Function and Evolution of a MicroRNA That Regulates a Ca2+-ATPase and Triggers the Formation of Phased Small Interfering RNAs in Tomato Reproductive Growth[W][OA

PubMed Central

Wang, Ying; Itaya, Asuka; Zhong, Xuehua; Wu, Yang; Zhang, Jianfeng; van der Knaap, Esther; Olmstead, Richard; Qi, Yijun; Ding, Biao

2011-01-01

MicroRNAs (miRNAs) regulate a wide variety of biological processes in most eukaryotes. We investigated the function and evolution of miR4376 in the family Solanaceae. We report that the 22-nucleotide miR4376 regulates the expression of an autoinhibited Ca2+-ATPase, tomato (Solanum lycopersicum) ACA10, which plays a critical role in tomato reproductive growth. Deep phylogenetic mapping suggested (1) an evolution course of MIR4376 loci and posttranscriptional processing of pre-miR4376 as a likely limiting step for the evolution of miR4376, (2) an independent phylogenetic origin of the miR4376 target site in ACA10 homologs, and (3) alternative splicing as a possible mechanism of eliminating such a target in some ACA10 homologs. Furthermore, miR4376 triggers the formation of phased small interfering RNAs (siRNAs) from Sl ACA10 and its Solanum tuberosum homolog. Together, our data provide experimental evidence of miRNA-regulated expression of universally important Ca2+-ATPases. The miR4376-regulated expression of ACA10 itself, and possibly also the associated formation of phased siRNAs, may function as a novel layer of molecular mechanisms underlying tomato reproductive growth. Finally, our data suggest that the stochastic emergence of a miRNA-target gene combination involves multiple molecular events at the genomic, transcriptional, and posttranscriptional levels that may vary drastically in even closely related species. PMID:21917547

Magnetic and structural transitions in La1-xAxCoO3 ( A=Ca , Sr, and Ba)

NASA Astrophysics Data System (ADS)

Kriener, M.; Braden, M.; Kierspel, H.; Senff, D.; Zabara, O.; Zobel, C.; Lorenz, T.

2009-06-01

We report thermal-expansion, lattice-constant, and specific-heat data of the series La1-xAxCoO3 for 0≤x≤0.30 with A=Ca , Sr, and Ba. For the undoped compound LaCoO3 , the thermal-expansion coefficient α(T) exhibits a pronounced maximum around T=50K caused by a temperature-driven spin-state transition from a low-spin state of the Co3+ ions at low temperatures toward a higher spin state at higher temperatures. The partial substitution of the La3+ ions by divalent Ca2+ , Sr2+ , or Ba2+ ions causes drastic changes in the macroscopic properties of LaCoO3 . The large maximum in α(T) is suppressed and completely vanishes for x≳0.125 . For A=Ca three different anomalies develop in α(T) with further increasing x , which are visible in specific-heat data as well. Together with temperature-dependent x-ray data, we identify several phase transitions as a function of the doping concentration x and temperature. From these data we propose an extended phase diagram for La1-xCaxCoO3 .

Cell-specific vacuolar calcium storage mediated by CAX1 regulates apoplastic calcium concentration, gas exchange, and plant productivity in Arabidopsis.

PubMed

Conn, Simon J; Gilliham, Matthew; Athman, Asmini; Schreiber, Andreas W; Baumann, Ute; Moller, Isabel; Cheng, Ning-Hui; Stancombe, Matthew A; Hirschi, Kendal D; Webb, Alex A R; Burton, Rachel; Kaiser, Brent N; Tyerman, Stephen D; Leigh, Roger A

2011-01-01

The physiological role and mechanism of nutrient storage within vacuoles of specific cell types is poorly understood. Transcript profiles from Arabidopsis thaliana leaf cells differing in calcium concentration ([Ca], epidermis <10 mM versus mesophyll >60 mM) were compared using a microarray screen and single-cell quantitative PCR. Three tonoplast-localized Ca(2+) transporters, CAX1 (Ca(2+)/H(+)-antiporter), ACA4, and ACA11 (Ca(2+)-ATPases), were identified as preferentially expressed in Ca-rich mesophyll. Analysis of respective loss-of-function mutants demonstrated that only a mutant that lacked expression of both CAX1 and CAX3, a gene ectopically expressed in leaves upon knockout of CAX1, had reduced mesophyll [Ca]. Reduced capacity for mesophyll Ca accumulation resulted in reduced cell wall extensibility, stomatal aperture, transpiration, CO(2) assimilation, and leaf growth rate; increased transcript abundance of other Ca(2+) transporter genes; altered expression of cell wall-modifying proteins, including members of the pectinmethylesterase, expansin, cellulose synthase, and polygalacturonase families; and higher pectin concentrations and thicker cell walls. We demonstrate that these phenotypes result from altered apoplastic free [Ca(2+)], which is threefold greater in cax1/cax3 than in wild-type plants. We establish CAX1 as a key regulator of apoplastic [Ca(2+)] through compartmentation into mesophyll vacuoles, a mechanism essential for optimal plant function and productivity.

Bedside Testing for Chronic Pelvic Pain: Discriminating Visceral from Somatic Pain

PubMed Central

Jarrell, John; Giamberardino, Maria Adele; Robert, Magali; Nasr-Esfahani, Maryam

2011-01-01

Objectives. This study was done to evaluate three bedside tests in discriminating visceral pain from somatic pain among women with chronic pelvic pain. Study Design. The study was an exploratory cross-sectional evaluation of 81 women with chronic pelvic pain of 6 or more months' duration. Tests included abdominal cutaneous allodynia (aCA), perineal cutaneous allodynia (pCA), abdominal and perineal myofascial trigger points (aMFTP) and (pMFTP), and reduced pain thresholds (RPTs). Results. Eighty-one women were recruited, and all women provided informed consent. There were 62 women with apparent visceral pain and 19 with apparent somatic sources of pain. The positive predictive values for pelvic visceral disease were aCA-93%, pCA-91%, aMFTP-93%, pMFTP-81%, and RPT-79%. The likelihood ratio (+) and 95% C.I. for the detection of visceral sources of pain were aCA-4.19 (1.46, 12.0), pCA-2.91 (1.19, 7.11), aMTRP-4.19 (1.46, 12.0), pMFTP-1.35 (0.86, 2.13), and RPT-1.14 (0.85, 1.52), respectively. Conclusions. Tests of cutaneous allodynia, myofascial trigger points, and reduced pain thresholds are easily applied and well tolerated. The tests for cutaneous allodynia appear to have the greatest likelihood of identifying a visceral source of pain compared to somatic sources of pain. PMID:22135736

Superconducting Sr 2- xAxCuO 2F 2+ δ( A=Ca, Ba): Synthetic Pathways and Associated Structural Rearrangements

NASA Astrophysics Data System (ADS)

Francesconi, M. G.; Slater, P. R.; Hodges, J. P.; Greaves, C.; Edwards, P. P.; Al-Mamouri, M.; Slaski, M.

1998-01-01

The low-temperature fluorination of a range of insulating alkaline earth cuprates Sr2-xAxCuO3(A=Ca (0≤x≤2);A=Ba (0≤x≤0.6)) can result in superconducting oxide fluorides Sr2-xAxCuO2F2+δ. In contrast, conventional high-temperature solid-state reactions produce thermodynamically more stable mixtures of oxides and fluorides. Various soft-chemistry fluorination pathways (utilizing F2gas, NH4F,MF2[M=Cu, Zn, Ni, Ag]) are compared with respect to their efficacy and mechanisms. Attention is also focused on the structural features of the mixed-oxide precursor and the final-oxide fluorides to highlight the remarkable structural rearrangements that occur during the low-temperature fluorination. The effects of fluorination of other Sr-Cu-O systems are used to identify the structural requirements of the precursor oxide in order to achieve such transformations.

Ca2+-pumping impairment during repetitive fatiguing contractions in single myofibers: role of cross-bridge cycling

PubMed Central

Shiah, Amy A.; Gandra, Paulo G.; Hogan, Michael C.

2013-01-01

The energy cost of contractions in skeletal muscle involves activation of both actomyosin and sarcoplasmic reticulum (SR) Ca2+-pump (SERCA) ATPases, which together determine the overall ATP demand. During repetitive contractions leading to fatigue, the relaxation rate and Ca2+ pumping become slowed, possibly because of intracellular metabolite accumulation. The role of the energy cost of cross-bridge cycling during contractile activity on Ca2+-pumping properties has not been investigated. Therefore, we inhibited cross-bridge cycling by incubating isolated Xenopus single fibers with N-benzyl-p-toluene sulfonamide (BTS) to study the mechanisms by which SR Ca2+ pumping is impaired during fatiguing contractions. Fibers were stimulated in the absence (control) and presence of BTS and cytosolic calcium ([Ca2+]c) transients or intracellular pH (pHi) changes were measured. BTS treatment allowed normal [Ca2+]c transients during stimulation without cross-bridge activation. At the time point that tension was reduced to 50% in the control condition, the fall in the peak [Ca2+]c and the increase in basal [Ca2+]c did not occur with BTS incubation. The progressively slower Ca2+ pumping rate and the fall in pHi during repetitive contractions were reduced during BTS conditions. However, when mitochondrial ATP supply was blocked during contractions with BTS present (BTS + cyanide), there was no further slowing in SR Ca2+ pumping during contractions compared with the BTS-alone condition. Furthermore, the fall in pHi was significantly less during the BTS + cyanide condition than in the control conditions. These results demonstrate that factors related to the energetic cost of cross-bridge cycling, possibly the accumulation of metabolites, inhibit the Ca2+ pumping rate during fatiguing contractions. PMID:23678027

The plasma membrane calcium pumps: focus on the role in (neuro)pathology.

PubMed

Brini, Marisa; Carafoli, Ernesto; Calì, Tito

2017-02-19

The plasma membrane Ca 2+ ATPase (PMCA pump) is a member of the superfamily of P-type pumps. It is organized in the plasma membrane with ten transmembrane helices and two main cytosolic loops, one of which contains the catalytic center. It also contains a long C-terminal tail that houses the binding site for calmodulin, the main regulator of the activity of the pump. The pump also contains a number of other regulators, among them acidic phospholipids, kinases, and numerous protein interactors. Separate genes code for 4 basic pump isoforms in mammals, additional isoform complexity being generated by the alternative splicing of primary transcripts. Pumps 1 and 4 are expressed ubiquitously, pumps 2 and 3 are tissue restricted, with preference for the nervous system. In essentially all cells, the pump coexists with much more powerful systems that clear Ca 2+ from the cytosol, e.g. the SERCA pump and the Na + /Ca 2+ exchanger. Its role in the global regulation of cellular Ca 2+ homeostasis is thus quantitatively marginal: its main function is the regulation of Ca 2+ signaling in selected sub-plasma membrane microdomains where Ca 2+ modulated interactors also reside. Malfunctions of the pump linked to genetic mutations are now described with increasing frequency, the disease phenotypes being especially severe in the nervous system where isoforms 2 and 3 predominate. The analysis of the pump defects suggests that the disease phenotypes are likely to be related to the imperfect modulation of Ca 2+ signaling in selected sub-plasma membrane microdomains, leading to the defective control of the activity of important Ca 2+ dependent interactors. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence that convergence rather than accommodation controls intermittent distance exotropia.

PubMed

Horwood, Anna M; Riddell, Patricia M

2012-03-01

This study considered whether vergence drives accommodation or accommodation drives vergence during the control of distance exotropia for near fixation. High accommodative convergence to accommodation (AC/A) ratios are often used to explain this control, but the role of convergence to drive accommodation (the CA/C relationship) is rarely considered. Atypical CA/C characteristics could equally, or better, explain common clinical findings. Nineteen distance exotropes, aged 4-11 years, were compared while controlling their deviation with 27 non-exotropic controls aged 5-9 years. Simultaneous vergence and accommodation responses were measured to a range of targets incorporating different combinations of blur, disparity and looming cues at four fixation distances between 2 m and 33 cm. Stimulus and response AC/A and CA/C ratios were calculated. Accommodation responses for near targets (p = 0.017) and response gains (p = 0.026) were greater in the exotropes than in the controls. Despite higher clinical stimulus AC/A ratios, the distance exotropes showed lower laboratory response AC/A ratios (p = 0.02), but significantly higher CA/C ratios (p = 0.02). All the exotropes, whether the angle changed most with lenses ('controlled by accommodation') or on occlusion ('controlled by fusion'), used binocular disparity not blur as their main cue to target distance. Increased vergence demand to control intermittent distance exotropia for near also drives significantly more accommodation. Minus lens therapy is more likely to act by correcting overaccommodation driven by controlling convergence, rather than by inducing blur-driven vergence. The use of convergence as a major drive to accommodation explains many clinical characteristics of distance exotropia, including apparently high near stimulus AC/A ratios. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Evidence that convergence rather than accommodation controls intermittent distance exotropia

PubMed Central

Horwood, Anna M; Riddell, Patricia M

2015-01-01

Purpose This study considered whether vergence drives accommodation or accommodation drives vergence during the control of distance exotropia for near fixation. High accommodative convergence to accommodation (AC/A) ratios are often used to explain this control, but the role of convergence to drive accommodation (the CA/C relationship) is rarely considered. Atypical CA/C characteristics could equally, or better, explain common clinical findings. Methods 19 distance exotropes, aged 4-11 years, were compared while controlling their deviation with 27 non-exotropic controls aged 5-9 years. Simultaneous vergence and accommodation responses were measured to a range of targets incorporating different combinations of blur, disparity and looming cues at four fixation distances between 2m and 33cm. Stimulus and response AC/A and CA/C ratios were calculated. Results Accommodation responses for near targets (p=0.017) response gains (p=0.026) were greater in the exotropes than the controls. Despite higher clinical stimulus AC/A ratios, the distance exotropes showed lower laboratory response AC/A ratios (p=0.02), but significantly higher CA/C ratios (p=0.02). All the exotropes, whether the angle changed most with lenses (“controlled by accommodation”) or on occlusion (“controlled by fusion”), used binocular disparity not blur as their main cue to target distance. Conclusions Increased vergence demand to control intermittent distance exotropia for near also drives significantly more accommodation. Minus lens therapy is more likely to act by correcting over-accommodation driven by controlling convergence, rather than by inducing blur-driven vergence. The use of convergence as a major drive to accommodation explains many clinical characteristics of distance exotropia, including apparently high near stimulus AC/A ratios. PMID:22280437

Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca(2+) exchangers

USDA-ARS?s Scientific Manuscript database

Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+) exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recen...

Model study of ATP and ADP buffering, transport of Ca(2+) and Mg(2+), and regulation of ion pumps in ventricular myocyte

NASA Technical Reports Server (NTRS)

Michailova, A.; McCulloch, A.

2001-01-01

We extended the model of the ventricular myocyte by Winslow et al. (Circ. Res 1999, 84:571-586) by incorporating equations for Ca(2+) and Mg(2+) buffering and transport by ATP and ADP and equations for MgATP regulation of ion transporters (Na(+)-K(+) pump, sarcolemmal and sarcoplasmic Ca(2+) pumps). The results indicate that, under normal conditions, Ca(2+) binding by low-affinity ATP and diffusion of CaATP may affect the amplitude and time course of intracellular Ca(2+) signals. The model also suggests that a fall in ATP/ADP ratio significantly reduces sarcoplasmic Ca(2+) content, increases diastolic Ca(2+), lowers systolic Ca(2+), increases Ca(2+) influx through L-type channels, and decreases the efficiency of the Na(+)/Ca(2+) exchanger in extruding Ca(2+) during periodic voltage-clamp stimulation. The analysis suggests that the most important reason for these changes during metabolic inhibition is the down-regulation of the sarcoplasmic Ca(2+)-ATPase pump by reduced diastolic MgATP levels. High Ca(2+) concentrations developed near the membrane might have a greater influence on Mg(2+), ATP, and ADP concentrations than that of the lower Ca(2+) concentrations in the bulk myoplasm. The model predictions are in general agreement with experimental observations measured under normal and pathological conditions.

Polyamines cause plasma membrane depolarization, activate Ca2+-, and modulate H+-ATPase pump activity in pea roots.

PubMed

Pottosin, Igor; Velarde-Buendía, Ana María; Bose, Jayakumar; Fuglsang, Anja T; Shabala, Sergey

2014-06-01

Polyamines regulate a variety of cation and K(+) channels, but their potential effects on cation-transporting ATPases are underexplored. In this work, noninvasive microelectrode ion flux estimation and conventional microelectrode techniques were applied to study the effects of polyamines on Ca(2+) and H(+) transport and membrane potential in pea roots. Externally applied spermine or putrescine (1mM) equally activated eosin yellow (EY)-sensitive Ca(2+) pumping across the root epidermis and caused net H(+) influx or efflux. Proton influx induced by spermine was suppressed by EY, supporting the mechanism in which Ca(2+) pump imports 2 H(+) per each exported Ca(2+). Suppression of the Ca(2+) pump by EY diminished putrescine-induced net H(+) efflux instead of increasing it. Thus, activities of Ca(2+) and H(+) pumps were coupled, likely due to the H(+)-pump inhibition by intracellular Ca(2+). Additionally, spermine but not putrescine caused a direct inhibition of H(+) pumping in isolated plasma membrane vesicles. Spermine, spermidine, and putrescine (1mM) induced membrane depolarization by 70, 50, and 35 mV, respectively. Spermine-induced depolarization was abolished by cation transport blocker Gd(3+), was insensitive to anion channels' blocker niflumate, and was dependent on external Ca(2+). Further analysis showed that uptake of polyamines but not polyamine-induced cationic (K(+)+Ca(2+)+H(+)) fluxes were a main cause of membrane depolarization. Polyamine increase is a common component of plant stress responses. Activation of Ca(2+) efflux by polyamines and contrasting effects of polyamines on net H(+) fluxes and membrane potential can contribute to Ca(2+) signalling and modulate a variety of transport processes across the plasma membrane under stress. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers.

PubMed

Young, Iain S; Harwood, Claire L; Rome, Lawrence C

2003-10-01

Because the major processes involved in muscle contraction require rapid utilization of ATP, measurement of ATP utilization can provide important insights into the mechanisms of contraction. It is necessary, however, to differentiate between the contribution made by cross-bridges and that of the sarcoplasmic reticulum (SR) Ca2+ pumps. Specific and potent SR Ca2+ pump blockers have been used in skinned fibers to permit direct measurement of cross-bridge ATP utilization. Up to now, there was no analogous cross-bridge blocker. Recently, N-benzyl-p-toluene sulfonamide (BTS) was found to suppress force generation at micromolar concentrations. We tested whether BTS could be used to block cross-bridge ATP utilization, thereby permitting direct measurement of SR Ca2+ pump ATP utilization in saponin-skinned fibers. At 25 microM, BTS virtually eliminates force and cross-bridge ATP utilization (both <4% of control value). By taking advantage of the toadfish swimbladder muscle's unique right shift in its force-Ca2+ concentration ([Ca2+]) relationship, we measured SR Ca2+ pump ATP utilization in the presence and absence of BTS. At 25 microM, BTS had no effect on SR pump ATP utilization. Hence, we used BTS to make some of the first direct measurements of ATP utilization of intact SR over a physiological range of [Ca2+]at 15 degrees C. Curve fits to SR Ca2+ pump ATP utilization vs. pCa indicate that they have much lower Hill coefficients (1.49) than that describing cross-bridge force generation vs. pCa (approximately 5). Furthermore, we found that BTS also effectively eliminates force generation in bundles of intact swimbladder muscle, suggesting that it will be an important tool for studying integrated SR function during normal motor behavior.

Arterial α2-Na+ pump expression influences blood pressure: lessons from novel, genetically engineered smooth muscle-specific α2 mice.

PubMed

Chen, Ling; Song, Hong; Wang, Youhua; Lee, Jane C; Kotlikoff, Michael I; Pritchard, Tracy J; Paul, Richard J; Zhang, Jin; Blaustein, Mordecai P

2015-09-01

Arterial myocytes express α1-catalytic subunit isoform Na(+) pumps (75-80% of total), which are ouabain resistant in rodents, and high ouabain affinity α2-Na(+) pumps. Mice with globally reduced α2-pumps (but not α1-pumps), mice with mutant ouabain-resistant α2-pumps, and mice with a smooth muscle (SM)-specific α2-transgene (α2 (SM-Tg)) that induces overexpression all have altered blood pressure (BP) phenotypes. We generated α2 (SM-DN) mice with SM-specific α2 (not α1) reduction (>50%) using nonfunctional dominant negative (DN) α2. We compared α2 (SM-DN) and α2 (SM-Tg) mice to controls to determine how arterial SM α2-pumps affect vasoconstriction and BP. α2 (SM-DN) mice had elevated basal mean BP (mean BP by telemetry: 117 ± 4 vs. 106 ± 1 mmHg, n = 7/7, P < 0.01) and enhanced BP responses to chronic ANG II infusion (240 ng·kg(-1)·min(-1)) and high (6%) NaCl. Several arterial Ca(2+) transporters, including Na(+)/Ca(2+) exchanger 1 (NCX1) and sarcoplasmic reticulum and plasma membrane Ca(2+) pumps [sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) and plasma membrane Ca(2+)-ATPase 1 (PMCA1)], were also reduced (>50%). α2 (SM-DN) mouse isolated small arteries had reduced myogenic reactivity, perhaps because of reduced Ca(2+) transporter expression. In contrast, α2 (SM-Tg) mouse aortas overexpressed α2 (>2-fold), NCX1, SERCA2, and PMCA1 (43). α2 (SM-Tg) mice had reduced basal mean BP (104 ± 1 vs. 109 ± 2 mmHg, n = 15/9, P < 0.02) and attenuated BP responses to chronic ANG II (300-400 ng·kg(-1)·min(-1)) with or without 2% NaCl but normal myogenic reactivity. NCX1 expression was inversely related to basal BP in SM-α2 engineered mice but was directly related in SM-NCX1 engineered mice. NCX1, which usually mediates arterial Ca(2+) entry, and α2-Na(+) pumps colocalize at plasma membrane-sarcoplasmic reticulum junctions and functionally couple via the local Na(+) gradient to help regulate cell Ca(2+). Altered Ca(2+) transporter expression in SM-α2 engineered mice apparently compensates to minimize Ca(2+) overload (α2 (SM-DN)) or depletion (α2 (SM-Tg)) and attenuate BP changes. In contrast, Ca(2+) transporter upregulation, observed in many rodent hypertension models, should enhance Ca(2+) entry and signaling and contribute significantly to BP elevation. Copyright © 2015 the American Physiological Society.

Preserved function of the plasma membrane calcium pump of red blood cells from diabetic subjects with high levels of glycated haemoglobin.

PubMed

Bookchin, Robert M; Etzion, Zipora; Lew, Virgilio L; Tiffert, Teresa

2009-03-01

The activity of the plasma membrane Ca(2+)-pump decreases steeply throughout the 120 days lifespan of normal human red blood cells. Experiments with isolated membrane preparations showed that glycation of a lysine residue near the catalytic site of the pump ATPase had a powerful inhibitory effect. This prompted the question of whether glycation is the mechanism of age-related decline in pump activity in vivo. It is important to investigate this mechanism because the Ca(2+) pump is a major regulator of Ca(2+) homeostasis in all cells. Its impaired activity in diabetic patients, continuously exposed to high glycation rates, may thus contribute to varied tissue pathology in this disease. We measured Ca(2+)-pump activity as a function of red cell age in red cells from diabetics continuously exposed to high glucose concentrations, as documented by their high mean levels of glycated haemoglobin. The distribution of Ca(2+)-pump activities was indistinguishable from that in non-diabetics, and the pattern of activity decline with cell age in the diabetics' red cells was identical to that observed in red cells from non-diabetics. These results indicate that in intact cells the Ca(2+) pump is protected from glycation-induced inactivation.

Bone bonding ability of a chemically and thermally treated low elastic modulus Ti alloy: gum metal.

PubMed

Tanaka, Masashi; Takemoto, Mitsuru; Fujibayashi, Shunsuke; Kawai, Toshiyuki; Yamaguchi, Seiji; Kizuki, Takashi; Matsushita, Tomiharu; Kokubo, Tadashi; Nakamura, Takashi; Matsuda, Shuichi

2014-03-01

The gum metal with composition Ti-36Nb-2Ta-3Zr-0.3O, is free from cytotoxic elements and exhibits a low elastic modulus as well as high mechanical strength. We have previously demonstrated that this gum metal, once subjected to a series of surface treatments--immersion in 1 M NaOH (alkali treatment) and then 100 mM CaCl2, before heating at 700 °C (sample: ACaH-GM), with an optional final hot water immersion (sample: ACaHW-GM)--has apatite-forming ability in simulated body fluid. To confirm the in vivo bioactivity of these treated alloys, failure loads between implants and bone at 4, 8, 16, and 26 weeks after implantation in rabbits' tibiae were measured for untreated gum metal (UT-GM), ACaH-GM and ACaHW-GM, as well as pure titanium plates after alkali and heat treatment (AH-Ti). The ACaH-GM and UT-GM plates showed almost no bonding, whereas ACaHW-GM and AH-Ti plates showed successful bonding by 4 weeks, and their failure loads subsequently increased with time. The histological findings showed a large amount of new bone in contact with the surface of ACaHW-GM and AH-Ti plates, suggesting that the ACaHW treatment could impart bone-bonding bioactivity to a gum metal in vivo. Thus, with this improved bioactive treatment, these advantageous gum metals become useful candidates for orthopedic and dental devices.

Loss of the Chloroplast Transit Peptide from an Ancestral C3 Carbonic Anhydrase Is Associated with C4 Evolution in the Grass Genus Neurachne.

PubMed

Clayton, Harmony; Saladié, Montserrat; Rolland, Vivien; Sharwood, Robert; Macfarlane, Terry; Ludwig, Martha

2017-03-01

Neurachne is the only known grass lineage containing closely related C 3 , C 3 -C 4 intermediate, and C 4 species, making it an ideal taxon with which to study the evolution of C 4 photosynthesis in the grasses. To begin dissecting the molecular changes that led to the evolution of C 4 photosynthesis in this group, the complementary DNAs encoding four distinct β-carbonic anhydrase (CA) isoforms were characterized from leaf tissue of Neurachne munroi (C 4 ), Neurachne minor (C 3 -C 4 ), and Neurachne alopecuroidea (C 3 ). Two genes ( CA1 and CA2 ) each encode two different isoforms: CA1a/CA1b and CA2a/CA2b. Transcript analyses found that CA1 messenger RNAs were significantly more abundant than transcripts from the CA2 gene in the leaves of each species examined, constituting ∼99% of all β-CA transcripts measured. Localization experiments using green fluorescent protein fusion constructs showed that, while CA1b is a cytosolic CA in all three species, the CA1a proteins are differentially localized. The N. alopecuroidea and N. minor CA1a isoforms were imported into chloroplasts of Nicotiana benthamiana leaf cells, whereas N. munroi CA1a localized to the cytosol. Sequence analysis indicated an 11-amino acid deletion in the amino terminus of N. munroi CA1a relative to the C 3 and C 3 -C 4 proteins, suggesting that chloroplast targeting of CA1a is the ancestral state and that loss of a functional chloroplast transit peptide in N. munroi CA1a is associated with the evolution of C 4 photosynthesis in Neurachne spp. Remarkably, this mechanism is homoplastic with the evolution of the C 4 -associated CA in the dicotyledonous genus Flaveria , although the actual mutations in the two lineages differ. © 2017 American Society of Plant Biologists. All Rights Reserved.

Loss of the Chloroplast Transit Peptide from an Ancestral C3 Carbonic Anhydrase Is Associated with C4 Evolution in the Grass Genus Neurachne1[OPEN

PubMed Central

Clayton, Harmony; Saladié, Montserrat; Sharwood, Robert; Macfarlane, Terry

2017-01-01

Neurachne is the only known grass lineage containing closely related C3, C3-C4 intermediate, and C4 species, making it an ideal taxon with which to study the evolution of C4 photosynthesis in the grasses. To begin dissecting the molecular changes that led to the evolution of C4 photosynthesis in this group, the complementary DNAs encoding four distinct β-carbonic anhydrase (CA) isoforms were characterized from leaf tissue of Neurachne munroi (C4), Neurachne minor (C3-C4), and Neurachne alopecuroidea (C3). Two genes (CA1 and CA2) each encode two different isoforms: CA1a/CA1b and CA2a/CA2b. Transcript analyses found that CA1 messenger RNAs were significantly more abundant than transcripts from the CA2 gene in the leaves of each species examined, constituting ∼99% of all β-CA transcripts measured. Localization experiments using green fluorescent protein fusion constructs showed that, while CA1b is a cytosolic CA in all three species, the CA1a proteins are differentially localized. The N. alopecuroidea and N. minor CA1a isoforms were imported into chloroplasts of Nicotiana benthamiana leaf cells, whereas N. munroi CA1a localized to the cytosol. Sequence analysis indicated an 11-amino acid deletion in the amino terminus of N. munroi CA1a relative to the C3 and C3-C4 proteins, suggesting that chloroplast targeting of CA1a is the ancestral state and that loss of a functional chloroplast transit peptide in N. munroi CA1a is associated with the evolution of C4 photosynthesis in Neurachne spp. Remarkably, this mechanism is homoplastic with the evolution of the C4-associated CA in the dicotyledonous genus Flaveria, although the actual mutations in the two lineages differ. PMID:28153918

The Plasma Membrane Calcium Pump: New Ways to Look at an Old Enzyme

PubMed Central

Lopreiato, Raffaele; Giacomello, Marta; Carafoli, Ernesto

2014-01-01

The three-dimensional structure of the PMCA pump has not been solved, but its basic mechanistic properties are known to repeat those of the other Ca2+ pumps. However, the pump also has unique properties. They concern essentially its numerous regulatory mechanisms, the most important of which is the autoinhibition by its C-terminal tail. Other regulatory mechanisms involve protein kinases and the phospholipids of the membrane in which the pump is embedded. Permanent activation of the pump, e.g. by calmodulin, is physiologically as harmful to cells as its absence. The concept is now emerging that the global control of cell Ca2+ may not be the main function of the pump; in some cell types, it could even be irrelevant. The main pump role would be the regulation of Ca2+ in cell microdomains in which the pump co-segregates with partners that modulate the Ca2+ message and transduce it to important cell functions. PMID:24570005

Effects of deoxygenation on active and passive Ca2+ transport and cytoplasmic Ca2+ buffering in normal human red cells.

PubMed Central

Tiffert, T; Etzion, Z; Bookchin, R M; Lew, V L

1993-01-01

1. The effects of deoxygenation on cytoplasmic Ca2+ buffering, saturated Ca2+ extrusion rate through the Ca2+ pump (Vmax), passive Ca2+ influx and physiological [Ca2+]i level were investigated in human red cells to assess whether or not their Ca2+ metabolism might be altered by deoxygenation in capillaries and venous circulation. 2. The study was performed in fresh human red cells maintained in a tonometer either fully oxygenated or deoxygenated. Cytoplasmic Ca2+ buffering was estimated from the equilibrium distribution of 45Ca2+ induced by the divalent cation ionophore A23187 and the Vmax of the Ca2+ pump was measured either by the Co(2+)-exposure method or following ionophore wash-out. The passive Ca2+ influx and physiological [Ca2+]i were determined in cells preloaded with the Ca2+ chelator benz-2 and resuspended in autologous plasma. 3. Deoxygenation increased the fraction of ionized Ca2+ in cell water by 34-74% and reduced the Vmax of the Ca2+ pump by 18-32%. 4. To elucidate whether or not these effects were secondary to deoxygenation-induced pH shifts, the effects of deoxygenation on cell and medium pH, and of pH on cytoplasmic Ca2+ binding and Ca2+ pump Vmax in oxygenated cells were examined in detail. 5. Deoxygenation generated large alkaline pH shifts that could be explained if the apparent isoelectric point (pI) of haemoglobin increased by 0.2-0.4 pH units in intact cells, consistently higher than the value of 0.15 reported for pure haemoglobin solutions. 6. In oxygenated cells, the fraction of ionized cell calcium, alpha, was little affected by pH within the 7.0-7.7 range. Ca2+ pump Vmax was maximal at a medium pH of about 7.55. Comparison between pH effects elicited by HCl-NaOH additions and by replacing Cl- with gluconate suggested that Vmax was inhibited by both internal acidification and external alkalinization. Since deoxygenation alkalinized cells and medium within a range stimulatory for Vmax, the inhibition observed was not due to pH. 7. There was no significant effect of deoxygenation on passive Ca2+ uptake, or steady-state physiological [Ca2+]i level. 8. The deoxygenation-induced reduction in Ca2+ binding capacity may result from the increased protonation of haemoglobin on deoxygenation and from binding of 2,3-diphosphoglyceric acid (2,3-DPG) and ATP to deoxyhaemoglobin; inhibition of the Ca2+ pump may result from shifts in the [Mg2+]i/[ATP]i ratio away from a near optimal stimulatory value in the oxygenated state. PMID:8229816

Integrating Membrane Transport with Male Gametophyte Development and Function through Transcriptomics.

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

Bock KW; D Honys; JM. Ward

Male fertility depends on the proper development of the male gametophyte, successful pollen germination, tube growth and delivery of the sperm cells to the ovule. Previous studies have shown that nutrients like boron, and ion gradients or currents of Ca2+, H+, and K+ are critical for pollen tube growth. However, the molecular identities of transporters mediating these fluxes are mostly unknown. As a first step to integrate transport with pollen development and function, a genome-wide analysis of transporter genes expressed in the male gametophyte at four developmental stages was conducted. About 1269 genes encoding classified transporters were collected from themore » Arabidopsis thaliana genome. Of 757 transporter genes expressed in pollen, 16% or 124 genes, including AHA6, CNGC18, TIP1.3 and CHX08, are specifically or preferentially expressed relative to sporophytic tissues. Some genes are highly expressed in microspores and bicellular pollen (COPT3, STP2, OPT9); while others are activated only in tricellular or mature pollen (STP11, LHT7). Analyses of entire gene families showed that a subset of genes, including those expressed in sporophytic tissues, were developmentally-regulated during pollen maturation. Early and late expression patterns revealed by transcriptome analysis are supported by promoter::GUS analyses of CHX genes and by other methods. Recent genetic studies based on a few transporters, including plasma membrane H+ pump AHA3, Ca2+ pump ACA9, and K+ channel SPIK, further support the expression patterns and the inferred functions revealed by our analyses. Thus, revealing the distinct expression patterns of specific transporters and unknown polytopic proteins during microgametogenesis provides new insights for strategic mutant analyses necessary to integrate the roles of transporters and potential receptors with male gametophyte development.« less

Integrating membrane transport with male gametophyte development and function through transcriptomics.

PubMed

Bock, Kevin W; Honys, David; Ward, John M; Padmanaban, Senthilkumar; Nawrocki, Eric P; Hirschi, Kendal D; Twell, David; Sze, Heven

2006-04-01

Male fertility depends on the proper development of the male gametophyte, successful pollen germination, tube growth, and delivery of the sperm cells to the ovule. Previous studies have shown that nutrients like boron, and ion gradients or currents of Ca2+, H+, and K+ are critical for pollen tube growth. However, the molecular identities of transporters mediating these fluxes are mostly unknown. As a first step to integrate transport with pollen development and function, a genome-wide analysis of transporter genes expressed in the male gametophyte at four developmental stages was conducted. Approximately 1,269 genes encoding classified transporters were collected from the Arabidopsis (Arabidopsis thaliana) genome. Of 757 transporter genes expressed in pollen, 16% or 124 genes, including AHA6, CNGC18, TIP1.3, and CHX08, are specifically or preferentially expressed relative to sporophytic tissues. Some genes are highly expressed in microspores and bicellular pollen (COPT3, STP2, OPT9), while others are activated only in tricellular or mature pollen (STP11, LHT7). Analyses of entire gene families showed that a subset of genes, including those expressed in sporophytic tissues, was developmentally regulated during pollen maturation. Early and late expression patterns revealed by transcriptome analysis are supported by promoter::beta-glucuronidase analyses of CHX genes and by other methods. Recent genetic studies based on a few transporters, including plasma membrane H+ pump AHA3, Ca2+ pump ACA9, and K+ channel SPIK, further support the expression patterns and the inferred functions revealed by our analyses. Thus, revealing the distinct expression patterns of specific transporters and unknown polytopic proteins during microgametogenesis provides new insights for strategic mutant analyses necessary to integrate the roles of transporters and potential receptors with male gametophyte development.

2.4 μm diode-pumped Dy2+:CaF2 laser

NASA Astrophysics Data System (ADS)

Švejkar, Richard; Papashvili, Alexander G.; Šulc, Jan; Němec, Michal; Jelínková, Helena; Doroshenko, Maxim E.; Batygov, Sergei H.; Osiko, Vyacheslav V.

2018-01-01

In this work, a cryogenic cooled, longitudinal diode-pumped Dy2+ :CaF2 laser was investigated for the first time. The temperature dependence of the spectroscopy and the laser properties of Dy2+ :CaF2 are presented. The tested Dy2+ :CaF2 crystal was a longitudinal pump in a near-IR region (926 nm) by laser diode radiation. The maximal mean output power and slope efficiency at 78 K during the pulse regime of the laser were 57.5 mW and 7%, respectively. Furthermore, the CW regime was successfully tested and a maximum output power of 0.37 W was obtained for the absorbed pumping power 5.7 W. The emission laser wavelength was 2367 nm.

Quantifying interactions between accommodation and vergence in a binocularly normal population.

PubMed

Sweeney, Laura E; Seidel, Dirk; Day, Mhairi; Gray, Lyle S

2014-12-01

Stimulation of the accommodation system results in a response in the vergence system via accommodative vergence cross-link interactions, and stimulation of the vergence system results in an accommodation response via vergence accommodation cross-link interactions. Cross-link interactions are necessary in order to ensure simultaneous responses in the accommodation and vergence systems. The crosslink interactions are represented most comprehensively by the response AC/A (accommodative vergence) and CA/C (vergence accommodation) ratios, although the stimulus AC/A ratio is measured clinically, and the stimulus CA/C ratio is seldom measured in clinical practice. The present study aims to quantify both stimulus and response AC/A and CA/C ratios in a binocularly normal population, and determine the relationship between them. 25 Subjects (mean ± SD age 21.0 ± 1.9 years) were recruited from the university population. A significant linear relationship was found between the stimulus and response ratios, for both AC/A (r² = 0.96, p < 0.001) and CA/C ratios (r² = 0.40, p < 0.05). Good agreement was found between the stimulus and response AC/A ratios (95% CI -0.06 to 0.24 MA/D). Stimulus and response CA/C ratios are linearly related. Stimulus CA/C ratios were higher than response ratios at low values, and lower than response ratios at high values (95% CI -0.46 to 0.42 D/MA). Agreement between stimulus and response CA/C ratios is poorer than that found for AC/A ratios due to increased variability in vergence responses when viewing the Gaussian blurred target. This study has shown that more work is needed to refine the methodology of CA/C ratio measurement.

[Mg2+, ATP-dependent plasma membrane calcium pump of smooth muscle cells. I. Structural organization and properties].

PubMed

Veklich, T O; Mazur, Iu Iu; Kosterin, S O

2015-01-01

Tight control of cytoplasm Ca2+ concentration is essential in cell functioning. Changing of Ca2+ concentration is thorough in smooth muscle cells, because it determines relaxation/constraint process. One of key proteins which control Ca2+ concentration in cytoplasm is Mg2+, ATP-dependent plasma membrane calcium pump. Thus, it is important to find compoumds which allowed one to change Mg2+, ATP-dependent plasma membrane calcium pump activity, as long as this topic is of current interest in biochemical research which regards energy and pharmacomechanical coupling mechanism of muscle excitation and contraction. In this article we generalized literatute and own data about properties of smooth muscle cell plasma membrane Ca(2+)-pump. Stuctural oganization, kinetical properties and molecular biology are considered.

Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca exchangers.

PubMed

Barkla, Bronwyn J; Hirschi, Kendal D; Pittman, Jon K

2008-05-01

Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+)exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H(+)-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca(2+)/H(+) exchangers and H(+) pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca(2+) flux. These results suggest cautious interpretation of mutant Ca(2+)/H(+) exchanger phenotypes that may be due to either perturbed Ca(2+) or H(+) transport.

Ca2+ Induces Spontaneous Dephosphorylation of a Novel P5A-type ATPase

PubMed Central

Sørensen, Danny Mollerup; Møller, Annette B.; Jakobsen, Mia K.; Jensen, Michael K.; Vangheluwe, Peter; Buch-Pedersen, Morten J.; Palmgren, Michael G.

2012-01-01

P5 ATPases constitute the least studied group of P-type ATPases, an essential family of ion pumps in all kingdoms of life. Although P5 ATPases are present in every eukaryotic genome analyzed so far, they have remained orphan pumps, and their biochemical function is obscure. We show that a P5A ATPase from barley, HvP5A1, locates to the endoplasmic reticulum and is able to rescue knock-out mutants of P5A genes in both Arabidopsis thaliana and Saccharomyces cerevisiae. HvP5A1 spontaneously forms a phosphorylated reaction cycle intermediate at the catalytic residue Asp-488, whereas, among all plant nutrients tested, only Ca2+ triggers dephosphorylation. Remarkably, Ca2+-induced dephosphorylation occurs at high apparent [Ca2+] (Ki = 0.25 mm) and is independent of the phosphatase motif of the pump and the putative binding site for transported ligands located in M4. Taken together, our results rule out that Ca2+ is a transported substrate but indicate the presence of a cytosolic low affinity Ca2+-binding site, which is conserved among P-type pumps and could be involved in pump regulation. Our work constitutes the first characterization of a P5 ATPase phosphoenzyme and points to Ca2+ as a modifier of its function. PMID:22730321

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue.

PubMed

Macdonald, W A; Stephenson, D G

2006-05-15

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 microm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (-log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 microm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 microm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres.

Small Ca2+ releases enable hour-long high-frequency contractions in midshipman swimbladder muscle.

