Second, the rise in circulating catecholamines during exercise not only facilitates adequate blood and nutrient delivery by stimulating heart function and mobilizing energy supplies but also enhances endothelial repair mechanisms and angiogenesis. Third, in the long term, regular exercise sustains a low resting heart rate that reduces the mechanical stress imposed to the endothelium of cerebral arteries by the cardiac cycle. Any chronic variation from a healthy environment will perturb metabolism and thus hasten endothelial damage, favoring hypoperfusion and neuronal stress.

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

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  8. Is Soil Development Controlling Ecohydrologic Response to Climate Change in the Southern Cascade and Sierra Nevada Watersheds, CA, USA?

    NASA Astrophysics Data System (ADS)

    Devine, S.; O'Geen, A. T.; Dahlke, H. E.

    2016-12-01

    Understanding climate change impacts on hydrology is especially relevant to areas already dealing with water scarcity, common in Mediterranean regions such as California (CA). For instance, warming is expected to drive up evapotranspiration (ET) fluxes from vegetation, which could impact runoff (Q) and water supply by up to 30% from CA's Sierra Nevadas by 2100. In this study, we hypothesize that the 1-2 oC increase during the 20th and early 21st centuries should have resulted in a trend of decreasing Q for a given amount of precipitation (P) due to increasing ET through time. We also hypothesize that any observed differences in watershed ET response to warming could be explained by soil controls, since Mediterranean biomes require soil moisture storage to endure dry summers. We analyzed unimpaired runoff from 10 major CA watersheds relative to P over a 110 year record and found trends of increasing P minus Q in the northern watersheds, supporting the hypothesis of mountain Q vulnerability to warming but not in the central and southern watersheds. This may be partly due to the faster rates of summertime warming we observed in the northern watersheds when potential ET is highest. Analysis of several soil investigations in the study area on bioclimosequences suggests that these inter-watershed differences in P minus Q may also be due to soils. Soils formed from volcanic rocks, which are more prevalent in the northern watersheds, tend to have higher clay contents and water holding capacity. Moreover, the higher elevation central and southern watersheds were more widely glaciated throughout the Pleistocene, resulting in a wider extent of scoured landscapes and soils shallow to hard bedrock. Thus, the northern watershed ET flux could have previously been temperature constrained with untapped soil moisture storage. Going forward, an analysis is planned to quantify the extent of various soil-vegetation-climate zones. For each zone, we will build simple water balance models

  9. Age and gender differences in self-control and its intergenerational transmission.

    PubMed

    Wang, L; Fan, C; Tao, T; Gao, W

    2017-03-01

    Few studies have been conducted in people of Asian descent that have reported to demonstrate the distinct developmental trends in good self-control and poor control. To fill this gap, we conducted a national cross-sectional survey among adolescents and young adults in China to further clarify the age and gender differences in self-control from a dual-systems perspective. A total of 2910 adolescents (female, n = 1698) and their parents from five different provinces in China were surveyed using the Dual-Modes of Self-Control Scale (DMSC-S) and the Parents' Perceived Self-Control Scale. The mean age of the adolescent sample was 17.47 years (ranging from 12.50 to 25.42 years). Boys exhibited greater good self-control than girls. Poor control increased between 12 and 17 years of age and declined thereafter; however, good self-control increased over the entire study period. Both good self-control and poor control in student participants were significantly associated with parents' perceived self-control; moreover, the association between good self-control and parental self-control was mediated by SES. The roles of age, gender, parental self-control and SES varied in a dual-systems model of self-control: good self-control and poor control. Implications of these results are discussed. © 2016 John Wiley & Sons Ltd.