PubMed

Nelson, Frank E; Hollingworth, Stephen; Marx, James O; Baylor, Stephen M; Rome, Lawrence C

2018-01-02

Type I males of the Pacific midshipman fish ( Porichthys notatus ) vibrate their swimbladder to generate mating calls, or "hums," that attract females to their nests. In contrast to the intermittent calls produced by male Atlantic toadfish ( Opsanus tau ), which occur with a duty cycle (calling time divided by total time) of only 3-8%, midshipman can call continuously for up to an hour. With 100% duty cycles and frequencies of 50-100 Hz (15°C), the superfast muscle fibers that surround the midshipman swimbladder may contract and relax as many as 360,000 times in 1 h. The energy for this activity is supported by a large volume of densely packed mitochondria that are found in the peripheral and central regions of the fiber. The remaining fiber cross section contains contractile filaments and a well-developed network of sarcoplasmic reticulum (SR) and triadic junctions. Here, to understand quantitatively how Ca 2+ is managed by midshipman fibers during calling, we measure (a) the Ca 2+ pumping-versus-pCa and force-versus-pCa relations in skinned fiber bundles and (b) changes in myoplasmic free [Ca 2+ ] (Δ[Ca 2+ ]) during stimulated activity of individual fibers microinjected with the Ca 2+ indicators Mag-fluo-4 and Fluo-4. As in toadfish, the force-pCa relation in midshipman is strongly right-shifted relative to the Ca 2+ pumping-pCa relation, and contractile activity is controlled in a synchronous, not asynchronous, fashion during electrical stimulation. SR Ca 2+ release per action potential is, however, approximately eightfold smaller in midshipman than in toadfish. Midshipman fibers have a larger time-averaged free [Ca 2+ ] during activity than toadfish fibers, which permits faster Ca 2+ pumping because the Ca 2+ pumps work closer to their maximum rate. Even with midshipman's sustained release and pumping of Ca 2+ , however, the Ca 2+ energy cost of calling (per kilogram wet weight) is less than twofold more in midshipman than in toadfish. © 2018 Nelson et al.

Is the Ca2+-ATPase from sarcoplasmic reticulum also a heat pump?

PubMed

Kjelstrup, Signe; de Meis, Leopoldo; Bedeaux, Dick; Simon, Jean-Marc

2008-11-01

We calculate, using the first law of thermodynamics, the membrane heat fluxes during active transport of Ca(2+) in the Ca(2+)-ATPase in leaky and intact vesicles, during ATP hydrolysis or synthesis conditions. The results show that the vesicle interior may cool down during hydrolysis and Ca(2+)-uptake, and heat up during ATP synthesis and Ca(2+)-efflux. The heat flux varies with the SERCA isoform. Electroneutral processes and rapid equilibration of water were assumed. The results are consistent with the second law of thermodynamics for the overall processes. The expression for the heat flux and experimental data, show that important contributions come from the enthalpy of hydrolysis for the medium in question, and from proton transport between the vesicle interior and exterior. The analysis give quantitative support to earlier proposals that certain, but not all, Ca(2+)-ATPases, not only act as Ca(2+)-pumps, but also as heat pumps. It can thus help explain why SERCA 1 type enzymes dominate in tissues where thermal regulation is important, while SERCA 2 type enzymes, with their lower activity and better ability to use the energy from the reaction to pump ions, dominate in tissues where this is not an issue.

Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells.

PubMed

Etzion, Z; Tiffert, T; Bookchin, R M; Lew, V L

1993-11-01

Elevated [Ca2+]i in deoxygenated sickle cell anemia (SS) red cells (RBCs) could trigger a major dehydration pathway via the Ca(2+)-sensitive K+ channel. But apart from an increase in calcium permeability, the effects of deoxygenation on the Ca2+ metabolism of sickle cells have not been previously documented. With the application of 45Ca(2+)-tracer flux methods and the combined use of the ionophore A23187, Co2+ ions, and intracellular incorporation of the Ca2+ chelator benz-2, in density-fractionated SS RBCs, we show here for the first time that upon deoxygenation, the mean [Ca2+]i level of SS discocytes was significantly increased, two- to threefold, from a normal range of 9.4 to 11.4 nM in the oxygenated cells, to a range of 21.8 to 31.7 nM in the deoxygenated cells, closer to K+ channel activatory levels. Unlike normal RBCs, deoxygenated SS RBCs showed a two- to fourfold increase in pump-leak Ca2+ turnover. Deoxygenation of the SS RBCs reduced their Ca2+ pump Vmax, more so in reticulocyte- and discocyte-rich than in dense cell fractions, and decreased their cytoplasmic Ca2+ buffering. Analysis of these results suggests that both increased Ca2+ influx and reduced Ca2+ pump extrusion contribute to the [Ca2+]i elevation.

The role of interactions between accommodation and vergence in human visual development

NASA Astrophysics Data System (ADS)

Teel, Danielle F. W.

Even in early infancy accommodation and vergence interact through neural coupling such that accommodation drives vergence (AC/A ratio) and vergence drives accommodation (CA/C ratio), to assist coordination and development of clear and single binocular vision. Infants have narrow inter-pupillary distances (IPD) requiring less vergence in angular units (degrees or prism diopters), and are typically hyperopic, requiring larger accommodative responses (diopters) than adults. The relative demands also change with emmetropization (decreasing hyperopia) and head growth (increasing IPD) over time. Therefore, adult-like couplings may not be optimal during development and the couplings may play a role in abnormality such as esotropia. A range of cues can drive accommodation and vergence. In addition to blur and disparity, proximity in the form of looming, size and perceived distance has been shown to influence the interactions between accommodation and vergence in adults. The role of this cue in measures of coupling is also poorly understood and may impact key clinical AC/A estimates in young children. Utilizing principles of eccentric photorefraction and Purkinje image eye tracking, this research examines the AC/A and CA/C ratios in infants, preschoolers and adults as a function of age, refractive error and interpupillary distance, plus the role proximity, specifically looming and size cues, plays in estimating the AC/A ratio in three year olds and adults. The AC/A (PD/D) was significantly higher in adults than three-year-olds or infants but similar across age groups in MA/D units. The CA/C was higher in infants than adults or three-year-olds (D/MA and D/PD). Although, not fully reciprocally related, a significant negative relationship was found between the response AC/A and CA/C. Similarly, higher AC/As (PD/D) and lower CA/Cs (D/PD) were associated with larger IPDs and less hyperopia. Although, not statistically significant the absence of proximity resulted in a trend toward a lower AC/A than in it's presence for children. These results provide insight into methods of measuring the AC/A ratio in children and determining whether the couplings are optimized to prevent over-convergence or under-accommodation during development and growth.

Highly efficient continuous-wave laser operation of LD-pumped Nd,Gd:CaF2 and Nd,Y:CaF2 crystals

NASA Astrophysics Data System (ADS)

Pang, Siyuan; Ma, Fengkai; Yu, Hao; Qian, Xiaobo; Jiang, Dapeng; Wu, Yongjing; Zhang, Feng; Liu, Jie; Xu, Jiayue; Su, Liangbi

2018-05-01

Spectroscopic properties of Nd:CaF2 crystals are investigated. The photoluminescence intensity in the near infrared region is drastically enhanced by co-doping Gd3+ ions and Y3+ in Nd:CaF2 crystals. Preliminary laser experiments are carried out with 0.3%Nd,5%Gd:CaF2 and 0.3%Nd,5%Y:CaF2 crystals under laser diode pumping; true continuous wave laser operation is achieved with slope efficiencies of 42% and 39%, respectively, and the maximum output power reaches 1.188 W.

Dramatic effects of external alkalinity on neuronal calcium recovery following a short-duration glutamate challenge: the role of the plasma membrane Ca2+/H+ pump.

PubMed

Khodorov, B; Pinelis, V; Vergun, O; Storozhevykh, T; Fajuk, D; Vinskaya, N; Arsenjeva, E; Khaspekov, L; Lyzin, A; Isaev, N

1995-09-11

Alkalinization of the external medium has been shown to suppress Ca2+ extrusion from neurons due to inhibition of the plasmalemmal Ca2+/H+ pump. In our experiments on fura-2-loaded rat cerebellar granule cells and mouse hippocampal neurons, an increase in pHo from 7.4 to 8.5 following a 1-min glutamate or NMDA challenge caused a dramatic delay in [Ca2+]i recovery which in some cases was accompanied by an additional increase in [Ca2+]i. Normalization of pHo, or removal of Ca2+ from the alkaline solution allowed [Ca2+]i to decrease rapidly again. External alkalinity did not affect the initial rapid decline in [Ca2+]i following a 25 mMK+ pulse. In cerebellar granule cells, the alkaline pHo considerably increased the 45Ca2+ uptake both at rest and following a 2-min GLU pulse. A comparison of these effects of alkaline pHo with those produced by removal of the external Na+ led us to conclude that the Ca2+/H+ pump plays a dominant role in the mechanism of the fast Ca2+ extrusion from glutamate- or NMDA-treated neurons.

Coordinate downregulation of CaM kinase II and phospholamban accompanies contractile phenotype transition in the hyperthyroid rabbit soleus.

PubMed

Jiang, M; Xu, A; Jones, D L; Narayanan, N

2004-09-01

This study investigated the effects of l-thyroxine-induced hyperthyroidism on Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaM kinase II)-mediated sarcoplasmic reticulum (SR) protein phosphorylation, SR Ca(2+) pump (Ca(2+)-ATPase) activity, and contraction duration in slow-twitch soleus muscle of the rabbit. Phosphorylation of Ca(2+)-ATPase and phospholamban (PLN) by endogenous CaM kinase II was found to be significantly lower (30-50%) in soleus of the hyperthyroid compared with euthyroid rabbit. Western blotting analysis revealed higher levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 1 ( approximately 150%) Ca(2+) pump isoform, unaltered levels of SERCA2 Ca(2+) pump isoform, and lower levels of PLN ( approximately 50%) and delta-, beta-, and gamma-CaM kinase II (40 approximately 70%) in soleus of the hyperthyroid rabbit. SR vesicles from hyperthyroid rabbit soleus displayed approximately twofold higher ATP-energized Ca(2+) uptake and Ca(2+)-stimulated ATPase activities compared with that from euthyroid control. The V(max) of Ca(2+) uptake (in nmol Ca(2+).mg SR protein(-1).min(-1): euthyroid, 818 +/- 73; hyperthyroid, 1,649 +/- 90) but not the apparent affinity of the Ca(2+)-ATPase for Ca(2+) (euthyroid, 0.97 +/- 0.02 microM, hyperthyroid, 1.09 +/- 0.04 microM) differed significantly between the two groups. CaM kinase II-mediated stimulation of Ca(2+) uptake by soleus muscle SR was approximately 60% lower in the hyperthyroid compared with euthyroid. Isometric twitch force of soleus measured in situ was significantly greater ( approximately 36%), and the time to peak force and relaxation time were significantly lower ( approximately 30-40%), in the hyperthyroid. These results demonstrate that thyroid hormone-induced transition in contractile properties of the rabbit soleus is associated with coordinate downregulation of the expression and function of PLN and CaM kinase II and selective upregulation of the expression and function of SERCA1, but not SERCA2, isoform of the SR Ca(2+) pump.

Diode pumped tunable lasers based on Tm:CaF2 and Tm:Ho:CaF2 ceramics

NASA Astrophysics Data System (ADS)

Šulc, Jan; Němec, Michal; Jelinková, Helena; Doroshenko, Maxim E.; Fedorov, Pavel P.; Osiko, Vyacheslav V.

2014-02-01

The Tm:CaF2 (4% of TmF3) and Tm:Ho:CaF2 (2% of TmF3, 0.3% of HoF3) ceramics, prepared using hot pressing, and hot formation technique had been used as an active medium of diode pumped mid-infrared tunable laser. A fibre (core diameter 400 μm, NA = 0.22) coupled laser diode (LIMO, HLU30F400-790) was used to longitudinal pumping. The laser diode was operating in the pulsed regime (6 ms pulse length, 10 Hz repetition rate). The duty-cycle 6% ensures a low thermal load even under the maximum diode pumping power amplitude 25W (ceramics samples were only air-cooled). The laser diode emission wavelength was 786 nm. The 80mm long semi-hemispherical laser resonator consisted of a flat pumping mirror (HR @ 1.85 - 2.15 μm, HT @ 0.78 μm) and a curved (r = 150mm) output coupler with a reflectivity of ˜ 98% @ 1.85 - 2.0 μm for Tm:CaF2 laser or ˜ 99.5% @ 2.0 - 2.15 μm for Ho:Tm:CaF2. Tuning of the laser was accomplished by using a birefringent filter (single 1.5mm thick quartz plate) placed inside the optical resonator at the Brewster angle. Both samples offered broad and smooth tuning possibilities in mid-IR spectral range and the lasers were continuously tunable over ˜ 100 nm. The obtained Tm:CaF2 tunability ranged from 1892 to 1992nm (the maximum output energy 1.8mJ was reached at 1952nm for absorbed pumping energy 78 mJ). In case of Tm:Ho:CaF2 laser tunability from 2016 to 2111nm was reached (the maximum output energy 1.5mJ was reached at 2083nm for absorbed pumping energy 53 mJ). Both these material are good candidates for a future investigation of high energy, ultra-short, laser pulse generation.

Genome-wide analysis of wheat calcium ATPases and potential role of selected ACAs and ECAs in calcium stress.

PubMed

Aslam, Roohi; Williams, Lorraine E; Bhatti, Muhammad Faraz; Virk, Nasar

2017-10-27

P 2 - type calcium ATPases (ACAs-auto inhibited calcium ATPases and ECAs-endoplasmic reticulum calcium ATPases) belong to the P- type ATPase family of active membrane transporters and are significantly involved in maintaining accurate levels of Ca 2+ , Mn 2+ and Zn 2+ in the cytosol as well as playing a very important role in stress signaling, stomatal opening and closing and pollen tube growth. Here we report the identification and possible role of some of these ATPases from wheat. In this study, ACA and ECA sequences of six species (belonging to Poaceae) were retrieved from different databases and a phylogenetic tree was constructed. A high degree of evolutionary relatedness was observed among P 2 sequences characterized in this study. Members of the respective groups from different plant species were observed to fall under the same clade. This pattern highlights the common ancestry of P 2- type calcium ATPases. Furthermore, qRT-PCR was used to analyse the expression of selected ACAs and ECAs from Triticum aestivum (wheat) under calcium toxicity and calcium deficiency. The data indicated that expression of ECAs is enhanced under calcium stress, suggesting possible roles of these ATPases in calcium homeostasis in wheat. Similarly, the expression of ACAs was significantly different in plants grown under calcium stress as compared to plants grown under control conditions. This gives clues to the role of ACAs in signal transduction during calcium stress in wheat. Here we concluded that wheat genome consists of nine P 2B and three P 2A -type calcium ATPases. Moreover, gene loss events in wheat ancestors lead to the loss of a particular homoeolog of a gene in wheat. To elaborate the role of these wheat ATPases, qRT-PCR was performed. The results indicated that when plants are exposed to calcium stress, both P 2A and P 2B gene expression get enhanced. This further gives clues about the possible role of these ATPases in wheat in calcium management. These findings can be useful in future for genetic manipulations as well as in wheat genome annotation process.

Near Heterophoria in Early Childhood

PubMed Central

Babinsky, Erin; Sreenivasan, Vidhyapriya; Candy, T. Rowan

2015-01-01

Purpose. The purpose of this study was to measure near heterophoria in young children to determine the impact of early growth and development on the alignment of the eyes. Methods. Fifty young children (≥2 and <7 years of age; range of spherical equivalent refractive error −1.25 diopters [D] to +3.75 D) and 13 adults participated. Their eye position and accommodation responses, in the absence of optical correction, were measured using simultaneous Purkinje image tracking and photorefraction technology (MCS PowerRefractor, PR). The resulting heterophorias, and both accommodative convergence/accommodation (AC/A) and convergence accommodation/convergence (CA/C) ratios were then computed as a function of age, refractive error, and an alternating cover test. Results. The mean heterophoria after approximately 60 seconds of dissociation at a 33-cm viewing distance was 5.0 prism diopters (pd) of exophoria (SD ± 3.7) in the children (78% of children > 2 pd exophoric) and 5.6 pd of exophoria (SD ± 4.7) in adults (69% of adults > 2pd exophoric; a nonsignificant difference), with no effect of age between 2 and 6 years. In these children, heterophoria was not significantly correlated with AC/A (r = 0.25), CA/C (r = 0.12), or refractive error (r = 0.21). The mean difference between heterophoria measurements from the PR and the clinical cover test was −2.4 pd (SD = ±3.4), with an exophoric bias in the PR measurements. Conclusions. Despite developmental maturation of interpupillary distance, refractive error, and AC/A, in a typical sample of young children the predominant dissociated position is one of exophoria. PMID:25634983

Intracellular calcium movements during relaxation and recovery of superfast muscle fibers of the toadfish swimbladder.

PubMed

Nelson, Frank E; Hollingworth, Stephen; Rome, Lawrence C; Baylor, Stephen M

2014-05-01

The mating call of the Atlantic toadfish is generated by bursts of high-frequency twitches of the superfast twitch fibers that surround the swimbladder. At 16°C, a calling period can last several hours, with individual 80-100-Hz calls lasting ∼ 500 ms interleaved with silent periods (intercall intervals) lasting ∼ 10 s. To understand the intracellular movements of Ca(2+) during the intercall intervals, superfast fibers were microinjected with fluo-4, a high-affinity fluorescent Ca(2+) indicator, and stimulated by trains of 40 action potentials at 83 Hz, which mimics fiber activity during calling. The fluo-4 fluorescence signal was measured during and after the stimulus trains; the signal was also simulated with a kinetic model of the underlying myoplasmic Ca(2+) movements, including the binding and transport of Ca(2+) by the sarcoplasmic reticulum (SR) Ca(2+) pumps. The estimated total amount of Ca(2+) released from the SR during a first stimulus train is ∼ 6.5 mM (concentration referred to the myoplasmic water volume). At 40 ms after cessation of stimulation, the myoplasmic free Ca(2+) concentration ([Ca(2+)]) is below the threshold for force generation (∼ 3 µM), yet the estimated concentration of released Ca(2+) remaining in the myoplasm (Δ[CaM]) is large, ∼ 5 mM, with ∼ 80% bound to parvalbumin. At 10 s after stimulation, [Ca(2+)] is ∼ 90 nM (three times the assumed resting level) and Δ[CaM] is ∼ 1.3 mM, with 97% bound to parvalbumin. Ca(2+) movements during the intercall interval thus appear to be strongly influenced by (a) the accumulation of Ca(2+) on parvalbumin and (b) the slow rate of Ca(2+) pumping that ensues when parvalbumin lowers [Ca(2+)] near the resting level. With repetitive stimulus trains initiated at 10-s intervals, Ca(2+) release and pumping come quickly into balance as a result of the stability (negative feedback) supplied by the increased rate of Ca(2+) pumping at higher [Ca(2+)].

Minocycline neuroprotection in a rat model of asphyxial cardiac arrest is limited.

PubMed

Keilhoff, Gerburg; Schweizer, Hannes; John, Robin; Langnaese, Kristina; Ebmeyer, Uwe

2011-03-01

The study investigated a possible neuroprotective potency of minocycline in an experimental asphyxial cardiac arrest (ACA) rat model. Clinically important survival times were evaluated thus broadening common experimental approaches. Adult rats were subjected to 5 min of ACA followed by resuscitation. There were two main treatment groups: ACA and sham operated. Relating to minocycline treatment each group consisted of three sub-groups: pre-, post-, and sans-mino, with three different survival times: 4, 7, and 21 days. Neurodegeneration and microgliosis were monitored by immunohistochemistry. Alterations of microglia-associated gene expression were analyzed by quantitative RT-PCR. ACA induced massive nerve cell loss and activation of microglia/macrophages in hippocampal CA1 cell layer intensifying with survival time. After 7 days, minocycline significantly decreased both, neuronal degeneration and microglia response in dependence on the application pattern; application post ACA was most effective. After 21 days, neuroprotective effects of minocycline were lost. ACA significantly induced expression of the microglia-associated factors Ccl2, CD45, Mac-1, F4-80, and Tnfa. Independent on survival time, minocycline affected these parameters not significantly. Expression of iNOS was unaffected by both, ACA and minocycline. In adult rat hippocampus microglia was significantly activated by ACA. Minocycline positive affected neuronal survival and microglial response temporary, even when applied up to 18 h after ACA, thus defining a therapeutically-relevant time window. As ACA-induced neuronal cell death involves acute and delayed events, longer minocycline intervention targeting also secondary injury cascades should manifest neuroprotective potency, a question to be answered by further experiments. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Suppression of the endoplasmic reticulum calcium pump during zebrafish gastrulation affects left-right asymmetry of the heart and brain.

PubMed

Kreiling, Jill A; Balantac, Zaneta L; Crawford, Andrew R; Ren, Yuexin; Toure, Jamal; Zchut, Sigalit; Kochilas, Lazaros; Creton, Robbert

2008-01-01

Vertebrate embryos generate striking Ca(2+) patterns, which are unique regulators of dynamic developmental events. In the present study, we used zebrafish embryos as a model system to examine the developmental roles of Ca(2+) during gastrulation. We found that gastrula stage embryos maintain a distinct pattern of cytosolic Ca(2+) along the dorsal-ventral axis, with higher Ca(2+) concentrations in the ventral margin and lower Ca(2+) concentrations in the dorsal margin and dorsal forerunner cells. Suppression of the endoplasmic reticulum Ca(2+) pump with 0.5 microM thapsigargin elevates cytosolic Ca(2+) in all embryonic regions and induces a randomization of laterality in the heart and brain. Affected hearts, visualized in living embryos by a subtractive imaging technique, displayed either a reversal or loss of left-right asymmetry. Brain defects include a left-right reversal of pitx2 expression in the dorsal diencephalon and a left-right reversal of the prominent habenular nucleus in the brain. Embryos are sensitive to inhibition of the endoplasmic reticulum Ca(2+) pump during early and mid gastrulation and lose their sensitivity during late gastrulation and early segmentation. Suppression of the endoplasmic reticulum Ca(2+) pump during gastrulation inhibits expression of no tail (ntl) and left-right dynein related (lrdr) in the dorsal forerunner cells and affects development of Kupffer's vesicle, a ciliated organ that generates a counter-clockwise flow of fluid. Previous studies have shown that Ca(2+) plays a role in Kupffer's vesicle function, influencing ciliary motility and translating the vesicle's counter-clockwise flow into asymmetric patterns of gene expression. The present results suggest that Ca(2+) plays an additional role in the formation of Kupffer's vesicle.

Effect of ADP on slow-twitch muscle fibres of the rat: implications for muscle fatigue

PubMed Central

Macdonald, W A; Stephenson, D G

2006-01-01

Slow-twitch mechanically skinned fibres from rat soleus muscle were bathed in solutions mimicking the myoplasmic environment but containing different [ADP] (0.1 μm to 1.0 mm). The effect of ADP on sarcoplasmic reticulum (SR) Ca2+-content was determined from the magnitude of caffeine-induced force responses, while temporal changes in SR Ca2+-content allowed determination of the effective rates of the SR Ca2+-pump and of the SR Ca2+-leak. The SR Ca2+-pump rate, estimated at pCa (−log10[Ca2+]) 7.8, was reduced by 20% as the [ADP] was increased from 0.1 to 40 μm, with no further alteration when the [ADP] was increased to 1.0 mm. The SR Ca2+-leak rate constant was not altered by increasing [ADP] from 0.1 to 40 μm, but was increased by 26% when the [ADP] was elevated to 1.0 mm. This ADP-induced SR Ca2+-leak was insensitive to ruthenium red but was abolished by 2,5-di(tert-butyl)-1,4-hydroquinone (TBQ), indicating that the leak pathway is via the SR Ca2+-pump and not the SR Ca2+-release channel. The decrease in SR Ca2+-pump rate and SR Ca2+-leak rate when [ADP] was increased led to a 40% decrease in SR Ca2+-loading capacity. Elevation of [ADP] had only minor direct effects on the contractile apparatus of slow-twitch fibres. These results suggest that ADP has only limited depressing effects on the contractility of slow-twitch muscle fibres. This is in contrast to the marked effects of ADP on force responses in fast-twitch muscle fibres and may contribute to the fatigue-resistant nature of slow-twitch muscle fibres. PMID:16556653

Airport Landside. Volume II. The Airport Landside Simulation Model (ALSIM) Description and Users Guide.

DTIC Science & Technology

1982-06-01

liii i i E-- .!ju a’sh " al !i 1. 5535 U, ;, , ,i l 0i I-J I I l l l l . . .... . . .. . .. i TABLE OF CONTENTS Section Page 1. INTRODUCTION...1Mti34S.GATZa34.SAGal?.tNTut.- ARY PLTPI~s9lO,ACaII. PAXvITI .TPAX.,I. AftRLNu9*T!M~vl1t4,GAT~u?1, SAGeS, ARRY FLT?4Ca3O,ACv74?.PAXw36S.TPAA.GO. AzIf ...tKTsl.PAX*T7. ,PA~fG. AIRLtZNuI2.TtIMEUli2I.SAGai7.0AT1522. ACmg. AMR PL’ axI2.4Tat .PAAa2Q0.TPAXsO. AlRLl~s12.TIMEnt240.IA~ al ?.GAr~o25, ACaI. ARR

Calcium Efflux Systems in Stress Signaling and Adaptation in Plants

PubMed Central

Bose, Jayakumar; Pottosin, Igor I.; Shabala, Stanislav S.; Palmgren, Michael G.; Shabala, Sergey

2011-01-01

Transient cytosolic calcium ([Ca2+]cyt) elevation is an ubiquitous denominator of the signaling network when plants are exposed to literally every known abiotic and biotic stress. These stress-induced [Ca2+]cyt elevations vary in magnitude, frequency, and shape, depending on the severity of the stress as well the type of stress experienced. This creates a unique stress-specific calcium “signature” that is then decoded by signal transduction networks. While most published papers have been focused predominantly on the role of Ca2+ influx mechanisms to shaping [Ca2+]cyt signatures, restoration of the basal [Ca2+]cyt levels is impossible without both cytosolic Ca2+ buffering and efficient Ca2+ efflux mechanisms removing excess Ca2+ from cytosol, to reload Ca2+ stores and to terminate Ca2+ signaling. This is the topic of the current review. The molecular identity of two major types of Ca2+ efflux systems, Ca2+-ATPase pumps and Ca2+/H+ exchangers, is described, and their regulatory modes are analyzed in detail. The spatial and temporal organization of calcium signaling networks is described, and the importance of existence of intracellular calcium microdomains is discussed. Experimental evidence for the role of Ca2+ efflux systems in plant responses to a range of abiotic and biotic factors is summarized. Contribution of Ca2+-ATPase pumps and Ca2+/H+ exchangers in shaping [Ca2+]cyt signatures is then modeled by using a four-component model (plasma- and endo-membrane-based Ca2+-permeable channels and efflux systems) taking into account the cytosolic Ca2+ buffering. It is concluded that physiologically relevant variations in the activity of Ca2+-ATPase pumps and Ca2+/H+ exchangers are sufficient to fully describe all the reported experimental evidence and determine the shape of [Ca2+]cyt signatures in response to environmental stimuli, emphasizing the crucial role these active efflux systems play in plant adaptive responses to environment. PMID:22639615

Stereoscopic Viewing Can Induce Changes in the CA/C Ratio.

PubMed

Neveu, Pascaline; Roumes, Corinne; Philippe, Matthieu; Fuchs, Philippe; Priot, Anne-Emmanuelle

2016-08-01

Stereoscopic displays challenge the neural cross-coupling between accommodation and vergence by inducing a constant accommodative demand and a varying vergence demand. Stereoscopic viewing calls for a decrease in the gain of vergence accommodation, which is the accommodation caused by vergence, quantified by using the convergence-accommodation to convergence (CA/C) ratio. However, its adaptability is still a subject of debate. Cross-coupling (CA/C and AC/A ratios) and tonic components of vergence and accommodation were assessed in 12 participants (27.5 ± 5 years, stereoacuity better than 60 arc seconds, 6/6 acuity with corrected refractive error) before and after a 20-minute exposure to stereoscopic viewing. During stimulation, vergence demand oscillated from 1 to 3 meter angles along a virtual sagittal line in sinusoidal movements, while accommodative demand was fixed at 1.5 diopters. Results showed a decreased CA/C ratio (-10.36%, df = 10, t = 2.835, P = 0.018), with no change in the AC/A ratio (P = 0.090), tonic vergence (P = 0.708), and tonic accommodation (P = 0.493). These findings demonstrated that the CA/C ratio can exhibit adaptive adjustments. The observed nature and amount of the oculomotor modification failed to compensate for the stereoscopic constraint.

Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish

PubMed Central

Harwood, Claire L; Young, Iain S; Tikunov, Boris A; Hollingworth, Stephen; Baylor, Stephen M; Rome, Lawrence C

2011-01-01

Abstract Superfast fibres of toadfish swimbladder muscle generate a series of superfast Ca2+ transients, a necessity for high-frequency calling. How is this accomplished with a relatively low rate of Ca2+ pumping by the sarcoplasmic reticulum (SR)? We hypothesized that there may not be complete Ca2+ saturation and desaturation of the troponin Ca2+ regulatory sites with each twitch during calling. To test this, we determined the number of regulatory sites by measuring the concentration of troponin C (TNC) molecules, 33.8 μmol per kg wet weight. We then estimated how much SR Ca2+ is released per twitch by measuring the recovery oxygen consumption in the presence of a crossbridge blocker, N-benzyl-p-toluene sulphonamide (BTS). The results agreed closely with SR release estimates obtained with a kinetic model used to analyse Ca2+ transient measurements. We found that 235 μmol of Ca2+ per kg muscle is released with the first twitch of an 80 Hz stimulus (15oC). Release per twitch declines dramatically thereafter such that by the 10th twitch release is only 48 μmol kg−1 (well below the concentration of TNC Ca2+ regulatory sites, 67.6 μmol kg−1). The ATP usage per twitch by the myosin crossbridges remains essentially constant at ∼25 μmol kg−1 throughout the stimulus period. Hence, for the first twitch, ∼80% of the energy goes into pumping Ca2+ (which uses 1 ATP per 2 Ca2+ ions pumped), but by the 10th and subsequent twitches the proportion is ∼50%. Even though by the 10th stimulus the Ca2+ release per twitch has dropped 5-fold, the Ca2+ remaining in the SR has declined by only ∼18%; hence dwindling SR Ca2+ content is not responsible for the drop. Rather, inactivation of the Ca2+ release channel by myoplasmic Ca2+ likely explains this reduction. If inactivation did not occur, the SR would run out of Ca2+ well before the end of even a 40-twitch call. Hence, inactivation of the Ca2+ release channel plays a critical role in swimbladder muscle during normal in vivo function. PMID:21946852

Cell-Wall-Bound Proteinase of Lactobacillus delbrueckii subsp. lactis ACA-DC 178: Characterization and Specificity for β-Casein

PubMed Central

Tsakalidou, E.; Anastasiou, R.; Vandenberghe, I.; van Beeumen, J.; Kalantzopoulos, G.

1999-01-01

Lactobacillus delbrueckii subsp. lactis ACA-DC 178, which was isolated from Greek Kasseri cheese, produces a cell-wall-bound proteinase. The proteinase was removed from the cell envelope by washing the cells with a Ca2+-free buffer. The crude proteinase extract shows its highest activity at pH 6.0 and 40°C. It is inhibited by phenylmethylsulfonyl fluoride, showing that the enzyme is a serine-type proteinase. Considering the substrate specificity, the enzyme is similar to the lactococcal PI-type proteinases, since it hydrolyzes β-casein mainly and α- and κ-caseins to a much lesser extent. The cell-wall-bound proteinase from L. delbrueckii subsp. lactis ACA-DC 178 liberates four main peptides from β-casein, which have been identified. PMID:10223997

Diode-pumped femtosecond mode-locked Nd, Y-codoped CaF2 laser

NASA Astrophysics Data System (ADS)

Zhu, Jiangfeng; Zhang, Lijuan; Gao, Ziye; Wang, Junli; Wang, Zhaohua; Su, Liangbi; Zheng, Lihe; Wang, Jingya; Xu, Jun; Wei, Zhiyi

2015-03-01

A passively mode-locked femtosecond laser based on an Nd, Y-codoped CaF2 disordered crystal was demonstrated. The Y3+-codoping in Nd : CaF2 markedly suppressed the quenching effect and improved the fluorescence quantum efficiency and emission spectra. With a fiber-coupled laser diode as the pump source, the continuous wave tuning range covering from 1042 to 1076 nm was realized, while the mode-locked operation generated 264 fs pulses with an average output power of 180 mW at a repetition rate of 85 MHz. The experimental results show that the Nd, Y-codoped CaF2 disordered crystal has potential in a new generation diode-pumped high repetition rate chirped pulse amplifier.

Anesthesia specific differences in a cardio-pulmonary resuscitation rat model; halothane versus sevoflurane.

PubMed

Esser, Torben; Keilhoff, Gerburg; Ebmeyer, Uwe

2016-12-01

Our asphyxia cardiac arrest (ACA) rat model is well established. The original model was designed in the 1990th using halothane and nitrous oxide for pre-insult anesthesia. Because of its hepato-toxicity and its potential to induce severe liver failures, halothane is no longer used in clinical anesthesia for several years. In order to minimize the health risk for our laboratory staff as well as to keep the experimental settings of our model on a clinically oriented basis we decided to replace halothane by sevoflurane. In this study we intended to determine if the change of the narcotic gas regiment causes changes in the neurological damage and how far our model had to be adjusted. Adult rats were subjected to 5min of ACA followed by resuscitation. There were four treatment groups: ACA - halothane, ACA - sevoflurane and with halothane or sevoflurane sham operated animals. Vital and blood parameters were monitored during the 45min post-resuscitation intensive care phase. After a survival time of 7 days histological evaluation of the hippocampus was performed. We observed that resuscitated rats anesthetized prior by sevoflurane (i) have had a lower heart rate and a higher MAP compared to halothane anesthetized animals; (ii) The neurological damaged were significantly reduced in the hippocampal CA1 region in sevoflurane treated rats. Using sevoflurane instead of halothane for anesthesia requires some physiological and experimental changes. However the model keeps its validity. Sevoflurane caused less pronounced neurodegeneration in the CA1 region of the hippocampus. This had to be considered in further resuscitation-studies containing sevoflurane as anesthetic. Institutional protocol number for animal studies: 42502-2-2-947 Uni MD. Copyright © 2016 Elsevier B.V. All rights reserved.

The influence of interactions between accommodation and convergence on the lag of accommodation.

PubMed

Schor, C

1999-03-01

Several models of myopia predict that growth of axial length is stimulated by blur. Accommodative lag has been suggested as an important source of blur in the development of myopia and this study has modeled how cross-link interactions between accommodation and convergence might interact with uncorrected distance heterophoria and refractive error to influence accommodative lag. Accommodative lag was simulated with two models of interactions between accommodation and convergence (one with and one without adaptable tonic elements). Simulations of both models indicate that both uncorrected hyperopia and esophoria increase the lag of accommodative and uncorrected myopia and exophoria decrease the lag or introduce a lead of accommodation in response to the near (40 cm) stimulus. These effects were increased when gain of either cross-link, accommodative convergence (AC/A) or convergence accommodation (CA/C), was increased within a moderate range of values while the other was fixed at a normal value (clamped condition). These effects were exaggerated when both the AC/A and CA/C ratios were increased (covaried condition) and affects of cross-link gain were negated when an increase of one cross-link (e.g. AC/A) was accompanied by a reduction of the other cross-link (e.g. CA/C) (reciprocal condition). The inclusion of tonic adaptation in the model reduced steady state errors of accommodation for all conditions except when the AC/A ratio was very high (2 MA/D). Combinations of cross-link interactions between accommodation and convergence that resemble either clamped or reciprocal patterns occur naturally in clinical populations. Simulations suggest that these two patterns of abnormal cross-link interactions could affect the progression of myopia differently. Adaptable tonic accommodation and tonic vergence could potentially reduce the progression of myopia by reducing the lag of accommodation.

The NADPH oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+ pump

PubMed Central

Tazzeo, T; Worek, F; Janssen, LJ

2009-01-01

Background and purpose: Diphenyleneiodonium (DPI) is often used as an NADPH oxidase inhibitor, but is increasingly being found to have unrelated side effects. We investigated its effects on smooth muscle contractions and the related mechanisms. Experimental approach: We studied isometric contractions in smooth muscle strips from bovine trachea. Cholinesterase activity was measured using a spectrophotometric assay; internal Ca2+ pump activity was assessed by Ca2+ uptake into smooth muscle microsomes. Key results: Contractions to acetylcholine were markedly enhanced by DPI (10−4 M), whereas those to carbachol (CCh) were not, suggesting a possible inhibition of cholinesterase. DPI markedly suppressed contractions evoked by CCh, KCl and 5-HT, and also unmasked phasic activity in otherwise sustained responses. Direct biochemical assays confirmed that DPI was a potent inhibitor of acetylcholinesterase and butyrylcholinesterase (IC50∼8 × 10−6 M and 6 × 10−7 M, respectively), following a readily reversible, mixed non-competitive type of inhibition. The inhibitory effects of DPI on CCh contractions were not mimicked by another NADPH oxidase inhibitor (apocynin), nor the Src inhibitors PP1 or PP2, ruling out an action through the NADPH oxidase signalling pathway. Several features of the DPI-mediated suppression of agonist-evoked responses (i.e. suppression of peak magnitudes and unmasking of phasic activity) are similar to those of cyclopiazonic acid, an inhibitor of the internal Ca2+ pump. Direct measurement of microsomal Ca2+ uptake revealed that DPI modestly inhibits the internal Ca2+ pump. Conclusions and implications: DPI inhibits cholinesterase activity and the internal Ca2+ pump in tracheal smooth muscle. PMID:19788497

Convergence accommodation to convergence (CA/C) ratio in patients with intermittent exotropia and decompensated exophoria.

PubMed

Nonaka, Fumitaka; Hasebe, Satoshi; Ohtsuki, Hiroshi

2004-01-01

To evaluate the convergence accommodation to convergence (CA/C) ratio in strabismic patients and to clarify its clinical implications. Seventy-eight consecutive patients (mean age: 12.9 +/- 6.0 years) with intermittent exotropia and decompensated exophoria who showed binocular fusion at least at near viewing were recruited. The CA/C ratio was estimated by measuring accommodative responses induced by horizontal prisms with different magnitudes under accommodation feedback open-loop conditions. The CA/C ratios were compared with accommodative convergence to accommodation (AC/A) ratios and other clinical parameters. A linear regression analysis indicated that the mean (+/-SD) CA/C ratio was 0.080 +/- 0.043 D/prism diopter or 0.48 +/- 0.26 D/meter angle. There was no inverse or reciprocal relationship between CA/C and AC/A ratios. The patients with lower CA/C ratios tended to have smaller tonic accommodation under binocular viewing conditions and larger exodeviation at near viewing. The CA/C ratio, like the AC/A ratio, is an independent parameter that characterizes clinical features. A lower CA/C may be beneficial for the vergence control system to compensate for ocular misalignment with minimum degradation of accommodation accuracy.

Ca2+ transport in plant cells and mechanisms of transformation of phytochrome-induced photosignals

NASA Astrophysics Data System (ADS)

Volotovski, Igor D.

1995-01-01

The recent data on the influence of phytochrome on the efficiency of Ca2+ translocation across the membranes of oat protoplasts are given. Ca2+ uptake in the protoplasts was shown to be influenced by the red light (R) illumination. This effect was reverted by the following far-red light (FR) illumination. To elucidate the sensitivity to phytochrome-controlling action the screening between the mechanisms of Ca2+ transport across the plasma membranes of oat protoplasts, Na+/Ca2+ and Ca2+/H+ exchangers, Ca2+-pump and Ca2+-channel was done. It was established that phytochrome modulated the activity of Na+/Ca2+-exchanger and Ca2+-pump. The light-mediated oscillations of cytoplasmic Ca2+ concentration in the oat protoplasts were demonstrated using fluorescence probe quin2 loaded into the cells and laser monitoring of fluorescence signal. The evidences were obtained that the oscillations were not the result of the elevation of cytoplasmic Ca2+ concentration and had no connection with Ca2+ pool of mitochondria. The possibility of the relation between the Ca2+ oscillations and phosphoinositide metabolism in plant cell membranes is analyzed. The mechanisms of transformation of primary phytochrome signal into biological effects were discussed.

Effects of elevated physiological temperatures on sarcoplasmic reticulum function in mechanically skinned muscle fibers of the rat.

PubMed

van der Poel, C; Stephenson, D G

2007-07-01

Properties of the sarcoplasmic reticulum (SR) with respect to Ca(2+) loading and release were measured in mechanically skinned fiber preparations from isolated extensor digitorum longus (EDL) muscles of the rat that were either kept at room temperature (23 degrees C) or exposed to temperatures in the upper physiological range for mammalian skeletal muscle (30 min at 40 or 43 degrees C). The ability of the SR to accumulate Ca(2+) was significantly reduced by a factor of 1.9-2.1 after the temperature treatments due to a marked increase in SR Ca(2+) leak, which persisted for at least 3 h after treatment. Results with blockers of Ca(2+) release channels (ruthenium red) and SR Ca(2+) pumps [2,5-di(tert-butyl)-1,4-hydroquinone] indicate that the increased Ca(2+) leak was not through the SR Ca(2+) release channel or the SR Ca(2+) pump, although it is possible that the leak pathway was via oligomerized Ca(2+) pump molecules. No significant change in the maximum SR Ca(2+)-ATPase activity was observed after the temperature treatment, although there was a tendency for a decrease in the SR Ca(2+)-ATPase. The observed changes in SR properties were fully prevented by the superoxide (O(2)(*-)) scavenger Tiron (20 mM), indicating that the production of O(2)(*-) at elevated temperatures is responsible for the increase in SR Ca(2+) leak. Results show that physiologically relevant elevated temperatures 1) induce lasting changes in SR properties with respect to Ca(2+) handling that contribute to a marked increase in the SR Ca(2+) leak and, consequently, to the reduction in the average coupling ratio between Ca(2+) transport and SR Ca(2+)-ATPase and muscle performance, and 2) that these changes are mediated by temperature-induced O(2)(*-) production.

Synthesis, crystal structure, and magnetism of A 2Co 12As 7 (A=Ca, Y, Ce–Yb)

DOE PAGES

Tan, Xiaoyan; Ovidiu Garlea, V.; Chai, Ping; ...

2015-08-28

In this study, ternary intermetallics, A 2Co 12As 7 (A=Ca, Y, Ce–Yb), have been synthesized by annealing mixtures of elements in molten Bi at 1223 K. The materials obtained crystallize in the P6 3/m variant of the Zr 2Fe 12P 7 structure type. The unit cell volume shows a monotonic decrease with the increasing atomic number of the rare-earth metal, with the exception of Ce-, Eu-, and Yb-containing compounds. An examination of these outliers with X-ray absorption near edge structures (XANES) spectroscopy revealed mixed valence of Ce, Eu, and Yb, with the average oxidation states of +3.20(1), +2.47(5), and +2.91(1),more » respectively, at room temperature. Magnetic behavior of A 2Co 12As 7 is generally characterized by ferromagnetic ordering of Co 3d moments at 100–140 K, followed by low-temperature ordering of rare-earth 4f moments. The 3d-4f magnetic coupling changes from antiferromagnetic for A=Pr–Sm to ferromagnetic for A=Ce and Eu–Yb. Finally, polarized neutron scattering experiments were performed to support the postulated ferro- and ferrimagnetic ground states for Ce 2Co 12As 7 and Nd 2Co 12As 7, respectively.« less

Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile systems for fine-tuning cellular Ca(2.).

PubMed

Strehler, Emanuel E

2015-04-24

The plasma membrane calcium ATPases (PMCAs) are ATP-driven primary ion pumps found in all eukaryotic cells. They are the major high-affinity calcium extrusion system for expulsion of Ca(2+) ions from the cytosol and help restore the low resting levels of intracellular [Ca(2+)] following the temporary elevation of Ca(2+) generated during Ca(2+) signaling. Due to their essential role in the maintenance of cellular Ca(2+) homeostasis they were initially thought to be "sump pumps" for Ca(2+) removal needed by all cells to avoid eventual calcium overload. The discovery of multiple PMCA isoforms and alternatively spliced variants cast doubt on this simplistic assumption, and revealed instead that PMCAs are integral components of highly regulated multi-protein complexes fulfilling specific roles in calcium-dependent signaling originating at the plasma membrane. Biochemical, genetic, and physiological studies in gene-manipulated and mutant animals demonstrate the important role played by specific PMCAs in distinct diseases including those affecting the peripheral and central nervous system, cardiovascular disease, and osteoporosis. Human PMCA gene mutations and allelic variants associated with specific disorders continue to be discovered and underline the crucial role of different PMCAs in particular cells, tissues and organs. Copyright © 2015 Elsevier Inc. All rights reserved.

The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump.

PubMed

Bennekou, P; Kristensen, B I; Christophersen, P

2003-09-01

The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow ( t(1/2) about 30 s), whereas the deactivation was fast ( t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl(-) concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca(2+) influx via the cation channel and ensuing efflux via the Ca(2+) pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca(2+) pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

Activation of TRPM2 and TRPV1 Channels in Dorsal Root Ganglion by NADPH Oxidase and Protein Kinase C Molecular Pathways: a Patch Clamp Study.

PubMed

Nazıroğlu, Mustafa

2017-03-01

Despite considerable research, the mechanisms of neuropathic pain induced by excessive oxidative stress production and overload calcium ion (Ca 2+ ) entry in dorsal root ganglion (DRG) remain substantially unidentified. The transient receptor potential melastatin 2 (TRPM2) and vanilloid 1 (TRPV1) channels are activated with different stimuli including oxidative stress. TRPM2 and TRPV1 have been shown to be involved in induction of neuropathic pain. However, the activation mechanisms of TRPM2 and TRPV1 via NADPH oxidase and protein kinase C (PKC) pathways are poorly understood. In this study, I investigated the roles of NADPH oxidase and PKC on Ca 2+ entry through TRPM2 and TRPV1 channels in in vitro DRG neurons of rats. Rat DRG neurons were used in whole-cell patch clamp experiments. The H 2 O 2 -induced TRPM2 current densities were decreased by N-(p-amylcinnamoyl)anthranilic acid (ACA), and dose-dependent capsaicin (CAP) and H 2 O 2 -induced TRPV1 currents were inhibited by capsazepine (CPZ). The TRPV1 channel is activated in the DRG neurons by 0.01 mM capsaicin but not 0.001 mM or 0.05 mM capsaicin. TRPM2 and TRPV1 currents were increased by the PKC activator, phorbol myristate acetate (PMA), although the currents were decreased by ACA, CPZ, and the PKC inhibitor, bisindolylmaleimide I (BIM). Both channel currents were further increased by PMA + H 2 O 2 as compared to H 2 O 2 only. In the combined presence of PMA + BIM, no TRPM2 or TRPV1 currents were observed. The CAP and H 2 O 2 -induced TRPM2 current densities were also decreased by the NADPH oxidase inhibitors apocynin and N-Acetylcysteine. In conclusion, these results demonstrate a protective role for NADPH oxidase and PKC inhibitors on Ca 2+ entry through TRPM2 and TRPV1 channels in DRG neurons. Since excessive oxidative stress production and Ca 2+ entry are implicated in the pathophysiology of neuropathic pain, the findings may be relevant to the etiology and treatment of neuropathology in DRG neurons.

Role of different types of Ca2+ channels and a reticulum-like Ca2+ pump in neurotransmitter release.

PubMed

Fossier, P; Baux, G; Tauc, L

1993-01-01

The factors controlling the Ca2+ concentration directly responsible for triggering acetylcholine (ACh) release were investigated at an identified neuro-neuronal synapse of the Aplysia buccal ganglion. The types of presynaptic voltage-gated Ca2+ channels associated with transmitter release were determined by using selective blockers such as nifedipine, omega-conotoxin and a partially purified extract from the venom of a funnel web spider (FTx). L-type, N-type and P-type Ca2+ channels are present in the presynaptic neuron. The influx of Ca2+ through both N- and P-types induces the release of ACh whereas Ca2+ flowing through L-type channels modulates the duration of the presynaptic action potential by controlling the Ca(2+)-dependent K+ current. tBuBHQ, a blocker of the reticulum Ca2+ pump, induces a potentiation of evoked release without modifying the presynaptic Ca2+ influx. This seems to indicate that a part of the Ca2+ entering the presynaptic terminal through N- and P-type Ca2+ channels is sequestered in a presynaptic reticulum-like Ca2+ buffer preventing these ions from contributing to ACh release. To exert its control, this Ca2+ buffer must be located close to both the presynaptic Ca2+ channels and the transmitter release mechanism.

Motion of the Ca2+-pump captured.

PubMed

Yokokawa, Masatoshi; Takeyasu, Kunio

2011-09-01

Studies of ion pumps, such as ATP synthetase and Ca(2+)-ATPase, have a long history. The crystal structures of several kinds of ion pump have been resolved, and provide static pictures of mechanisms of ion transport. In this study, using fast-scanning atomic force microscopy, we have visualized conformational changes in the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) in real time at the single-molecule level. The analyses of individual SERCA molecules in the presence of both ATP and free Ca(2+) revealed up-down structural changes corresponding to the Albers-Post scheme. This fluctuation was strongly affected by the ATP and Ca(2+) concentrations, and was prevented by an inhibitor, thapsigargin. Interestingly, at a physiological ATP concentrations, the up-down motion disappeared completely. These results indicate that SERCA does not transit through the shortest structure, and has a catalytic pathway different from the ordinary Albers-Post scheme under physiological conditions. © 2011 The Authors Journal compilation © 2011 FEBS.

The Ins and Outs of Cellular Ca2+ Transport

PubMed Central

Spalding, Edgar P.; Harper, Jeffrey F.

2011-01-01

The cytoplasmic Ca2+ signals that participate in nearly all aspects of plant growth and development encode information as binary switches or information-rich signatures. They are the result of influx (thermodynamically passive) and efflux (thermodynamically active) activities mediated by membrane transport proteins. On the influx side, confirming the molecular identities of Ca2+-permeable channels is still a major research topic. Cyclic nucleotide-gated channels and glutamate receptor-like channels are candidates well supported by evidence. On the efflux side, CAX antiporters and P-type ATPase pumps are the principal molecular entities. Both of these active transporters load Ca2+ into specific compartments and have the potential to reduce the magnitude and duration of a Ca2+ transient. Recent studies indicate calmodulin-activated Ca2+ pumps in endomembrane systems can dampen the magnitude and duration of a Ca2+ transient that could otherwise grow into a Ca2+ cell-death signature. An important challenge following molecular characterization of the influx and efflux pathways is to understand how they are coordinately regulated to produce a Ca2+ switch or encode specific information into a Ca2+ signature. PMID:21865080

The erythrocyte calcium pump is inhibited by non-enzymic glycation: studies in situ and with the purified enzyme.

PubMed Central

González Flecha, F L; Castello, P R; Caride, A J; Gagliardino, J J; Rossi, J P

1993-01-01

In a previous paper we demonstrated that incubation of either intact erythrocytes or erythrocytes membranes with glucose decreases the activity of the membrane Ca(2+)-ATPase [González Flecha, Bermúdez, Cédola, Gagliardino and Rossi (1990) Diabetes 39, 707-711]. The aim of the present work was to obtain information about the mechanism of this inhibition. For this purpose, experiments were carried out with purified Ca(2+)-ATPase, inside-out vesicles and membranes from human erythrocytes. Incubation of the purified Ca(2+)-ATPase with glucose led to a decay in the enzyme activity of up to 50% of the control activity under the conditions used. The decrease in ATPase activity was concomitant with labelling by [6-3H]glucose of the purified Ca2+ pump; the kinetic properties of both processes were almost identical, suggesting that inhibition is a consequence of the incorporation of glucose into the Ca(2+)-ATPase molecule. In inside-out vesicles, glucose also promoted inhibition of Ca(2+)-ATPase activity as well as of active Ca2+ transport. Arabinose, xylose, mannose, ribose, fructose and glucose 6-phosphate (but not mannitol) were also able to inactive the ATPase. The activation energy for both the decrease in ATPase activity by glucose and the labelling of the pump with [6-3H]glucose was about 65 kJ/mol. Furthermore, inorganic phosphate enhanced the inactivation of the Ca(2+)-ATPase by glucose. This evidence strongly suggests that inhibition is a non-enzymically catalysed process. Inactivation of the Ca(2+)-ATPase by glucose was enhanced by reductive alkylation with sodium borohydride. Aminoguanidine, an inhibitor of the formation of the advanced end products of glycosylation, did not prevent the deleterious effect of glucose on the enzyme activity. Therefore it is concluded that inactivation of the Ca2+ pump is a consequence of the glycation of this protein. PMID:8393658

Exchangers man the pumps

PubMed Central

Barkla, Bronwyn J; Hirschi, Kendal D

2008-01-01

Tonoplast-localised proton-coupled Ca2+ transporters encoded by cation/H+ exchanger (CAX) genes play a critical role in sequestering Ca2+ into the vacuole. These transporters may function in coordination with Ca2+ release channels, to shape stimulus-induced cytosolic Ca2+ elevations. Recent analysis of Arabidopsis CAX knockout mutants, particularly cax1 and cax3, identified a variety of phenotypes including sensitivity to abiotic stresses, which indicated that these transporters might play a role in mediating the plant's stress response. A common feature of these mutants was the perturbation of H+-ATPase activity at both the tonoplast and the plasma membrane, suggesting a tight interplay between the Ca2+/H+ exchangers and H+ pumps. We speculate that indirect regulation of proton flux by the exchangers may be as important as the direct regulation of Ca2+ flux. These results suggest cautious interpretation of mutant Ca2+/H+ exchanger phenotypes that may be due to either perturbed Ca2+ or H+ transport. PMID:19841670

Calcium Pumps and Interacting BON1 Protein Modulate Calcium Signature, Stomatal Closure, and Plant Immunity1[OPEN

PubMed Central

Bao, Yongmei; Yang, Ziyuan; Yu, Huiyun; Li, Yun; Wang, Shu; Zou, Baohong; Xu, Dachao; Ma, Zhiqi

2017-01-01

Calcium signaling is essential for environmental responses including immune responses. Here, we provide evidence that the evolutionarily conserved protein BONZAI1 (BON1) functions together with autoinhibited calcium ATPase10 (ACA10) and ACA8 to regulate calcium signals in Arabidopsis. BON1 is a plasma membrane localized protein that negatively regulates the expression of immune receptor genes and positively regulates stomatal closure. We found that BON1 interacts with the autoinhibitory domains of ACA10 and ACA8, and the aca10 loss-of-function (LOF) mutants have an autoimmune phenotype similar to that of the bon1 LOF mutants. Genetic evidences indicate that BON1 positively regulates the activities of ACA10 and ACA8. Consistent with this idea, the steady level of calcium concentration is increased in both aca10 and bon1 mutants. Most strikingly, cytosolic calcium oscillation imposed by external calcium treatment was altered in aca10, aca8, and bon1 mutants in guard cells. In addition, calcium- and pathogen-induced stomatal closure was compromised in the aca10 and bon1 mutants. Taken together, this study indicates that ACA10/8 and BON1 physically interact on plasma membrane and function in the generation of cytosol calcium signatures that are critical for stomatal movement and impact plant immunity. PMID:28701352

A simple biomineralization model to explain Li, Mg, and Sr incorporation into aragonitic foraminifera and corals

NASA Astrophysics Data System (ADS)

Marchitto, T. M.; Bryan, S. P.; Doss, W.; McCulloch, M. T.; Montagna, P.

2018-01-01

In contrast to Li/Ca and Mg/Ca, Li/Mg is strongly anticorrelated with temperature in aragonites precipitated by the benthic foraminifer Hoeglundina elegans and a wide range of scleractinian coral taxa. We propose a simple conceptual model of biomineralization that explains this pattern and is consistent with available abiotic aragonite partition coefficients. Under this model the organism actively modifies seawater within its calcification pool by raising its [Ca2+], using a pump that strongly discriminates against both Li+ and Mg2+. Rayleigh fractionation during calcification effectively reverses this process, removing Ca2+ while leaving most Li+ and Mg2+ behind in the calcifying fluid. The net effect of these two processes is that Li/Mg in the calcifying fluid remains very close to the seawater value, and temperature-dependent abiotic partition coefficients are expressed in the biogenic aragonite Li/Mg ratio. We further show that coral Sr/Ca is consistent with this model if the Ca2+ pump barely discriminates against Sr2+. In H. elegans the covariation of Sr/Ca and Mg/Ca requires either that the pump more strongly discriminates against Sr2+, or that cation incorporation is affected by aragonite precipitation rate via the mechanism of surface entrapment. In either case Li/Mg is minimally affected by such 'vital effects' which plague other elemental ratio paleotemperature proxies.

Synthesis of layered perovskite oxides, ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs), and characterization of new solid acids, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (O < x [le] 2), exhibiting variable Bronsted acidity

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

Gopalakrishnan, J.; Uma, S.; Bhat, V.

1993-01-01

Layered perovskite oxides of the formula ACa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10] (A = K, Rb, Cs and 0 , x [le] 2) have been prepared. The members adopt the structures of the parent ACa[sub 2]Nb[sub 3]O[sub 10]. Interlayer alkali cations in the niobium-titanium oxide series can be ion-exchanged with Li[sup +], Na[sup +], NG[sub 4][sup +], of H[sup +] to give new derivatives. Intercalation of the protonated derivatives with organic bases reveals that the Bronsted acidity of the solid solution series, HCa[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10], depends on the titanium content. While the x = 1 member (HCaLaNb[submore » 2]TiO[sub 10]) is nearly as acidic as the parent HCa[sub 2]Nb[sub 3]O[sub 10], the x = 2 member (HLA[sub 2]NbTi[sub 2]O[sub 10]) is a weak acid hardly intercalating organic bases with pK[sub a] [approximately] 11.3. The variation of acidity is probably due to an ordering of Nb/Ti atoms in the triple octahedral perovskite slabs, [Ca[sub 2-x]La[sub x]Nb[sub 3-x]Ti[sub x]O[sub 10

A plasma membrane-type Ca[sup 2+]-ATPase of 120 kilodaltons on the endoplasmic reticulum from carrot (Daucus carota) cells

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

Chen, F.H.; Ratterman, D.M.; Sze, H.

1993-06-01

Cytosolic Ca[sup 2+] levels are regulated in part by Ca[sup 2+]-pumping ATPases that export Ca[sup 2+] from the cytoplasm; The types and properties of Ca[sup 2+] pumps in plants are not well understood. The kinetic properties of a 120-kD phosphoenzyme (PE) intermediate formed during the reaction cycle of a Ca[sup 2+]-ATPase from suspension-cultured carrot (Daucus carota) cells are characterized. Only one Ca[sup 2+]-dependent phosphoprotein was formed when carrot membrane vesicles were incubated with [[gamma]-[sup 32]P]ATP. Formation of this 120-kD phosphoprotein was inhibited by vanadate, enhanced by La[sup 3+], and decreased by hydroxylamine, confirming its identification as an intermediate of amore » phosphorylated-type Ca[sup 2+]-translocating ATPase. The 120-kD Ca[sup 2+]-ATPase was most abundant in endoplasmic reticulum-enriched fractions, in which the Ca[sup 2+]-ATPase was estimated to be 0.1% of membrane protein. Direct quantitation of Ca[sup 2+]-dependent phosphoprotein was used to examine the kinetics of PE formation. PE formation exhibited a K[sub m] for Ca[sup 2+] of 1 to 2 [mu]m and a K[sub m] for ATP of 67 nm. Relative affinities of substrates, determined by competition experiments, were 0.075 [mu]m for ATP, 1 [mu]m for ADP, 100 [mu]m for ITP, and 250 [mu]m for GTP. Thapsigargin and cyclopiazonic acid, specific inhibitors of animal sarcoplasmic/endoplasmic reticulum Ca[sup 2+]-ATPase, had no effect on PE formation; erythrosin B inhibited with 50% inhibition at <0.1 [mu]m. Calmodulin (1 [mu]m) stimulated PE formation by 25%. The results indicate that the carrot 120-kD Ca[sup 2+]-ATPase is similar but not identical to animal plasma membrane-type Ca[sup 2+]-ATPase and yet is located on endomembranes, such as the endoplasmic reticulum. This type of Ca[sup 2+] pump may reside on the cortical endoplasmic reticulum, thought to play a major role in anchoring the cytoskeleton and in facilitating secretion. 34 refs., 9 figs., 3 tabs.« less

Ca2+ removal mechanisms in rat cerebral resistance size arteries.

PubMed Central

Kamishima, T; McCarron, J G

1998-01-01

Tissue blood flow and blood pressure are each regulated by the contractile behavior of resistance artery smooth muscle. Vascular diseases such as hypertension have also been attributed to changes in vascular smooth muscle function as a consequence of altered Ca2+ removal. In the present study of Ca2+ removal mechanisms, in dissociated single cells from resistance arteries using fura-2 microfluorimetry and voltage clamp, Ca2+ uptake by the sarcoplasmic reticulum and extrusion by the Ca2+ pump in the cell membrane were demonstrably important in regulating Ca2+. In contrast, the Na+-Ca2+ exchanger played no detectable role in clearing Ca2+. Thus a voltage pulse to 0 mV, from a holding potential of -70 mV, triggered a Ca2+ influx and increased intracellular Ca2+ concentration ([Ca2+]i). On repolarization, [Ca2+]i returned to the resting level. The decline in [Ca2+]i consisted of three phases. Ca2+ removal was fast immediately after repolarization (first phase), then plateaued (second phase), and finally accelerated just before [Ca2+]i returned to resting levels (third phase). Thapsigargin or ryanodine, which each inhibit Ca2+ uptake into stores, did not affect the first but significantly inhibited the third phase. On the other hand, Na+ replacement with choline+ did not affect either the phasic features of Ca2+ removal or the absolute rate of its decline. Ca2+ removal was voltage-independent; holding the membrane potential at 120 mV, rather than at -70 mV, after the voltage pulse to 0 mV, did not attenuate Ca2+ removal rate. These results suggest that Ca2+ pumps in the sarcoplasmic reticulum and the plasma membrane, but not the Na+-Ca2+ exchanger, are important in Ca2+ removal in cerebral resistance artery cells. PMID:9746518

Oxidative impairment of hippocampal long-term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies.

PubMed

Maalouf, Marwan; Rho, Jong M

2008-11-15

Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease. In the present study, we explored the effects of the KB acetoacetate (ACA) and beta-hydroxybutyrate (BHB) on impairment of hippocampal long-term potentiation (LTP) in rats by hydrogen peroxide (H(2)O(2)) using electrophysiological, fluorescence imaging, and enzyme assay techniques. We found that: 1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H(2)O(2) (200 microM); 2) KB significantly lowered intracellular levels of reactive oxygen species (ROS)--measured with the fluorescent indicator carboxy-H(2)DCFDA (carboxy-2',7'-dichlorodihydrofluorescein diacetate)--in CA1 pyramidal neurons exposed to H(2)O(2); 3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; 4) KB prevented impairment of LTP by the PP2A activator C(6) ceramide; 5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H(2)O(2), and C(6) ceramide did not increase ROS levels; 6) PP2A activity was enhanced by both H(2)O(2) and rotenone (a mitochondrial complex I inhibitor that increases endogenous superoxide production); and 7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H(2)O(2) or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism.

Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats.

PubMed

Chen, Bihua; Chen, Gang; Dai, Chenxi; Wang, Pei; Zhang, Lei; Huang, Yuanyuan; Li, Yongqin

2018-04-01

Quantitative electroencephalogram (EEG) analysis has shown promising results in studying brain injury and functional recovery after cardiac arrest (CA). However, whether the quantitative characteristics of EEG, as potential indicators of neurological prognosis, are influenced by CA causes is unknown. The purpose of this study was designed to compare the quantitative characteristics of early post-resuscitation EEG between asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) in rats. Thirty-two Sprague-Dawley rats of both sexes were randomized into either ACA or VFCA group. Cardiopulmonary resuscitation was initiated after 5-min untreated CA. Characteristics of early post-resuscitation EEG were compared, and the relationships between quantitative EEG features and neurological outcomes were investigated. Compared with VFCA, serum level of S100B, neurological deficit score and brain histopathologic damage score were dramatically higher in the ACA group. Quantitative measures of EEG, including onset time of EEG burst, time to normal trace, burst suppression ratio, and information quantity, were significantly lower for CA caused by asphyxia and correlated with the 96-h neurological outcome and survival. Characteristics of earlier post-resuscitation EEG differed between cardiac and respiratory causes. Quantitative measures of EEG not only predicted neurological outcome and survival, but also have the potential to stratify CA with different causes.

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

PubMed

Hofmann, Laurie C; Koch, Marguerite; de Beer, Dirk

2016-01-01

Presently, an incomplete mechanistic understanding of tropical reef macroalgae photosynthesis and calcification restricts predictions of how these important autotrophs will respond to global change. Therefore, we investigated the mechanistic link between inorganic carbon uptake pathways, photosynthesis and calcification in a tropical crustose coralline alga (CCA) using microsensors. We measured pH, oxygen (O2), and calcium (Ca2+) dynamics and fluxes at the thallus surface under ambient (8.1) and low (7.8) seawater pH (pHSW) and across a range of irradiances. Acetazolamide (AZ) was used to inhibit extracellular carbonic anhydrase (CAext), which mediates hydrolysis of HCO3-, and 4,4' diisothiocyanatostilbene-2,2'-disulphonate (DIDS) that blocks direct HCO3- uptake by anion exchange transport. Both inhibited photosynthesis, suggesting both diffusive uptake of CO2 via HCO3- hydrolysis to CO2 and direct HCO3- ion transport are important in this CCA. Surface pH was raised approximately 0.3 units at saturating irradiance, but less when CAext was inhibited. Surface pH was lower at pHSW 7.8 than pHSW 8.1 in the dark, but not in the light. The Ca2+ fluxes were large, complex and temporally variable, but revealed net Ca2+ uptake under all conditions. The temporal variability in Ca2+ dynamics was potentially related to localized dissolution during epithallial cell sloughing, a strategy of CCA to remove epiphytes. Simultaneous Ca2+ and pH dynamics suggest the presence of Ca2+/H+ exchange. Rapid light-induced H+ surface dynamics that continued after inhibition of photosynthesis revealed the presence of a light-mediated, but photosynthesis-independent, proton pump. Thus, the study indicates metabolic control of surface pH can occur in CCA through photosynthesis and light-inducible H+ pumps. Our results suggest that complex light-induced ion pumps play an important role in biological processes related to inorganic carbon uptake and calcification in CCA.

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

PubMed Central

Hofmann, Laurie C.; Koch, Marguerite; de Beer, Dirk

2016-01-01

Presently, an incomplete mechanistic understanding of tropical reef macroalgae photosynthesis and calcification restricts predictions of how these important autotrophs will respond to global change. Therefore, we investigated the mechanistic link between inorganic carbon uptake pathways, photosynthesis and calcification in a tropical crustose coralline alga (CCA) using microsensors. We measured pH, oxygen (O2), and calcium (Ca2+) dynamics and fluxes at the thallus surface under ambient (8.1) and low (7.8) seawater pH (pHSW) and across a range of irradiances. Acetazolamide (AZ) was used to inhibit extracellular carbonic anhydrase (CAext), which mediates hydrolysis of HCO3-, and 4,4′ diisothiocyanatostilbene-2,2′-disulphonate (DIDS) that blocks direct HCO3- uptake by anion exchange transport. Both inhibited photosynthesis, suggesting both diffusive uptake of CO2 via HCO3- hydrolysis to CO2 and direct HCO3- ion transport are important in this CCA. Surface pH was raised approximately 0.3 units at saturating irradiance, but less when CAext was inhibited. Surface pH was lower at pHSW 7.8 than pHSW 8.1 in the dark, but not in the light. The Ca2+ fluxes were large, complex and temporally variable, but revealed net Ca2+ uptake under all conditions. The temporal variability in Ca2+ dynamics was potentially related to localized dissolution during epithallial cell sloughing, a strategy of CCA to remove epiphytes. Simultaneous Ca2+ and pH dynamics suggest the presence of Ca2+/H+ exchange. Rapid light-induced H+ surface dynamics that continued after inhibition of photosynthesis revealed the presence of a light-mediated, but photosynthesis-independent, proton pump. Thus, the study indicates metabolic control of surface pH can occur in CCA through photosynthesis and light-inducible H+ pumps. Our results suggest that complex light-induced ion pumps play an important role in biological processes related to inorganic carbon uptake and calcification in CCA. PMID:27459463

Rate-dependent Ca2+ signalling underlying the force-frequency response in rat ventricular myocytes: a coupled electromechanical modeling study

PubMed Central

2013-01-01

Background Rate-dependent effects on the Ca2+ sub-system in a rat ventricular myocyte are investigated. Here, we employ a deterministic mathematical model describing various Ca2+ signalling pathways under voltage clamp (VC) conditions, to better understand the important role of calmodulin (CaM) in modulating the key control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII), calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect various intracellular targets. In particular, we study the frequency dependence of the peak force generated by the myofilaments, the force-frequency response (FFR). Methods Our cell model incorporates frequency-dependent CaM-mediated spatially heterogenous interaction of CaMKII and CaN with their principal targets (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel (ICa,L); and the enhancement in SERCA pump activity via phosphorylation of PLB. Results Our model reproduces positive peak FFR observed in rat ventricular myocytes during voltage-clamp studies both in the presence/absence of cAMP mediated β-adrenergic stimulation. This study provides quantitative insight into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the frequency-dependence of the trigger current (ICa,L) and RyR-release. It also highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA pump at higher frequencies, as well as the rate-dependence of sarcoplasmic reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation of these Ca2+ signalling pathways clarifies their individual roles. Here, we present a coupled electromechanical study emphasizing the rate-dependence of isometric force developed and also investigate the temperature-dependence of FFR. Conclusions Our model provides mechanistic biophysically based explanations for the rate-dependence of CICR, generating useful and testable hypotheses. Although rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of beta-adrenergic stimulation, they show a characteristic increase in the positive slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up-regulation of ICa,L as the key mechanisms underlying the aforementioned positive FFR. PMID:24020888

Heterogeneous expression of Ca(2+) handling proteins in rabbit sinoatrial node.

PubMed

Musa, Hanny; Lei, Ming; Honjo, Hauro; Jones, Sandra A; Dobrzynski, Halina; Lancaster, Mathew K; Takagishi, Yoshiko; Henderson, Zaineb; Kodama, Itsuo; Boyett, Mark R

2002-03-01

We investigated the densities of the L-type Ca(2+) current, i(Ca,L), and various Ca(2+) handling proteins in rabbit sinoatrial (SA) node. The density of i(Ca,L), recorded with the whole-cell patch-clamp technique, varied widely in sinoatrial node cells. The density of i(Ca,L) was significantly (p<0.001) correlated with cell capacitance (measure of cell size) and the density was greater in larger cells (likely to be from the periphery of the SA node) than in smaller cells (likely to be from the center of the SA node). Immunocytochemical labeling of the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger, sarcoplasmic reticulum Ca(2+) release channel (RYR2), and sarcoplasmic reticulum Ca(2+) pump (SERCA2) also varied widely in SA node cells. In all cases there was significantly (p<0.05) denser labeling of cells from the periphery of the SA node than of cells from the center. In contrast, immunocytochemical labeling of the Na(+)-K(+) pump was similar in peripheral and central cells. We conclude that Ca(2+) handling proteins are sparse and poorly organized in the center of the SA node (normally the leading pacemaker site), whereas they are more abundant in the periphery (at the border of the SA node with the surrounding atrial muscle).

Effect of calcium ions on the evolution of biofouling by Bacillus subtilis in plate heat exchangers simulating the heat pump system used with treated sewage in the 2008 Olympic Village.

PubMed

Tian, Lei; Chen, Xiao Dong; Yang, Qian Peng; Chen, Jin Chun; Shi, Lin; Li, Qiong

2012-06-01

Heat pump systems using treated sewage water as the heat source were used in the Beijing Olympic Village for domestic heating and cooling. However, considerable biofouling occurred in the plate heat exchangers used in the heat pump system, greatly limiting the system efficiency. This study investigates the biofouling characteristics using a plate heat exchanger in parallel with a flow cell system to focus on the effect of calcium ions on the biofilm development. The interactions between the microorganisms and Ca(2+) enhances both the extent and the rate of biofilm development with increasing Ca(2+) concentration, leading to increased heat transfer and flow resistances. Three stages of biofouling development were identified in the presence of Ca(2+) from different biofouling mass growth rates with an initial stage, a rapid growth stage and an extended growth stage. Each growth stage had different biofouling morphologies influenced by the Ca(2+) concentration. The effects of Ca(2+) on the biofouling heat transfer and flow resistances had a synergistic effect related to both the biofouling mass and the morphology. The effect of Ca(2+) on the biofouling development was most prominent during the rapid growth stage. Copyright © 2012 Elsevier B.V. All rights reserved.

Purification and characterization of two wheat-embryo protein phosphatases.

PubMed

Polya, G M; Haritou, M

1988-04-15

Two protein phosphatases (enzymes I and II) were extensively purified from wheat embryo by a procedure involving chromatography on DEAE-cellulose, phenyl-Sepharose CL-4B, DEAE-Sephacel and Ultrogel AcA 44. Preparations of enzyme I (Mr 197,000) are heterogeneous. Preparations of enzyme II (Mr 35,000) contain only one major polypeptide (Mr 17,500), which exactly co-purifies with protein phosphatase II on gel filtration and is not present in preparations of enzyme I. However, this major polypeptide has been identified as calmodulin. Calmodulin and protein phosphatase II can be separated by further chromatography on phenyl-Sepharose CL-4B. Protein phosphatases I and II do not require Mg2+ or Ca2+ for activity. Both enzymes catalyse the dephosphorylation of phosphohistone H1 (phosphorylated by wheat-germ Ca2+-dependent protein kinase) and of phosphocasein (phosphorylated by wheat-germ Ca2+-independent casein kinase), but neither enzyme dephosphorylates a range of non-protein phosphomonoesters tested. Both enzymes are inhibited by Zn2+, Hg2+, vanadate, molybdate, F-, pyrophosphate and ATP.

Ca(2+) homeostasis in the budding yeast Saccharomyces cerevisiae: Impact of ER/Golgi Ca(2+) storage.

PubMed

D'hooge, Petra; Coun, Catherina; Van Eyck, Vincent; Faes, Liesbeth; Ghillebert, Ruben; Mariën, Lore; Winderickx, Joris; Callewaert, Geert

2015-08-01

Yeast has proven to be a powerful tool to elucidate the molecular aspects of several biological processes in higher eukaryotes. As in mammalian cells, yeast intracellular Ca(2+) signalling is crucial for a myriad of biological processes. Yeast cells also bear homologs of the major components of the Ca(2+) signalling toolkit in mammalian cells, including channels, co-transporters and pumps. Using yeast single- and multiple-gene deletion strains of various plasma membrane and organellar Ca(2+) transporters, combined with manipulations to estimate intracellular Ca(2+) storage, we evaluated the contribution of individual transport systems to intracellular Ca(2+) homeostasis. Yeast strains lacking Pmr1 and/or Cod1, two ion pumps implicated in ER/Golgi Ca(2+) homeostasis, displayed a fragmented vacuolar phenotype and showed increased vacuolar Ca(2+) uptake and Ca(2+) influx across the plasma membrane. In the pmr1Δ strain, these effects were insensitive to calcineurin activity, independent of Cch1/Mid1 Ca(2+) channels and Pmc1 but required Vcx1. By contrast, in the cod1Δ strain increased vacuolar Ca(2+) uptake was not affected by Vcx1 deletion but was largely dependent on Pmc1 activity. Our analysis further corroborates the distinct roles of Vcx1 and Pmc1 in vacuolar Ca(2+) uptake and point to the existence of not-yet identified Ca(2+) influx pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

The protective effect of clavulanic acid in a combined formulation on the concentration of amoxycillin in the urine of patients with urinary tract infections.

PubMed

Lindeque, K P

1982-07-28

Three paraplegic patients with urinary tract infections caused by a beta-lactamase-producing Klebsiella pneumoniae were treated with a combination of amoxycillin and clavulanic acid (A-CA) (Augmentin; Beecham), after initial and unsuccessful therapy with amoxycillin alone. The administration of A-CA resulted in a rapid decrease in the urinary bacterial cell count, coupled with a dramatic increase in urinary amoxycillin concentrations.

A non-equilibrium thermodynamics model of reconstituted Ca(2+)-ATPase.

PubMed

Waldeck, A R; van Dam, K; Berden, J; Kuchel, P W

1998-01-01

A non-equilibrium thermodynamics (NET) model describing the action of completely coupled or 'slipping' reconstituted Ca(2+)-ATPase is presented. Variation of the coupling stoichiometries with the magnitude of the electrochemical gradients, as the ATPase hydrolyzes ATP, is an indication of molecular slip. However, the Ca2+ and H+ membrane-leak conductances may also be a function of their respective gradients. Such non-ohmic leak typically yields 'flow-force' relationships that are similar to those that are obtained when the pump slips; hence, caution needs to be exercised when interpreting data of Ca(2+)-ATPase-mediated fluxes that display a non-linear dependence on the electrochemical proton (delta mu H) and/or calcium gradients (delta mu Ca). To address this issue, three experimentally verifiable relationships differentiating between membrane leak and enzymic slip were derived. First, by measuring delta mu H as a function of the rate of ATP hydrolysis by the enzyme. Second, by measuring the overall 'efficiency' of the pump as a function of delta mu H. Third, by measuring the proton ejection rate by the pump as a function of its ATP hydrolysis rate.

Noncanonical Wnt5a-Ca(2+) -NFAT signaling axis in pesticide induced bone marrow aplasia mouse model: A study to explore the novel mechanism of pesticide toxicity.

PubMed

Chattopadhyay, Sukalpa; Chatterjee, Ritam; Law, Sujata

2016-10-01

According to case-control studies, long-term pesticide exposure can cause bone marrow aplasia like hematopoietic degenerative disease leading to impaired hematopoiesis and increased risk of aplastic anemia in human subjects. However, the exact mechanism of pesticide mediated hematotoxicity still remains elusive. In this study, we investigated the role of noncanonical Wnt signaling pathway, a crucial regulator of adult hematopoiesis, in pesticide induced bone marrow aplasia mouse model. Aplasia mouse model was developed following inhalation and dermal exposure of 5% aqueous mixture of common agriculturally used pesticides for 6 h/day for 5 days a week up to 90 days. After that, blood hemogram, marrow smear, cellularity, scanning electron microscopy, extramedullary hematopoiesis and flowcytometric expression analysis of noncanonical Wnt signaling components, such as Wnt 5a, fzd5, NFAT, IFN-γ, intracellular Ca(2+) level were evaluated in the bone marrow hematopoietic stem/progenitor compartment of the control and pesticide induced aplasia groups of animals. Results showed that pesticide exposed mice were anemic with peripheral blood pancytopenia, hypocellular degenerative marrow, and extramedullary hematopoiesis in the spleen. Upon pesticide exposure, Wnt 5a expression was severely downregulated with a decline in intracellular Ca(2+) level. Moreover, downstream of Wnt5a, we observed sharp downregulation of NFATc2 transcription factor expression, the major target of pesticide toxicity and its target molecule IFN-γ. Taken together, our result suggests that deregulation of Wnt5a-Ca(2+) -NFAT signaling axis in the hematopoietic stem/progenitor compartment plays a crucial role behind the pathogenesis of pesticide mediated bone marrow aplasia by limiting primitive hematopoietic stem cells' ability to maintain hematopoietic homeostasis and reconstitution mechanism in vivo during xenobiotic stress leading to ineffective hematopoiesis and evolution of bone marrow aplasia. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1163-1175, 2016. © 2015 Wiley Periodicals, Inc.

Characterization of sarcoplasmic reticulum Ca(2+) ATPase pumps in muscle of patients with myotonic dystrophy and with hypothyroid myopathy.

PubMed

Guglielmi, V; Oosterhof, A; Voermans, N C; Cardani, R; Molenaar, J P; van Kuppevelt, T H; Meola, G; van Engelen, B G; Tomelleri, G; Vattemi, G

2016-06-01

Sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) pumps play the major role in lowering cytoplasmic calcium concentration in skeletal muscle by catalyzing the ATP-dependent transport of Ca(2+) from the cytosol to the lumen of the sarcoplasmic reticulum (SR). Although SERCA abnormalities have been hypothesized to contribute to the dysregulation of intracellular Ca(2+) homeostasis and signaling in muscle of patients with myotonic dystrophy (DM) and hypothyroid myopathy, the characterization of SERCA pumps remains elusive and their impairment is still unclear. We assessed the activity of SR Ca(2+)-ATPase, expression levels and fiber distribution of SERCA1 and SERCA2, and oligomerization of SERCA1 protein in muscle of patients with DM type 1 and 2, and with hypothyroid myopathy. Our data provide evidence that SR Ca(2+) ATPase activity, protein levels and muscle fiber distribution of total SERCA1 and SERCA2, and SERCA1 oligomerization pattern are similar in patients with both DM1 and DM2, hypothyroid myopathy and in control subjects. We prove that SERCA1b, the neonatal isoform of SERCA1, is expressed at protein level in muscle of patients with DM2 and, in lower amount, of patients with DM1. Our present study demonstrates that SERCA function is not altered in muscle of patients with DM and with hypothyroid myopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure of H/ACA RNP protein Nhp2p reveals cis/trans isomerization of a conserved proline at the RNA and Nop10 binding interface

PubMed Central

Koo, Bon-Kyung; Park, Chin-Ju; Fernandez, Cesar F.; Chim, Nicholas; Ding, Yi; Chanfreau, Guillaume; Feigon, Juli

2011-01-01

H/ACA small nucleolar and Cajal body ribonucleoproteins (RNPs) function in site-specific pseudouridylation of eukaryotic rRNA and snRNA, rRNA processing, and vertebrate telomerase biogenesis. Nhp2, one of four essential protein components of eukaryotic H/ACA RNPs, forms a core trimer with the pseudouridylase Cbf5 and Nop10 that specifically binds to H/ACA RNAs. Crystal structures of archaeal H/ACA RNPs have revealed how the protein components interact with each other and with the H/ACA RNA. However, in place of Nhp2p, archaeal H/ACA RNPs contain L7Ae, which binds specifically to an RNA K-loop motif absent in eukaryotic H/ACA RNPs, while Nhp2 binds a broader range of RNA structures. We report solution NMR studies of S. cerevisiae Nhp2 (Nhp2p), which reveal that Nhp2p exhibits two major conformations in solution due to cis/trans isomerization of the evolutionarily conserved Pro83. The equivalent proline is in the cis conformation in all reported structures of L7Ae and other homologous proteins. Nhp2p has the expected α-β-α fold, but the solution structures of the major conformation of Nhp2p with trans Pro83 and of Nhp2p-S82W with cis Pro83 reveal that Pro83 cis/trans isomerization affects the positions of numerous residues at the Nop10- and RNA-binding interface. An S82W substitution, which stabilizes the cis conformation, also stabilizes the association of Nhp2p with H/ACA snoRNPs in vivo. We propose that Pro83 plays a key role in the assembly of the eukaryotic H/ACA RNP, with the cis conformation locking in a stable Cbf5-Nop10-Nhp2 ternary complex and positioning the protein backbone to interact with the H/ACA RNA. PMID:21708174

Activation of endoplasmic reticulum calcium leak by 2-APB depends on the luminal calcium concentration.

PubMed

Leon-Aparicio, Daniel; Chavez-Reyes, Jesus; Guerrero-Hernandez, Agustin

2017-07-01

It has been shown that 2-APB is a nonspecific modulator of ion channel activity, while most of the channels are inhibited by this compound, there are few examples of channels that are activated by 2-APB. Additionally, it has been shown that, 2-APB leads to a reduction in the luminal endoplasmic reticulum Ca 2+ level ([Ca 2+ ] ER ) and we have carried out simultaneous recordings of both [Ca 2+ ] i and the [Ca 2+ ] ER in HeLa cell suspensions to assess the mechanism involved in this effect. This approach allowed us to determine that 2-APB induces a reduction in the [Ca 2+ ] ER by activating an ER-resident Ca 2+ permeable channel more than by inhibiting the activity of SERCA pumps. Interestingly, this effect of 2-APB of reducing the [Ca 2+ ] ER is auto-limited because depends on a replete ER Ca 2+ store; a condition that thapsigargin does not require to decrease the [Ca 2+ ] ER . Additionally, our data indicate that the ER Ca 2+ permeable channel activated by 2-APB does not seem to participate in the ER Ca 2+ leak revealed by inhibiting SERCA pump with thapsigargin. This work suggests that, prolonged incubations with even low concentrations of 2-APB (5μM) would lead to the reduction in the [Ca 2+ ] ER that might explain the inhibitory effect of this compound on those signals that require Ca 2+ release from the ER store. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of calcium isotopes in natural and synthetic barite

USGS Publications Warehouse

Griffith, E.M.; Schauble, E.A.; Bullen, T.D.; Paytan, A.