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

    PubMed

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

    2005-04-26

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

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  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. Global Research in an Age of Export Controls

    ERIC Educational Resources Information Center

    Monastersky, Richard

    2008-01-01

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

  17. 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

  18. Age-related changes in strategic variations during arithmetic problem solving: The role of executive control.

    PubMed

    Hinault, T; Lemaire, P

    2016-01-01

    In this review, we provide an overview of how age-related changes in executive control influence aging effects in arithmetic processing. More specifically, we consider the role of executive control in strategic variations with age during arithmetic problem solving. Previous studies found that age-related differences in arithmetic performance are associated with strategic variations. That is, when they accomplish arithmetic problem-solving tasks, older adults use fewer strategies than young adults, use strategies in different proportions, and select and execute strategies less efficiently. Here, we review recent evidence, suggesting that age-related changes in inhibition, cognitive flexibility, and working memory processes underlie age-related changes in strategic variations during arithmetic problem solving. We discuss both behavioral and neural mechanisms underlying age-related changes in these executive control processes. © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-02-01

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

  20. 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

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

    PubMed Central

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

    1989-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  3. 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.

  4. 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

  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. 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.

  7. 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

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

    PubMed

    Chen, Mingyue; Xia, Zhiguo; Liu, Quanlin

    2016-11-07

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

  9. 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.

  10. 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. © 2015 FEBS.

  11. Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae.

    PubMed

    McCleary, David F; Rine, Jasper

    2017-03-01

    Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD(+)-dependent deacetylases known as Sirtuins in this process, particularly in the yeast Saccharomyces cerevisiae, is controversial. We measured chronological life span of wild-type and sir2Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2Δ extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly developed genetic strategy revealed that sir2Δ shortened life span in low glucose while having little effect in high glucose, again revealing a partial role for Sir2 In complete minimal media, Sir2 shortened life span as glucose levels increased; whereas in rich media, Sir2 extended life span as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing at HML, we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein. Copyright © 2017 by the Genetics Society of America.

  12. 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.

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2015-01-01

    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. 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. 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. 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). 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.

  15. 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

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

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2014-01-01

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

  19. 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

  20. Calcium signalling in the ciliated protozoan model, Paramecium: strict signal localisation by epigenetically controlled positioning of different Ca²⁺-channels.

    PubMed

    Plattner, Helmut

    2015-03-01

    The Paramecium tetraurelia cell is highly organised, with regularly spaced elements pertinent to Ca(2+) signalling under epigenetic control. Vesicles serving as stationary Ca(2+) stores or undergoing trafficking contain Ca(2+)-release channels (PtCRCs) which, according to sequence and domain comparison, are related either to inositol 1,4,5-trisphosphate (InsP3) receptors (IP3R) or to ryanodine receptor-like proteins (RyR-LP) or to both, with intermediate characteristics or deviation from conventional domain structure. Six groups of such PtCRCs have been found. The ryanodine-InsP3-receptor homology (RIH) domain is not always recognisable, in contrast to the channel domain with six trans-membrane domains and the pore between transmembrane domain 5 and 6. Two CRC subtypes tested more closely, PtCRC-II and PtCRC-IV, with and without an InsP3-binding domain, reacted to InsP3 and to caffeine, respectively, and hence represent IP3Rs and RyR-LPs. IP3Rs occur in the contractile vacuole complex where they allow for stochastic constitutive Ca(2+) reflux into the cytosol. RyR-LPs are localised to cortical Ca(2+) stores; they are engaged in dense core-secretory vesicle exocytosis by Ca(2+) release, superimposed by Ca(2+)-influx via non-ciliary Ca(2+)-channels. One or two different types of PtCRCs also occur in other vesicles undergoing trafficking. Since the PtCRCs described combine different features they are considered derivatives of primitive precursors. The highly regular, epigenetically controlled design of a Paramecium cell allows it to make Ca(2+) available very locally, in a most efficient way, along predetermined trafficking pathways, including regulation of exocytosis, endocytosis, phagocytosis and recycling phenomena. The activity of cilia is also regulated by Ca(2+), yet independently from any CRCs, by de- and hyperpolarisation of the cell membrane potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  2. Controllable synthesis and luminescent properties of novel erythrocyte-like CaMoO4 hierarchical nanostructures via a simple surfactant-free hydrothermal route.