2008-01-01

The mineral barite (BaSO4) accommodates calcium in its crystal lattice, providing an archive of Ca-isotopes in the highly stable sulfate mineral. Holocene marine (pelagic) barite samples from the major ocean basins are isotopically indistinguishable from each other (??44/40Ca = -2.01 ?? 0.15???) but are different from hydrothermal and cold seep barite samples (??44/40Ca = -4.13 to -2.72???). Laboratory precipitated (synthetic) barite samples are more depleted in the heavy Ca-isotopes than pelagic marine barite and span a range of Ca-isotope compositions, ??44/40Ca = -3.42 to -2.40???. Temperature, saturation state, a Ba2 + / a SO42 -, and aCa2+/aBa2+ each influence the fractionation of Ca-isotopes in synthetic barite; however, the fractionation in marine barite samples is not strongly related to any measured environmental parameter. First-principles lattice dynamical modeling predicts that at equilibrium Ca-substituted barite will have much lower 44Ca/40Ca than calcite, by -9??? at 0 ??C and -8??? at 25 ??C. Based on this model, none of the measured barite samples appear to be in isotopic equilibrium with their parent solutions, although as predicted they do record lower ??44/40Ca values than seawater and calcite. Kinetic fractionation processes therefore most likely control the extent of isotopic fractionation exhibited in barite. Potential fractionation mechanisms include factors influencing Ca2+ substitution for Ba2+ in barite (e.g. ionic strength and trace element concentration of the solution, competing complexation reactions, precipitation or growth rate, temperature, pressure, and saturation state) as well as nucleation and crystal growth rates. These factors should be considered when investigating controls on isotopic fractionation of Ca2+ and other elements in inorganic and biogenic minerals. ?? 2008 Elsevier Ltd.

The impact of chemical doping on the magnetic state of the Sr{sub 2}YRuO{sub 6} double perovskite

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

Kayser, Paula; Ranjbar, Ben; Kennedy, Brendan J.

The impact of chemical doping of the type Sr{sub 2−x}A{sub x}YRuO{sub 6} (A=Ca, Ba) on the low temperature magnetic properties of Sr{sub 2}YRuO{sub 6}, probed using variable temperature magnetic susceptibility, neutron diffraction and heat capacity measurements, are described. Specific-heat measurements of un-doped Sr{sub 2}YRuO{sub 6} reveal two features at ∼26 and ∼30 K. Neutron scattering measurements at these temperatures are consistent with a change from a 2D ordered state to the 3D type 1 AFM state. Magnetic and structural studies of a number of doped oxides are described that highlight the unique low temperature behavior of Sr{sub 2}YRuO{sub 6} andmore » demonstrate that doping destabilizes the intermediate 2D ordered state. - Graphical abstract: Neutron diffraction measurements of the ordered double perovskite Sr{sub 2}YRuO{sub 6}reveal a with a change from a 2D ordered state to the 3D type 1 AFM state upon cooling. The impact of chemical doping Sr{sub 2−x}A{sub x}YRuO{sub 6} (A=Ca, Ba) on the low temperature magnetic properties have also been investigated and these highlight the unique low temperature behavior of Sr{sub 2}YRuO{sub 6} with doping destabilizing the intermediate 2D ordered state. - Highlights: • Crystal and Magnetic Structure of Sr{sub 2}YRuO{sub 3} was studied using Neutron Diffraction. • Effect of doping on the magnetic ground state established. • Origin of two low temperature transitions discussed.« less

9. SOUTH END OF GENE PUMPING STATION LOOKING WEST WITH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. SOUTH END OF GENE PUMPING STATION LOOKING WEST WITH DELIVERY LINES IN BACKGROUND. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

3. LOOKING EAST OVER GENE PUMP PLANT AND CAMP; PARKER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. LOOKING EAST OVER GENE PUMP PLANT AND CAMP; PARKER DAM VILLAGE IN BACKGROUND. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.

PubMed

Lalli, M J; Yong, J; Prasad, V; Hashimoto, K; Plank, D; Babu, G J; Kirkpatrick, D; Walsh, R A; Sussman, M; Yatani, A; Marbán, E; Periasamy, M

2001-07-20

Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.

Efficient RNA pseudouridylation by eukaryotic H/ACA ribonucleoproteins requires high affinity binding and correct positioning of guide RNA

PubMed Central

Caton, Evan A; Kelly, Erin K; Kamalampeta, Rajashekhar

2018-01-01

Abstract H/ACA ribonucleoproteins (H/ACA RNPs) are responsible for introducing many pseudouridines into RNAs, but are also involved in other cellular functions. Utilizing a purified and reconstituted yeast H/ACA RNP system that is active in pseudouridine formation under physiological conditions, we describe here the quantitative characterization of H/ACA RNP formation and function. This analysis reveals a surprisingly tight interaction of H/ACA guide RNA with the Cbf5p–Nop10p–Gar1p trimeric protein complex whereas Nhp2p binds comparably weakly to H/ACA guide RNA. Substrate RNA is bound to H/ACA RNPs with nanomolar affinity which correlates with the GC content in the guide-substrate RNA base pairing. Both Nhp2p and the conserved Box ACA element in guide RNA are required for efficient pseudouridine formation, but not for guide RNA or substrate RNA binding. These results suggest that Nhp2p and the Box ACA motif indirectly facilitate loading of the substrate RNA in the catalytic site of Cbf5p by correctly positioning the upper and lower parts of the H/ACA guide RNA on the H/ACA proteins. In summary, this study provides detailed insight into the molecular mechanism of H/ACA RNPs. PMID:29177505

Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency.

PubMed

Singh, Neeraj Kumar; Mani, Revathy; Hussaindeen, Jameel Rizwana

To evaluate the changes in the stimulus and response Accommodative Convergence to Accommodation (AC/A) ratio following vision therapy (VT) in Convergence Insufficiency (CI). Stimulus and response AC/A ratio were measured on twenty five CI participants, pre and post 10 sessions of VT. Stimulus AC/A ratio was measured using the gradient method and response AC/A ratio was calculated using modified Thorington technique with accommodative responses measured using WAM-5500 open-field autorefractor. The gradient stimulus and response AC/A cross-link ratios were compared with thirty age matched controls. Mean age of the CI and control participants were 23.3±5.2 years and 22.7±4.2 years, respectively. The mean stimulus and response AC/A ratio for CI pre therapy was 2.2±0.72 and 6.3±2.0 PD/D that changed to 4.2±0.9 and 8.28±3.31 PD/D respectively post vision therapy and these changes were statistically significant (paired t-test; p<0.001). The mean stimulus and response AC/A ratio for controls was 3.1±0.81 and 8.95±2.5 PD/D respectively. Stimulus and response AC/A ratio increased following VT, accompanied by clinically significant changes in vergence and accommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

21. ORIGINAL COMPANY HOUSE AT CORNER OF SANTA ANA AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. ORIGINAL COMPANY HOUSE AT CORNER OF SANTA ANA AND ANAHEIM BLVDS. (BEHIND HOUSE IN CA-242-20), WHICH IS BEING PREPARED FOR DEMOLITION. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Activation of calcineurin by phosphotidylserine containing vesicles

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

Politino, M.; King, M.M.

1986-05-01

Calcineurin (CaN) is a Ca/sup 2 +/- and calmodulin-regulated phosphatase. Recent findings suggested an association of CaN with biological membranes and prompted the present investigation into the interactions of the phosphatase with phospholipids in vitro. In the absence of calmodulin, sonicated preparations of phosphatidylserine (PS) provided a five-fold activation of the Ni- and Mn-supported activities of CaN towards (/sup 32/P) histone Hl; activation in the presence of calmodulin was much less pronounced. Half-maximal activation in the absence of calmodulin required approximately 0.1 mg/ml of PS. Activation of CaN was also observed with mixed vesicles of phosphatidylcholine (PC) containing 20% PSmore » but not with PC alone, or with phosphatidylethanolamine (PE). Molecular sieve chromatography on Ultrogel AcA 34 provided further evidence that CaN associates with phospholipid vesicles composed of PS, or PC containing 20% PS, but not with vesicles of PC or PE. Complete association with medium sized vesicles of PS and PC/PS required Ca/sup 2 +/ ions; in the absence of the metal ion at least 60% of the enzyme failed to interact with the lipids while the remainder preferentially migrated with larger vesicles. These results suggest a role for Ca/sup 2 +/ in regulating CaN's interaction with phospholipids.« less

cAMP-dependent protein kinase phosphorylates and activates nuclear Ca2+-ATPase

PubMed Central

Rogue, Patrick J.; Humbert, Jean-Paul; Meyer, Alphonse; Freyermuth, Solange; Krady, Marie-Marthe; Malviya, Anant N.

1998-01-01

A Ca2+-pump ATPase, similar to that in the endoplasmic reticulum, has been located on the outer membrane of rat liver nuclei. The effect of cAMP-dependent protein kinase (PKA) on nuclear Ca2+-ATPase (NCA) was studied by using purified rat liver nuclei. Treatment of isolated nuclei with the catalytic unit of PKA resulted in the phosphorylation of a 105-kDa band that was recognized by antibodies specific for sarcoplasmic reticulum Ca2+-ATPase type 2b. Partial purification and immunoblotting confirmed that the 105-kDa protein band phosphorylated by PKA is NCA. The stoichiometry of phosphorylation was 0.76 mol of phosphate incorporated/mol of partially purified enzyme. Measurement of ATP-dependent 45Ca2+ uptake into purified nuclei showed that PKA phosphorylation enhanced the Ca2+-pumping activity of NCA. We show that PKA phosphorylation of Ca2+-ATPase enhances the transport of 10-kDa fluorescent-labeled dextrans across the nuclear envelope. The findings reported in this paper are consistent with the notion that the crosstalk between the cAMP/PKA- and Ca2+-dependent signaling pathways identified at the cytoplasmic level extends to the nucleus. Furthermore, these data support a function for crosstalk in the regulation of calcium-dependent transport across the nuclear envelope. PMID:9689054

High-potential defense mechanisms of neocortex in a rat model of transient asphyxia induced cardiac arrest.

PubMed

Keilhoff, Gerburg; Esser, Torben; Titze, Maximilian; Ebmeyer, Uwe; Schild, Lorenz

2017-11-01

Cardiac arrest (CA) is a common cause of disability and mortality and thus an important risk for human health. Circulatory failure has dramatic consequences for the brain as one of the most oxygen-consuming organs. Hippocampus, striatum and neocortex rate among the most vulnerable brain regions. The neocortex is less sensitive to hypoxia/reperfusion in comparison with the hippocampal CA1 region. That implicates the existence of efficient defense mechanisms in the neocortex against hypoxia/reperfusion injury, which we analyzed in a well-established CA rat model. We explored different immunohistochemical markers (NeuN, MAP2, GFAP, IBA1, NOX4, MnSOD, Bax, caspase 3, cfos, nNOS, eNOS, iNOS, TUNEL), amount of mitochondria, activities of respiratory chain complexes and amount/composition of cardiolipin. CA induced a moderate degeneration of cortical neurons. As possible defense mechanisms the study revealed: (i) increased activities of respiratory chain complexes of cortical mitochondria as response to increased energy demand after ACA-induced cell stress; (ii) increase of cardiolipin content as cellular stress response, which might contribute to the promotion of mitochondrial ATP synthesis; (iii) strengthening of the fast, effective and long-lasting mitochondrial MnSOD defense system; (iv) ACA-induced increase in expression of eNOS and nNOS in vasculature being able to reduce ischemic injury by vasodilation. Copyright © 2017 Elsevier B.V. All rights reserved.

Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability.

PubMed

Dhumal, Ravindra S; Biradar, Shailesh V; Aher, Suyog; Paradkar, Anant R

2009-06-01

Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

Identification of Genetic Defects Underlying FXII Deficiency in Four Unrelated Chinese Patients.

PubMed

Yang, Lihong; Wang, Yingyu; Zhou, Jianpin; Cheng, Xiaoli; Hao, Xiuping; Xie, Haixiao; Jin, Yanhui; Wang, Mingshan

2016-01-01

Congenital factor XII (FXII) dexFB01;ciency is a rare autosomal recessive disorder, characterized by a great variability in its clinical manifestations. In this study, we screened for mutations in the F12 gene of 4 unrelated patients with FXII coagulant activity <10% of that of normal human plasma. To investigate the molecular defects in these FXII-deficient patients, we performed FXII mutation screening. By sequencing all coding exons as well as xFB02;anking intronic regions of the F12 gene, 6 different mutations, including 3 missense mutations (Gly341Arg, Glu502Lys and Gly542 Ser), 1 insertion (7142insertC) and 2 deletions (5741-5742 delCA and 6753-6755delACA), were identixFB01;ed on the F12 gene. Three of them (Gly341Arg, 5741-5742delCA and 6753-6755delACA) are reported here for the first time. Computer-based algorithms predicted these missense mutations to be deleterious. This study has increased our knowledge of the mutational spectrum underlying FXII deficiency. © 2016 S. Karger AG, Basel.

Mitosis in sand dollar embryos is inhibited by antibodies directed against the calcium transport enzyme of muscle.

PubMed

Silver, R B

1986-06-01

Monospecific antibodies to the calcium transport enzyme (alpha-Ca pump) inhibit mitosis when microinjected into sand dollar embryos. Immunoglobulins were raised against the calcium transport enzyme (Ca pump) of sarcoplasmic reticulum (SR) from rat skeletal muscle and guinea pig ileum smooth muscle. Specific antibodies were further isolated from IgG fractions by using electrophoretically purified SR Ca-pump protein as the immobilized ligand for immunoaffinity chromatography. ELISA demonstrated that common antigenic determinants are shared by SR, SR Ca pump (of rat skeletal and guinea pig ileum smooth muscle), and isolated membrane containing "native" mitotic apparatus (MA). Preimmune sera gave negative results in identical control assays. Triton X-100 extraction of MA removes the Ca-pump antigen. SR Ca pump and the MA Ca pump have nearly identical molecular masses as determined by NaDodSO4/PAGE. These alpha-SR Ca-pump IgGs inhibit ATP-dependent Ca2+ sequestration by purified SR and MA membranes. Indirect immunofluorescence of isolated native MA demonstrated coincident localization of the MA Ca pump, sequestered calcium, and membrane vesicles. Fluorescent foci were regionally concentrated within the volumes of the asters and spindle. Microinjection of the anti-Ca-pump IgGs into one of two sister blastomeres at second metaphase resulted in mitotic arrest of the injected cell accompanied by a rapid loss of spindle birefringence. Karyomeres formed and fused to form nuclei either at the site of the metaphase plate or at the position the chromosomes occupied during anaphase A. The cleavage furrow did not develop in the injected cell, while the sister and neighbor cells continued normal mitotic cycling. Injection later in mitosis yielded cells with two nuclei whose cleavage furrow relaxed completely. Routine control injections of boiled immune IgG, preimmune IgG, Wesson oil, buffer, or goat anti-rabbit IgG did not affect mitosis, birefringence of the MA, or cleavage furrow activity.

Mitosis in sand dollar embryos is inhibited by antibodies directed against the calcium transport enzyme of muscle.

PubMed Central

Silver, R B

1986-01-01

Monospecific antibodies to the calcium transport enzyme (alpha-Ca pump) inhibit mitosis when microinjected into sand dollar embryos. Immunoglobulins were raised against the calcium transport enzyme (Ca pump) of sarcoplasmic reticulum (SR) from rat skeletal muscle and guinea pig ileum smooth muscle. Specific antibodies were further isolated from IgG fractions by using electrophoretically purified SR Ca-pump protein as the immobilized ligand for immunoaffinity chromatography. ELISA demonstrated that common antigenic determinants are shared by SR, SR Ca pump (of rat skeletal and guinea pig ileum smooth muscle), and isolated membrane containing "native" mitotic apparatus (MA). Preimmune sera gave negative results in identical control assays. Triton X-100 extraction of MA removes the Ca-pump antigen. SR Ca pump and the MA Ca pump have nearly identical molecular masses as determined by NaDodSO4/PAGE. These alpha-SR Ca-pump IgGs inhibit ATP-dependent Ca2+ sequestration by purified SR and MA membranes. Indirect immunofluorescence of isolated native MA demonstrated coincident localization of the MA Ca pump, sequestered calcium, and membrane vesicles. Fluorescent foci were regionally concentrated within the volumes of the asters and spindle. Microinjection of the anti-Ca-pump IgGs into one of two sister blastomeres at second metaphase resulted in mitotic arrest of the injected cell accompanied by a rapid loss of spindle birefringence. Karyomeres formed and fused to form nuclei either at the site of the metaphase plate or at the position the chromosomes occupied during anaphase A. The cleavage furrow did not develop in the injected cell, while the sister and neighbor cells continued normal mitotic cycling. Injection later in mitosis yielded cells with two nuclei whose cleavage furrow relaxed completely. Routine control injections of boiled immune IgG, preimmune IgG, Wesson oil, buffer, or goat anti-rabbit IgG did not affect mitosis, birefringence of the MA, or cleavage furrow activity. Images PMID:2940599

Reduction of perifusate magnesium alters inotropic response of papillary muscle to ion channel modulators.

PubMed

Manju, L; Nair, R Renuka

2005-09-01

Magnesium has a significant role in the regulation of ion transport. Marginal deficiency of Mg can therefore affect myocardial excitability and contractility. This study was taken up with the objective of examining the inotropic response of the myocardium to variation in extracellular [Mg]o and identifying the ion channels and pumps mediating the inotropic changes. Electrically stimulated rat papillary muscle was used as the experimental model and mechanical changes were recorded using a physiograph. Channel specific antagonists were used to identify the channels mediating the functional changes. Diastolic Ca2+ levels were determined in isolated myocytes by the ratiometric method using the fluorescent indicator Fura2-AM. A negative association was observed between the level of [Mg]o and force of contraction, with a peak at 0.48 mM Mg. The force of contraction in Mg deficient medium (0.48 mM) was 158% of control (1.2 mM Mg) (p < 0.001). Inotropic response to the L-type channel antagonist (verapamil-1 microm) and NaK ATPase inhibitor (Ouabain-0.3 mM) was augmented in Mg deficiency (p < 0.005), indicating activation of the channel and the pump. The response to T-type channel inhibitor (NiCl2-40 microM) was attenuated in Mg deficiency (p < 0.05). The response to the sarcoplasmic reticular Ca pump inhibitor (caffeine-10 mM) and the SR Ca2+ release channel inhibitor (ryanodine-1 microM) were not significantly affected by Mg deficiency. Diastolic level of Ca2+ increased with a decrease in Mg (p < 0.05). The observations of the study lead to the conclusion that the positive inotropic response in Mg deficiency is mediated by an increase in basal Ca2+ combined with Ca-induced-Ca release consequent to Ca2+ influx through L-type Ca channel. Variation in sensitivity to Ca channel blockers and NaK ATPase inhibitor in Mg deficiency can have pharmacological implications.

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 local Mg2+/Ca2+ at the time of precipitation determines the calcite composition, independent of whether growth occurs via an amorphous intermediate or classical pathway for a range of supersaturations and pH conditions. The findings reiterate the need to revisit the traditional picture of chemical and physical controls on CaCO3 polymorph selection. Mineralization by pathways involving ACC can lead to the formation of crystalline phases whose polymorphs and compositions are out of equilibrium with local growth media. As such, classical thermodynamic equilibria may not provide a reliable predictor of observed compositions.

The Endoplasmic Reticulum: A Central Player in Cell Signalling and Protein Synthesis

NASA Astrophysics Data System (ADS)

Llewelyn Roderick, H.; Berridge, Michael J.; Bootman, Martin D.

In addition to being the principle intracellular Ca 2+ store, the endoplasmic reticulum (ER) is the initial site of synthesis and folding of membrane and secretory proteins. These two roles of the ER are intimately linked. First, the function of many proteins involved in Ca 2+ handling are modulated by Ca 2+ and second, ER lumenal Ca 2+ modulates protein synthesis and folding. Within the ER, Ca 2+ is stored by low affinity high capacity Ca 2+ binding proteins and is maintained at a free concentration between 0.1 and 1 μM relative to 0.1 μM cytosolic Ca 2+. This concentration gradient is maintained by the action of the Sarco-Endoplasmic Reticulum ATPases (SERCa) which hydrolyse ATP to pump Ca 2+ into the ER. Following stimulation Ca 2+ is released from the ER through several classes of ligand gated channels. The most well characterized of these being the inositol 1,4,5-trisphosphate receptor ( IP 3 R) and the Ryanodine receptor (RyR) families of proteins. This release of Ca 2+ results in a drop of ER free Ca 2+ to levels as low as 10 μM. This decrease in lumenal Ca 2+ inhibits further release through the channels and increases the rate of re-sequestration of Ca 2+ into the ER by the SERCa pumps. Under these conditions, in addition to effects on Ca 2+ handling proteins, protein synthesis is inhibited, chaperones dissociate from their substrates, secondary modifications of proteins are inhibited and the retention of many proteins within the ER is lost. Furthermore, a signalling cascade resulting in the up-regulation of many proteins involved in protein folding and Ca 2+ homeostasis is initiated. This review will focus on the proteins involved in the regulation ER lumenal Ca 2+ and the role of ER lumenal Ca 2+ in cell signalling and protein synthesis.

Carbonate mineralization via an amorphous calcium carbonate (ACC) pathway: Tuning polymorph selection by Mg, pH, and mixing environment

NASA Astrophysics Data System (ADS)

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

2017-12-01

Mineral formation by nonclassical processes is widespread with many pathways that include aggregation of nanoparticles, oriented attachment of fully formed crystals, and sequential nucleation/transformation of amorphous phases (De Yoreo et al., 2015, Science). Field observations indicate amorphous calcium carbonate (ACC) can be the initial precipitate when local conditions promote high supersaturations for short time periods. Examples include microbial mats, marine porewaters that undergo pulses of increased alkalinity, closed basin lakes, and sabkhas. The crystalline products exhibit diverse morphologies and complex elemental and isotopic signatures. This study quantifies relationships between solution composition and the crystalline polymorphs that transform from ACC (Blue et al., GCA, 2017). Our experimental design synthesized ACC under controlled conditions for a suite of compositions by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within output suspensions under stirred or quiescent mixing while characterizing the polymorph and composition of evolving solutions and solids. We find that ACC transforms to crystalline polymorphs with a systematic relationship to solution composition to give a quantitative framework based upon solution aMg2+/aCa2+ and aCO32-/aCa2+. We also measure a polymorph-specific evolution of pH and Mg/Ca during the transformation that indicates the initial polymorph to form. Pathway is further modulated by stirring versus quiescent conditions. The findings reconcile discrepancies among previous studies of ACC to crystalline products and supports claims that monohydrocalcite may be an overlooked, transient phase during formation of some aragonite and calcite deposits. Organic additives and extreme pH are not required to tune composition and polymorph. Insights from this study reiterate the need to revisit long-standing dogmas regarding controls on CaCO3 polymorph selection. Classical models assume thermodynamic equilibria but cannot provide a reliable predictor of compositions when kinetic factors are driving mineralization. Nonclassical pathways to mineralization may be the missing link to interpreting unusual CaCO3 polymorphs, compositions and textures in modern and ancient carbonates.

Anatomical Assessment of the Temporopolar Artery for Revascularization of Deep Recipients.

PubMed

Tayebi Meybodi, Ali; Benet, Arnau; Griswold, Dylan; Dones, Flavia; Preul, Mark C; Lawton, Michael T

2018-05-30

Intracranial-intracranial and extracranial-intracranial bypass options for revascularization of deep cerebral recipients are limited and technically demanding. To assess the anatomical feasibility of using the temporopolar artery (TPA) for revascularization of the anterior cerebral artery (ACA), posterior cerebral artery (PCA), and superior cerebellar arteries (SCA). Orbitozygomatic craniotomy was performed bilaterally on 8 cadaveric heads. The cisternal segment of the TPA was dissected. The TPA was cut at M3-M4 junction with its proximal and distal calibers and the length of the cisternal segment measured. Feasibility of the TPA-A1-ACA, TPA-A2-ACA, TPA-SCA, and TPA-PCA bypasses were assessed. A total of 17 TPAs were identified in 16 specimens. The average distal TPA caliber was 1.0 ± 0.2 mm, and the average cisternal length was 37.5 ± 9.4 mm. TPA caliber was ≥ 1.0 mm in 12 specimens (70%). The TPA-A1-ACA bypass was feasible in all specimens, whereas the TPA reached the A2-ACA, SCA, and PCA in 94% of specimens (16/17). At the point of anastomosis, the average recipient caliber was 2.5 ± 0.5 mm for A1-ACA, and 2.3 ± 0.7 mm for A2-ACA. The calibers of the SCA and PCA at the anastomosis points were 2.0 ± 0.6 mm, and 2.7 ± 0.8 mm, respectively. The TPA-ACA, TPA-PCA, and TPA-SCA bypasses are anatomically feasible and may be used when the distal caliber of the TPA stump is optimal to provide adequate blood flow. This study lays foundations for clinical use of the TPA for ACA revascularization in well-selected cases.

Femtosecond diode-pumped mode-locked neodymium lasers

NASA Astrophysics Data System (ADS)

Kubeček, Václav; Jelínek, Michal; Čech, Miroslav; Vyhlídal, David; Su, Liangbi; Jiang, Dapeng; Ma, Fengkai; Qian, Xiaobo; Wang, Jingya; Xu, Jun

2016-12-01

Fluoride-type crystals (CaF2, SrF2) doped with neodymium Nd3+ and codoped with buffer ions for breaking clusters of active ions and increasing fluorescence efficiency, present interesting alternative as laser active media for the diode-pumped mode-locked lasers. In comparison with widely used materials as Nd:YAG or Nd:YVO4, they have broad emission spectra as well as longer fluorescence lifetime, in comparison with Nd:glass, SrF2 and CaF2 have better thermal conductivity. In spite of the fact, that this thermal conductivity decreases with Nd3+ doping concentration, these crystals are alternative for the Nd:glass in subpicosecond mode-locked laser systems. In this paper we review the basic results reported recently on these active materials and in the second part we present our results achieved in low power diode pumped passively mode locked lasers with Nd,La:CaF2 and Nd,Y:SrF2 crystals. The pulses as short as 258 fs at wavelength of 1057 nm were obtained in the first case, while 5 ps long pulses at 1065 nm were generated from the second laser system.

14. GENE PUMPING STATION CONTROL ROOM AS SEEN FROM MAIN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. GENE PUMPING STATION CONTROL ROOM AS SEEN FROM MAIN STATION MANAGER'S CONTROL DESK. ELECTRICAL CONTROL INDICATORS AND CONTROLS FOR REGULATING ELECTRICITY INTO PLANT AS WELL AS SYNCHRONIZING STARTUP OF PUMPS. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Nonradiative Decay Dynamics of METHYL-4-HYDROXYCINNAMATE and its Monohydrated Complex Revealed by Picosecond Pump-Probe Spectroscopy

NASA Astrophysics Data System (ADS)

Ebata, T.; Shimada, D.; Kusaka, R.; Inokuchi, Y.; Ehara, M.

2012-06-01

The lifetimes of methyl 4-hydroxycinnamate (OMpCA) and its mono-hydrated complex (OMpCA-H_2O) in the S_1 state have been measured by picosecond pump-probe spectroscopy in a supersonic beam. For OMpCA, the lifetime of the S_1 - S_0 origin is 8 - 9 ps. On the other hand, the lifetime of OMpCA-H_2O complex at the origin is 930 ps, which is 100 times longer than that. Furthermore, in the complex the S_1 lifetime shows rapid decrease at an energy of 200 cm-1 above the origin and becomes as short as 9 ps at 500 cm-1. Theoretical calculations with symmetry-adapted cluster-configuration interaction (SAC-CI) method suggest that in OMpCA, the trans - cis isomerization occurs smoothly without a barrier on the S_1surface, while in OMpCA-H_2O complex, there exists a barrier along the isomerization coordinate. The calculated barrier height of OMpCA-H_2O is in good agreement with that estimated from the lifetime measurements.

Nitroxyl Improves Cellular Heart Function by Directly Enhancing Cardiac Sarcoplasmic Reticulum Ca2+ Cycling

PubMed Central

Tocchetti, Carlo G.; Wang, Wang; Froehlich, Jeffrey P.; Huke, Sabine; Aon, Miguel A.; Wilson, Gerald M.; Benedetto, Giulietta Di; O’Rourke, Brian; Gao, Wei Dong; Wink, David A.; Toscano, John P.; Zaccolo, Manuela; Bers, Donald M.; Valdivia, Hector H.; Cheng, Heping; Kass, David A.; Paolocci, Nazareno

2009-01-01

Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development of effective therapies to stimulate contraction has proven difficult. This is thought to be attributable to their frequent reliance on cAMP stimulation to increase activator Ca2+. A potential alternative is nitroxyl (HNO), the 1-electron reduction product of nitric oxide (NO) that improves contraction and relaxation in normal and failing hearts in vivo. The mechanism for myocyte effects remains unknown. Here, we show that this activity results from a direct interaction of HNO with the sarcoplasmic reticulum Ca2+ pump and the ryanodine receptor 2, leading to increased Ca2+ uptake and release from the sarcoplasmic reticulum. HNO increases the open probability of isolated ryanodine-sensitive Ca2+-release channels and accelerates Ca2+ reuptake into isolated sarcoplasmic reticulum by stimulating ATP-dependent Ca2+ transport. Contraction improves with no net rise in diastolic calcium. These changes are not induced by NO, are fully reversible by addition of reducing agents (redox sensitive), and independent of both cAMP/protein kinase A and cGMP/protein kinase G signaling. Rather, the data support HNO/thiolate interactions that enhance the activity of intracellular Ca2+ cycling proteins. These findings suggest HNO donors are attractive candidates for the pharmacological treatment of heart failure. PMID:17138943

5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

2. GENE CAMP FROM ABOVE COPPER BASIN, LOOKING NORTHEAST (NEGATIVE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. GENE CAMP FROM ABOVE COPPER BASIN, LOOKING NORTHEAST (NEGATIVE FLARED FROM BADLY SEATED FILM HOLDER, RETAINED BECAUSE OF USEFUL INFORMATION ON GEOGRAPHY OF GENE CAMP). - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Effects of intravenous aminocaproic acid on exercise-induced pulmonary haemorrhage (EIPH).

PubMed

Buchholz, B M; Murdock, A; Bayly, W M; Sides, R H

2010-11-01

The antifibrinolytic, 6-aminohexanoic acid, also named aminocaproic acid (ACA), has been used empirically as a treatment for exercise-induced pulmonary haemorrhage (EIPH) on the unsubstantiated basis that transient coagulation dysfunction may contribute to its development. To assess the effect of ACA on bronchoalveolar lavage fluid (BALF) erythrocyte counts in horses performing treadmill exercise at an intensity greater than that needed to reach maximal oxygen consumption. Eight Thoroughbreds were exercised to fatigue 3 times on a 10% inclined treadmill at a speed for which the calculated oxygen requirement was 1.15 times VO2max. Horses were treated with a saline placebo, 2 and 7 g ACA i.v. 4 h before exercise, with a crossover design being used to determine the order of the injections. Exercise-induced pulmonary haemorrhage severity was quantified via the erythrocyte count in BALF. Bronchoalveolar lavage fluid was collected 4 h before and 30-60 min post exercise. Results were expressed as mean ± s.e.m. and analysed by one way repeated measures ANOVA (P < 0.05). Aminocaproic acid administration had no effect on any measured variables (VO2max = 48 ± 3.0 [C]; 148 ± 3.0 [2 g ACA]; 145 ± 3.0 [7 g ACA] ml/kg bwt/min, respectively; run time = 77 ± 3 [C]; 75 ± 2 [2 g ACA]; 79 ± 3 [7 g ACA] seconds, respectively). All horses developed EIPH: 1691 ± 690 vs. 9637 ± 3923 (C); 2149 ± 935 vs. 3378 ± 893 (2 g ACA); 1058 ± 340 vs. 4533 ± 791 (7 g ACA) erythrocytes/µl pre- vs. post exercise recovered in BALF, respectively. Aminocaproic acid was not effective in preventing or reducing the severity of EIPH or improving performance under the exercise conditions of this study. © 2010 EVJ Ltd.

[Effects of hypoxic acclimatization on myocardial sarcoplasmic reticulum ATPase and 45Ca2+ uptake in rats].

PubMed

Long, Chao-liang; Zhang, Yan-fang; Yin, Zhao-yun; Wang, Hai

2005-08-01

To study the effect of acute hypoxia and hypoxic acclimatization on myocardial function of rats. Eighteen male Wistar rats were randomly divided into three groups: normoxic control, acute hypoxia and intermittent hypoxic acclimatization group (n=6). After being exposed to hypoxia (8000 m) for 4 h before and after intermittent hypoxic acclimatization (3000 m and 5000 m, 14 d respectively, 4 h/d), the rats were decapitated and then myocardial sarcoplasmic reticulum (SR) were derived from cardiac muscles. Activities of Na+, K(+)-ATPase, Ca2+, Mg2(+)-ATPase in SR, phosphorylation of phospholamban (PLB) and the ability of 45Ca2+ uptake in SR were observed in all these three groups. 1) Hypoxia had no effects on the activity of Na+, K(+)-ATPase in rats myocardial SR of rats. 2) Compared with normoxic control rats, the activity of Ca2+, Mg2(+)-ATPase in myocardial SR of rats after acute hypoxia was reduced significantly (P<0.01). After intermittent hypoxic acclimatization, its activity increased significantly as compared with that of acute hypoxic rats (P<0.01). 3) The phosphorylation of PLB in acute hypoxic rats was reduced significantly compared with normoxic control rats. After intermittent hypoxic acclimatization, its phosphorylation was increased significantly compared with that of acute hypoxic rats. It suggests that hypoxic acclimatization could alleviate the inhibition of calcium pump. 4) The ability of 45Ca2+ uptake of SR in acute hypoxic rats was decreased significantly. After hypoxic acclimatization, its ability was strengthened significantly. These results suggest that the increased function of myocardial SR calcium pump, the strengthened phosphorylation of PLB to alleviate the inhibition of calcium pump and the increased function of Ca2+ transport in SR are the mechanisms of hypoxic acclimatization protecting cardiac functions from injury induced by severe hypoxia.

Cytosolic Ca2+ Buffers

PubMed Central

Schwaller, Beat

2010-01-01

“Ca2+ buffers,” a class of cytosolic Ca2+-binding proteins, act as modulators of short-lived intracellular Ca2+ signals; they affect both the temporal and spatial aspects of these transient increases in [Ca2+]i. Examples of Ca2+ buffers include parvalbumins (α and β isoforms), calbindin-D9k, calbindin-D28k, and calretinin. Besides their proven Ca2+ buffer function, some might additionally have Ca2+ sensor functions. Ca2+ buffers have to be viewed as one of the components implicated in the precise regulation of Ca2+ signaling and Ca2+ homeostasis. Each cell is equipped with proteins, including Ca2+ channels, transporters, and pumps that, together with the Ca2+ buffers, shape the intracellular Ca2+ signals. All of these molecules are not only functionally coupled, but their expression is likely to be regulated in a Ca2+-dependent manner to maintain normal Ca2+ signaling, even in the absence or malfunctioning of one of the components. PMID:20943758

How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt-dependent hypertension

PubMed Central

Leenen, Frans H. H.; Chen, Ling; Golovina, Vera A.; Hamlyn, John M.; Pallone, Thomas L.; Van Huysse, James W.; Zhang, Jin; Wier, W. Gil

2012-01-01

Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na+ and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid [Na+]. This leads, via the Na+-sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction. Plasma levels of endogenous ouabain (EO), the Na+ pump ligand, also become elevated. Remarkably, high cerebrospinal fluid [Na+]-evoked, locally secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na+ channels, EO, ouabain-sensitive α2 Na+ pumps, and angiotensin II (ANG II). The EO increases (e.g.) hypothalamic ANG-II type-1 receptor and NADPH oxidase and decreases neuronal nitric oxide synthase protein expression. The aldosterone-epithelial Na+ channel-EO-α2 Na+ pump-ANG-II pathway modulates the activity of brain cardiovascular control centers that regulate the BP set point and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex directly enhances vasoconstriction via an EO-α2 Na+ pump-Na+/Ca2+ exchanger-Ca2+ signaling pathway. Circulating EO also activates an EO-α2 Na+ pump-Src kinase signaling cascade. This increases the expression of the Na+/Ca2+ exchanger-transient receptor potential cation channel Ca2+ signaling pathway in arterial smooth muscle but decreases the expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may directly participate in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP. PMID:22058154

Determination of the calcium elemental abundance for 43 flares from SMM-XRP solar X-ray spectra

NASA Astrophysics Data System (ADS)

Lemen, J. R.; Sylwester, J.; Bentley, R. D.

The helium and lithium-like X-ray transitions of Ca XVIII-XIX have been used to make an absolute measurement of the coronal calcium elemental abundance relative to hydrogen (ACa) in solar flares. Cooling phase spectra of 43 flares obtained in channel 1 of the Bent Crystal Spectrometer on the Solar Maximum Mission have been analyzed. The abundance is determined from the intensity ratio of the Ca XIX resonance line (1S0 - 1P1) and nearby continuum. Attempts to correlate the ACa measurements with other observable features are discussed.

Endocrine disrupting alkylphenols: structural requirements for their adverse effects on Ca2+ pumps, Ca2+ homeostasis & Sertoli TM4 cell viability.

PubMed

Michelangeli, Francesco; Ogunbayo, Oluseye A; Wootton, Laura L; Lai, Pei F; Al-Mousa, Fawaz; Harris, Robert M; Waring, Rosemary H; Kirk, Christopher J

2008-11-25

Alkylphenols such as nonylphenol are pollutants that are widely dispersed within our environment. They bio-accumulate within man, with levels in the muM concentration range reported in human tissues. These chemicals act as endocrine disruptors, having xenoestrogenic activity. More recently alkylphenols have also been shown to affect Ca2+ signalling pathways. Here we show that alkylphenols are potent inhibitors of sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) activity. For linear chain alkylphenols the potency of inhibition is related to chain length, with the IC50 values for inhibition ranging from 8 microM for 4-n-nonylphenol (C9) to 1.3 mM for 4-n-propylphenol (C3). Branched chain alkylphenols generally had lower potencies than their linear chain counterparts, however, good correlations for all alkylphenols were observed between their Ca2+ pump inhibition and hydrophobicity, molecular volume and flexibility, indicating that these parameters are all important factors. Alkylphenols cause abnormal elevations of intracellular [Ca2+] within TM4 Sertoli cells (cells involved in sperm maturation) depolarise their mitochondria and induce cell death in these cells, in an alkyl chain size-dependent manner.

Update on vascular endothelial Ca(2+) signalling: A tale of ion channels, pumps and transporters.

PubMed

Moccia, Francesco; Berra-Romani, Roberto; Tanzi, Franco

2012-07-26

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca(2+) signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca(2+) levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca(2+) signals, ranging from brief, localized Ca(2+) pulses to prolonged Ca(2+) oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca(2+) signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca(2+) releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca(2+) removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca(2+) machinery in vascular ECs under both physiological and pathological conditions.

Update on vascular endothelial Ca2+ signalling: A tale of ion channels, pumps and transporters

PubMed Central

Moccia, Francesco; Berra-Romani, Roberto; Tanzi, Franco

2012-01-01

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca2+ signals, ranging from brief, localized Ca2+ pulses to prolonged Ca2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca2+ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca2+ machinery in vascular ECs under both physiological and pathological conditions. PMID:22905291

Developmental changes in cerebral and visceral blood flow velocity in healthy neonates and infants.

PubMed

Ilves, Pilvi; Lintrop, Mare; Talvik, Inga; Muug, Külli; Asser, Karin; Veinla, Maie

2008-02-01

The purpose of this study was to evaluate the changes in Doppler blood flow velocity (BFV) in cerebral and visceral arteries during infancy. The BFV was measured in 37 healthy term neonates in the anterior cerebral artery (ACA), middle cerebral artery (MCA), basilar artery, internal carotid artery (ICA), celiac artery (CA), superior mesenteric artery (SMA), and renal artery (RA). The mean BFV increased and the resistive index decreased (P < .05) in all cerebral arteries, SMA, and CA by the age of 12 to 23.9 hours and in the RA by the age of 24 to 35.9 hours compared with 2 to 11.9 hours. A further significant increase (P < .05) of the mean BFV occurred in all arteries except the ICA and CA by the age of 72 to 120 hours compared with 12 to 23.9 hours. By the age of 21 to 59 days, the mean BVF doubled in all investigated arteries compared with 2 to 11.9 hours, with a further significant increase (P < .05) by the age of 150 to 240 days in cerebral and renal arteries. There was no correlation between the mean blood pressure (BP) and mean BFV in the ACA and MCA. However, there was a positive correlation (r > or = 0.5; P < .05) between the BP and BFV in the RA and SMA at the age of 12 to 23.9 hours. A significant increase in the cerebral and visceral BFV occurs normally throughout infancy, with the visceral BFV affected by BP changes during the first day of life.

Minocycline reduces neuronal death and attenuates microglial response after pediatric asphyxial cardiac arrest.

PubMed

Tang, Minke; Alexander, Henry; Clark, Robert S B; Kochanek, Patrick M; Kagan, Valerian E; Bayir, Hülya

2010-01-01

The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. Rats were randomized to treatment with minocycline, (90 mg/kg, intraperitoneally (i.p.)) or vehicle (saline, i.p.) at 1 h after return of spontaneous circulation. Thereafter, minocycline (22.5 mg/kg, i.p.) was administrated every 12 h until sacrifice. Microglial activation (evaluated by immunohistochemistry using ionized calcium-binding adapter molecule-1 (Iba1) antibody) coincided with DNA fragmentation and neurodegeneration in CA1 hippocampus and cortex (assessed by deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), Fluoro-Jade-B and Nissl stain). Minocycline significantly decreased both the microglial response and neuronal degeneration compared with the vehicle. Asphyxial CA significantly enhanced proinflammatory cytokine and chemokine levels in hippocampus versus control (assessed by multiplex bead array assay), specifically tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha), regulated upon activation, normal T-cell expressed and secreted (RANTES), and growth-related oncogene (GRO-KC) (P<0.05). Minocycline attenuated ACA-induced increases in MIP-1alpha and RANTES (P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target.

Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells

NASA Astrophysics Data System (ADS)

Friel, David D.

Ionized free Ca ( Ca 2+) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca 2+ channels, pumps and exchangers that regulate cellular Ca 2+ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca 2+]. This review summarizes recent progress in characterizing Ca 2+ transporters in sympathetic neurons, which provide an ideal model for studying Ca 2+ dynamics in neurons. Our results show how the functional interplay between Ca 2+ transport systems that are regulated by Ca 2+ in quantitatively differ-ent ways leads to emergent properties of Ca 2+ signaling that are expected to play a critical role in defining how Ca 2+ serves its role as a signaling ion.

Interplay of Dirac electrons and magnetism in CaMnBi 2 and SrMnBi 2

DOE PAGES

Zhang, Anmin; Liu, Changle; Yi, Changjiang; ...