    PubMed

    Luo, Yong-Song; Dai, Xiao-Jun; Zhang, Wei-Dong; Yang, Yang; Sun, Chang Q; Fu, Shao-Yun

    2010-03-07

    Synthesis of metal molybdates (XMoO(4), X = Ca, Sr, Ba) have received much attention recently because of their interesting structural and luminescent properties. Here novel erythrocyte-like CaMoO(4) hierarchical nanostructures are synthesized via a simple surfactant-free hydrothermal route. The formation of the calcium molybdate erythrocytes is controllable through adjusting the fundamental experimental parameters including reaction time, temperature and DMAc to H(2)O ratio. The as-synthesized products are characterized using X-ray powder diffraction, scanning electron microscopy, Brunauer-Emmett-Teller and transmission electron microscopy. The results show that the nucleation and growth of the novel erythrocyte-like CaMoO(4) hierarchical nanostructures are governed by an oriented attachment growth mechanism. The luminescent properties of the CaMoO(4) erythrocytes are then studied using a spectrophotometer and the erythrocyte-like CaMoO(4) nanostructures display a strong blue emission. This study provides an easy surfactant-free synthetic route for the controllable construction of inorganic materials with high hierarchy in the absence of any surfactants.

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

    PubMed

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

    2014-04-01

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

  4. High mutational burden in the mtDNA control region from aged muscles: a single-fiber study.

    PubMed

    Del Bo, Roberto; Crimi, Marco; Sciacco, Monica; Malferrari, Giulia; Bordoni, Andreina; Napoli, Laura; Prelle, Alessandro; Biunno, Ida; Moggio, Maurizio; Bresolin, Nereo; Scarlato, Guglielmo; Pietro Comi, Giacomo

    2003-10-01

    The ageing process is associated with the accumulation of somatic mutations of mitochondrial DNA (mtDNA). The aged human skeletal muscle tissue presents a mosaic of fibers when stained histochemically for cytochrome c oxidase (COX) activity with a proportion of COX negative fibers. Given the potential relevance of any alteration in the mtDNA control region for replication, we analysed the correlation between the presence of mutations and their degree of heteroplasmy and the COX phenotype in individual muscle fibers of aged healthy donors.A region of the mtDNA D-loop was cloned from single fiber-derived DNA and multiple clones were analysed. This strategy showed that a high level of mutational burden is present in all fibers and that several types of mtDNA rearrangements are detectable: recurrent (A189G, T408A and T414G) and rare point mutations, length variations affecting the homopolymeric tract and the (CA)(n) repeat and macrodeletions. The aggregate mutational load in the D-loop region correlated with the single fiber COX phenotype, suggesting that the cumulative burden of multiple, individually rare, mtDNA alterations might functionally impair the mitochondrial genetic machinery.

  5. 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…

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

  7. 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…

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

    PubMed

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

    2005-11-15

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

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

    PubMed

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

    2012-01-27

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

  11. 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

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

    PubMed

    Manard, Marine; Carabin, Delphine; Jaspar, Mathieu; Collette, Fabienne

    2014-01-08

    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. 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). 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.

  13. Impact of Aging and Exercise on Mitochondrial Quality Control in Skeletal Muscle

    PubMed Central

    Kim, Yuho; Triolo, Matthew

    2017-01-01

    Mitochondria are characterized by its pivotal roles in managing energy production, reactive oxygen species, and calcium, whose aging-related structural and functional deteriorations are observed in aging muscle. Although it is still unclear how aging alters mitochondrial quality and quantity in skeletal muscle, dysregulation of mitochondrial biogenesis and dynamic controls has been suggested as key players for that. In this paper, we summarize current understandings on how aging regulates muscle mitochondrial biogenesis, while focusing on transcriptional regulations including PGC-1α, AMPK, p53, mtDNA, and Tfam. Further, we review current findings on the muscle mitochondrial dynamic systems in aging muscle: fusion/fission, autophagy/mitophagy, and protein import. Next, we also discuss how endurance and resistance exercises impact on the mitochondrial quality controls in aging muscle, suggesting possible effective exercise strategies to improve/maintain mitochondrial health. PMID:28656072