2016-12-16

Dirac materials exhibit intriguing low-energy carrier dynamics that offer a fertile ground for novel physics discovery. Something of particular interest is the interplay of Dirac carriers with other quantum phenomena such as magnetism. We report on a two-magnon Raman scattering study of AMnBi 2 (A=Ca, Sr), a prototypical magnetic Dirac system comprising alternating Dirac carrier and magnetic layers. We present the first accurate determination of the exchange energies in these compounds and, by comparison with the reference compound BaMn 2Bi 2, we show that the Dirac carrier layers in AMnBi 2 significantly enhance the exchange coupling between the magnetic layers,more » which in turn drives a charge-gap opening along the Dirac locus. These findings break new grounds in unveiling the fundamental physics of magnetic Dirac materials, which offer a novel platform for probing a distinct type of spin–Fermion interaction. Our results also hold great promise for applications in magnetic Dirac devices.« less

Interplay of Dirac electrons and magnetism in CaMnBi2 and SrMnBi2

PubMed Central

Zhang, Anmin; Liu, Changle; Yi, Changjiang; Zhao, Guihua; Xia, Tian-long; Ji, Jianting; Shi, Youguo; Yu, Rong; Wang, Xiaoqun; Chen, Changfeng; Zhang, Qingming

2016-01-01

Dirac materials exhibit intriguing low-energy carrier dynamics that offer a fertile ground for novel physics discovery. Of particular interest is the interplay of Dirac carriers with other quantum phenomena such as magnetism. Here we report on a two-magnon Raman scattering study of AMnBi2 (A=Ca, Sr), a prototypical magnetic Dirac system comprising alternating Dirac carrier and magnetic layers. We present the first accurate determination of the exchange energies in these compounds and, by comparison with the reference compound BaMn2Bi2, we show that the Dirac carrier layers in AMnBi2 significantly enhance the exchange coupling between the magnetic layers, which in turn drives a charge-gap opening along the Dirac locus. Our findings break new grounds in unveiling the fundamental physics of magnetic Dirac materials, which offer a novel platform for probing a distinct type of spin–Fermion interaction. The results also hold great promise for applications in magnetic Dirac devices. PMID:27982036

Ca3La2(BO3)4 crystal: a new candidate host material for the ytterbium ion

NASA Astrophysics Data System (ADS)

Wang, Yeqing; You, Zhenyu; Zhu, Zhaojie; Xu, Jinlong; Li, Jianfu; Wang, Yan; Wang, Hongyan; Tu, Chaoyang

2013-10-01

A disordered laser crystal Yb3+-doped Ca3La2(BO3)4 crystal was grown by the Czochralski technique. The characterized room temperature polarized spectra, re-absorption possibility and laser performance showed that this crystal should be a promising gain material, not only suitable for diode pumping, but also a good candidate for the generation of tunable and short pulse lasers. End pumped by a diode laser at 976 nm in plano-concave and plano-plano cavity, a 3.65 W output power with a slope efficiency of 65% was achieved by using a c-cut Yb3+:Ca3La2(BO3)4 crystal. The output laser wavelength shifted from 1042 to 1062 nm.

Comparison of sarcoplasmic reticulum capabilities in toadfish (Opsanus tau) sonic muscle and rat fast twitch muscle.

PubMed

Feher, J J; Waybright, T D; Fine, M L

1998-08-01

The sonic muscle of the oyster toadfish, Opsanus tau, can produce unfused contractions at 300 Hz. Electron microscopy shows a great abundance of the Sarcoplasmic reticulum (SR) in this muscle, but no functional characterization of the capabilities of the SR has been reported. We measured the oxalate-supported Ca2+ uptake rate and capacities of homogenates of toadfish sonic muscle and rat extensor digitorum longus (EDL) muscle, and estimated the number of pump units by titration with thapsigargin, a high-affinity, specific inhibitor of the SR Ca-ATPase. The Ca2+ uptake rate averaged 70.9 +/- 9.5 mumol min -1 per g tissue for the toad fish sonic muscle, and 73.5 +/- 3.7 mumol min -1 g-1 for rat EDL. The capacity for Ca2+ -oxalate uptake was 161 +/- 20 mumol g -1 and 33 +/- 2 mumol g -1 for toadfish sonic muscle and rat EDL, respectively. Thus, the rates of Ca2+ uptake were similar in the two muscles, but the toadfish sonic muscle had about five times the capacity of the rat EDL. The number of pumps as estimated by thapsigargin titration was 68 +/- 4 nmol of Ca-ATPase per g tissue in the toadfish, and 42 +/- 5 nmol Ca-ATPase per g tissue in the rat EDL. The turnover number, defined as the Ca2+ uptake divided by the number of pumps, was 1065 +/- 150 min -1 for toadfish and 1786 +/- 230 min -1 for rat EDL (p < 0.05) at 37 degrees C. The Ca2+ uptake rate of toadfish sonic muscle at 22 degree C, a typical temperature for calling toadfish, averaged 42 +/- 1% of its rate at 37 degree C. At these operating temperatures, the toadfish SR is likely to be slower than the rat fast-twitch SR, yet the toadfish sonic muscle supports more rapid contractions. One explanation for this is that the voluminous SR provides activator Ca2+ for contraction, but the abundant parvalbumin plays a major role in relaxation.

Does the pre-operative serum phosphate level predict early hypocalcaemia following parathyroidectomy for primary hyperparathyroidism?

PubMed

Ellul, David; Townsley, Richard Brendan; Clark, Louise Jane

2013-06-01

Hypocalcaemia is a significant post-operative complication following parathyroidectomy. Early identification of risk factors can help pre-empt hypocalcaemia and avoid serious sequelae. It can also help identify those patients that are not suitable for day-case surgery. The aim of this study was to analyse the predictive value of the pre-operative serum phosphate level as an indicator for developing hypocalcaemia post-operatively in patients undergoing parathyroidectomy for primary hyperparathyroidism. We performed a retrospective review of all patients who underwent parathyroidectomy between 2008 and 2010 at the Southern General Hospital in Glasgow. Data collected included the number of parathyroid glands excised and their histology, pre-operative adjusted calcium (aCa) and phosphate levels, post-operative aCa at 6 and 24 h following surgery, and the fall in aCa levels in the first 6 h and 24 h following surgery. Minitab Statistical Analysis (Version 15) was used for data analysis. Fifty-six patients underwent parathyroidectomy in the study period. Twelve patients were excluded for various reasons including incomplete records and secondary hyperparathyroidism. Patients given calcium or Vitamin D supplements immediately post-operatively were also excluded. Statistical analysis showed no significant correlation between the pre-operative phosphate level and the post-operative decline in aCa level 6 h or 24 h following surgery. Patients with a lower phosphate level pre-operatively were not at risk of a more drastic fall in calcium levels following parathyroidectomy. The pre-operative phosphate level was not found to be predictive of post-operative hypocalcaemia in our study. Copyright © 2012 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

13. CONTROL ROOM OF GENE PUMPING STATION. CONTROL CUBICLES ARRAYED ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. CONTROL ROOM OF GENE PUMPING STATION. CONTROL CUBICLES ARRAYED BEHIND MANAGER'S ART DECO-STYLE CONTROL DESK, WITH CONTROL CUBICLE 1 AT FAR RIGHT AND CONTROL CUBICLE 9 AT FAR LEFT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Cross-coupling between accommodation and convergence is optimized for a broad range of directions and distances of gaze.

PubMed

Nguyen, Dorothy; Vedamurthy, Indu; Schor, Clifton

2008-03-01

Accommodation and convergence systems are cross-coupled so that stimulation of one system produces responses by both systems. Ideally, the cross-coupled responses of accommodation and convergence match their respective stimuli. When expressed in diopters and meter angles, respectively, stimuli for accommodation and convergence are equal in the mid-sagittal plane when viewed with symmetrical convergence, where historically, the gains of the cross coupling (AC/A and CA/C ratios) have been quantified. However, targets at non-zero azimuth angles, when viewed with asymmetric convergence, present unequal stimuli for accommodation and convergence. Are the cross-links between the two systems calibrated to compensate for stimulus mismatches that increase with gaze-azimuth? We measured the response AC/A and stimulus CA/C ratios at zero azimuth, 17.5 and 30 deg of rightward gaze eccentricities with a Badal Optometer and Wheatstone-mirror haploscope. AC/A ratios were measured under open-loop convergence conditions along the iso-accommodation circle (locus of points that stimulate approximately equal amounts of accommodation to the two eyes at all azimuth angles). CA/C ratios were measured under open-loop accommodation conditions along the iso-vergence circle (locus of points that stimulate constant convergence at all azimuth angles). Our results show that the gain of accommodative-convergence (AC/A ratio) decreased and the bias of convergence-accommodation increased at the 30 deg gaze eccentricity. These changes are in directions that compensate for stimulus mismatches caused by spatial-viewing geometry during asymmetric convergence.

Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

PubMed

Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

2016-09-15

Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. Copyright © 2016 Elsevier Inc. All rights reserved.

Strain Dependent Electronic Structure and Band Offset Tuning at Heterointerfaces of ASnO3 (A=Ca, Sr, and Ba) and SrTiO3

PubMed Central

Baniecki, John D.; Yamazaki, Takashi; Ricinschi, Dan; Van Overmeere, Quentin; Aso, Hiroyuki; Miyata, Yusuke; Yamada, Hiroaki; Fujimura, Norifumi; Maran, Ronald; Anazawa, Toshihisa; Valanoor, Nagarajan; Imanaka, Yoshihiko

2017-01-01

The valence band (VB) electronic structure and VB alignments at heterointerfaces of strained epitaxial stannate ASnO3 (A=Ca, Sr, and Ba) thin films are characterized using in situ X-ray and ultraviolet photoelectron spectroscopies, with band gaps evaluated using spectroscopic ellipsometry. Scanning transmission electron microscopy with geometric phase analysis is used to resolve strain at atomic resolution. The VB electronic structure is strain state dependent in a manner that correlated with a directional change in Sn-O bond lengths with strain. However, VB offsets are found not to vary significantly with strain, which resulted in ascribing most of the difference in band alignment, due to a change in the band gaps with strain, to the conduction band edge. Our results reveal significant strain tuning of conduction band offsets using epitaxial buffer layers, with strain-induced offset differences as large as 0.6 eV possible for SrSnO3. Such large conduction band offset tunability through elastic strain control may provide a pathway to minimize the loss of charge confinement in 2-dimensional electron gases and enhance the performance of photoelectrochemical stannate-based devices. PMID:28195149

Metal (Fe, Co, Ni) supported on different aluminas as Fischer-Tropsch catalyst

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

Dahlan; Marsih, I. Nyoman, E-mail: nyoman@chem.itb.ac.id; Ismunandar

2015-09-30

This research aimed to compare the physico-chemical properties of the same metal M (M = iron, cobalt, nickel) supported on aluminas with different morphology and pore size as Fischer-Tropsch catalyst. The aluminas applied as support were alumina synthesized through hydrothermal process, alumina formed by pretreatment of catapal and commercial alumina which named as Ahy, Aca, and Aco respectively. Ahy has uniform morphology of nanotubes while Aca and Aco showed non-uniform morphology of particle lumps. The particle lumps of Aca were larger than those of Aco. Ahy, Aca, and Aco respectively has average pore diameter of 2.75, 2.86 and 2.9 nm. Metalsmore » were deposited on the supports by incipient-wetness impregnation method. The catalysts were characterized by XRD, H{sub 2}-TPR, and H{sub 2} chemisorption. Catalyst acitivity test for Fischer-Tropsch reaction was carried out in a micro reactor at 200 °C and 1 atm, and molar ratio of H{sub 2}/CO = 2:1. The metal oxide particle size increased in the order M/Aco < M/Aca < M/Ahy. The catalysts reducibility also increased according to the order M/Aco < M/Aca < M/Ahy suggesting that the larger metal oxide particles are more reducible. The number of active site was not proportional to the reducibility because during the reduction, larger metal oxide particles were converted into larger metal particles. On the other hand, the number of active sites was inversely proportional to the particle sizes. The number of active site increased in the order M/Ahy < M/Aco < M/Aca. The catalytic activity also increased in the following order M/Ahy < M/Aco < M/Aca. The activity per active site increased according to the order M/Aca < M/Aco < M/Ahy meaning that for M/Ahy, a little increase in active site will lead to a significance increase in catalytic activity. It showed that Ahy has potential for the better support.« less

Method for production of hydrocarbons from hydrates

DOEpatents

McGuire, Patrick L.

1984-01-01

A method of recovering natural gas entrapped in frozen subsurface gas hydrate formations in arctic regions. A hot supersaturated solution of CaCl.sub.2 or CaBr.sub.2, or a mixture thereof, is pumped under pressure down a wellbore and into a subsurface hydrate formation so as to hydrostatically fracture the formation. The CaCl.sub.2 /CaBr.sub.2 solution dissolves the solid hydrates and thereby releases the gas entrapped therein. Additionally, the solution contains a polymeric viscosifier, which operates to maintain in suspension finely divided crystalline CaCl.sub.2 /CaBr.sub.2 that precipitates from the supersaturated solution as it is cooled during injection into the formation.

Plasma membrane calcium ATPases and related disorders.

PubMed

Giacomello, Marta; De Mario, Agnese; Scarlatti, Chiara; Primerano, Simona; Carafoli, Ernesto

2013-03-01

The plasma membrane Ca(2+) ATPases (PMCA pumps) cooperate with other transport systems in the plasma membrane and in the organelles in the regulation of cell Ca(2+). They have high Ca(2+) affinity and are thus the fine tuners of cytosolic Ca(2+). They belong to the superfamily of P-type ATPases: their four basic isoforms share the essential properties of the reaction cycle and the general membrane topography motif of 10 transmembrane domains and three large cytosolic units. However they also differ in other important properties, e.g., tissue distribution and regulatory mechanisms. Their chief regulator is calmodulin, that removes their C-terminal cytosolic tail from autoinhibitory binding sites next to the active site of the pump, restoring activity. The number of pump isoforms is increased to over 30 by alternative splicing of the transcripts at a N-terminal site (site A) and at site C within the C-terminal calmodulin binding domain: the splice variants are tissue specific and developmentally regulated. The importance of PMCAs in the maintenance of cellular Ca(2+) homeostasis is underlined by the disease phenotypes, genetic or acquired, caused by their malfunction. Non-genetic PMCA deficiencies have long been considered possible causative factors in disease conditions as important as cancer, hypertension, or neurodegeneration. Those of genetic origin are better characterized: some have now been discovered in humans as well. They concern all four PMCA isoforms, and range from cardiac dysfunctions, to deafness, to hypertension, to cerebellar ataxia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disparity-driven vs blur-driven models of accommodation and convergence in binocular vision and intermittent strabismus

PubMed Central

Horwood, Anna M.; Riddell, Patricia M.

2014-01-01

Purpose To propose an alternative and practical model to conceptualize clinical patterns of concomitant intermittent strabismus, heterophoria, and convergence and accommodation anomalies. Methods Despite identical ratios, there can be a disparity- or blur-biased “style” in three hypothetical scenarios: normal; high ratio of accommodative convergence to accommodation (AC/A) and low ratio of convergence accommodation to convergence (CA/C); low AC/A and high CA/C. We calculated disparity bias indices (DBI) to reflect these biases and provide early objective data from small illustrative clinical groups that fit these styles. Results Normal adults (n = 56) and children (n = 24) showed disparity bias (adult DBI 0.43 [95% CI, 0.50-0.36], child DBI 0.20 [95% CI, 0.31-0.07]; P = 0.001). Accommodative esotropia (n = 3) showed less disparity-bias (DBI 0.03). In the high AC/A–low CA/C scenario, early presbyopia (n = 22) showed mean DBI of 0.17 (95% CI, 0.28-0.06), compared to DBI of −0.31 in convergence excess esotropia (n=8). In the low AC/A–high CA/C scenario near exotropia (n = 17) showed mean DBI of 0.27. DBI ranged between 1.25 and −1.67. Conclusions Establishing disparity or blur bias adds to AC/A and CA/C ratios to explain clinical patterns. Excessive bias or inflexibility in near-cue use increases risk of clinical problems. PMID:25498466

Disparity-driven vs blur-driven models of accommodation and convergence in binocular vision and intermittent strabismus.

PubMed

Horwood, Anna M; Riddell, Patricia M

2014-12-01

To propose an alternative and practical model to conceptualize clinical patterns of concomitant intermittent strabismus, heterophoria, and convergence and accommodation anomalies. Despite identical ratios, there can be a disparity- or blur-biased "style" in three hypothetical scenarios: normal; high ratio of accommodative convergence to accommodation (AC/A) and low ratio of convergence accommodation to convergence (CA/C); low AC/A and high CA/C. We calculated disparity bias indices (DBI) to reflect these biases and provide early objective data from small illustrative clinical groups that fit these styles. Normal adults (n = 56) and children (n = 24) showed disparity bias (adult DBI 0.43 [95% CI, 0.50-0.36], child DBI 0.20 [95% CI, 0.31-0.07]; P = 0.001). Accommodative esotropia (n = 3) showed less disparity-bias (DBI 0.03). In the high AC/A-low CA/C scenario, early presbyopia (n = 22) showed mean DBI of 0.17 (95% CI, 0.28-0.06), compared to DBI of -0.31 in convergence excess esotropia (n=8). In the low AC/A-high CA/C scenario near exotropia (n = 17) showed mean DBI of 0.27. DBI ranged between 1.25 and -1.67. Establishing disparity or blur bias adds to AC/A and CA/C ratios to explain clinical patterns. Excessive bias or inflexibility in near-cue use increases risk of clinical problems. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

New members of the A{sub 2}M′M{sub 2}{sup ″} structure family (A=Ca, Sr, Yb, La; M′=In,Sn,Pb; M″=Si,Ge)

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

Jehle, Michael; Dürr, Ines; Fink, Saskia

The new mixed tetrelides Sr{sub 2}PbGe{sub 2} and Yb{sub 2}SnGe{sub 2}, several mixed Ca/Sr (A{sup II}) germanides A{sub 2}{sup II}(Sn,Pb)Ge{sub 2} and two polymorphs of La{sub 2}InSi{sub 2} represent new members of the general structure family of ternary alkaline-earth/lanthanoid main group silicides/germanides A{sub 2}M′M{sub 2}{sup ″}(M′=In,Sn,Pb;M″=Si,Ge). All compounds were synthesized from melts of the elements and their crystal structures have been determined by means of single crystal X-ray diffraction. Sr{sub 2}PbGe{sub 2} (Cmmm, a=402.36(11), b=1542.3(4), c=463.27(10) pm) crystallizes with the Mn{sub 2}AlB{sub 2}-type structure. In exhibiting infinite planar Ge zig-zag chains, it represents one border of the compound series. Themore » other borderline case, where only [Ge{sub 2}] dumbbells are left as Ge building units, is represented by the Ca/Yb tin germanides Ca{sub 2}SnGe{sub 2} and Yb{sub 2}SnGe{sub 2} (Mo{sub 2}FeB{sub 2}-type; P4/mbm, a=748.58(13)/740.27(7), c=445.59(8)/435.26(5) pm). In between these two border structures compounds with variable Si/Ge chain lengths could be obtained by varying the averaged size of the A{sup II} cations: Ca{sub 0.45}Sr{sub 1.55}PbGe{sub 2} (new structure type; Pbam, a=791.64(5), b=2311.2(2), c=458.53(3) pm) contains planar six-membered chain segments [Ge{sub 6}]. Tetrameric pieces [Ge{sub 4}] are the conspicuous structure elements in Ca{sub 1.16}Sr{sub 0.84}SnGe{sub 2} and La{sub 2}InSi{sub 2} (La{sub 2}InNi{sub 2}-type; Pbam, a=781.01(2)/762.01(13), b=1477.95(3)/1494.38(6), c=457.004(9)/442.1(3) pm). The tetragonal form of ’La{sub 2}InSi{sub 2}{sup ′} (exact composition: La{sub 2}In{sub 1.07}Si{sub 1.93}, P4/mbm, a=1309.11(12), c=443.32(4) pm) also crystallizes in a new structure type, containing only [Si{sub 3}] trimers as cutouts of the planar chains. In all structures the Si/Ge zig-zag chains/chain segments are connected by In/Sn/Pb atoms to form planar M layers, which are separated by pure A layers. Band structure calculations within the FP-LAPW DFT approach together with the Zintl formalism, extended by the presence of hypervalent bonding of the heavier M′ elements, give insight into the chemical bonding of this series of p-block metallides. An analysis of the band structure for the border phases Sr{sub 2}PbGe{sub 2} and Ca{sub 2}SnGe{sub 2} shows the considerable π bonding contributions within the Ge building units, which also become apparent from the short Ge–Ge bond lengths. - Graphical abstract: Example of one of the mixed metallides A{sub 2}(In/Sn/Pb)(Si/Ge){sub 2} with planar Si/Ge zig-zag chain segments of variable lengths. - Highlights: • Mixed metallides A{sub 2}(In/Sn/Pb)(Si/Ge){sub 2} were prepared for A=Ca, Sr, Yb, La. • The structures exhibit planar Si/Ge zig-zag chain segments of variable lengths. • In, Sn and Pb atoms are connecting the Si/Ge anions to planar nets. • Atomic size effects are investigated by the synthesis of mixed Ca/Sr germanides. • Bandstructure calculations indicate Si/Ge–Si/Ge π bonding contributions.« less

Homer2 protein regulates plasma membrane Ca²⁺-ATPase-mediated Ca²⁺ signaling in mouse parotid gland acinar cells.

PubMed

Yang, Yu-Mi; Lee, Jiae; Jo, Hae; Park, Soonhong; Chang, Inik; Muallem, Shmuel; Shin, Dong Min

2014-09-05

Homer proteins are scaffold molecules with a domain structure consisting of an N-terminal Ena/VASP homology 1 protein-binding domain and a C-terminal leucine zipper/coiled-coil domain. The Ena/VASP homology 1 domain recognizes proline-rich motifs and binds multiple Ca(2+)-signaling proteins, including G protein-coupled receptors, inositol 1,4,5-triphosphate receptors, ryanodine receptors, and transient receptor potential channels. However, their role in Ca(2+) signaling in nonexcitable cells is not well understood. In this study, we investigated the role of Homer2 on Ca(2+) signaling in parotid gland acinar cells using Homer2-deficient (Homer2(-/-)) mice. Homer2 is localized at the apical pole in acinar cells. Deletion of Homer2 did not affect inositol 1,4,5-triphosphate receptor localization or channel activity and did not affect the expression and activity of sarco/endoplasmic reticulum Ca(2+)-ATPase pumps. In contrast, Homer2 deletion markedly increased expression of plasma membrane Ca(2+)-ATPase (PMCA) pumps, in particular PMCA4, at the apical pole. Accordingly, Homer2 deficiency increased Ca(2+) extrusion by acinar cells. These findings were supported by co-immunoprecipitation of Homer2 and PMCA in wild-type parotid cells and transfected human embryonic kidney 293 (HEK293) cells. We identified a Homer-binding PPXXF-like motif in the N terminus of PMCA that is required for interaction with Homer2. Mutation of the PPXXF-like motif did not affect the interaction of PMCA with Homer1 but inhibited its interaction with Homer2 and increased Ca(2+) clearance by PMCA. These findings reveal an important regulation of PMCA by Homer2 that has a central role on PMCA-mediated Ca(2+) signaling in parotid acinar cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook.

PubMed

Jarius, S; Wildemann, B

2015-09-17

Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa head antibodies' due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook.

Sphingosine inhibits the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA) activity

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

Benaim, Gustavo, E-mail: gbenaim@idea.gob.ve; Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela; Pimentel, Adriana A., E-mail: adriana.pimentel@ucv.ve

2016-04-29

The increase in the intracellular Ca{sup 2+} concentration ([Ca{sup 2+}]{sub i}) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca{sup 2+}]{sub i} by inhibiting the sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca{sup 2+} pump. The results showed that addition of sphingosine produced a release of Ca{sup 2+} from the endoplasmic reticulum followed by a Ca{sup 2+} entrance from the outside mileu. The results presented in this work support thatmore » this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca{sup 2+}]{sub I} in mammalian cells.« less

NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy

PubMed Central

Brandt, Moritz; Garlapati, Venkata; Oelze, Matthias; Sotiriou, Efthymios; Knorr, Maike; Kröller-Schön, Swenja; Kossmann, Sabine; Schönfelder, Tanja; Morawietz, Henning; Schulz, Eberhard; Schultheiss, Heinz-Peter; Daiber, Andreas; Münzel, Thomas; Wenzel, Philip

2016-01-01

Alcoholic cardiomyopathy (ACM) resulting from excess alcohol consumption is an important cause of heart failure (HF). Although it is assumed that the cardiotoxicity of the ethanol (EtOH)-metabolite acetaldehyde (ACA) is central for its development and progression, the exact mechanisms remain obscure. Murine cardiomyocytes (CMs) exposed to ACA or EtOH showed increased superoxide (O2•−) levels and decreased mitochondrial polarization, both being normalized by NADPH oxidase (NOX) inhibition. C57BL/6 mice and mice deficient for the ACA-degrading enzyme mitochondrial aldehyde dehydrogenase (ALDH-2−/−) were fed a 2% EtOH diet for 5 weeks creating an ACA-overload. 2% EtOH-fed ALDH-2−/− mice exhibited a decreased cardiac function, increased heart-to-body and lung-to-body weight ratios, increased cardiac levels of the lipid peroxidation product malondialdehyde (MDA) as well as increased NOX activity and NOX2/glycoprotein 91phox (NOX2/gp91phox) subunit expression compared to 2% EtOH-fed C57BL/6 mice. Echocardiography revealed that ALDH-2−/−/gp91phox−/− mice were protected from ACA-overload-induced HF after 5 weeks of 2% EtOH-diet, demonstrating that NOX2-derived O2•− contributes to the development of ACM. Translated to human pathophysiology, we found increased gp91phox expression in endomyocardial biopsies of ACM patients. In conclusion, ACM is promoted by ACA-driven mitochondrial dysfunction and can be improved by ablation of NOX2/gp91phox. NOX2/gp91phox therefore might be a potential pharmacological target to treat ACM. PMID:27624556

Investigation into Deep-Draft Vessel Berthing Problems at Selected U. S. Naval Facilities.

DTIC Science & Technology

1980-10-01

AOR I WICHITA Alameda, CA 1-24-75 AOR 2 MILWAUKEE Norfolk, VA 1-01-74 AOR 3 KANSAS CITY Alameda, CA 2-16-74 AOR 4 SAVANNAH Norfolk, VA 12-05-70 AOR...auger-cutter assembly dislodges and delivers the material to the pump suction intake. The slurry is pumped to a pipeline for transmission to a remote...complete loss of control of the course steered. Large current eddies having the same effect are found in the vicinity of the foundation piers of the San

Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy

PubMed Central

Gong, Zimu; Medeiros, L. Jeffrey; Cortes, Jorge E.; Chen, Zi; Zheng, Lan; Li, Yan; Bai, Shi; Lin, Pei; Miranda, Roberto N.; Jorgensen, Jeffrey L.; McDonnell, Timothy J.; Wang, Wei; Kantarjian, Hagop M.

2017-01-01

The high fatality of patients with blast phase (BP) chronic myeloid leukemia (CML) necessitates identification of high-risk (HR) patients to prevent onset of BP. Here, we investigated the risk of BP based on additional chromosomal abnormality (ACA) profiles in a cohort of 2326 CML patients treated with tyrosine kinase inhibitors (TKIs). We examined the time intervals from initial diagnosis to ACA emergence (interval 1), from ACA emergence to onset of BP (interval 2), and survival after onset of BP (interval 3). Based on BP risk associated with each ACA, patients were stratified into intermediate-1, intermediate-2, and HR groups, with a median duration of interval 2 of unreached, 19.2 months, and 1.9 months, respectively. There was no difference in durations of intervals 1 or 3 among 3 groups. Including patients without ACAs who formed the standard-risk group, the overall 5-year cumulative probability of BP was 9.8%, 28.0%, 41.7%, and 67.4% for these 4 groups, respectively. The pre-BP disease course in those who developed BP was similar regardless of cytogenetic alterations, and 84.4% of BP patients developed BP within the first 5 years of diagnosis. In summary, interval 2 is the predominant determinant of BP risk and patient outcome. By prolonging the duration of interval 2, TKI therapy mitigates BP risk associated with low-risk ACAs or no ACAs but does not alter the natural course of CML with HR ACAs. Thus, we have identified a group of patients who have HR of BP and may benefit from timely alternative treatment to prevent onset of BP. PMID:29296906

The influence of first near-spectacle reading correction on accommodation and its interaction with convergence.

PubMed

Vedamurthy, Indu; Harrison, Wendy W; Liu, Yue; Cox, Ian; Schor, Clifton M

2009-09-01

Accommodation and convergence can adapt to blur and disparity stimuli and to age-related changes in accommodative amplitude. Does this ability decline with age? The authors investigated short-term adaptation to first near-spectacle reading correction on the accommodative-stimulus response (ASR) function, accommodative amplitude (AA), AC/A, and CA/C ratios in a pre-presbyopic and an incipient presbyopic population and determined whether changes in these functions recovered after discontinuation of the use of near spectacles. Thirty subjects with normal vision participated; their ages ranged from 21 to 30 years (n = 15) and 38 to 44 years (n = 15). Oculomotor functions were measured before and after single-vision reading spectacles were worn for near tasks over a 2-month period and then 2 months after the use of near spectacles was discontinued. The slope of the ASR function and the AC/A and CA/C ratios did not change significantly after near spectacles were worn. There was a hyperopic shift of the ASR function that significantly reduced the near point of accommodation (NPA) and lowered the far-point refraction. These changes were age invariant and did not recover after 2 months of discontinuation of near spectacle wear. These results imply that the NPA may be enhanced normally by tonic bias of accommodation that elevates the entire ASR function and produces myopic refraction bias. When this bias relaxes after reading spectacles are worn, there is a hyperopic shift of the refractive state and a reduction of the NPA, specified from optical infinity.

The Influence of First Near-Spectacle Reading Correction on Accommodation and Its Interaction with Convergence

PubMed Central

Vedamurthy, Indu; Harrison, Wendy W.; Liu, Yue; Cox, Ian; Schor, Clifton M.

2010-01-01

PURPOSE Accommodation and convergence can adapt to blur and disparity stimuli and to age-related changes in accommodative amplitude. Does this ability decline with age? The authors investigated short-term adaptation to first near-spectacle reading correction on the accommodative-stimulus response (ASR) function, accommodative amplitude (AA), AC/A, and CA/C ratios in a pre-presbyopic and an incipient presbyopic population and determined whether changes in these functions recovered after discontinuation of the use of near spectacles. METHODS Thirty subjects with normal vision participated; their ages ranged from 21 to 30 years (n = 15) and 38 to 44 years (n = 15). Oculomotor functions were measured before and after single-vision reading spectacles were worn for near tasks over a 2-month period and then 2 months after the use of near spectacles was discontinued. RESULTS The slope of the ASR function and the AC/A and CA/C ratios did not change significantly after near spectacles were worn. There was a hyperopic shift of the ASR function that significantly reduced the near point of accommodation (NPA) and lowered the far-point refraction. These changes were age invariant and did not recover after 2 months of discontinuation of near spectacle wear. CONCLUSIONS These results imply that the NPA may be enhanced normally by tonic bias of accommodation that elevates the entire ASR function and produces myopic refraction bias. When this bias relaxes after reading spectacles are worn, there is a hyperopic shift of the refractive state and a reduction of the NPA, specified from optical infinity. PMID:19264892

Rooting depth explains [CO2] x drought interaction in Eucalyptus saligna.

PubMed

Duursma, Remko A; Barton, Craig V M; Eamus, Derek; Medlyn, Belinda E; Ellsworth, David S; Forster, Michael A; Tissue, David T; Linder, Sune; McMurtrie, Ross E

2011-09-01

Elevated atmospheric [CO(2)] (eC(a)) often decreases stomatal conductance, which may delay the start of drought, as well as alleviate the effect of dry soil on plant water use and carbon uptake. We studied the interaction between drought and eC(a) in a whole-tree chamber experiment with Eucalyptus saligna. Trees were grown for 18 months in their C(a) treatments before a 4-month dry-down. Trees grown in eC(a) were smaller than those grown in ambient C(a) (aC(a)) due to an early growth setback that was maintained throughout the duration of the experiment. Pre-dawn leaf water potentials were not different between C(a) treatments, but were lower in the drought treatment than the irrigated control. Counter to expectations, the drought treatment caused a larger reduction in canopy-average transpiration rates for trees in the eC(a) treatment compared with aC(a). Total tree transpiration over the dry-down was positively correlated with the decrease in soil water storage, measured in the top 1.5 m, over the drying cycle; however, we could not close the water budget especially for the larger trees, suggesting soil water uptake below 1.5 m depth. Using neutron probe soil water measurements, we estimated fractional water uptake to a depth of 4.5 m and found that larger trees were able to extract more water from deep soil layers. These results highlight the interaction between rooting depth and response of tree water use to drought. The responses of tree water use to eC(a) involve interactions between tree size, root distribution and soil moisture availability that may override the expected direct effects of eC(a). It is essential that these interactions be considered when interpreting experimental results.

Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals

PubMed Central

Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

2016-01-01

The spectral properties and laser performance of Er:SrF2 single crystals were investigated and compared with Er:CaF2. Er:SrF2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er3+:4I11/2 level) than those of Er:CaF2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W. PMID:27811994

Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals.

PubMed

Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

2016-11-04

The spectral properties and laser performance of Er:SrF 2 single crystals were investigated and compared with Er:CaF 2 . Er:SrF 2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er 3+ : 4 I 11/2 level) than those of Er:CaF 2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF 2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF 2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W.

Highly efficient dual-wavelength mid-infrared CW Laser in diode end-pumped Er:SrF2 single crystals

NASA Astrophysics Data System (ADS)

Ma, Weiwei; Qian, Xiaobo; Wang, Jingya; Liu, Jingjing; Fan, Xiuwei; Liu, Jie; Su, Liangbi; Xu, Jun

2016-11-01

The spectral properties and laser performance of Er:SrF2 single crystals were investigated and compared with Er:CaF2. Er:SrF2 crystals have larger absorption cross-sections at the pumping wavelength, larger mid-infrared stimulated emission cross-sections and much longer fluorescence lifetimes of the upper laser level (Er3+:4I11/2 level) than those of Er:CaF2 crystals. Dual-wavelength continuous-wave (CW) lasers around 2.8 μm were demonstrated in both 4at.% and 10at.% Er:SrF2 single crystals under 972 nm laser diode (LD) end pumping. The laser wavelengths are 2789.3 nm and 2791.8 nm in the former, and 2786.4 nm and 2790.7 nm in the latter, respectively. The best laser performance has been demonstrated in lightly doped 4at.% Er:SrF2 with a low threshold of 0.100 W, a high slope efficiency of 22.0%, an maximum output power of 0.483 W.

[Analysis of AC/A ratio after myopic excimer laser in situ keratomileusis].

PubMed

Wu, Xiao-ying; Liu, Shuang-zhen

2003-03-01

To study the changes of AC/A ratio of myopia after excimer laser in situ keratomileusis (LASIK). 135 myopia patients were treated by LASIK, their AC/A ratios were measured with synoptohore before surgery and 3 months after surgery. The average AC/A ratios of naked eyes or eyes wearing glasses before surgery and the naked after surgery were (0.724 +/- 0.587) (Delta)/D, (2.754 +/- 1.565) (Delta)/D, (1.618 +/- 1.027) (Delta)/D in turn. There were significant difference among those groups (P < 0.001). That also appeared in different degree of myopia naked before surgery (P < 0.01). We found no significant difference between the groups wearing glasses before surgery and naked after surgery (P > 0.05). A positive correlation was built up between postoperative AC/A ratio and AC/A ratio of wearing glasses or refractive diopter before surgery (r = 0.550, P < 0.001; r = 0.185, P < 0.005). And the postoperative AC/A ratios had a negative correlation to age or length of ocular axis (r = -0.340, P < 0.001; r = -0.192, P < 0.002). The regression equation for postoperative AC/A ratios was figured out as Y((Delta)/D) = 4.080 0 - 0.031 8X(1) - 0.097 1X(2) + 0.325 0X(3) (P < 0.001). X(1) = age (year), X(2) = length of ocular axis (mm), X(3) = preoperative AC/A ratio with weaning glasses ((Delta)/D). The naked AC/A ratios are higher than the preoperative's after LASIK, but lower than the wearing glasses's before surgery. It is influenced by the factors, such as: the preoperative AC/A ratio of wearing glasses, the length of ocular axis and the age.

Calcium Signaling enhancement during oocyte maturation

NASA Astrophysics Data System (ADS)

Jung, Peter; Ullah, Ghanim; Machaca, Khaled

2006-03-01

A Ca2+ signal with a special spatial and temporal characteristic universally removes cell-cycle arrest after fertilization of a mature egg cell. The Ca2+ signal is characterized by a fast rise of intracellular Ca2+ and a slow decay on the time scale of minutes. We use computational modeling of Ca2+ release on the microscale (Ca2+ puffs) and cell-scale in conjunction with experimental knowledge of the changes in the Ca2+ signaling apparatus during oocyte maturation and changing signaling patterns to explore the relationship between organization and sensitivity of IP3 receptors and SERCA pumps and the resulting signaling patterns. We hypothesize that potentiation of the IP3 receptors during oocyte maturation is the main cause for the differentiation in the signaling patterns.

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2014-08-01

GAC CTT CAA CAC CCC GTG GCC ATC TCC TGC TCG AAG TC Meredith et al 2011* Mstn ACT GGA CCT CTC GAT AGA ACA CTC ACT TAG TGC TGT GTG TGT GGA GAT...NM_010834.2 IGF-1 CAG ACA GGA GCC CAG GAA AG AAG TGC CGT ATC CCA GAG GA NM_184052 MHC ACA GTC AGA GGT GTG ACTC AGC CG CCG ACT TGC GGA GGA AAG GTG C...AGC AGA GA TGA GTG CCT GCG GTA CAG AT NM_007553.2 RUNX-2 GGA AAG GCA CTG ACT GAC CTA ACA AAT TCT AAG CTT GGG AGG A NM_009820 Osx ACT ACC CAC CCT TCC

Targeting PRMT5 as a Novel Radiosensitization Approach for Primary and Recurrent Prostate Cancer Treatment

DTIC Science & Technology

2013-08-01

CCT G-30; KLK2 F: 50- TGG CTG TGT ACA GTC ATG GA-30; KLK2 R: 50- CCT GTG TCT TCA GGC TCA AA-30; TMPRSS2 F: 50-AGG TGC ATC CGG CTC AGT A-30; TMPRSS2 R...50-GGG TCA AGG TGA TGC ACA GT-30; PCDH11 F: 50-GCG TTT CTG ACT GTG GCT ATC-30; PCDH11 R: 50-GGA AGG GGA ATG GAA TTT TG-30; UGT2B15 F: 50-TCA AATc-Jun...GAPDH F: 50-CTG ACT TCA ACA GCG ACA CC-30; GAPDH R: 50-CCC TGT TGC TGT AGC CAA AT-30; AR F: 50- GTG GAA GCT GCA AGG TCT TC-30; AR R 50-CGA AGA CGA

Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

PubMed Central

Cha, Chae Young; Nakamura, Yasuhiko; Himeno, Yukiko; Wang, JianWu; Fujimoto, Shinpei; Inagaki, Nobuya; Earm, Yung E

2011-01-01

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings. PMID:21708953

Modeling CICR in rat ventricular myocytes: voltage clamp studies

PubMed Central

2010-01-01

Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses. PMID:21062495

The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes

PubMed Central

Garrity, Abigail G; Wang, Wuyang; Collier, Crystal MD; Levey, Sara A; Gao, Qiong; Xu, Haoxing

2016-01-01

Impaired homeostasis of lysosomal Ca2+ causes lysosome dysfunction and lysosomal storage diseases (LSDs), but the mechanisms by which lysosomes acquire and refill Ca2+ are not known. We developed a physiological assay to monitor lysosomal Ca2+ store refilling using specific activators of lysosomal Ca2+ channels to repeatedly induce lysosomal Ca2+ release. In contrast to the prevailing view that lysosomal acidification drives Ca2+ into the lysosome, inhibiting the V-ATPase H+ pump did not prevent Ca2+ refilling. Instead, pharmacological depletion or chelation of Endoplasmic Reticulum (ER) Ca2+ prevented lysosomal Ca2+ stores from refilling. More specifically, antagonists of ER IP3 receptors (IP3Rs) rapidly and completely blocked Ca2+ refilling of lysosomes, but not in cells lacking IP3Rs. Furthermore, reducing ER Ca2+ or blocking IP3Rs caused a dramatic LSD-like lysosome storage phenotype. By closely apposing each other, the ER may serve as a direct and primary source of Ca2+for the lysosome. DOI: http://dx.doi.org/10.7554/eLife.15887.001 PMID:27213518

Effect of cryogenic temperature on spectroscopic and laser properties of Er,La:SrF2-CaF2 crystal

NASA Astrophysics Data System (ADS)

Švejkar, Richard; Šulc, Jan; Němec, Michal; Jelínková, Helena; Doroshenko, Maxim E.; Nakladov, Andrei N.; Osiko, Vjatcheslav V.

2016-03-01

The laser and spectroscopic properties of crystal Er,La:SrF2-CaF2 at temperature range 80 - 300 K, which is appropriate for generation of radiation around 2.7 um is presented. The sample of Er,La:SrF2-CaF2 (concentration Er(0.04), La(0.12):Ca(0.77)Sr(0.07)) had plan-parallel face-polished faces without anti-reflection coatings (thickness 8.2 mm). During spectroscopy and laser experiments the Er,La:SrF2-CaF2 was attached to temperature controlled copper holder and it was placed in vacuum chamber. The transmission and emission spectra of Er,La:SrF2-CaF2 together with the fluorescence decay time were measured in dependence on temperature. The excitation of Er,La:SrF2-CaF2 was carried out by a laser diode radiation (pulse duration 5 ms, repetition rate 20 Hz, pump wavelength 973 nm). Laser resonator was hemispherical, 140 mm in length with at pumping mirror (HR @ 2.7 µm) and spherical output coupler (r = 150 mm, R = 95 % @ 2.5 - 2.8 µm). Tunability of laser at 80 K in range 2690 - 2765 nm was obtained using MgF2 birefringent filter. With decreasing temperature of sample the fluorescence lifetime of manifold 4I11/2 (upper laser level) became shorter and intensity of up-conversion radiation was increasing. The highest slope efficiency with respect to absorbed power was 2.3 % at 80 K. The maximum output of peak amplitude power was 0.3 W at 80 K, i.e. 1.5 times higher than measured this value at 300 K. The wavelength generated by Er,La:SrF2-CaF2 laser (2.7 µm) is relatively close to absorption peak of water (3 µm) and so, one of the possible usage should be in medicine and spectroscopy.

Effect of the environmental pollutant bisphenol A dimethacylate (BAD) on Ca2+ movement and viability in OC2 human oral cancer cells.