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

    SciTech Connect

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

    2014-08-15

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Slagsvold, Britt; Sørensen, Annemette

    2008-01-01

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

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

    PubMed

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

    2006-02-01

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

  18. MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death

    PubMed Central

    Aurora, Arin B.; Mahmoud, Ahmed I.; Luo, Xiang; Johnson, Brett A.; van Rooij, Eva; Matsuzaki, Satoshi; Humphries, Kenneth M.; Hill, Joseph A.; Bassel-Duby, Rhonda; Sadek, Hesham A.; Olson, Eric N.

    2012-01-01

    Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca2+ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca2+ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca2+ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca2+ influx; and to repression of several downstream effectors of Ca2+ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca2+ homeostasis and survival during cardiac injury. PMID:22426211

  19. A study on alkaline heat treated Mg-Ca alloy for the control of the biocorrosion rate.

    PubMed

    Gu, X N; Zheng, W; Cheng, Y; Zheng, Y F

    2009-09-01

    To reduce the biocorrosion rate by surface modification, Mg-Ca alloy (1.4wt.% Ca content) was soaked in three alkaline solutions (Na(2)HPO(4), Na(2)CO(3) and NaHCO(3)) for 24h, respectively, and subsequently heat treated at 773K for 12h. Scanning electron microscopy and energy-dispersive spectroscopy results revealed that magnesium oxide layers with the thickness of about 13, 9 and 26microm were formed on the surfaces of Mg-Ca alloy after the above different alkaline heat treatments. Atomic force microscopy showed that the surfaces of Mg-Ca alloy samples became rough after three alkaline heat treatments. The in vitro corrosion tests in simulated body fluid indicated that the corrosion rates of Mg-Ca alloy were effectively decreased after alkaline heat treatments, with the following sequence: NaHCO(3) heatedCa alloy samples induced toxicity to L-929 cells during 7days culture.

  20. A synaptotagmin suppressor screen indicates SNARE binding controls the timing and Ca(2+) cooperativity of vesicle fusion.

    PubMed

    Guan, Zhuo; Bykhovskaia, Maria; Jorquera, Ramon A; Sutton, Roger Bryan; Akbergenova, Yulia; Littleton, J Troy

    2017-09-12

    The synaptic vesicle Ca(2+) sensor Synaptotagmin binds Ca(2+) through its two C2 domains to trigger membrane interactions. Beyond membrane insertion by the C2 domains, other requirements for Synaptotagmin activity are still being elucidated. To identify key residues within Synaptotagmin required for vesicle cycling, we took advantage of observations that mutations in the C2B domain Ca(2+)-binding pocket dominantly disrupt release from invertebrates to humans. We performed an intragenic screen for suppressors of lethality induced by expression of Synaptotagmin C2B Ca(2+)-binding mutants in Drosophila. This screen uncovered essential residues within Synaptotagmin that suggest a structural basis for several activities required for fusion, including a C2B surface implicated in SNARE complex interaction that is required for rapid synchronization and Ca(2+) cooperativity of vesicle release. Using electrophysiological, morphological and computational characterization of these mutants, we propose a sequence of molecular interactions mediated by Synaptotagmin that promote Ca(2+) activation of the synaptic vesicle fusion machinery.

  1. 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.

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

    ERIC Educational Resources Information Center

    Nehrke, Milton F.; And Others

    1980-01-01

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

  3. Effect of early age woody and herbaceous competition control on wood properties of loblolly pine

    Treesearch

    F. Antony; L. R. Schimleck; L. Jordan; Alexander Clark; R. F. Daniels

    2011-01-01

    Early age competition control has been reported to significantly improve the growth and yield of plantation grown loblolly pine. The objective of this paper is to understand the changes in wood properties: basal area weighted whole disk SG, earlywood SG (EWSG), latewood SG (LWSG) and latewood percent (LWP) of 14 year-old trees which received early age herbaceous and...

  4. 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.

  5. Inhibitory control of sensory gating in a computer model of the CA3 region of the hippocampus

    PubMed Central

    Moxon, Karen A.; Gerhardt, Greg A.; Gulinello, Maria; Adler, Lawrence E.

    2014-01-01

    A model of the CA3 region of the hippocampus was used to simulate the P50 auditory-evoked potential response to repeated stimuli in order to study the neuronal circuits involved in a sensory-processing deficit associated with schizophrenia. Normal subjects have a reduced P50 auditory-evoked potential amplitude in response to the second of two paired auditory click stimuli spaced 0.5 s apart. However, schizophrenic patients do not gate or reduce their response to the second click. They have equal auditory-evoked response amplitudes to both clicks. When schizophrenic patients were medicated with traditional neuroleptics, the evoked potential amplitude to both clicks increased, but gating of the second response was not restored or improved. Animal studies suggest a role for septohippocampal cholinergic activity in sensory gating. We used a computational model of this system in order to study the relative contributions of local processing and afferent activity in sensory gating. We first compared the effect of information representation as average firing rate to information representation as cell assemblies in order to evaluate the best method to represent the response of hippocampal neurons to the auditory click. We then studied the effects of nicotinic cholinergic input on the response of the network and the effect of GABAB receptor activation on the ability of the local network to suppress the test response. The results of our model showed that nicotinic cholinergic input from the septum to the hippocampus can control the flow of sensory information from the cortex into the hippocampus. In addition, postsynaptic GABAB receptor activation was not sufficient to suppress the test response when the interstimulus interval was 500 ms. However, presynaptic GABAB receptor activity may be responsible for the suppression of the test response at this interstimulus interval. PMID:12690484

  6. In cold-hardy insects, seasonal, temperature, and reversible phosphorylation controls regulate sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).

    PubMed

    McMullen, David C; Ramnanan, Christopher J; Storey, Kenneth B

    2010-01-01

    Winter cold hardiness of insects typically involves one of two major strategies for survival below 0 degrees C: freeze avoidance and freeze tolerance. The two strategies have some common features, including the accumulation of high concentrations of cryoprotectant polyols and the frequent occurrence of diapause. Entry into the hypometabolic state of diapause requires coordinated suppression of major ATP-consuming metabolic processes, and ion motive ATPases are important targets for regulation. This study documents the suppression of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) activity in the overwintering larvae of two cold-hardy species, the freeze-avoiding gall moth Epiblema scudderiana and the freeze-tolerant gall fly Eurosta solidaginis. Activity was reduced despite a lack of change in SERCA protein levels in E. solidaginis larvae over the winter and a six- to eightfold increase in SERCA protein in E. scudderiana. This implicated posttranslational modification as the mechanism of SERCA suppression, and in vitro incubations indicated that enzyme phosphorylation by protein kinases A, G, or C strongly reduced enzyme activity. A stable reduction in SERCA activity was also seen in cold-acclimated larvae of both species compared with 15 degrees C controls, with significant changes in the kinetic parameters of the E. scudderiana enzyme (e.g., K(m) ATP was 3.2-fold higher in -20 degrees C-acclimated larvae) that were consistent with reduced enzyme function at low temperature. Epiblema scudderiana SERCA was also subject to regulation by differential temperature effects (Arrhenius activation energy increased by approximately threefold below 10 degrees C) and by seasonal changes in the levels of a SERCA inhibitor protein, phospholamban.