PubMed

Chien, Jau-Min; Chou, Chiang-Ting; Lu, Yi-Chau; Lu, Ti; Chi, Chao-Chuan; Tseng, Li-Ling; Liu, Shiuh-Inn; Cheng, Jin-Shiung; Kuo, Chun-Chi; Liang, Wei-Zhe; Jan, Chung-Ren

2013-03-01

The environmental pollutant bisphenol A dimethacylate (BAD) has been used as a dental composite. The effect of BAD on cytosolic Ca(2+) concentrations ([Ca(2+)]i) and viability in OC2 human oral cancer cells was explored. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)]i. BAD induced [Ca(2+)]i rises in a concentration-dependent manner. The response was reduced by removing extracellular Ca(2+). BAD-evoked Ca(2+) entry was suppressed by nifedipine, econazole, and SK&F96365. In Ca(2+)-free medium, incubation with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished BAD-induced [Ca(2+)]i rise. Inhibition of phospholipase C with U73122 did not alter BAD-induced [Ca(2+)]i rise. At 10-30μM, BAD inhibited cell viability, which was not reversed by chelating cytosolic Ca(2+). BAD (20-30μM) also induced apoptosis. Collectively, in OC2 cells, BAD induced a [Ca(2+)]i rise by evoking phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. BAD also caused apoptosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of 1-chloro-2,4-dinitrobenzene on K+ transport in normal and sickle human red blood cells.

PubMed

Muzyamba, M C; Gibson, J S

2003-03-15

1-Chloro-2,4-dinitrobenzene (CDNB), which causes oxidative stress through depletion of reduced glutathione (GSH), increases the passive K+ permeability of red cells. In this paper, we investigated the effects of CDNB (1 mM) on the activities of the K+-Cl- cotransporter (KCC; measured as Cl--dependent K+ influx) and the Gardos channel (taken as clotrimazole-sensitive K+ influx, 5 microM) in human red cells, using 86Rb+ as a K+ congener. 45Ca2+ was used to study passive Ca2+ entry and active Ca2+ efflux via the plasma membrane Ca2+ pump. Both the Gardos channel and KCC were stimulated in both normal and sickle red cells. In sickle cells, stimulation of KCC was similar in oxygenated and deoxygenated cells; that of the Gardos channel was greater in deoxygenated cells. In normal red cells, stimulation of both pathways was greater in oxygenated cells (by 4 +/- 1-fold; all means +/- S.E.M., n = 3). The effects on the Gardos channel were dependent on extracellular Ca2+ and were associated with inhibition of the plasma membrane Ca2+ pump (by 29 +/- 3 %, P < 0.01) and increased Ca2+ sensitivity of the channel (EC50 for [Ca2+]i reduced from 260 +/- 26 to 175 +/- 15 nM; P < 0.05). Cell volume, pHi, ATP levels and passive Ca2+ entry were not affected by CDNB. The effects on KCC were inhibited (93 +/- 6 %) by prior treatment with the protein phosphatase inhibitor calyculin A (100 nM) and were not additive with stimulation by N-ethylmaleimide (1 mM), regardless of the order of addition. These findings are therefore consistent with inhibition of a regulatory protein kinase, although stimulation of the conjugate protein phosphatase(s) may also occur. KCC stimulation was also Ca2+ dependent. These findings are important for understanding how GSH depletion alters membrane permeability and how to protect against red cell dehydration.

Inositol trisphosphate modification of ion transport in rough endoplasmic reticulum.

PubMed

Muallem, S; Schoeffield, M; Pandol, S; Sachs, G

1985-07-01

The ion transport properties of the rough endoplasmic reticulum (RER) from liver have been defined by using measurements of active and potential gradient-driven transport. The Ca2+ pump is shown to be electrogenic, and both ATP and potential difference is able to drive vanadate-inhibitable Ca2+ uptake into the RER. ATP-dependent Ca2+ transport into the RER depends on the presence of tetraethylammonium-sensitive cation conductance and a furosemide-inhibited cation/chloride cotransport pathway. Inositol trisphosphate does not affect either of the monovalent ion translocation systems but activates a Ca2+ conductance in the RER, allowing efflux of RER Ca2+ stores into the cytosol in exchange for K+ uptake.

Inositol trisphosphate modification of ion transport in rough endoplasmic reticulum.

PubMed Central

Muallem, S; Schoeffield, M; Pandol, S; Sachs, G

1985-01-01

The ion transport properties of the rough endoplasmic reticulum (RER) from liver have been defined by using measurements of active and potential gradient-driven transport. The Ca2+ pump is shown to be electrogenic, and both ATP and potential difference is able to drive vanadate-inhibitable Ca2+ uptake into the RER. ATP-dependent Ca2+ transport into the RER depends on the presence of tetraethylammonium-sensitive cation conductance and a furosemide-inhibited cation/chloride cotransport pathway. Inositol trisphosphate does not affect either of the monovalent ion translocation systems but activates a Ca2+ conductance in the RER, allowing efflux of RER Ca2+ stores into the cytosol in exchange for K+ uptake. PMID:3874400

The Effect of Medicaid Expansion on Utilization in Maryland Emergency Departments.

PubMed

Klein, Eili Y; Levin, Scott; Toerper, Matthew F; Makowsky, Michael D; Xu, Tim; Cole, Gai; Kelen, Gabor D

2017-11-01

A proposed benefit of expanding Medicaid eligibility under the Patient Protection and Affordable Care Act (ACA) was a reduction in emergency department (ED) utilization for primary care needs. Pre-ACA studies found that new Medicaid enrollees increased their ED utilization rates, but the effect on system-level ED visits was less clear. Our objective was to estimate the effect of Medicaid expansion on aggregate and individual-based ED utilization patterns within Maryland. We performed a retrospective cross-sectional study of ED utilization patterns across Maryland, using data from Maryland's Health Services Cost Review Commission. We also analyzed utilization differences between pre-ACA (July 2012 to December 2013) uninsured patients who returned post-ACA (July 2014 to December 2015). The total number of ED visits in Maryland decreased by 36,531 (-1.2%) between the 6 quarters pre-ACA and the 6 quarters post-ACA. Medicaid-covered ED visits increased from 23.3% to 28.9% (159,004 additional visits), whereas uninsured patient visits decreased from 16.3% to 10.4% (181,607 fewer visits). Coverage by other insurance types remained largely stable between periods. We found no significant relationship between Medicaid expansion and changes in ED volume by hospital. For patients uninsured pre-ACA who returned post-ACA, the adjusted visits per person during 6 quarters was 2.38 (95% confidence interval 2.35 to 2.40) for those newly enrolled in Medicaid post-ACA compared with 1.66 (95% confidence interval 1.64 to 1.68) for those remaining uninsured. There was a substantial increase in patients covered by Medicaid in the post-ACA period, but this did not significantly affect total ED volume. Returning patients newly enrolled in Medicaid visited the ED more than their uninsured counterparts; however, this cohort accounted for only a small percentage of total ED visits in Maryland. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Mechanisms underlying ketoconazole-induced Ca(2+) mobilization in Madin-Darby canine kidney cells.

PubMed

Jan, C; Tseng, C

2000-04-15

The effect of ketoconazole on Ca(2+) signaling in Madin-Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Ketoconazole evoked increases in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) concentration dependently. The response was decreased by external Ca(2+) removal. In Ca(2+)-free medium, pretreatment with ketoconazole abolished the [Ca(2+)](i) rise induced by thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+) pump. Addition of 3 mM Ca(2+) induced a significant [Ca(2+)](i) rise after preincubation with 150 microM ketoconazole in Ca(2+)-free medium. Pretreatment with aristolochic acid (40 microM) to inhibit phospholipase A(2) inhibited the 150-microM-ketoconazole-induced internal Ca(2+) release by 37%, but inhibition of phospholipase C with 1-(6-((17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122) (2 microM) had no effect. Collectively, we found that ketoconazole increases [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from thapsigargin-sensitive pools in a manner independent of the production of inositol-1,4,5-trisphosphate, followed by Ca(2+) influx from the external space.

11. PUMP ROOM FLOOR OF GENE PLANT FROM NORTH END, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. PUMP ROOM FLOOR OF GENE PLANT FROM NORTH END, CENTRIFUGAL PUMPS DESIGNED BY BYRON JACKSON CO., MANUFACTURED BY PELTON WATER WHEEL CO. OF SAN FRANCISCO. POWERED BY G.E. SYNCHRONOUS MOTOR 9000 HP, 6900 VOLTS, 612 AMPS, 7320 KVA, 3 PHASE, 60 CYCLES, 400 RPM, EXCITATION AT 125 VOLTS, 540 AMPS. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Bone bonding bioactivity of Ti metal and Ti-Zr-Nb-Ta alloys with Ca ions incorporated on their surfaces by simple chemical and heat treatments.

PubMed

Fukuda, A; Takemoto, M; Saito, T; Fujibayashi, S; Neo, M; Yamaguchi, S; Kizuki, T; Matsushita, T; Niinomi, M; Kokubo, T; Nakamura, T

2011-03-01

Ti15Zr4Nb4Ta and Ti29Nb13Ta4.6Zr, which do not contain the potentially cytotoxic elements V and Al, represent a new generation of alloys with improved corrosion resistance, mechanical properties, and cytocompatibility. Recently it has become possible for the apatite forming ability of these alloys to be ascertained by treatment with alkali, CaCl2, heat, and water (ACaHW). In order to confirm the actual in vivo bioactivity of commercially pure titanium (cp-Ti) and these alloys after subjecting them to ACaHW treatment at different temperatures, the bone bonding strength of implants made from these materials was evaluated. The failure load between implant and bone was measured for treated and untreated plates at 4, 8, 16, and 26 weeks after implantation in rabbit tibia. The untreated implants showed almost no bonding, whereas all treated implants showed successful bonding by 4 weeks, and the failure load subsequently increased with time. This suggests that a simple and economical ACaHW treatment could successfully be used to impart bone bonding bioactivity to Ti metal and Ti-Zr-Nb-Ta alloys in vivo. In particular, implants heat treated at 700 °C exhibited significantly greater bone bonding strength, as well as augmented in vitro apatite formation, in comparison with those treated at 600 °C. Thus, with this improved bioactive treatment process these advantageous Ti-Zr-Nb-Ta alloys can serve as useful candidates for orthopedic devices. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Generation of Kerr combs centered at 4.5 μm in crystalline microresonators pumped with quantum-cascade lasers.

PubMed

Savchenkov, Anatoliy A; Ilchenko, Vladimir S; Di Teodoro, Fabio; Belden, Paul M; Lotshaw, William T; Matsko, Andrey B; Maleki, Lute

2015-08-01

We report on the generation of mid-infrared Kerr frequency combs in high-finesse CaF2 and MgF2 whispering-gallery-mode resonators pumped with continuous-wave room-temperature quantum cascade lasers. The combs were centered at 4.5 μm, the longest wavelength to date. A frequency comb wider than one half of an octave was demonstrated when approximately 20 mW of pump power was coupled to an MgF2 resonator characterized with quality factor exceeding 10(8).

19. GENE CAMP ADMINISTRATIVE COMPLEX WITH HEADQUARTERS IN MIDDLE GROUND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. GENE CAMP ADMINISTRATIVE COMPLEX WITH HEADQUARTERS IN MIDDLE GROUND AND SUPPLY LINES IN BACKGROUND. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Nonradiative decay dynamics of methyl-4-hydroxycinnamate and its hydrated complex revealed by picosecond pump-probe spectroscopy.

PubMed

Shimada, Daiki; Kusaka, Ryoji; Inokuchi, Yoshiya; Ehara, Masahiro; Ebata, Takayuki

2012-07-07

The lifetimes of methyl 4-hydroxycinnamate (OMpCA) and its mono-hydrated complex (OMpCA-H(2)O) in the S(1) state have been measured by picosecond pump-probe spectroscopy in a supersonic beam. For OMpCA, the lifetime of the S(1)-S(0) origin is 8-9 ps. On the other hand, the lifetime of the OMpCA-H(2)O complex at the origin is 930 ps, which is ∼100 times longer than that of OMpCA. Furthermore, in the complex the S(1) lifetime shows rapid decrease at an energy of ∼200 cm(-1) above the origin and finally becomes as short as 9 ps at ∼500 cm(-1). Theoretical calculations with a symmetry-adapted cluster-configuration interaction (SAC-CI) method suggest that the observed lifetime behavior of the two species is described by nonradiative decay dynamics involving trans → cis isomerization. That is both OMpCA and OMpCA-H(2)O in the S(1) state decay due to the trans → cis isomerization, and the large difference of the lifetimes between them is due to the difference of the isomerization potential energy curve. In OMpCA, the trans → cis isomerization occurs smoothly without a barrier on the S(1) surface, while in the OMpCA-H(2)O complex, there exists a barrier along the isomerization coordinate. The calculated barrier height of OMpCA-H(2)O is in good agreement with that observed experimentally.

Thapsigargin-induced increase in cytoplasmic Ca2+ concentration and aldosterone production in rat adrenal glomerulosa cells: interaction with potassium and angiotensin-II.

PubMed

Hajnóczky, G; Várnai, P; Holló, Z; Christensen, S B; Balla, T; Enyedi, P; Spät, A

1991-05-01

Thapsigargin (Tg), a microsomal Ca2+ pump inhibitor, dose-dependently increases the cytoplasmic Ca2+ concentration and aldosterone production without having any striking effect on the formation of inositol phosphates in isolated rat adrenal glomerulosa cells. The interaction of Tg with the major Ca2(+)-mediated stimuli of glomerulosa cells on aldosterone production was also examined. The effects of Tg and the Ca2(+)-mobilizing angiotensin-II (AII) were additive. The aldosterone production stimulatory effect of potassium, which induces Ca2+ influx via voltage-operated Ca2+ channels, was potentiated by Tg. The positive interaction between Tg and potassium on aldosterone production raises the possibility that stimuli generating Ca2+ signal by depleting intracellular Ca2+ stores, such as Tg or AII, enhance the response of the cell to depolarization. Such an interaction between AII and potassium may have an important role in the physiological control of aldosterone production.

Dyskeratosis congenita mutations in the H/ACA domain of human telomerase RNA affect its assembly into a pre-RNP

PubMed Central

Trahan, Christian; Dragon, François

2009-01-01

Dyskeratosis congenita (DC) is an inherited disorder that implicates defects in the biology of telomeres, which are maintained by telomerase, a ribonucleoprotein with reverse transcriptase activity. Like all H/ACA RNAs, the H/ACA domain of nascent human telomerase RNA (hTR) forms a pre-RNP with H/ACA proteins NAF1, dyskerin, NOP10, and NHP2 in vivo. To assess the pre-RNP assembly of hTR mutants that poorly accumulate in vivo, we developed an in vitro system that uses components of human origin. Pre-RNPs were reconstituted with synthetic 32P-labeled RNAs and 35S-labeled proteins produced in rabbit reticulocyte lysate, and immunoprecipitations were carried out to analyze RNP formation. We show that human NAF1 cannot bind directly to the H/ACA domain of hTR, and requires the core trimer dyskerin-NOP10-NHP2 to be efficiently incorporated into the pre-RNP. This order of assembly seems common to H/ACA RNAs since it was observed with snoRNA ACA36 and scaRNA U92, which are predicted to guide pseudouridylation of 18S rRNA and U2 snRNA, respectively. However, the processing H/ACA snoRNA U17 did not conform to this rule, as NAF1 alone was able to bind it. We also provide the first evidence that DC-related mutations of hTR C408G and Δ378-451 severely impair pre-RNP assembly. Integrity of boxes H and ACA of hTR are also crucial for pre-RNP assembly, while the CAB box is dispensable. Our results offer new insights into the defects caused by some mutations located in the H/ACA domain of hTR. PMID:19095616

7. TRANSFORMER BANK. NOTE CONCRETE BARRIER WALL FROM WWII ON ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. TRANSFORMER BANK. NOTE CONCRETE BARRIER WALL FROM WWII ON LEFT TO PROTECT TRANSFORMERS FROM JAPANESE BOMBS. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase function in skinned rat slow- and fast-twitch fibres.

PubMed

Bouhlel, Aicha; Joumaa, Wissam H; Léoty, Claude

2003-09-01

The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.

Preparation, Delivery, and Evaluation of Picomole Vapor Standards

DTIC Science & Technology

2013-07-10

brass bellows vacuum valve (Part No. BFLM-K40, Duniway Stockroom Corp., Mountain View, CA USA). A scroll pump was used rather than a mechanical...evacuated 1 L ballast canister, while the dead volume of the quick connect is evacuated with a turbomolecular vacuum pump . 3 Figure 1: Valve layout...mL canister for 2 min. GC Splitless Inlet GC Splitless Inlet Turbomolecular Vacuum Pump Turbomolecular Vacuum Pump QT Quick

Multifaceted plasma membrane Ca(2+) pumps: From structure to intracellular Ca(2+) handling and cancer.

PubMed

Padányi, Rita; Pászty, Katalin; Hegedűs, Luca; Varga, Karolina; Papp, Béla; Penniston, John T; Enyedi, Ágnes

2016-06-01

Plasma membrane Ca(2+) ATPases (PMCAs) are intimately involved in the control of intracellular Ca(2+) concentration. They reduce Ca(2+) in the cytosol not only by direct ejection, but also by controlling the formation of inositol-1,4,5-trisphosphate and decreasing Ca(2+) release from the endoplasmic reticulum Ca(2+) pool. In mammals four genes (PMCA1-4) are expressed, and alternative RNA splicing generates more than twenty variants. The variants differ in their regulatory characteristics. They localize into highly specialized membrane compartments and respond to the incoming Ca(2+) with distinct temporal resolution. The expression pattern of variants depends on cell type; a change in this pattern can result in perturbed Ca(2+) homeostasis and thus altered cell function. Indeed, PMCAs undergo remarkable changes in their expression pattern during tumorigenesis that might significantly contribute to the unbalanced Ca(2+) homeostasis of cancer cells. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy.

PubMed

Chen, Z; Shao, C; Wang, W; Zuo, Z; Mou, X; Hu, S J; DiGiuseppe, J A; Zu, Y; Medeiros, L J; Hu, S

2017-03-01

The landscape of additional chromosomal alterations (ACAs) and their impact in chronic myeloid leukemia, blast phase (CML-BP) treated with tyrosine kinase inhibitors (TKIs) have not been well studied. Here, we investigated a cohort of 354 CML-BP patients treated with TKIs. We identified +8, an extra Philadelphia chromosome (Ph), 3q26.2 rearrangement, -7 and isochromosome 17q (i(17q)) as the major-route changes with a frequency of over 10%. In addition, +21 and +19 had a frequency of over 5%. These ACAs demonstrated lineage specificity: +8, 3q26.2 rearrangement, i(17q) and +19 were significantly more common in myeloid BP, and -7 more common in lymphoid BP; +Ph and +21 were equally distributed between two groups. Pearson correlation analysis revealed clustering of common ACAs into two groups: 3q26.2 rearrangement, -7 and i(17q) formed one group, and other ACAs formed another group. The grouping correlated with risk stratification of ACAs in CML, chronic phase. Despite the overall negative prognostic impact of ACAs, stratification of ACAs into major vs minor-route changes provided no prognostic relevance in CML-BP. The emergence of 3q26.2 rearrangement as a major-route change in the TKI era correlated with a high frequency of ABL1 mutations, supporting a role for TKI resistance in the changing cytogenetic landscape in CML-BP.

2. Credit BG. View looks west southwest (245°) at Building ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Credit BG. View looks west southwest (245°) at Building 4317, Deluge Water Pumping Station. The machinery in this structure draws water from an inground reservoir, Building 4316, whose round roof is visible at left rear of this view. - Edwards Air Force Base, North Base, Deluge Water Pumping Station, Near Second & D Streets, Boron, Kern County, CA

Calcium Signals: The Lead Currency of Plant Information Processing

PubMed Central

Kudla, Jörg; Batistič, Oliver; Hashimoto, Kenji

2010-01-01

Ca2+ signals are core transducers and regulators in many adaptation and developmental processes of plants. Ca2+ signals are represented by stimulus-specific signatures that result from the concerted action of channels, pumps, and carriers that shape temporally and spatially defined Ca2+ elevations. Cellular Ca2+ signals are decoded and transmitted by a toolkit of Ca2+ binding proteins that relay this information into downstream responses. Major transduction routes of Ca2+ signaling involve Ca2+-regulated kinases mediating phosphorylation events that orchestrate downstream responses or comprise regulation of gene expression via Ca2+-regulated transcription factors and Ca2+-responsive promoter elements. Here, we review some of the remarkable progress that has been made in recent years, especially in identifying critical components functioning in Ca2+ signal transduction, both at the single-cell and multicellular level. Despite impressive progress in our understanding of the processing of Ca2+ signals during the past years, the elucidation of the exact mechanistic principles that underlie the specific recognition and conversion of the cellular Ca2+ currency into defined changes in protein–protein interaction, protein phosphorylation, and gene expression and thereby establish the specificity in stimulus response coupling remain to be explored. PMID:20354197

A Solid State Ultraviolet Lasers Based on Cerium-Doped LiCaAIF(sub 6) Crystal Resonator

NASA Technical Reports Server (NTRS)

Yu, Nan; Le, Thanh; Schowalter, Steven J.; Rellergert, Wade; Jeet, Justin; Lin, Guoping; Hudson, Eric

2012-01-01

We report the first demonstration of a UV laser using a high-Q whispering gallery mode (WGM) resonator of Ce+: LiCaAlF6. We show that WGM resonators from LiCaAlF6 can achieve a Q of 2.6 x 10(sup 7) at UV. We demonstrated a UV laser at 290 nm with a pulsed pump laser at 266 nm. The experiments showed the low pump threshold intensity of 7.5 x 10(sup 9) W/m(sup 2) and slope efficiency of 25%. We have also observed lasing delay dynamics. These results are consistent with our modeling and theoretical estimates, and pave the way for a low threshold cw UV laser using WGM resonator cavity.

Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

PubMed

Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

2018-05-22

Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P < 0.05 as significant. Correlation of AlbBCG and AlbBCP was r = 0.948 (p < 0.0001), but mean difference was large. Bland-Altman plots showed greater bias at lower albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (< 1 g/L). The AlbBCG assay bias shows a good correlation with alpha-1-globulin concentrations (r = 0.758); moderate and weak correlations were observed with CRP (r = 0.729) and alpha-2-globulin (r = 0.585); we found no correlation with beta-globulin (r = 0.120) or gamma-globulin (r = -0.303). Mean aCa based on AlbBCG and AlbBCP methods were 2.34 ± 0.15 mmol/L and 2.46 ± 0.16 mmol/L (p < 0.01), with a mean BCG-BCP difference of -0.12. Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

PubMed Central

de Angelis, Martin Hrabé; Fuchs, Helmut; Lim, Dmitry; Ortolano, Saida; Ingham, Neil J.; Brini, Marisa; Carafoli, Ernesto; Mammano, Fabio; Steel, Karen P.

2008-01-01

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone. PMID:18974863

Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.

PubMed

Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

2016-06-15

Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it was determined that firing was stochastic in nature. Ca(2+) transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 μm) significantly increased the occurrence of Ca(2+) transients, suggesting that ICC-DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca(2+) transients were minimally affected after 12 min in Ca(2+) free solution, indicating these events do not depend immediately upon Ca(2+) influx. However, inhibitors of sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3 R) and ryanodine receptor (RyR) channels blocked ICC Ca(2+) transients. These data suggest an interdependence between RyR and InsP3 R in the generation of Ca(2+) transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high-resolution recording of the subcellular Ca(2+) dynamics that control the behaviour of ICC-DMP in situ. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

PubMed Central

Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.

2016-01-01

Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was determined that firing was stochastic in nature. Ca2+ transients were tabulated in multiple cells within fields of view, and no correlation was found between the events in adjacent cells. TTX (1 μm) significantly increased the occurrence of Ca2+ transients, suggesting that ICC‐DMP contributes to the tonic inhibition conveyed by ongoing activity of inhibitory motor neurons. Ca2+ transients were minimally affected after 12 min in Ca2+ free solution, indicating these events do not depend immediately upon Ca2+ influx. However, inhibitors of sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump and blockers of inositol triphosphate receptor (InsP3R) and ryanodine receptor (RyR) channels blocked ICC Ca2+ transients. These data suggest an interdependence between RyR and InsP3R in the generation of Ca2+ transients. Itpr1 and Ryr2 were the dominant transcripts expressed by ICC. These findings provide the first high‐resolution recording of the subcellular Ca2+ dynamics that control the behaviour of ICC‐DMP in situ. PMID:26824875

An overview of techniques for the measurement of calcium distribution, calcium fluxes, and cytosolic free calcium in mammalian cells.

PubMed Central

Borle, A B

1990-01-01

An array of techniques can be used to study cell calcium metabolism that comprises several calcium compartments and many types of transport systems such as ion channels, ATP-dependent pumps, and antiporters. The measurement of total cell calcium brings little information of value since 60 to 80% of total cell calcium is actually bound to the extracellular glycocalyx. Cell fractionation and differential centrifugation have been used to study intracellular Ca2+ compartmentalization, but the methods suffer from the possibility of Ca2+ loss or redistribution among cell fractions. Steady-state kinetic analyses of 45Ca uptake or desaturation curves have been used to study the distribution of Ca2+ among various kinetic pools in living cells and their rate of Ca2+ exchange, but the analyses are constrained by many limitations. Nonsteady-state tracer studies can provide information about rapid changes in calcium influx or efflux in and out of the cell. Zero-time kinetics of 45Ca uptake can detect instantaneous changes in calcium influx, while 45Ca fractional efflux ratio, can detect rapid stimulations or inhibitions of calcium efflux out of cells. Permeabilized cells have been successfully used to gauge the relative role of intracellular organelles in controlling [Ca2+]i. The measurement of the cytosolic ionized calcium ([Ca2+]i) is undoubtedly the most important and, physiologically, the most relevant method available. The choice of the appropriate calcium indicator, fluorescent, bioluminescent, metallochromic, or Ca2(+)-sensitive microelectrodes depends on the cell type and the magnitude and time constant of the event under study. Each probe has specific assets and drawbacks. The study of plasma membrane vesicles derived from baso-lateral or apical plasmalemma can also bring important information on the (Ca2(+)-Mg2+) ATPase-dependent calcium pump and on the kinetics and stoichiometry of the Na(+)-Ca2+ antiporter. The best strategy to study cell calcium metabolism is to use several different methods that focus on a specific problem from widely different angles. PMID:2190818

The Ca2+ pump inhibitor, thapsigargin, inhibits root gravitropism in Arabidopsis thaliana.

PubMed

Urbina, Daniela C; Silva, Herman; Meisel, Lee A

2006-01-01

Thapsigargin, a specific inhibitor of most animal intracellular SERCA-type Ca2+ pumps present in the sarcoplasmic/endoplasmic reticulum, was originally isolated from the roots of the Mediterranean plant Thapsia gargancia L. Here, we demonstrate that this root-derived compound is capable of altering root gravitropism in Arabidopsis thaliana. Thapsigargin concentrations as low as 0.1 microM alter root gravitropism whereas under similar conditions cyclopiazonic acid does not. Furthermore, a fluorescently conjugated thapsigargin (BODIPY FL thapsigargin) suggests that target sites for thapsigargin are located in intracellular organelles in the root distal elongation zone and the root cap, regions known to regulate root gravitropism.

2. Photocopy of photograph, U.S. Army, ca. 1943 (original print ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Photocopy of photograph, U.S. Army, ca. 1943 (original print located at Rocky Mountain Arsenal, Commerce City, Colorado). R.M.A. - 746 - 745-A&B-744 LOOKING EAST. - Rocky Mountain Arsenal, Valve-Pump House, 630 feet South of December Seventh Avenue; 2600 feet East of D Street, Commerce City, Adams County, CO

Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

PubMed Central

López-Sanjurjo, Cristina I.; Tovey, Stephen C.; Prole, David L.; Taylor, Colin W.

2013-01-01

Summary Most intracellular Ca2+ signals result from opening of Ca2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca2+ into mitochondria. Ca2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca2+ signalling, but the role of lysosomal Ca2+ uptake in Ca2+ signalling is unexplored. Inhibition of lysosomal Ca2+ uptake by dissipating the H+ gradient (using bafilomycin A1), perforating lysosomal membranes (using glycyl-L-phenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation. Bafilomycin A1 amplified the Ca2+ signals evoked by photolysis of caged Ins(1,4,5)P3 or by inhibition of ER Ca2+ pumps, and it slowed recovery from them. Ca2+ signals evoked by store-operated Ca2+ entry were unaffected by bafilomycin A1. Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca2+ released by Ins(1,4,5)P3 receptors. PMID:23097044

Characterization of ryanodine receptor and Ca2+-ATPase isoforms in the thermogenic heater organ of blue marlin (Makaira nigricans).

PubMed

Morrissette, Jeffery M; Franck, Jens P G; Block, Barbara A

2003-03-01

A thermogenic organ is found beneath the brain of billfishes (Istiophoridae), swordfish (Xiphiidae) and the butterfly mackerel (Scombridae). The heater organ has been shown to warm the brain and eyes up to 14 degrees C above ambient water temperature. Heater cells are derived from extraocular muscle fibers and express a modified muscle phenotype with an extensive transverse-tubule (T-tubule) network and sarcoplasmic reticulum (SR) enriched in Ca(2+)-ATPase (SERCA) pumps and ryanodine receptors (RyRs). Heater cells have a high mitochondria content but have lost most of the contractile myofilaments. Thermogenesis has been hypothesized to be associated with release and reuptake of Ca(2+). In this study, Ca(2+) fluxes in heater SR vesicles derived from blue marlin (Makaira nigricans) were measured using fura-2 fluorescence. Upon the addition of MgATP, heater SR vesicles rapidly sequestered Ca(2+). Uptake of Ca(2+) was thapsigargin sensitive, and maximum loading ranged between 0.8 micro mol Ca(2+) mg(-1) protein and 1.0 micro mol Ca(2+) mg(-1) protein. Upon the addition of 10 mmol l(-1) caffeine or 350 micro mol l(-1) ryanodine, heater SR vesicles released only a small fraction of the loaded Ca(2+). However, ryanodine could elicit a much larger Ca(2+) release event when the activity of the SERCA pumps was reduced. RNase protection assays revealed that heater tissue expresses an RyR isoform that is also expressed in fish slow-twitch skeletal muscle but is distinct from the RyR expressed in fish fast-twitch skeletal muscle. The heater and slow-twitch muscle RyR isoform has unique physiological properties. In the presence of adenine nucleotides, this RyR remains open even though cytoplasmic Ca(2+) is elevated, a condition that normally closes RyRs. The fast Ca(2+) sequestration by the heater SR, coupled with a physiologically unique RyR, is hypothesized to promote Ca(2+) cycling, ATP turnover and heat generation. A branch of the oculomotor nerve innervates heater organs, and, in this paper, we demonstrate that heater cells contain large 'endplate-like' clusters of acetylcholine receptors that appear to provide a mechanism for nervous control of thermogenesis.

Human H/ACA Small Nucleolar RNPs and Telomerase Share Evolutionarily Conserved Proteins NHP2 and NOP10

PubMed Central

Pogacic, Vanda; Dragon, François; Filipowicz, Witold

2000-01-01

The H/ACA small nucleolar RNAs (snoRNAs) are involved in pseudouridylation of pre-rRNAs. In the yeast Saccharomyces cerevisiae, four common proteins are associated with H/ACA snoRNAs: Gar1p, Cbf5p, Nhp2p, and Nop10p. In vitro reconstitution studies showed that four proteins also specifically interact with H/ACA snoRNAs in mammalian cell extracts. Two mammalian proteins, NAP57/dyskerin (the ortholog of Cbf5p) and hGAR1, have been characterized. In this work we describe properties of hNOP10 and hNHP2, human orthologs of yeast Nop10p and Nhp2p, respectively, and further characterize hGAR1. hNOP10 and hNHP2 complement yeast cells depleted of Nhp2p and Nop10p, respectively. Immunoprecipitation experiments with extracts from transfected HeLa cells indicated that epitope-tagged hNOP10 and hNHP2 specifically associate with hGAR1 and H/ACA RNAs; they also interact with the RNA subunit of telomerase, which contains an H/ACA-like domain in its 3′ moiety. Immunofluorescence microscopy experiments showed that hGAR1, hNOP10, and hNHP2 are localized in the dense fibrillar component of the nucleolus and in Cajal (coiled) bodies. Deletion analysis of hGAR1 indicated that its evolutionarily conserved core domain contains all the signals required for localization, but progressive deletions from either the N or the C terminus of the core domain abolish localization in the nucleolus and/or the Cajal bodies. PMID:11074001

Shortwave direct radiative effects of above cloud aerosols over global oceans derived from eight years of CALIOP and MODIS observations

NASA Astrophysics Data System (ADS)

Zhang, Z.; Meyer, K.; Yu, H.; Platnick, S.; Colarco, P.; Liu, Z.; Oreopoulos, L.

2015-09-01

In this paper, we studied the frequency of occurrence and shortwave direct radiative effects (DRE) of above-cloud aerosols (ACAs) over global oceans using eight years of collocated CALIOP and MODIS observations. Similar to previous work, we found high ACA occurrence in four regions: Southeast (SE) Atlantic region where ACAs are mostly light-absorbing aerosols, i.e., smoke and polluted dust according to CALIOP classification, originating from biomass burning over African Savanna; Tropical Northeast Atlantic and Arabian Sea where ACAs are predominantly windblown dust from the Sahara and Arabian desert, respectively; and Northwest Pacific where ACAs are mostly transported smoke and polluted dusts from Asian. From radiative transfer simulations based on CALIOP-MODIS observations and a set of the preselected aerosol optical models, we found the DREs of ACAs at the top of atmosphere (TOA) to be positive (i.e., warming) in the SE Atlantic and NW Pacific regions, but negative (i.e., cooling) in TNE Atlantic and Arabian Sea. The cancellation of positive and negative regional DREs results in a global ocean annual mean diurnally averaged cloudy-sky DRE of 0.015 W m-2 (range of -0.03 to 0.06 W m-2) at TOA. The DREs at surface and within atmosphere are -0.15 W m-2 (range of -0.09 to -0.21 W m-2), and 0.17 W m-2 (range of 0.11 to 0.24 W m-2), respectively. The regional and seasonal mean DREs are much stronger. For example, in the SE Atlantic region the JJA (July ~ August) seasonal mean cloudy-sky DRE is about 0.7 W m-2 (range of 0.2 to 1.2 W m-2) at TOA. The uncertainty in our DRE computations is mainly cause by the uncertainties in the aerosol optical properties, in particular aerosol absorption, and uncertainties in the CALIOP operational aerosol optical thickness retrieval. In situ and remotely sensed measurements of ACA from future field campaigns and satellite missions, and improved lidar retrieval algorithm, in particular vertical feature masking, would help reduce the uncertainty.

Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome.

PubMed

Doyle, Lesley; Saunders, Kathryn J; Little, Julie-Anne

2017-01-10

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6-16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation.

Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome

PubMed Central

Doyle, Lesley; Saunders, Kathryn J.; Little, Julie-Anne

2017-01-01

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6–16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation. PMID:28071728

Molecular identification and antibiotic resistant bacteria isolated from primary dentition infections.

PubMed

Loyola-Rodriguez, J P; Garcia-Cortes, J O; Martinez-Martinez, R E; Patiño-Marin, N; Martinez-Castañon, G A; Zavala-Alonso, N V; Amano, A

2014-12-01

Bacterial resistance to antibiotics is a health problem in many parts of the world. The aim of this study was to identify bacteria from dental infections and determine bacterial resistance to antibiotics used in dental care in the primary dentition. This cross-sectional study comprised 60 children who presented for dental treatment for active dental infections in the primary dentition. Samples from dental infections were collected and bacteria were identified by polymerase chain reaction (PCR) assay. Bacterial resistance to antibiotics was determined by colony forming units on agar plates containing amoxicillin, clindamycin and amoxillicin-clavulanic acid (A-CA) tested at 8 μg/ml or 16 μg/ml. Clindamycin in both concentrations tested (8 μg/ml and 16 μg/ml) showed the highest bacterial resistance (85.9%), followed by amoxicillin (43.7%) and A-CA (12.0%). All comparisons among the three antibiotics used in the study exhibited statistical significance (p = <0.05) in both concentrations tested (8 μg/ml and 16 μg/ml), and under aerobic and anaerobic conditions. The most prevalent resistant species identified by PCR in primary dentition infections were: Streptococcus oralis and Prevotella intermedia (75.0%); Treponema denticola and Porphyromonas gingivalis (48.3%); Streptococcus mutans (45.0%); Campylobacter rectus; and Streptococcus salivarius (40%). This study demonstrated that A-CA exhibited the lowest bacterial resistance for clinical isolates in primary dentition infections. © 2014 Australian Dental Association.

Tunneling barrier in nanoparticle junctions of La2/3(Ca,Sr)1/3MnO3: Nonlinear current-voltage characteristics

NASA Astrophysics Data System (ADS)

Niebieskikwiat, D.; Sánchez, R. D.; Lamas, D. G.; Caneiro, A.; Hueso, L. E.; Rivas, J.

2003-05-01

We study the nonlinear current-voltage (I-V) characteristics and analyze the voltage-dependent tunneling conductance in nanoparticles of La2/3A1/3MnO3 (A=Ca, Sr). The powders were prepared by different wet-chemical routes and low calcination temperatures were used to obtain an average particle size D≈30 nm. The data are comprehensively explained in terms of the tunneling picture, which allows one to estimate the height of the grain boundary insulating barrier (φ) for each sample. For constant D, our results show that the sample preparation route is mainly responsible for the value of φ in nanoparticles, while the Coulomb gap in the Coulomb blockade regime is ˜3 times higher for Sr- than for Ca-doping. We also show that a small fraction of the barriers contribute to the nonlinear transport, and the current is mainly carried through low-resistive percolated paths. In addition, despite the different barrier strengths, the low-field magnetoresistance (LFMR) is similar for all samples, implying that φ is not the fundamental parameter determining the LFMR.

Effect of 1-chloro-2,4-dinitrobenzene on K+ transport in normal and sickle human red blood cells

PubMed Central

Muzyamba, M C; Gibson, J S

2003-01-01

1-Chloro-2,4-dinitrobenzene (CDNB), which causes oxidative stress through depletion of reduced glutathione (GSH), increases the passive K+ permeability of red cells. In this paper, we investigated the effects of CDNB (1 mm) on the activities of the K+−Cl− cotransporter (KCC; measured as Cl−-dependent K+ influx) and the Gardos channel (taken as clotrimazole-sensitive K+ influx, 5 μm) in human red cells, using 86Rb+ as a K+ congener. 45Ca2+ was used to study passive Ca2+ entry and active Ca2+ efflux via the plasma membrane Ca2+ pump. Both the Gardos channel and KCC were stimulated in both normal and sickle red cells. In sickle cells, stimulation of KCC was similar in oxygenated and deoxygenated cells; that of the Gardos channel was greater in deoxygenated cells. In normal red cells, stimulation of both pathways was greater in oxygenated cells (by 4 ± 1-fold; all means ±s.e.m., n = 3). The effects on the Gardos channel were dependent on extracellular Ca2+ and were associated with inhibition of the plasma membrane Ca2+ pump (by 29 ± 3 %, P < 0.01) and increased Ca2+ sensitivity of the channel (EC50 for [Ca2+]i reduced from 260 ± 26 to 175 ± 15 nm; P < 0.05). Cell volume, pHi, ATP levels and passive Ca2+ entry were not affected by CDNB. The effects on KCC were inhibited (93 ± 6 %) by prior treatment with the protein phosphatase inhibitor calyculin A (100 nm) and were not additive with stimulation by N-ethylmaleimide (1 mm), regardless of the order of addition. These findings are therefore consistent with inhibition of a regulatory protein kinase, although stimulation of the conjugate protein phosphatase(s) may also occur. KCC stimulation was also Ca2+ dependent. These findings are important for understanding how GSH depletion alters membrane permeability and how to protect against red cell dehydration. PMID:12576491

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma.

PubMed

Tang, Juan; Guo, Yun-Shan; Yu, Xiao-Ling; Huang, Wan; Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-10-27

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC.

CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma

PubMed Central

Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

2015-01-01

Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+ refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC. PMID:26498680

A steady-state mechanism can account for the properties of inositol 2,4,5-trisphosphate-stimulated Ca2+ release from permeabilized L1210 cells.

PubMed Central

Loomis-Husselbee, J W; Dawson, A P

1993-01-01

We have investigated the effects of sub-maximal Ins(2,4,5)P3 concentrations on the Ca2+ permeability of the residual undischarged Ca2+ stores in electroporated or digitonin-permeabilized L1210 cells by measuring Ca(2+)-efflux rate after addition of the ATPase inhibitor thapsigargin. Low concentrations of Ins(2,4,5)P3, causing rapid discharge of a small proportion of the releasable Ca2+, result in a substantial stimulation of Ca2+ efflux after thapsigargin addition. This indicates firstly that in the absence of thapsigargin there must have been a substantial, counterbalancing, increase in rate of Ca2+ pumping, and secondly that the increased Ca2+ permeability is more consistent with a steady state than with a quantal model of Ca2+ release. Similar increases in passive Ca2+ permeability are produced by addition of concentrations of ionomycin which produce equivalent changes in Ca2+ loading to those produced by Ins(2,4,5)P3, although the time course and initial rate of Ca2+ release are very much slower. In the presence of a Ca(2+)-buffering system, the time course of Ca2+ release by Ins(2,4,5)P3 becomes superimposable on that of ionomycin, indicating that the initial rapid phase of Ins(2,4,5)P3-stimulated Ca2+ is at least partially due to positive feedback from extravesicular Ca2+. PMID:8382056

Transport mechanism of the sarcoplasmic reticulum Ca2+ -ATPase pump.

PubMed

Møller, Jesper V; Nissen, Poul; Sørensen, Thomas L-M; le Maire, Marc

2005-08-01

The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1a) belongs to the group of P-type ATPases, which actively transport inorganic cations across membranes at the expense of ATP hydrolysis. Three-dimensional structures of several transport intermediates of SERCA1a, stabilized by structural analogues of ATP and phosphoryl groups, are now available at atomic resolution. This has enabled the transport cycle of the protein to be described, including the coupling of Ca(2+) occlusion and phosphorylation by ATP, and of proton counter-transport and dephosphorylation. From these structures, Ca(2+)-ATPase gradually emerges as a molecular mechanical device in which some of the transmembrane segments perform Ca(2+) transport by piston-like movements and by the transmission of reciprocating movements that affect the chemical reactivity of the cytosolic globular domains.

Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca2+

PubMed Central

Scullin, Chessa S.; Partridge, L. Donald

2010-01-01

The presynaptic Ca2+ signal, which triggers vesicle release, disperses to a broadly distributed residual [Ca2+] ([Ca2+]res) that plays an important role in synaptic plasticity. We have previously reported a slowing in the decay timecourse of [Ca2+]res during the second of paired pulses. In this study, we investigated the contributions of organelle and plasma membrane Ca2+ flux pathways to the reduction of effectiveness of [Ca2+]res clearance during short-term plasticity in Schaffer collateral terminals in the CA1 field of the hippocampus. We show that the slowed decay timecourse is mainly the result of a transport-dependent Ca2+ clearance process; that presynaptic caffeine-sensitive Ca2+ stores are not functionally loaded in the unstimulated terminal, but that these stores can effectively take up Ca2+ even during high frequency trains of stimuli; and that a rate limiting step of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) kinetics following the first pulse is responsible for a large portion of the observed slowing of [Ca2+]res clearance during the second pulse. We were able to accurately fit our [Ca2+]res data with a kinetic model based on these observations and this model predicted a reduction in availability of unbound SERCA during paired pulses, but no saturation of Ca2+ buffer in the endoplasmic reticulum. PMID:20153896

Caffeine-induced [Ca2+] oscillations in neurones of frog sympathetic ganglia

PubMed Central

Cseresnyés, Zoltán; Bustamante, Alexander I; Schneider, Martin F

1999-01-01

Single cell fluorimetry was used to monitor caffeine-induced oscillations of cytosolic [Ca2+] in frog sympathetic ganglion neurones in 2.0 mm K+ Ringer solution.[Ca2+] oscillations decreased in frequency and exhibited three different amplitude patterns after the first large peak of [Ca2+]: (a) a series of big oscillations (BOs) of constant large amplitude (300–;400 nm), (b) a series of much smaller oscillations (SOs) (40–60 nm), or (c) a series of decaying oscillations (DOs) of rapidly decreasing amplitude.A model in which the oscillation amplitude was determined by the Ca2+ content of the endoplasmic reticulum (ER) whereas the oscillation frequency was controlled by how rapidly the cytosolic [Ca2+] reached the threshold for Ca2+-induced Ca2+ release (CICR) was able to simulate each observed pattern by varying the level of activity of the ER Ca2+ pump (SERCA), CICR and release-activated Ca2+ transport (RACT). A cumulative, cytosolic Ca2+-dependent inactivation of the plasma membrane (PM) Ca2+ influx or of the Ca2+-sensitive leak coefficient of the ryanodine receptors caused the oscillation frequency to decrease in the model.Transitions between BOs and SOs and changes in [Ca2+] oscillations caused by ryanodine, thapsigargin, lanthanum and FCCP could also be simulated.We conclude that RACT, SERCA, CICR and Ca2+-dependent PM Ca2+ influx are major mechanisms underlying [Ca2+] oscillations in these neurones. PMID:9831718

Calsequestrin content and SERCA determine normal and maximal Ca2+ storage levels in sarcoplasmic reticulum of fast- and slow-twitch fibres of rat.

PubMed

Murphy, Robyn M; Larkins, Noni T; Mollica, Janelle P; Beard, Nicole A; Lamb, Graham D

2009-01-15

Whilst calsequestrin (CSQ) is widely recognized as the primary Ca2+ buffer in the sarcoplasmic reticulum (SR) in skeletal muscle fibres, its total buffering capacity and importance have come into question. This study quantified the absolute amount of CSQ isoform 1 (CSQ1, the primary isoform) present in rat extensor digitorum longus (EDL) and soleus fibres, and related this to their endogenous and maximal SR Ca2+ content. Using Western blotting, the entire constituents of minute samples of muscle homogenates or segments of individual muscle fibres were compared with known amounts of purified CSQ1. The fidelity of the analysis was proven by examining the relative signal intensity when mixing muscle samples and purified CSQ1. The CSQ1 contents of EDL fibres, almost exclusively type II fibres, and soleus type I fibres [SOL (I)] were, respectively, 36 +/- 2 and 10 +/- 1 micromol (l fibre volume)(-1), quantitatively accounting for the maximal SR Ca2+ content of each. Soleus type II [SOL (II)] fibres (approximately 20% of soleus fibres) had an intermediate amount of CSQ1. Every SOL (I) fibre examined also contained some CSQ isoform 2 (CSQ2), which was absent in every EDL and other type II fibre except for trace amounts in one case. Every EDL and other type II fibre had a high density of SERCA1, the fast-twitch muscle sarco(endo)plasmic reticulum Ca2+-ATPase isoform, whereas there was virtually no SERCA1 in any SOL (I) fibre. Maximal SR Ca2+ content measured in skinned fibres increased with CSQ1 content, and the ratio of endogenous to maximal Ca2+ content was inversely correlated with CSQ1 content. The relative SR Ca2+ content that could be maintained in resting cytoplasmic conditions was found to be much lower in EDL fibres than in SOL (I) fibres (approximately 20 versus >60%). Leakage of Ca2+ from the SR in EDL fibres could be substantially reduced with a SR Ca2+ pump blocker and increased by adding creatine to buffer cytoplasmic [ADP] at a higher level, both results indicating that at least part of the Ca2+ leakage occurred through SERCA. It is concluded that CSQ1 plays an important role in EDL muscle fibres by providing a large total pool of releasable Ca2+ in the SR whilst maintaining free [Ca2+] in the SR at sufficiently low levels that Ca2+ leakage through the high density of SERCA1 pumps does not metabolically compromise muscle function.

Na+/Ca2+ exchange and Na+/K+-ATPase in the heart

PubMed Central

Shattock, Michael J; Ottolia, Michela; Bers, Donald M; Blaustein, Mordecai P; Boguslavskyi, Andrii; Bossuyt, Julie; Bridge, John H B; Chen-Izu, Ye; Clancy, Colleen E; Edwards, Andrew; Goldhaber, Joshua; Kaplan, Jack; Lingrel, Jerry B; Pavlovic, Davor; Philipson, Kenneth; Sipido, Karin R; Xie, Zi-Jian

2015-01-01

This paper is the third in a series of reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation–contraction coupling and arrhythmias: Na+ channel and Na+ transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on cardiac Na+/Ca2+ exchange (NCX) and Na+/K+-ATPase (NKA). While the relevance of Ca2+ homeostasis in cardiac function has been extensively investigated, the role of Na+ regulation in shaping heart function is often overlooked. Small changes in the cytoplasmic Na+ content have multiple effects on the heart by influencing intracellular Ca2+ and pH levels thereby modulating heart contractility. Therefore it is essential for heart cells to maintain Na+ homeostasis. Among the proteins that accomplish this task are the Na+/Ca2+ exchanger (NCX) and the Na+/K+ pump (NKA). By transporting three Na+ ions into the cytoplasm in exchange for one Ca2+ moved out, NCX is one of the main Na+ influx mechanisms in cardiomyocytes. Acting in the opposite direction, NKA moves Na+ ions from the cytoplasm to the extracellular space against their gradient by utilizing the energy released from ATP hydrolysis. A fine balance between these two processes controls the net amount of intracellular Na+ and aberrations in either of these two systems can have a large impact on cardiac contractility. Due to the relevant role of these two proteins in Na+ homeostasis, the emphasis of this review is on recent developments regarding the cardiac Na+/Ca2+ exchanger (NCX1) and Na+/K+ pump and the controversies that still persist in the field. PMID:25772291

Altered Ca2+ Kinetics Associated with α-Actinin-3 Deficiency May Explain Positive Selection for ACTN3 Null Allele in Human Evolution

PubMed Central

Houweling, Peter J.; Quinlan, Kate G. R.; Murphy, Robyn; Wagner, Sören; Friedrich, Oliver; North, Kathryn N.

2015-01-01

Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X) in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more “energy efficient” in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR) are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i) an increased rate of decay of the twitch transient; (ii) a fourfold increase in the rate of SR Ca2+ leak; (iii) a threefold increase in the rate of SR Ca2+ pumping; and (iv) enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments during recent evolution. PMID:25590636

Pump for spawning channels includes a turbine and motor. Turbine ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Pump for spawning channels includes a turbine and motor. Turbine is Berkeley H-17500, model 8C2PH, Serial No. 2889, B.M. No. 4886 - Berkeley Pump Co. The Motor is G.E. Induction Motor, model 5K4256XA3YI, serial no. GAJ728337, Tri-Clad. View looking northeast. - Prairie Creek Fish Hatchery, Hwy. 101, Orick, Humboldt County, CA

Effects of the Affordable Care Act on Young Women With Gynecologic Cancers.

PubMed

Smith, Anna Jo Bodurtha; Fader, Amanda N

2018-06-01

To evaluate the effects of the dependent coverage mandate of the 2010 Affordable Care Act (ACA) on insurance status, stage at diagnosis, and receipt of fertility-sparing treatment among young women with gynecologic cancer. We used a difference-in-differences design to assess insurance status, stage at diagnosis (stage I-II vs III-IV), and receipt of fertility-spearing treatment before and after the 2010 ACA among young women aged 21-26 years vs women aged 27-35 years. We used the National Cancer Database with the 2004-2009 surveys as the pre-ACA years and the 2011-2014 surveys as the post-ACA years. Women with uterine, cervical, ovarian, vulvar, or vaginal cancer were included. We analyzed outcomes for women overall and by cancer and insurance type, adjusting for race, nonrural area, and area-level household income and education level. A total of 1,912 gynecologic cancer cases pre-ACA and 2,059 post-ACA were identified for women aged 21-26 years vs 9,782 cases pre-ACA and 10,456 post-ACA for women aged 27-35 years. The ACA was associated with increased insurance (difference in differences 2.2%, 95% CI -4.0 to 0.1, P=.04) for young women aged 21-26 years vs women aged 27-35 years and with a significant improvement in early stage at cancer diagnosis (difference in differences 3.6%, 95% CI 0.4-6.9, P=.03) for women aged 21-26 years. Receipt of fertility-sparing treatment increased for women in both age groups post-ACA (P for trend=.004 for women aged 21-26 years and .001 for women aged 27-35 years); there was no significant difference in differences between age groups. Privately insured women were more likely to be diagnosed at an early stage and receive fertility-sparing treatment than publicly insured or uninsured women throughout the study period (P<.001). Under the ACA's dependent coverage mandate, young women with gynecologic cancer were more likely to be insured and diagnosed at an early stage of disease.

Rapid Recycling of Ca2+ between IP3-Sensitive Stores and Lysosomes

PubMed Central

López Sanjurjo, Cristina I.; Tovey, Stephen C.; Taylor, Colin W.

2014-01-01

Inositol 1,4,5-trisphosphate (IP3) evokes release of Ca2+ from the endoplasmic reticulum (ER), but the resulting Ca2+ signals are shaped by interactions with additional intracellular organelles. Bafilomycin A1, which prevents lysosomal Ca2+ uptake by inhibiting H+ pumping into lysosomes, increased the amplitude of the initial Ca2+ signals evoked by carbachol in human embryonic kidney (HEK) cells. Carbachol alone and carbachol in combination with parathyroid hormone (PTH) evoke Ca2+ release from distinct IP3-sensitive Ca2+ stores in HEK cells stably expressing human type 1 PTH receptors. Bafilomycin A1 similarly exaggerated the Ca2+ signals evoked by carbachol or carbachol with PTH, indicating that Ca2+ released from distinct IP3-sensitive Ca2+ stores is sequestered by lysosomes. The Ca2+ signals resulting from store-operated Ca2+ entry, whether evoked by thapsigargin or carbachol, were unaffected by bafilomycin A1. Using Gd3+ (1 mM) to inhibit both Ca2+ entry and Ca2+ extrusion, HEK cells were repetitively stimulated with carbachol to assess the effectiveness of Ca2+ recycling to the ER after IP3-evoked Ca2+ release. Blocking lysosomal Ca2+ uptake with bafilomycin A1 increased the amplitude of each carbachol-evoked Ca2+ signal without affecting the rate of Ca2+ recycling to the ER. This suggests that Ca2+ accumulated by lysosomes is rapidly returned to the ER. We conclude that lysosomes rapidly, reversibly and selectively accumulate the Ca2+ released by IP3 receptors residing within distinct Ca2+ stores, but not the Ca2+ entering cells via receptor-regulated, store-operated Ca2+ entry pathways. PMID:25337829

Rapid recycling of Ca2+ between IP3-sensitive stores and lysosomes.

PubMed

López Sanjurjo, Cristina I; Tovey, Stephen C; Taylor, Colin W

2014-01-01

Inositol 1,4,5-trisphosphate (IP3) evokes release of Ca2+ from the endoplasmic reticulum (ER), but the resulting Ca2+ signals are shaped by interactions with additional intracellular organelles. Bafilomycin A1, which prevents lysosomal Ca2+ uptake by inhibiting H+ pumping into lysosomes, increased the amplitude of the initial Ca2+ signals evoked by carbachol in human embryonic kidney (HEK) cells. Carbachol alone and carbachol in combination with parathyroid hormone (PTH) evoke Ca2+ release from distinct IP3-sensitive Ca2+ stores in HEK cells stably expressing human type 1 PTH receptors. Bafilomycin A1 similarly exaggerated the Ca2+ signals evoked by carbachol or carbachol with PTH, indicating that Ca2+ released from distinct IP3-sensitive Ca2+ stores is sequestered by lysosomes. The Ca2+ signals resulting from store-operated Ca2+ entry, whether evoked by thapsigargin or carbachol, were unaffected by bafilomycin A1. Using Gd3+ (1 mM) to inhibit both Ca2+ entry and Ca2+ extrusion, HEK cells were repetitively stimulated with carbachol to assess the effectiveness of Ca2+ recycling to the ER after IP3-evoked Ca2+ release. Blocking lysosomal Ca2+ uptake with bafilomycin A1 increased the amplitude of each carbachol-evoked Ca2+ signal without affecting the rate of Ca2+ recycling to the ER. This suggests that Ca2+ accumulated by lysosomes is rapidly returned to the ER. We conclude that lysosomes rapidly, reversibly and selectively accumulate the Ca2+ released by IP3 receptors residing within distinct Ca2+ stores, but not the Ca2+ entering cells via receptor-regulated, store-operated Ca2+ entry pathways.

Changes in functioning of rat submandibular salivary gland under streptozotocin-induced diabetes are associated with alterations of Ca2+ signaling and Ca2+ transporting pumps.

PubMed

Fedirko, N V; Kruglikov, I A; Kopach, O V; Vats, J A; Kostyuk, P G; Voitenko, N V

2006-03-01

Xerostomia and pathological thirst are troublesome complications of diabetes mellitus associated with impaired functioning of salivary glands; however, their cellular mechanisms are not yet determined. Isolated acinar cells were loaded with Ca2+ indicators fura-2/AM for measuring cytosolic Ca2+ concentration ([Ca2+]i) or mag-fura-2/AM-inside the endoplasmic reticulum (ER). We found a dramatic decrease in pilocarpine-stimulated saliva flow, protein content and amylase activity in rats after 6 weeks of diabetes vs. healthy animals. This was accompanied with rise in resting [Ca2+]i and increased potency of acetylcholine (ACh) and carbachol (CCh) but not norepinephrine (NE) to induce [Ca2+]i transients in acinar cells from diabetic animals. However, [Ca2+]i transients mediated by Ca2+ release from ER stores (induced by application of either ACh, CCh, NE, or ionomycin in Ca2+-free extracellular medium) were decreased under diabetes. Application of inositol-1,4,5-trisphosphate led to smaller Ca2+ release from ER under the diabetes. Both plasmalemma and ER Ca2+-ATPases activity was reduced and the latter showed the increased affinity to ATP under the diabetes. We conclude that the diabetes caused impairment of salivary cells functions that, on the cellular level, associates with Ca2+ overload, increased Ca2+-mobilizing ability of muscarinic but not adrenergic receptors, decreased Ca2+-ATPases activity and ER Ca2+ content.

Anterior segment biometry using ultrasound biomicroscopy and the Artemis-2 very high frequency ultrasound scanner

PubMed Central

Al-Farhan, Haya M; AlMutairi, Reem N

2013-01-01

Purpose To compare the precision of anterior chamber angle (ACA) and anterior chamber depth (ACD) measurements taken with ultrasound biomicroscopy (UBM) and the Artemis-2 Very High Frequency Ultrasound Scanner (VHFUS) in normal subjects. Design Prospective study. Methods We randomly selected one eye from each of 59 normal subjects in this study. Two subjects dropped out of the study; the associated data were excluded from analysis. ACA and ACD measurements were obtained using the VHFUS and the UBM. The results were compared statistically using repeated-measures analysis of variance for the intraobserver repeatability, unpaired t-test, and limits of agreement. Results The average ACA values for the UBM and the VHFUS (±standard deviation) were 41.83° ± 5.03° and 33.36° ± 6.03°, respectively. The average ACD values were 2.96 ± 0.34 mm and 2.87 ± 0.31 mm. The intraobserver repeatability analysis of variance P-values for ACA and ACD measurements using UBM were 0.10 and 0.68, respectively; for the Artemis-2 VHFUS, the respective values were 0.68 and 0.09. The difference in ACA measurements was statistically significant (t = 8.41; P < 0.0001), while the difference in ACD values was not (t = 1.51; P < 0.13). The mean ACA difference was 8.50° ± 2.50°, and the limits of agreement were +13.30° to −3.60°. The mean ACD difference was 0.09 ± 0.27 mm, and the limits of agreement ranged from 0.61 mm to −0.43 mm. The mean difference percentage of ACD was 3.1% for both instruments. Conclusion In case of the ACD, both instruments can be used interchangeably; however, with the ACA instruments, they cannot be used interchangeably. PMID:23345968

The investigation of minoxidil-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.

PubMed

Chen, I-Shu; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Yu, Chia-Cheng; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

2017-02-01

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca 2+ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca 2+ levels ([Ca 2+ ] i ) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca 2+ ] i rises in a concentration-dependent manner. This Ca 2+ signal was inhibited by 60% by removal of extracellular Ca 2+ . Minoxidil-induced Ca 2+ influx was confirmed by Mn 2+ -induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca 2+ signal in Ca 2+ containing medium by 60%. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca 2+ -free medium abolished minoxidil-induced [Ca 2+ ] i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca 2+ ] i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca 2+ ] i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca 2+ ] i rises that involved Ca 2+ entry through PKC-regulated store-operated Ca 2+ channels and PLC-dependent Ca 2+ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca 2+ -independent manner.

Changes in CaCO3 Burial Trump the Biological Pump

NASA Astrophysics Data System (ADS)

Toggweiler, J.; Dunne, J. P.

2008-12-01

The dramatic increases in atmospheric CO2 at the ends of ice ages are usually attributed to a one-two punch coming from the ocean. First, a weakened biological pump vents organically cycled CO2 from the deep ocean via changes in the ventilation of the deep ocean around Antarctica. The initial CO2 increase is then augmented by an enhancement of CaCO3 burial due to a process called CaCO3 compensation (after Broecker, W. S and T.-H. Peng, Global Biogeochem. Cycles, 1, 15-29, 1987). Here, we argue that the importance of the biological pump has been exaggerated. The main effect comes from circulation-induced changes in the burial of CaCO3. As shown in a recent paper by Andreas Schmittner and co-authors (Schmittner, A., E. Brook and J. Ahn, Impact of the ocean's overturning circulation on atmospheric CO2, in Ocean Circulation: Mechanisms and Impacts, Geophys. Monogr. 173, A. Schmittner, J. Chiang, and S. Hemming, eds., pp. 209-246, AGU, 2007) changes in the ventilation of the deep ocean around Antarctica gave rise to 20-30 ppm increases in atmospheric CO2 every 5,000-7,000 years during isotope stages 3 and 4 (30,000 to 70,000 years ago). None of these venting events gave rise to a compensation response. Meanwhile, Jaccard et al. (Science, 308, 1003-1006, 2005) show that all the big CO2 increases during terminations through stage 11 were accompanied by huge increases in CaCO3 burial. This suggests that the enhanced burial of CaCO3 is obligatory rather than compensatory with respect to the dramatic CO2 increases. Broecker and Peng's compensation idea is based on an assumption that the rain of CaCO3 to the sea floor is the same everywhere. More specifically, it assumes that there is no spatial correlation between the production of CaCO3 at the surface and the burial on the sea floor. We find instead that the production and burial of CaCO3 tend to be co-located in regional "hot spots" and that burial in the hot spots balances the input of Ca++ and HCO3- ions in rivers. The hot spots can also move from place to place in response to changes in circulation. The main hot spots today are the eastern Atlantic and southern Indian; the main hot spot during the last glacial was the equatorial Pacific. Renewed deep-water formation in the Atlantic at the end of the last ice age shifted the locus of CaCO3 burial back to the Atlantic and southern Indian and led to a huge drawdown in global alkalinity, which is ongoing today and accounts for most of the deglacial rise in atmospheric CO2.

Dual-wavelength vortex beam with high stability in a diode-pumped Yb:CaGdAlO4 laser

NASA Astrophysics Data System (ADS)

Shen, Yijie; Meng, Yuan; Fu, Xing; Gong, Mali

2018-05-01

We present a stable dual-wavelength vortex beam carrying orbital angular momentum (OAM) with two spectral peaks separated by a few terahertz in a diode-pumped Yb:CaGdAlO4 (CALGO) laser. The dual-wavelength spectrum is controlled by the pump power and off-axis loss in a laser resonator, arising from the broad emission bandwidth of Yb:CALGO. The OAM beam is obtained by a pair of cylindrical lenses serving as a π/2 convertor for high-order Hermite–Gaussian modes. The stability is verified by the fact that a 1\\hbar OAM beam with two spectral peaks at 1046.1 nm and 1057.2 nm (3.01 THz interval) can steadily operate for more than 3 h. It has great potential for scaling the application of OAM beams in terahertz spectroscopy, high-resolution interferometry, and so on.

Hyaluronan-Based Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-09-01

forward 5′-TGT GAC TTT GGT TGT TCC GTT GC-3′ and reverse 5′-ACC TGA GCC GAT GCA ACA ACA G-3′; DR5, forward 5′- AAG ACC CTT GTG CTC GTT GT-3′ and...reverse 5′-AGG TGG ACA CAA TCC CTC TG-3′; actin, forward 5′- TCC CTG GAG AAG AGC TAC GA-3′ and reverse 5′-AGC ACT GTG TTG GCG TAC AG-3′. 2.2.5. Death

Effect of clomiphene on Ca(2+) movement in human prostate cancer cells.

PubMed

Jiann, Bang-Ping; Lu, Yih-Chau; Chang, Hong-Tai; Huang, Jong-Khing; Jan, Chung-Ren

2002-05-17

The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in populations of PC3 human prostate cancer cells was explored by using fura-2 as a Ca(2+) indicator. Clomiphene at concentrations between 10-50 microM increased [Ca(2+)](i) in a concentration-dependent manner. The [Ca(2+)](i) signal was biphasic with an initial rise and a slow decay. Ca(2+) removal inhibited the Ca(2+) signal by 41%. Adding 3 mM Ca(2+) increased [Ca(2+)](i) in cells pretreated with clomiphene in Ca(2+)-free medium, confirming that clomiphene induced Ca(2+) entry. In Ca(2+)-free medium, pretreatment with 50 microM brefeldin A (to permeabilize the Golgi complex), 1 microM thapsigargin (to inhibit the endoplasmic reticulum Ca(2+) pump), and 2 microM carbonylcyanide m-chlorophenylhydrazone (to uncouple mitochondria) inhibited 25% of 50 microM clomiphene-induced store Ca(2+) release. Conversely, pretreatment with 50 microM clomiphene in Ca(2+)-free medium abolished the [Ca(2+)](i) increase induced by brefeldin A, thapsigargin or carbonylcyanide m-chlorophenylhydrazone. The 50 microM clomiphene-induced Ca(2+)release was unaltered by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Trypan blue exclusion assay suggested that incubation with clomiphene (50 microM) for 2-15 min induced time-dependent decrease in cell viability by 10-50%. Collectively, the results suggest that clomiphene induced [Ca(2+)](i) increases in PC3 cells by releasing store Ca(2+) from multiple stores in an phospholipase C-independent manner, and by activating Ca(2+) influx; and clomiphene was of mild cytotoxicity.

Effect of Nano-SiO2 on the Early Hydration of Alite-Sulphoaluminate Cement

PubMed Central

Sun, Jinfeng; Xu, Zhiqiang; Li, Weifeng; Shen, Xiaodong

2017-01-01

The impact of nano-SiO2 on the early hydration properties of alite-sulphoaluminate (AC$A) cement was investigated with a fixed water to solid ratio (w/s) of one. Nano-SiO2 was used in partial substitution of AC$A cement at zero, one and three wt %. Calorimetry, X-ray diffraction (XRD), thermogravimetric/derivative thermogravimetric (TG/DTG), mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) analyses were used to characterize the hydration and hydrates of the blended cement. The hydration of the AC$A cement was significantly promoted, resulting in an increase of the heat released with the addition of nano-SiO2. Phase development composition analysis showed that nano-SiO2 had no effect on the type of crystalline hydration products of the AC$A cement. Moreover, nano-SiO2 showed significant positive effects on pore refinement where the total porosity decreased by 54.09% at three days with the inclusion of 3% nano-SiO2. Finally, from the SEM observations, nano-SiO2 was conducive to producing a denser microstructure than that of the control sample. PMID:28467348

Plasma Membrane Ca2+-ATPase 4 in Murine Epididymis: Secretion of Splice Variants in the Luminal Fluid and a Role in Sperm Maturation1

PubMed Central

Patel, Ramkrishna; Al-Dossary, Amal A.; Stabley, Deborah L.; Barone, Carol; Galileo, Deni S.; Strehler, Emanuel E.; Martin-DeLeon, Patricia A.

2013-01-01

ABSTRACT Plasma membrane Ca2+-ATPase isoform 4 (PMCA4) is the primary Ca2+ efflux pump in murine sperm, where it regulates motility. In Pmca4 null sperm, motility loss results in infertility. We have shown that murine sperm PMCA4b interacts with Ca2+/CaM-dependent serine kinase (CASK) in regulating Ca2+ homeostasis and motility. However, recent work indicated that the bovine PMCA4a splice variant (missing in testis) is epididymally expressed, along with 4b, and may be transferred to sperm. Here we show, via conventional and in situ RT-PCR, that both the splice variants of Pmca4 mRNA are expressed in murine testis and throughout the epididymis. Immunofluorescence localized PMCA4a to the apical membrane of the epididymal epithelium, and Western analysis not only confirmed its presence but showed for the first time that PMCA4a and PMCA4b are secreted in the epididymal luminal fluid (ELF), from which epididymosomes containing PMCA4a were isolated. Flow cytometry indicated the presence of PMCA4a on mature caudal sperm where it was increased ∼5-fold compared to caput sperm (detected by Western blotting) and ∼2-fold after incubation in ELF, revealing in vitro uptake and implicating PMCA4a in epididymal sperm maturation. Coimmunoprecipitation using pan-PMCA4 antibodies, revealed that both variants associate with CASK, suggesting their presence in a complex. Because they have different kinetic properties for Ca2+ transport and different abilities to bind to CASK, our study suggests a mechanism for combining the functional attributes of both PMCA4 variants, leading to heightened efficiency of the pump in the maintenance of Ca2+ homeostasis, which is crucial for normal motility and male fertility. PMID:23699388

Plasma membrane Ca2+-ATPase 4 in murine epididymis: secretion of splice variants in the luminal fluid and a role in sperm maturation.

PubMed

Patel, Ramkrishna; Al-Dossary, Amal A; Stabley, Deborah L; Barone, Carol; Galileo, Deni S; Strehler, Emanuel E; Martin-DeLeon, Patricia A

2013-07-01

Plasma membrane Ca(2+)-ATPase isoform 4 (PMCA4) is the primary Ca(2+) efflux pump in murine sperm, where it regulates motility. In Pmca4 null sperm, motility loss results in infertility. We have shown that murine sperm PMCA4b interacts with Ca(2+)/CaM-dependent serine kinase (CASK) in regulating Ca(2+) homeostasis and motility. However, recent work indicated that the bovine PMCA4a splice variant (missing in testis) is epididymally expressed, along with 4b, and may be transferred to sperm. Here we show, via conventional and in situ RT-PCR, that both the splice variants of Pmca4 mRNA are expressed in murine testis and throughout the epididymis. Immunofluorescence localized PMCA4a to the apical membrane of the epididymal epithelium, and Western analysis not only confirmed its presence but showed for the first time that PMCA4a and PMCA4b are secreted in the epididymal luminal fluid (ELF), from which epididymosomes containing PMCA4a were isolated. Flow cytometry indicated the presence of PMCA4a on mature caudal sperm where it was increased ~5-fold compared to caput sperm (detected by Western blotting) and ~2-fold after incubation in ELF, revealing in vitro uptake and implicating PMCA4a in epididymal sperm maturation. Coimmunoprecipitation using pan-PMCA4 antibodies, revealed that both variants associate with CASK, suggesting their presence in a complex. Because they have different kinetic properties for Ca(2+) transport and different abilities to bind to CASK, our study suggests a mechanism for combining the functional attributes of both PMCA4 variants, leading to heightened efficiency of the pump in the maintenance of Ca(2+) homeostasis, which is crucial for normal motility and male fertility.

SERCA directs cell migration and branching across species and germ layers

PubMed Central

Lansdale, Nick; Navarro, Sonia; Truong, Thai V.; Bower, Dan J.; Featherstone, Neil C.; Connell, Marilyn G.; Al Alam, Denise; Frey, Mark R.; Trinh, Le A.; Fernandez, G. Esteban; Warburton, David; Fraser, Scott E.; Bennett, Daimark; Jesudason, Edwin C.

2017-01-01

ABSTRACT Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding. PMID:28821490

Effect of [6]-shogaol on cytosolic Ca2+ levels and proliferation in human oral cancer cells (OC2).

PubMed

Chen, Chung-Yi; Yang, Yu-Han; Kuo, Soong-Yu

2010-08-27

The effect of [6]-shogaol (1) on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) and viability has not been explored previously in oral epithelial cells. The present study has examined whether 1 alters [Ca(2+)](i) and viability in OC2 human oral cancer cells. Compound 1 at concentrations > or = 5 microM increased [Ca(2+)](i) in a concentration-dependent manner with a 50% effective concentration (EC(50)) value of 65 microM. The Ca(2+) signal was reduced substantially by removing extracellular Ca(2+). In a Ca(2+)-free medium, the 1-induced [Ca(2+)](i) elevation was mostly attenuated by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The [Ca(2+)](i) signal was inhibited by La(3+) but not by L-type Ca(2+) channel blockers. The elevation of [Ca(2+)](i) caused by 1 in a Ca(2+)-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 82% with the phospholipase A2 inhibitor aristolochic acid I (20 microM). U73122, a selective inhibitor of phospholipase C, abolished 1-induced [Ca(2+)](i) release. At concentrations of 5-100 microM, 1 killed cells in a concentration-dependent manner. These findings suggest that [6]-shogaol induces a significant rise in [Ca(2+)](i) in oral cancer OC2 cells by causing stored Ca(2+) release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-dependent manner and by inducing Ca(2+) influx via a phospholipase A2- and La(3+)-sensitive pathway.

Evaluation of anterior chamber angle under dark and light conditions in angle closure glaucoma: An anterior segment OCT study.

PubMed

Masoodi, Habibeh; Jafarzadehpur, Ebrahim; Esmaeili, Alireza; Abolbashari, Fereshteh; Ahmadi Hosseini, Seyed Mahdi

2014-08-01

To evaluate changes of nasal and temporal anterior chamber angle (ACA) in subjects with angle closure glaucoma using Spectralis AS-OCT (SAS-OCT) under dark and light conditions. Based on dark-room gonioscopy, 24 subjects with open angles and 86 with narrow angles participated in this study. The nasal and temporal angle opening distance at 500 μm anterior to the scleral spur (AOD500), nasal and temporal ACA were measured using SAS-OCT in light and dark conditions. In 2 groups, ACA and AOD500 in nasal and temporal quadrants were significantly greater in light compared to dark (all with p=0.000). The AOD500 and ACA were significantly higher in nasal than temporal in measured conditions for 2 groups except the ACA and AOD500 of normal group measured in light. The difference between nasal and temporal in dark (29.07 ± 65.71 μm for AOD500 and 5.7 ± 4.07° for ACA) was greater than light (24.86 ± 79.85 μm for AOD500 and 2.09 ± 7.21° for ACA) condition. But the difference was only significant for ACA (p=0.000). The correlation analysis showed a negative correlation between AOD500 and pupil diameter in temporal and nasal quadrants (both with p=0.000). While temporal AOD500 difference correlated with spherical equivalent, temporal and asal gonioscopy, nasal AOD correlated with IOP, temporal and nasal gonioscopy. Clinically important changes in ACA structure could be detected with SAS-OCT in nasal and temporal quadrants under different illumination intensity. The results could help in improvement of examination condition for better and more accurate assessment of individuals with angle closure glaucoma. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Orai3 channel is the 2-APB-induced endoplasmic reticulum calcium leak.

PubMed

Leon-Aparicio, Daniel; Pacheco, Jonathan; Chavez-Reyes, Jesus; Galindo, Jose M; Valdes, Jesus; Vaca, Luis; Guerrero-Hernandez, Agustin

2017-07-01

We have studied in HeLa cells the molecular nature of the 2-APB induced ER Ca 2+ leak using synthetic Ca 2+ indicators that report changes in both the cytoplasmic ([Ca 2+ ] i ) and the luminal ER ([Ca 2+ ] ER ) Ca 2+ concentrations. We have tested the hypothesis that Orai channels participate in the 2-APB-induced ER Ca 2+ leak that was characterized in the companion paper. The expression of the dominant negative Orai1 E106A mutant, which has been reported to block the activity of all three types of Orai channels, inhibited the effect of 2-APB on the [Ca 2+ ] ER but did not decrease the ER Ca 2+ leak after thapsigargin (TG). Orai3 channel, but neither Orai1 nor Orai2, colocalizes with expressed IP 3 R and only Orai3 channel supported the 2-APB-induced ER Ca 2+ leak, while Orai1 and Orai2 inhibited this type of ER Ca 2+ leak. Decreasing the expression of Orai3 inhibited the 2-APB-induced ER Ca 2+ leak but did not modify the ER Ca 2+ leak revealed by inhibition of SERCA pumps with TG. However, reducing the expression of Orai3 channel resulted in larger [Ca 2+ ] i response after TG but only when the ER store had been overloaded with Ca 2+ by eliminating the acidic internal Ca 2+ store with bafilomycin. These data suggest that Orai3 channel does not participate in the TG-revealed ER Ca 2+ leak but forms an ER Ca 2+ leak channel that is limiting the overloading with Ca 2+ of the ER store. Copyright © 2017 Elsevier Ltd. All rights reserved.

Signal transduction in red blood cells of the lizards Ameiva ameiva and Tupinambis merianae (Squamata, Teiidae).

PubMed

Beraldo, F H; Sartorello, R; Lanari, R D; Garcia, C R

2001-06-01

The fluorescent calcium probe, Fluo-3, AM was used to measure the intracellular calcium concentration in red blood cells (RBCs) of the teiid lizards Ameiva ameiva and Tupinambis merianae. The cytosolic [Ca2+] is maintained around 20 nM and the cells contain membrane-bound Ca2+ pools. One pool appears to be identifiable with the endoplasmic reticulum (ER) inasmuch as addition of the sarco-endoplasmic reticulum Ca2+ ATPase, SERCA, inhibitor thapsigargin induces an increase in cytosolic [Ca2+ both in the presence and in the absence of extracellular Ca2+. In addition to the ER, an acidic compartment appears to be involved in Ca2+ storage, as collapse of intracellular pHgradients by monensin, a Na+ -H+ exchanger, and nigericin, a K+ -H+ exchanger, induce the release of Ca2+ from internal pools. A vacuolar H+ pump, sensitive to NBD-Cl and bafilomycin appears to be necessary to load the acidic Ca2+ pools. Finally, the purinergic agonist ATP triggers a rapid and transient increase of [Ca2+]c in the cells from both lizard species, mostly by mobilization of the cation from internal stores. Copyright 2001 Harcourt Publishers Ltd.

Shortwave direct radiative effects of above-cloud aerosols over global oceans derived from 8 years of CALIOP and MODIS observations

NASA Astrophysics Data System (ADS)

Zhang, Zhibo; Meyer, Kerry; Yu, Hongbin; Platnick, Steven; Colarco, Peter; Liu, Zhaoyan; Oreopoulos, Lazaros

2016-03-01

In this paper, we studied the frequency of occurrence and shortwave direct radiative effects (DREs) of above-cloud aerosols (ACAs) over global oceans using 8 years (2007-2014) of collocated CALIOP and MODIS observations. Similar to previous work, we found high ACA occurrence in four regions: southeastern (SE) Atlantic region, where ACAs are mostly light-absorbing aerosols, i.e., smoke and polluted dust according to CALIOP classification, originating from biomass burning over the African Savanna; tropical northeastern (TNE) Atlantic and the Arabian Sea, where ACAs are predominantly windblown dust from the Sahara and Arabian deserts, respectively; and the northwestern (NW) Pacific, where ACAs are mostly transported smoke and polluted dusts from Asian. From radiative transfer simulations based on CALIOP-MODIS observations and a set of the preselected aerosol optical models, we found the DREs of ACAs at the top of atmosphere (TOA) to be positive (i.e., warming) in the SE Atlantic and NW Pacific regions, but negative (i.e., cooling) in the TNE Atlantic Ocean and the Arabian Sea. The cancellation of positive and negative regional DREs results in a global ocean annual mean diurnally averaged cloudy-sky DRE of 0.015 W m-2 (range of -0.03 to 0.06 W m-2) at TOA. The DREs at surface and within the atmosphere are -0.15 W m-2 (range of -0.09 to -0.21 W m-2), and 0.17 W m-2 (range of 0.11 to 0.24 W m-2), respectively. The regional and seasonal mean DREs are much stronger. For example, in the SE Atlantic region, the JJA (July-August) seasonal mean cloudy-sky DRE is about 0.7 W m-2 (range of 0.2 to 1.2 W m-2) at TOA. All our DRE computations are publicly available1. The uncertainty in our DRE computations is mainly caused by the uncertainties in the aerosol optical properties, in particular aerosol absorption, the uncertainties in the CALIOP operational aerosol optical thickness retrieval, and the ignorance of cloud and potential aerosol diurnal cycle. In situ and remotely sensed measurements of ACA from future field campaigns and satellite missions and improved lidar retrieval algorithm, in particular vertical feature masking, would help reduce the uncertainty.

Shortwave Direct Radiative Effects of Above-Cloud Aerosols Over Global Oceans Derived From 8 Years of CALIOP and MODIS Observations

NASA Technical Reports Server (NTRS)

Zhang, Zhibo; Meyer, Kerry; Yu, Hongbin; Platnick, Steven; Colarco, Peter; Liu, Zhaoyan; Oraiopoulos, Lazaros

2016-01-01

In this paper, we studied the frequency of occurrence and shortwave direct radiative effects (DREs) of above-cloud aerosols (ACAs) over global oceans using 8 years (2007-2014) of collocated CALIOP and MODIS observations. Similar to previous work, we found high ACA occurrence in four regions: southeastern (SE) Atlantic region, where ACAs are mostly light-absorbing aerosols, i.e., smoke and polluted dust according to CALIOP classification, originating from biomass burning over the African Savanna; tropical northeastern (TNE) Atlantic and the Arabian Sea, where ACAs are predominantly windblown dust from the Sahara and Arabian deserts, respectively; and the northwestern (NW) Pacific, where ACAs are mostly transported smoke and polluted dusts from Asia. From radiative transfer simulations based on CALIOP-MODIS observations and a set of the preselected aerosol optical models, we found the DREs of ACAs at the top of atmosphere (TOA) to be positive (i.e., warming) in the SE Atlantic and NW Pacific regions, but negative (i.e., cooling) in the TNE Atlantic Ocean and the Arabian Sea. The cancellation of positive and negative regional DREs results in a global ocean annual mean diurnally averaged cloudy-sky DRE of 0.015 W m(exp. -2) [range of -0.03 to 0.06 W m (exp. -2)] at TOA. The DREs at surface and within the atmosphere are -0.015 W m(exp. -2) [range of -0.09 to -0.21 W m(exp. -2)], and 0.17 W m(exp. -2) [range of 0.11 to 0.24 W m(exp. -2)], respectively. The regional and seasonal mean DREs are much stronger. For example, in the SE Atlantic region, the JJA (July-August) seasonal mean cloudy-sky DRE is about 0.7 W m(exp. -2) [range of 0.2 to 1.2 W m(exp. -2)] at TOA. All our DRE computations are publicly available. The uncertainty in our DRE computations is mainly caused by the uncertainties in the aerosol optical properties, in particular aerosol absorption, the uncertainties in the CALIOP operational aerosol optical thickness retrieval, and the ignorance of cloud and potential aerosol diurnal cycle. In situ and remotely sensed measurements of ACA from future field campaigns and satellite missions and improved lidar retrieval algorithm, in particular vertical feature masking, would help reduce the uncertainty.

The quantal nature of calcium release to caffeine in single smooth muscle cells results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase.

PubMed

Steenbergen, J M; Fay, F S

1996-01-26

Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.

Lipase-catalyzed preparation of optically active 1'-acetoxychavicol acetates and their structure-activity relationships in apoptotic activity against human leukemia HL-60 cells.

PubMed

Azuma, Hideki; Miyasaka, Keita; Yokotani, Tsuyoshi; Tachibana, Taro; Kojima-Yuasa, Akiko; Matsui-Yuasa, Isao; Ogino, Kenji

2006-03-15

Structure-activity relationships of 1'-acetoxychavicol acetate (ACA) for apoptotic activity against human leukemia HL-60 cells were investigated using optically active ACA and various racemic ACA analogues. Natural-type (or with different acyl group) ACA showed a high apoptotic activity, but the ortho or meta isomers, 4-deacetoxy analogue, and the 2'-3' dehydrogenated derivative had no effect, or a weak activity. Optically active (R)- and (S)-ACA were prepared by a lipase-catalyzed esterification. Using a mixture of vinyl acetate-tetrahydrofuran (1:1 v/v) as a solvent at refluxing temperature, optically pure (R)- and (S)-ACA were obtained (99.7% ee and 99.1% ee, respectively). The apoptosis-inducing effects of both enantiomers were compared by means of an MTT assay and the detection of typical apoptotic phenomena (DNA fragmentation, caspase-3 activation, and PARP cleavage) and these two activities were almost equal. These results indicate that the essential moieties of ACA for apoptotic activity against HL-60 cells are both the presence of a 4-acetoxyl group and an unsaturated double bond between C-2' and C-3', and that the configuration at the 1'-position is unrelated to activity.

Effect of heterophoria measurement technique on the clinical accommodative convergence to accommodation ratio.