  7. Opiate Exposure State Controls a D2-CaMKIIα-Dependent Memory Switch in the Amygdala-Prefrontal Cortical Circuit

    PubMed Central

    Rosen, Laura G; Zunder, Jordan; Renard, Justine; Fu, Jennifer; Rushlow, Walter; Laviolette, Steven R

    2016-01-01

    The mammalian basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) comprise a functionally interconnected circuit that is critical for processing opiate-related associative memories. In the opiate-naïve state, reward memory formation in the BLA involves a functional link between dopamine (DA) D1 receptor (D1R) and extracellular signal-related kinase 1/2 (ERK1/2) signaling substrates, but switches to a DA D2 (D2R)/Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-dependent memory substrate following chronic opiate exposure and spontaneous withdrawal. Using conditioned place preference (CPP) in rats paired with molecular analyses, we examined the role of intra-mPFC CaMKII, ERK and DAergic activity during the formation of opiate associative memories, and how opiate exposure state may regulate the functions of these molecular memory pathways. We report that the role of CaMKIIα signaling is functionally reversed within the BLA-mPFC pathway depending on opiate exposure state. Thus, in the opiate-naïve state, intra-mPFC but not intra-BLA blockade of CaMKII signaling prevents formation of opiate reward memory. However, following chronic opiate exposure and spontaneous withdrawal, the role of CaMKII signaling in the BLA-mPFC is functionally reversed. This behavioral memory switch corresponds to a selective increase in the expression of D2R and CaMKIIα, but not other calcium/calmodulin-related molecules, nor D1R expression levels within the mPFC. PMID:26174594

  8. Age-Related Decline in Controlled Retrieval: The Role of the PFC and Sleep

    PubMed Central

    Wilckens, Kristine A.; Erickson, Kirk I.; Wheeler, Mark E.

    2012-01-01

    Age-related cognitive impairments often include difficulty retrieving memories, particularly those that rely on executive control. In this paper we discuss the influence of the prefrontal cortex on memory retrieval, and the specific memory processes associated with the prefrontal cortex that decline in late adulthood. We conclude that preretrieval processes associated with preparation to make a memory judgment are impaired, leading to greater reliance on postretrieval processes. This is consistent with the view that impairments in executive control significantly contribute to deficits in controlled retrieval. Finally, we discuss age-related changes in sleep as a potential mechanism that contributes to deficiencies in executive control that are important for efficient retrieval. The sleep literature points to the importance of slow-wave sleep in restoration of prefrontal cortex function. Given that slow-wave sleep significantly declines with age, we hypothesize that age-related changes in slow-wave sleep could mediate age-related decline in executive control, manifesting a robust deficit in controlled memory retrieval processes. Interventions, like physical activity, that improve sleep could be effective methods to enhance controlled memory processes in late life. PMID:22970389

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

    PubMed

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

    2014-08-01

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

  10. Age-related changes in force control under different task contexts.

    PubMed

    Temprado, Jean-Jacques; Vieluf, Solveig; Sleimen-Malkoun, Rita

    2017-01-01

    We investigated age-related differences in motor behavior under different task contexts of isometric force control. The tasks involved rapid force production and force maintenance, either separately or in combination. For the combined context, we used Fitts-like tasks, in which we scaled either the force level (D manipulation, i.e., manipulation of the amplitude of the force to be produced) or the tolerance range (W manipulation, i.e., manipulation of the target width in which force is allowed to fluctuate). We studied two age groups and analyzed mainly variables that quantify behavioral variability (SD), information processing (signal-to-noise ratio and efficiency functions), and age-related slowing (slowing ratio). For rapid force control, age-related differences were more pronounced when preplanned processes were primarily involved, that is, in the rapid force production and Fitts-D manipulation tasks. Further, older adults were comparable to the younger adults in terms of end-point variability at the cost of being slower and more variable in timing. For force maintenance control, requiring mainly online control, age-related differences were the most visible in the stabilized phase of Fitts-D manipulation, followed by Fitts-W manipulation for SD, and then the force maintenance task. In sum, our findings reveal an age-related reorganization of how preplanned and online control processes are combined under different force control contexts. Indeed, both behavioral slowing and the overreliance on online control processes seem to be dependent on the task. In this respect, beyond the study of force control, we show the interest of investigating age effects using functionally different tasks.

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

    PubMed

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

    2006-06-01

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