PubMed

Escalante, Jaime Bernal; Rosenfield, Mark

2006-05-01

Measurement of the stimulus accommodative convergence to accommodation (AC/A) ratio is a standard procedure in clinical optometric practice. Typically, heterophoria is assessed at several accommodative stimulus levels, and the gradient of the vergence to accommodation function computed. A number of procedures are available for the subjective measurement of heterophoria, but it is unclear whether the use of different vergence measurement techniques will alter the obtained AC/A value. Accordingly, the current study compared AC/A ratios measured using 3 clinical subjective heterophoria tests, namely the von Graefe (VG), Maddox Rod (MR), and Modified Thorington (MT) procedures. The AC/A ratio was measured in 60 visually normal subjects between 20 and 25 years of age using each of the 3 procedures listed above. The accommodative stimulus was varied by the introduction of +/-1.00 diopter (D) spherical lenses over the distance refractive correction while subjects viewed a target at a viewing distance of 40 cm. To examine the repeatability of each procedure, the AC/A ratio was measured on 2 separate occasions for each measurement technique, with the 2 sessions being separated by at least 24 hours. Mean values of stimulus AC/A ratio measured using the VG, MR, and MT procedures were 3.47, 2.99, and 2.46Delta/D, respectively. These differences were significant (p=0.0001). In addition, the coefficient of repeatability for the 3 techniques was 2.22, 1.99, and 1.20 Delta/D, respectively. Ratios obtained using the Modified Thorington technique with +/-1.00 D lenses showed the best repeatability, whereas the poorest repeatability was found with the von Graefe technique when only +1.00 D lenses were used to vary the accommodative stimulus. Accordingly, we recommend that that Modified Thorington procedure with +/-1.00 D lenses be used to quantify heterophoria during clinical measurement of the stimulus AC/A ratio.

Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

PubMed Central

Lo, Yuan Hung; Peachey, Tom; Abramson, David; McCulloch, Andrew

2013-01-01

Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004) to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling. PMID:24222910

Overexpression of Human Senescence Marker Protein 30 in Mice Fails to Offer Protection Against Challenge with Organophosphorus Compounds

DTIC Science & Technology

2011-09-01

poisoning. Toxicology 233: 145-154. 2. Gray AP (1984) Design and structure- activity relationships of antidotes to organophosphorus anticholinesterase ...and is being actively pursued. One approach under investigation is the development of human proteins as bioscavengers that sequester or hydrolyze...the major roles described for SMP30 is in maintaining Ca2+ homeostasis by activating enzymes involved in the regulation of Ca2+ pumps localized in

Clomiphene, an ovulation-inducing agent, causes [Ca2+]i increases in human osteoblast-like cells.

PubMed

Chen, Y C; Wang, J L; Liu, C P; Cheng, J S; Chang, H T; Yuk-Keung, L; Su, W; Law, Y P; Chen, W C; Jan, C R

2001-06-30

The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca2+ levels ([Ca2+]i) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca2+ indicator. Clomiphene at concentrations between 5-75 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 of 50 microM. The [Ca2+]i signal consisted of an initial rise and a sustained phase. Ca2+ removal reduced the Ca2+ signal by 40+/-10%. The [Ca2+]i increase induced by 50 microM clomiphene was inhibited by 80+/-5% by 10 microM nifedipine, but was insensitive to 50 microM La3+ or 10 microM verapamil. In Ca2+-free medium, pretreatment with 50 microM brefeldin A (to disrupt the Golgi complex Ca2+ store), 1 microM thapsigargin (to inhibit the endoplasmic reticulum Ca2+ pump), and carbonylcyanide m-chlorophenylhydrazone (CCCP; to uncouple mitochondria) inhibited 51+/-3% of 50 microM clomiphene-induced Ca2+ release; conversely, pretreatment with 50 microM clomiphene abolished the [Ca2+]i increase induced by thapsigargin, CCCP, and brefeldin A. The Ca2+ release-induced by 50 pM clomiphene was unchanged by inhibition of phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Collectively, the results suggest that clomiphene increased [Ca2+]i, in osteoblast-like cells, by releasing intracellular Ca2+ in a phospholipase C-independent manner and by causing nifedipine-sensitive Ca2+ influx.

Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells.

PubMed

Cheng, H-H; Chou, C-T; Sun, T-K; Liang, W-Z; Cheng, J-S; Chang, H-T; Tseng, H-W; Kuo, C-C; Chen, F-A; Kuo, D-H; Shieh, P; Jan, C-R

2015-11-01

Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca(2+)) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca(2+)](i) and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 μM and 300 μM, naproxen induced [Ca(2+)](i) rises in a concentration-dependent manner. This Ca(2+) signal was reduced partly when extracellular Ca(2+) was removed. The Ca(2+) signal was inhibited by a Ca(2+) channel blocker nifedipine but not by store-operated Ca(2+) channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca(2+)-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+) pumps, partly inhibited naproxen-induced Ca(2+) signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca(2+)](i) rises. At concentrations between 15 μM and 30 μM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca(2+) with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca(2+)](i) rises by inducing Ca(2+) release from multiple stores that included the endoplasmic reticulum and Ca(2+) entry via nifedipine-sensitive Ca(2+) channels. Naproxen induced cell death that involved apoptosis. © The Author(s) 2015.

Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

PubMed Central

Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

2016-01-01

Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum.

PubMed

Espinoza-Fonseca, L Michel

2017-03-28

Ca 2+ transport across the sarco/endoplasmic reticulum (SR) plays an essential role in intracellular Ca 2+ homeostasis, signalling, cell differentiation and muscle contractility. During SR Ca 2+ uptake and release, proton fluxes are required to balance the charge deficit generated by the exchange of Ca 2+ and other ions across the SR. During Ca 2+ uptake by the SR Ca 2+ -ATPase (SERCA), two protons are countertransported from the SR lumen to the cytosol, thus partially compensating for the charge moved by Ca 2+ transport. Studies have shown that protons are also transported from the cytosol to the lumen during Ca 2+ release, but a transporter that facilitates proton transport into the SR lumen has not been described. In this article we propose that SERCA forms pores that facilitate bidirectional proton transport across the SR. We describe the location and structure of water-filled pores in SERCA that form cytosolic and luminal pathways for protons to cross the SR membrane. Based on this structural information, we suggest mechanistic models for proton translocation to the cytosol during active Ca 2+ transport, and into the SR lumen during SERCA inhibition by endogenous regulatory proteins. Finally, we discuss the physiological consequences of SERCA-mediated bidirectional proton transport across the SR membrane of muscle and non-muscle cells.

Dynamic Ca2+ signalling in rat arterial smooth muscle cells under the control of local renin–angiotensin system

PubMed Central

Asada, Yukinori; Yamazawa, Toshiko; Hirose, Kenzo; Takasaka, Tomonori; Iino, Masamitsu

1999-01-01

We visualized the changes in intracellular Ca2+ concentration ([Ca2+]i), using fluo-3 as an indicator, in individual smooth muscle cells within intact rat tail artery preparations. On average in about 45 % of the vascular smooth muscle cells we found spontaneous Ca2+ waves and oscillations (≈0.13 Hz), which we refer to here as Ca2+ ripples because the peak amplitude of [Ca2+]i was about one-seventh of that of Ca2+ oscillations evoked by noradrenaline. We also found another pattern of spontaneous Ca2+ transients often in groups of two to three cells. They were rarely observed and are referred to as Ca2+ flashes because their peak amplitude was nearly twice as large as that in noradrenaline-evoked responses. Sympathetic nerve activity was not considered responsible for the Ca2+ ripples, and they were abolished by inhibitors of either the Ca2+ pump in the sarcoplasmic reticulum (cyclopiazonic acid) or phospholipase C (U-73122). Both angiotensin antagonists ([Sar1,Ile8]-angiotensin II and losartan) and an angiotensin converting enzyme inhibitor (captopril) inhibited the Ca2+ ripples. The extracellular Ca2+-dependent tension borne by unstimulated arterial rings was reduced by the angiotensin antagonist by ≈50 %. These results indicate that the Ca2+ ripples are generated via inositol 1,4,5-trisphosphate-induced Ca2+ release from the intracellular Ca2+ stores in response to locally produced angiotensin II, which contributes to the maintenance of vascular tone. PMID:10581318

The effect of magnolol on Ca2+ homeostasis and its related physiology in human oral cancer cells.

PubMed

Hsieh, Shu-Feng; Chou, Chiang-Ting; Liang, Wei-Zhe; Kuo, Chun-Chi; Wang, Jue-Long; Hao, Lyh-Jyh; Jan, Chung-Ren

2018-05-01

Magnolol, a polyphenol compound from herbal medicines, was shown to alter physiology in various cell models. However, the effect of magnolol on Ca 2+ homeostasis and its related physiology in oral cancer cells is unclear. This study examined whether magnolol altered Ca 2+ signaling and cell viability in OC2 human oral cancer cells. Cytosolic Ca 2+ concentrations ([Ca 2+ ] i ) in suspended cells were measured by using the fluorescent Ca 2+ -sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay. Magnolol at concentrations of 20-100 μM induced [Ca 2+ ] i rises. Ca 2+ removal reduced the signal by approximately 50%. Magnolol (100 μM) induced Mn 2+ influx suggesting of Ca 2+ entry. Magnolol-induced Ca 2+ entry was partially suppressed by protein kinase C (PKC) regulators, and inhibitors of store-operated Ca 2+ channels. In Ca 2+ -free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished magnolol-evoked [Ca 2+ ] i rises. Conversely, treatment with magnolol abolished BHQ-evoked [Ca 2+ ] i rises. Inhibition of phospholipase C (PLC) with U73122 partially inhibited magnolol-induced [Ca 2+ ] i rises. Magnolol at 20-100 μM decreased cell viability, which was not reversed by pretreatment with the Ca 2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in OC2 cells, magnolol induced [Ca 2+ ] i rises by evoking partially PLC-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via PKC-sensitive store-operated Ca 2+ entry. Magnolol also caused Ca 2+ -independent cell death. Therefore, magnolol-induced cytotoxicity may not be involved in activation mechanisms associated with intracellular Ca 2+ mobilization in oral cancer cells. Copyright © 2018. Published by Elsevier Ltd.

Human intron-encoded Alu RNAs are processed and packaged into Wdr79-associated nucleoplasmic box H/ACA RNPs

PubMed Central

Jády, Beáta E.; Ketele, Amandine; Kiss, Tamás

2012-01-01

Alu repetitive sequences are the most abundant short interspersed DNA elements in the human genome. Full-length Alu elements are composed of two tandem sequence monomers, the left and right Alu arms, both derived from the 7SL signal recognition particle RNA. Since Alu elements are common in protein-coding genes, they are frequently transcribed into pre-mRNAs. Here, we demonstrate that the right arms of nascent Alu transcripts synthesized within pre-mRNA introns are processed into metabolically stable small RNAs. The intron-encoded Alu RNAs, termed AluACA RNAs, are structurally highly reminiscent of box H/ACA small Cajal body (CB) RNAs (scaRNAs). They are composed of two hairpin units followed by the essential H (AnAnnA) and ACA box motifs. The mature AluACA RNAs associate with the four H/ACA core proteins: dyskerin, Nop10, Nhp2, and Gar1. Moreover, the 3′ hairpin of AluACA RNAs carries two closely spaced CB localization motifs, CAB boxes (UGAG), which bind Wdr79 in a cumulative fashion. In contrast to canonical H/ACA scaRNPs, which concentrate in CBs, the AluACA RNPs accumulate in the nucleoplasm. Identification of 348 human AluACA RNAs demonstrates that intron-encoded AluACA RNAs represent a novel, large subgroup of H/ACA RNAs, which are apparently confined to human or primate cells. PMID:22892240

Laser Demonstration of Diode-Pumped Nd3+-Doped Fluorapatite Anisotropic Ceramics

NASA Astrophysics Data System (ADS)

Akiyama, Jun; Sato, Yoichi; Taira, Takunori

2011-02-01

We report the first demonstration of a diode-pumped anisotropic ceramic laser that uses microdomain-controlled neodymium-doped hexagonal fluorapatite [Nd3+:Ca10(PO4)6F2, Nd:FAP] polycrystalline ceramics as the gain medium, which were fabricated by the rare-earth-assisted magnetic grain-orientation control method, as a step toward achieving giant micro photonics. The laser delivers 1063.10 and 1063.22 nm output beams when pumped with a central wavelength of 807.5 nm and a 2 nm bandwidth diode laser operating in quasi-continuous-wave (QCW) mode. We obtained a maximum QCW peak power of 255 mW with an uncoated 2 at. % Nd:FAP material.

Secretory cargo sorting by Ca2+-dependent Cab45 oligomerization at the trans-Golgi network

PubMed Central

Blank, Birgit; Maiser, Andreas; Emin, Derya; Prescher, Jens; Beck, Gisela; Kienzle, Christine; Bartnik, Kira; Habermann, Bianca; Pakdel, Mehrshad; Leonhardt, Heinrich; Lamb, Don C.

2016-01-01

Sorting and export of transmembrane cargoes and lysosomal hydrolases at the trans-Golgi network (TGN) are well understood. However, elucidation of the mechanism by which secretory cargoes are segregated for their release into the extracellular space remains a challenge. We have previously demonstrated that, in a reaction that requires Ca2+, the soluble TGN-resident protein Cab45 is necessary for the sorting of secretory cargoes at the TGN. Here, we report that Cab45 reversibly assembles into oligomers in the presence of Ca2+. These Cab45 oligomers specifically bind secretory proteins, such as COMP and LyzC, in a Ca2+-dependent manner in vitro. In intact cells, mutation of the Ca2+-binding sites in Cab45 impairs oligomerization, as well as COMP and LyzC sorting. Superresolution microscopy revealed that Cab45 colocalizes with secretory proteins and the TGN Ca2+ pump (SPCA1) in specific TGN microdomains. These findings reveal that Ca2+-dependent changes in Cab45 mediate sorting of specific cargo molecules at the TGN. PMID:27138253

Generation of 103 fs mode-locked pulses by a gain linewidth-variable Nd,Y:CaF2 disordered crystal.

PubMed

Qin, Z P; Xie, G Q; Ma, J; Ge, W Y; Yuan, P; Qian, L J; Su, L B; Jiang, D P; Ma, F K; Zhang, Q; Cao, Y X; Xu, J

2014-04-01

We have demonstrated a diode-pumped passively mode-locked femtosecond Nd,Y:CaF2 disordered crystal laser for the first time to our knowledge. By choosing appropriate Y-doping concentration, a broad fluorescence linewidth of 31 nm has been obtained from the gain linewidth-variable Nd,Y:CaF2 crystal. With the Nd,Y:CaF2 disordered crystal as gain medium, the mode-locked laser generated pulses with pulse duration as short as 103 fs, average output power of 89 mW, and repetition rate of 100 MHz. To our best knowledge, this is the shortest pulse generated from Nd-doped crystal lasers so far. The research results show that the Nd,Y:CaF2 disordered crystal will be a potential alternative as gain medium of repetitive chirped pulse amplification for high-peak-power lasers.

Effect of angiotensin II-induced arterial hypertension on the voltage-dependent contractions of mouse arteries.

PubMed

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

2016-02-01

Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+) channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)-induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4 weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels were studied in vaso-reactive studies in vitro in isolated aortic and femoral arteries by using extracellular K(+) concentration-response (KDR) experiments. In aortic segments, AngII-induced AHT significantly sensitized isometric contractions induced by elevated extracellular K(+) and depolarization. This sensitization was partly prevented by normalizing blood pressure with hydralazine, suggesting that it was caused by AHT rather than by direct AngII effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained in vitro correlated significantly with the rise in arterial blood pressure induced by AngII in vivo. The AHT-induced sensitization persisted when aortic segments were exposed to levcromakalim or to inhibitors of basal nitric oxide release. Consistent with these observations, AngII-treatment also sensitized the vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)-induced contractions. Unlike aorta, AngII-treatment desensitized the isometric contractions to depolarization in femoral arteries pointing to vascular bed specific responses of arteries to hypertension. AHT affects the voltage-dependent L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may contribute to the decreased vascular compliance in AHT and explain the efficacy of Ca(2+) channel blockers to reduce vascular stiffness and central blood pressure in AHT.

Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts.

PubMed

Itoh, Hideki; Oyama, Kotaro; Suzuki, Madoka; Ishiwata, Shin'ichi

2014-01-01

Temperature-sensitive Ca(2+) dynamics occur primarily through transient receptor potential channels, but also by means of Ca(2+) channels and pumps on the endoplasmic reticulum membrane. As such, cytoplasmic Ca(2+) concentration ([Ca(2+)]cyt) is re-equilibrated by changes in ambient temperature. The present study investigated the effects of heat pulses (heating duration: 2 s or 150 s) on [Ca(2+)]cyt in single WI-38 fibroblasts, which are considered as normal cells. We found that Ca(2+) burst occurred immediately after short (2 s) heat pulse, which is similar to our previous report on HeLa cells, but with less thermosensitivity. The heat pulses originated from a focused 1455-nm infrared laser light were applied in the vicinity of cells under the optical microscope. Ca(2+) bursts induced by the heat pulse were suppressed by treating cells with inhibitors for sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) or inositol trisphosphate receptor (IP3R). Long (150 s) heat pulses also induced Ca(2+) bursts after the onset of heating and immediately after re-cooling. Cells were more thermosensitive at physiological (37°C) than at room (25°C) temperature; however, at 37°C, cells were responsive at a higher temperature (ambient temperature+heat pulse). These results strongly suggest that the heat pulse-induced Ca(2+) burst is caused by a transient imbalance in Ca(2+) flow between SERCA and IP3R, and offer a potential new method for thermally controlling Ca(2+)-regulated cellular functions.

Thermodynamic properties of calcium-bismuth alloys determined by emf measurements

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

Kim, H; Boysen, DA; Bradwell, DJ

2012-01-15

The thermodynamic properties of Ca-Bi alloys were determined by electromotive force (emf) measurements to assess the suitability of Ca-Bi electrodes for electrochemical energy storage applications. Emf was measured at ambient pressure as a function of temperature between 723 K and 1173 K using a Ca(s)vertical bar CaF2(s)vertical bar Ca(in Bi) cell for twenty different Ca-Bi alloys spanning the entire range of composition from chi(Ca) = 0 to 1. Reported are the temperature-independent partial molar entropy and enthalpy of calcium for each Ca-Bi alloy. Also given are the measured activities of calcium, the excess partial molar Gibbs energy of bismuth estimatedmore » from the Gibbs-Duhem equation, and the integral change in Gibbs energy for each Ca-Bi alloy at 873 K, 973 K, and 1073 K. Calcium activities at 973 K were found to be nearly constant at a value a(Ca) = 1 x 10(-8) over the composition range chi(Ca) = 0.32-0.56, yielding an emf of similar to 0.77 V. Above chi(Ca) = 0.62 and coincident with Ca5Bi3 formation, the calcium activity approached unity. The Ca-Bi system was also characterized by differential scanning calorimetry over the entire range of composition. Based upon these data along with the emf measurements, a revised Ca-Bi binary phase diagram is proposed. (C) 2011 Elsevier Ltd. All rights reserved.« less

An Arg-Gly-Asp peptide stimulates Ca2+ efflux from osteoclast precursors through a novel mechanism

NASA Technical Reports Server (NTRS)

Yamakawa, K.; Duncan, R.; Hruska, K. A.

1994-01-01

We examined the effect of a peptide containing the Arg-Gly-Asp (RGD) sequence on 45Ca2+ efflux from osteoclast precursors. 45Ca(2+)-loaded osteoclast precursors were treated with GRGDSP (170 microM) for 10 min after 30 min of basal perfusion with a bicarbonate-containing buffer. GRGDSP significantly increased fractional efflux of Ca2+ from treated cells compared with vehicle-treated cells (P < 0.01) or cells treated with up to 200 micrograms/ml of a control peptide containing GRGESP. The effect of RGD was sustained for 15 min after the peptide was removed from the perfusate, but control levels of Ca2+ efflux returned by 1 h. The Ca2+ efflux effect of GRGDSP was most likely due to activation of the plasma membrane Ca(2+)-adenosinetriphosphatase (Ca(2+)-ATPase) pump, as indicated by its inhibition with vanadate and a calmodulin antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, and the absence of an effect of Na+/Ca2+ exchange inhibition. An inhibitor of cyclic nucleotide-dependent protein kinases, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (0.1 mM), failed to inhibit GRGDSP-stimulated Ca2+ efflux. However, genistein and herbimycin A, inhibitors of protein-tyrosine kinases, blocked Ca2+ efflux stimulated by GRGDSP. The results indicate that RGD sequences of matrix proteins may stimulate Ca2+ efflux from osteoclasts through activation of protein-tyrosine kinases and suggest that GRGDSP-stimulated Ca2+ efflux is mediated via the plasma membrane Ca(2+)-ATPase.

Resveratrol and polydatin as modulators of Ca2+ mobilization in the cardiovascular system.

PubMed

Liu, Wenjuan; Chen, Peiya; Deng, Jianxin; Lv, Jingzhang; Liu, Jie

2017-09-01

In the cardiovascular system, Ca 2+ controls cardiac excitation-contraction coupling and vascular contraction and dilation. Disturbances in intracellular Ca 2+ homeostasis induce malfunctions of the cardiovascular system, including cardiac pump dysfunction, arrhythmia, remodeling, and apoptosis, as well as hypertension and impairment of vascular reactivity. Therefore, developing drugs and strategies manipulating Ca 2+ handling are highly valued in the treatment of cardiovascular disease. Resveratrol (Res) and polydatin (PD), a Res glucoside, have been well established to have beneficial effects on improving cardiovascular function. Studies from our laboratory and others have demonstrated that they exhibit inotropic effects on normal heart and therapeutic effects on hypertension, cardiac ischemia/reperfusion injury, hypertrophy, and heart failure by manipulating Ca 2+ mobilization. The actions of Res and PD on Ca 2+ signals delicately manipulated by multiple Ca 2+ -handling proteins are pleiotropic and somewhat controversial, depending on cellular species and intracellular oxidative status. Here, we focus on the effects of Res and PD on controlling Ca 2+ homeostasis in the heart and vasculature under normal and diseased conditions and highlight the key direct and indirect molecules mediating these effects. © 2017 New York Academy of Sciences.

Photocopy of drawing located at National Archives, San Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, San Bruno, California (Navy # 110-A-1 1 of 5. Scofiled Construction Company Mafre Island Office, Mare Island Cal. Details of skylight for pump house stone and concrete dry-dock for US Navy Yard Mare Island Cal, contract no. 257; September 2, 1908. - Mare Island Naval Shipyard, Pump House, California Avenue, east side between Dry Dock 1 & Dry Dock 2, near Ninth Street, Vallejo, Solano County, CA

The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.

PubMed

Hsu, Shu-Shong; Chou, Chiang-Ting; Liao, Wei-Chuan; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-25

Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is unknown. This study explored whether gallic acid affected Ca(2+) homeostasis and induced Ca(2+)-associated cytotoxicity in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. Gallic acid (20-40 μM) concentration-dependently induced cytotoxicity and intracellular Ca(2+) level ([Ca(2+)]i) increases in DBTRG-05MG cells but not in CTX TNA2 cells. In DBTRG-05MG cells, the Ca(2+) response was decreased by half by removal of extracellular Ca(2+). In Ca(2+)-containing medium, gallic acid-induced Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (2-APB, econazole and SKF96365). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished gallic acid-induced [Ca(2+)]i increases. Conversely, incubation with gallic acid also abolished thapsigargin-induced [Ca(2+)]i increases. Inhibition of phospholipase C with U73122 abolished gallic acid-induced [Ca(2+)]i increases. Gallic acid significantly caused cytotoxicity in DBTRG-05MG cells, which was partially prevented by prechelating cytosolic Ca(2+) with BAPTA-AM. Moreover, gallic acid activated mitochondrial apoptotic pathways that involved ROS production. Together, in DBTRG-05MG cells but not in CTX TNA2 cells, gallic acid induced [Ca(2+)]i increases by causing Ca(2+) entry via 2-APB, econazole and SKF96365-sensitive store-operated Ca(2+) entry, and phospholipase C-dependent release from the endoplasmic reticulum. This Ca(2+) signal subsequently evoked mitochondrial pathways of apoptosis that involved ROS production. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

First-Principles Prediction of Two-Dimensional Electron Gas Driven by Polarization Discontinuity in Nonpolar/Nonpolar AHfO3/SrTiO3 (A=Ca, Sr, and Ba) Heterostructures

NASA Astrophysics Data System (ADS)

Cheng, Jianli; Nazir, Safdar; Yang, Kesong

By using first-principles electronic structure calculations, we explored the possibility of producing two-dimensional electron gas (2DEG) in nonpolar/nonpolar AHfO3/SrTiO3 (A = Ca, Sr, and Ba) heterostructures (HS). Two types of interfaces, AO/TiO2 and HfO2/SrO, each with AO and HfO2 surface terminations, are modeled, respectively. The polarization domain and resulting interfacial electronic property are found to be more sensitive to the surface termination of the film rather than the interface model. As film thickness increases, an insulator-to-metal transition (IMT) is found in all the HS with HfO2 surface termination: for AO/TiO2 interfaces, predicted critical film thickness for an IMT is about 7, 6, and 3 unit cells for CaHfO3/SrTiO3, SrHfO3/SrTiO3, and BaHfO3/SrTiO3, respectively; for HfO2/SrO interfaces, the critical film thickness is about 7.5, 5.5, and 4.5 unit cells, respectively. In contrast, for the HS with AO surface termination, only CaHfO3/SrTiO3 exhibits an IMT with a much larger critical film thickness about 11 - 12 unit cells. This work is expected to stimulate further experimental investigation to the interfacial conductivity in the nonpolar/nonpolar AHfO3/SrTiO3 HS. National Science Foundation and Department of Defense National Security Science and Engineering Faculty Fellowship.

Homeostasis and secretion of calcium in the oviductal mucosa of toad Rhinella arenarum.

PubMed

Crespo, Claudia A; Medina, Marcela F; Ramos, Inés; Fernández, Silvia N

2014-10-01

The presence of a calcium pump, calbindin D-28KD, and calmodulin in the secretory cells (SC) of the oviductal pars convoluta (PC) of Rhinella arenarum was established for the first time in amphibians using immunohistochemical techniques. Marked variations were observed in the localization and degree of expression of these proteins according to the duct segment and the period of the sexual cycle analyzed. During the preovulatory and ovulatory periods the calcium pump colocalized with calbindin D-28KD can be seen mainly in the apical border of the SC, which are located in the first zones of PC and synthesize and secrete the components of the inner jelly coat layers. These envelopes, which surround the oocytes, contain the molecules indispensable for fertilization, probably inducing the sperm acrosome reaction (AR). Our results suggest that calmodulin, colocalized with the calcium pump at the SC cytoplasmic level, would be involved in the active transport of the cation inside the secretory granules, maintaining adequate levels of intracellular Ca(2+) . During the postreproductive period, a calcium pump colocalized with calbindin D-28KD appears for the first time in the cycle in the basal zones of the SC. This system may be related to the replenishing of intracellular Ca(2+) stores. In contrast, in R. arenarum the Ca(2+) present in the jelly coats that surround the oocytes participates in the AR during fertilization, suggesting that this secretion system of the cation provided by the oviductal mucosa is functionally more active during the reproductive period of this species. © 2014 Wiley Periodicals, Inc.

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Precipitation and Solubility of Calcium Hydrogenurate Hexahydrate

PubMed Central

Babić-Ivančić, V.; Füredi-Milhofer, H.; Brničević, N.; Marković, M.

1992-01-01

Solid phases formed in the quaternary system: uric acid—calcium hydroxide —hydrochloric acid—water aged for 2 months at 310 K were studied to determine conditions for calcium hydrogenurate hexahydrate, Ca(C5H3N4O)2 · 6H2O precipitation. The precipitates were identified by chemical and thermogravimetric analyses, x-ray powder diffraction, infrared spectroscopy, light microscopy, and scanning electron microscopy. In the precipitation diagram the concentration region in which calcium hydrogenurate hexahydrate precipitated as a single solid phase was established. The solubility of calcium hydrogenurate hexahydrate was investigated in the pH range from 6.2 to 10.1 at different temperatures. The total soluble and ionic concentration of calcium (atomic absorption spectroscopy and Ca-selective electrode), total urate concentration (spectrophotometry), and pH were determined in equilibrated solutions. The data are presented in the form of tables and chemical potential diagrams. By using these data the thermodynamic solubility products of calcium hydrogenurate hexahydrate, Ks = a(Ca2+) · a2(C5H3N4O3−), were determined: pKs=10.12±0.07at288K,pKs=9.81±0.09at298K,pKs=9.28±0.04at310K,andpKs=9.01±0.03at318K.The formation of calcium hydrogenurate hexahydrate crystals in urinary tract of patients with pathologically high concentrations of calcium and urates (hypercalciuria and hyperuricosiuria) is possible. PMID:28053438

Changes in Self-reported Insurance Coverage, Access to Care, and Health Under the Affordable Care Act.

PubMed

Sommers, Benjamin D; Gunja, Munira Z; Finegold, Kenneth; Musco, Thomas

2015-07-28

The Affordable Care Act (ACA) completed its second open enrollment period in February 2015. Assessing the law's effects has major policy implications. To estimate national changes in self-reported coverage, access to care, and health during the ACA's first 2 open enrollment periods and to assess differences between low-income adults in states that expanded Medicaid and in states that did not expand Medicaid. Analysis of the 2012-2015 Gallup-Healthways Well-Being Index, a daily national telephone survey. Using multivariable regression to adjust for pre-ACA trends and sociodemographics, we examined changes in outcomes for the nonelderly US adult population aged 18 through 64 years (n = 507,055) since the first open enrollment period began in October 2013. Linear regressions were used to model each outcome as a function of a linear monthly time trend and quarterly indicators. Then, pre-ACA (January 2012-September 2013) and post-ACA (January 2014-March 2015) changes for adults with incomes below 138% of the poverty level in Medicaid expansion states (n = 48,905 among 28 states and Washington, DC) vs nonexpansion states (n = 37,283 among 22 states) were compared using a differences-in-differences approach. Beginning of the ACA's first open enrollment period (October 2013). Self-reported rates of being uninsured, lacking a personal physician, lacking easy access to medicine, inability to afford needed care, overall health status, and health-related activity limitations. Among the 507,055 adults in this survey, pre-ACA trends were significantly worsening for all outcomes. Compared with the pre-ACA trends, by the first quarter of 2015, the adjusted proportions who were uninsured decreased by 7.9 percentage points (95% CI, -9.1 to -6.7); who lacked a personal physician, -3.5 percentage points (95% CI, -4.8 to -2.2); who lacked easy access to medicine, -2.4 percentage points (95% CI, -3.3 to -1.5); who were unable to afford care, -5.5 percentage points (95% CI, -6.7 to -4.2); who reported fair/poor health, -3.4 percentage points (95% CI, -4.6 to -2.2); and the percentage of days with activities limited by health, -1.7 percentage points (95% CI, -2.4 to -0.9). Coverage changes were largest among minorities; for example, the decrease in the uninsured rate was larger among Latino adults (-11.9 percentage points [95% CI, -15.3 to -8.5]) than white adults (-6.1 percentage points [95% CI, -7.3 to -4.8]). Medicaid expansion was associated with significant reductions among low-income adults in the uninsured rate (differences-in-differences estimate, -5.2 percentage points [95% CI, -7.9 to -2.6]), lacking a personal physician (-1.8 percentage points [95% CI, -3.4 to -0.3]), and difficulty accessing medicine (-2.2 percentage points [95% CI, -3.8 to -0.7]). The ACA's first 2 open enrollment periods were associated with significantly improved trends in self-reported coverage, access to primary care and medications, affordability, and health. Low-income adults in states that expanded Medicaid reported significant gains in insurance coverage and access compared with adults in states that did not expand Medicaid.

Sudden Death in Heart Failure With Preserved Ejection Fraction: A Competing Risks Analysis From the TOPCAT Trial.

PubMed

Vaduganathan, Muthiah; Claggett, Brian L; Chatterjee, Neal A; Anand, Inder S; Sweitzer, Nancy K; Fang, James C; O'Meara, Eileen; Shah, Sanjiv J; Hegde, Sheila M; Desai, Akshay S; Lewis, Eldrin F; Rouleau, Jean; Pitt, Bertram; Pfeffer, Marc A; Solomon, Scott D

2018-03-04

This study investigated the rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). We studied 1,767 patients with HFpEF (EF ≥45%) enrolled in the Americas region of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. We identified independent predictors of composite SD/ACA with stepwise backward selection using competing risks regression analysis that accounted for nonsudden causes of death. During a median 3.0-year (25 th to 75 th percentile: 1.9 to 4.4 years) follow-up, 77 patients experienced SD/ACA, and 312 experienced non-SD/ACA. Corresponding incidence rates were 1.4 events/100 patient-years (25 th to 75 th percentile: 1.1 to 1.8 events/100 patient-years) and 5.8 events/100 patient-years (25 th to 75 th percentile: 5.1 to 6.4 events/100 patient-years). SD/ACA was numerically lower but not statistically reduced in those randomized to spironolactone: 1.2 events/100 patient-years (25 th to 75 th percentile: 0.9 to 1.7 events/100 patient-years) versus 1.6 events/100 patient-years (25 th to 75 th percentile: 1.2 to 2.2 events/100 patient-years); the subdistributional hazard ratio was 0.74 (95% confidence interval: 0.47 to 1.16; p = 0.19). After accounting for competing risks of non-SD/ACA, male sex and insulin-treated diabetes mellitus were independently predictive of composite SD/ACA (C-statistic = 0.65). Covariates, including eligibility criteria, age, ejection fraction, coronary artery disease, left bundle branch block, and baseline therapies, were not independently associated with SD/ACA. Sex and diabetes mellitus status remained independent predictors in sensitivity analyses, excluding patients with implantable cardioverter-defibrillators and when predicting SD alone. SD accounted for ∼20% of deaths in HFpEF. Male sex and insulin-treated diabetes mellitus identified patients at higher risk for SD/ACA with modest discrimination. These data might guide future SD preventative efforts in HFpEF. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]); NCT00094302. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The effect of oleuropein from olive leaf (Olea europaea) extract on Ca²⁺ homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells.

PubMed

Cheng, Jin-Shiung; Chou, Chiang-Ting; Liu, Yuan-Yuarn; Sun, Wei-Chih; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-01

Oleuropein, a phenolic compound found in the olive leaf (Olea europaea), has been shown to have biological activities in different models. However, the effects of oleuropein on Ca(2+) homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in liver cells have not been analyzed. Oleuropein induced [Ca(2+)]i rises only in HepG2 cells but not in AML12, HA22T or HA59T cells due to the different status of 3-hydroxy-3-methylglutaryl-CoA reductase expression. In HepG2 cells, this Ca(2+) signaling response was reduced by removing extracellular Ca(2+), and was inhibited by the store-operated Ca(2+) channel blockers 2-APB and SKF96365. In Ca(2+)-free medium, pretreatment with the ER Ca(2+) pump inhibitor thapsigargin abolished oleuropein-induced [Ca(2+)]i rises. Oleuropein induced cell cycle arrest which was associated with the regulation of p53, p21, CDK1 and cyclin B1 levels. Furthermore, oleuropein elevated intracellular ROS levels but reduced GSH levels. Treatment with the intracellular Ca(2+) chelator BAPTA-AM or the antioxidant NAC partially reversed oleuropein-induced cytotoxicity. Together, in HepG2 cells, oleuropein induced [Ca(2+)]i rises by releasing Ca(2+) from the ER and causing Ca(2+) influx through store-operated Ca(2+) channels. Moreover, oleuropein induced Ca(2+)-associated cytotoxicity that involved ROS signaling and cell cycle arrest. This compound may offer a potential therapy for treatment of human hepatoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

RNA-seq analysis identifies potential modulators of gravity response in spores of Ceratopteris (Parkeriaceae): evidence for modulation by calcium pumps and apyrase activity.

PubMed

Bushart, Thomas J; Cannon, Ashley E; Ul Haque, Aeraj; San Miguel, Phillip; Mostajeran, Kathy; Clark, Gregory B; Porterfield, D Marshall; Roux, Stanley J

2013-01-01

Gravity regulates the magnitude and direction of a trans-cell calcium current in germinating spores of Ceratopteris richardii. Blocking this current with nifedipine blocks the spore's downward polarity alignment, a polarization that is fixed by gravity ∼10 h after light induces the spores to germinate. RNA-seq analysis at 10 h was used to identify genes potentially important for the gravity response. The data set will be valuable for other developmental and phylogenetic studies. De novo Newbler assembly of 958 527 reads from Roche 454 sequencing was executed. The sequences were identified and analyzed using in silico methods. The roles of endomembrane Ca(2+)-ATPase pumps and apyrases in the gravity response were further tested using pharmacological agents. Transcripts related to calcium signaling and ethylene biosynthesis were identified as notable constituents of the transcriptome. Inhibiting the activity of endomembrane Ca(2+)-ATPase pumps with 2,5-di-(t-butyl)-1,4-hydroquinone diminished the trans-cell current, but increased the orientation of the polar axis to gravity. The effects of applied nucleotides and purinoceptor antagonists gave novel evidence implicating extracellular nucleotides as regulators of the gravity response in these fern spores. In addition to revealing general features of the transcriptome of germinating spores, the results highlight a number of calcium-responsive and light-receptive transcripts. Pharmacologic assays indicate endomembrane Ca(2+)-ATPases and extracellular nucleotides may play regulatory roles in the gravity response of Ceratopteris spores.

Effects of calcium (Ca(2+)) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: insight from a mathematical model.

PubMed

Horn, Kyle G; Solomon, Irene C

2014-01-01

Spike-frequency dynamics and spike shape can provide insight into the types of ion channels present in any given neuron and give a sense for the precise response any neuron may have to a given input stimulus. Motoneuron firing frequency over time is especially important due to its direct effect on motor output. Of particular interest is intracellular Ca(2+), which exerts a powerful influence on both firing properties over time and spike shape. In order to better understand the cellular mechanisms for the regulation of intracellular Ca(2+) and their effect on spiking behavior, we have modified a computational model of an HM to include a variety of Ca(2+) handling processes. For the current study, a series of HM models that include Ca(2+) pumps, Na(+)/Ca(2+) exchangers, and a generic exponential decay of excess Ca(2+) were generated. Simulations from these models indicate that although each extrusion mechanism exerts a similar effect on voltage, the firing properties change distinctly with the inclusion of additional Ca(2+)-related mechanisms: BK channels, Ca(2+) buffering, and diffusion of [Ca(2+)]i modeled via a linear diffusion partial differential equation. While an exponential decay of Ca(2+) seems to adequately capture short-term changes in firing frequency seen in biological data, internal diffusion of Ca(2+) appears to be necessary for capturing longer term frequency changes. © 2014 Elsevier B.V. All rights reserved.

Ca2+-induced delayed afterdepolarizations are triggered by dyadic subspace Ca2+ affirming that increasing SERCA reduces aftercontractions

PubMed Central

Noble, Penelope J.; Noble, Denis

2011-01-01

Ca2+-induced delayed afterdepolarizations (DADs) are depolarizations that occur after full repolarization. They have been observed across multiple species and cell types. Experimental results have indicated that the main cause of DADs is Ca2+ overload. The main hypothesis as to their initiation has been Ca2+ overflow from the overloaded sarcoplasmic reticulum (SR). Our results using 37 previously published mathematical models provide evidence that Ca2+-induced DADs are initiated by the same mechanism as Ca2+-induced Ca2+ release, i.e., the modulation of the opening of ryanodine receptors (RyR) by Ca2+ in the dyadic subspace; an SR overflow mechanism was not necessary for the induction of DADs in any of the models. The SR Ca2+ level is better viewed as a modulator of the appearance of DADs and the magnitude of Ca2+ release. The threshold for the total Ca2+ level within the cell (not only the SR) at which Ca2+ oscillations arise in the models is close to their baseline level (∼1- to 3-fold). It is most sensitive to changes in the maximum sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) pump rate (directly proportional), the opening probability of RyRs, and the Ca2+ diffusion rate from the dyadic subspace into the cytosol (both indirectly proportional), indicating that the appearance of DADs is multifactorial. This shift in emphasis away from SR overload as the trigger for DADs toward a multifactorial analysis could explain why SERCA overexpression has been shown to suppress DADs (while increasing contractility) and why DADs appear during heart failure (at low SR Ca2+ levels). PMID:21666112

Mitochondrial calcium handling within the interstitial cells of Cajal

PubMed Central

Cheng, Leo K.

2014-01-01

The interstitial cells of Cajal (ICC) drive rhythmic pacemaking contractions in the gastrointestinal system. The ICC generate pacemaking signals by membrane depolarizations associated with the release of intracellular calcium (Ca2+) in the endoplasmic reticulum (ER) through inositol-trisphosphate (IP3) receptors (IP3R) and uptake by mitochondria (MT). This Ca2+ dynamic is hypothesized to generate pacemaking signals by calibrating ER Ca2+ store depletions and membrane depolarization with ER store-operated Ca2+ entry mechanisms. Using a biophysically based spatio-temporal model of integrated Ca2+ transport in the ICC, we determined the feasibility of ER depletion timescale correspondence with experimentally observed pacemaking frequencies while considering the impact of IP3R Ca2+ release and MT uptake on bulk cytosolic Ca2+ levels because persistent elevations of free intracellular Ca2+ are toxic to the cell. MT densities and distributions are varied in the model geometry to observe MT influence on free cytosolic Ca2+ and the resulting frequencies of ER Ca2+ store depletions, as well as the sarco-endoplasmic reticulum Ca2+ ATP-ase (SERCA) and IP3 agonist concentrations. Our simulations show that high MT densities observed in the ICC are more relevant to ER establishing Ca2+ depletion frequencies than protection of the cytosol from elevated free Ca2+, whereas the SERCA pump is more relevant to containing cytosolic Ca2+ elevations. Our results further suggest that the level of IP3 agonist stimulating ER Ca2+ release, subsequent MT uptake, and eventual activation of ER store-operated Ca2+ entry may determine frequencies of rhythmic pacemaking exhibited by the ICC across species and tissue types. PMID:24789203

Department of the Navy Justification of Estimates FY 1991 Budget Estimates Submitted to Congress January 1990: Military Personnel, Marine Corps.

DTIC Science & Technology

1990-01-01

01CC - Ca a - C’a CC-. v~ e - 0% eeeo -Ca Ca ~ a a - - aCa C - - Ca - US 0. C a -.g a- 0 CU= a. -(.1 - aa - a a as’. a a0 0 1-0. as - O 0 a a a -~ a asCU ...a a - a - ’a a .fl - a -o a -, a a - - ’ ag -.. 4=a - - - a a en a en 4= 4- .- C C C C C C Ca en a - - a - - C .fl .O ’a aa - I -,a - - - - - - - a

The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-Na+ pump endocrine system.

PubMed

Blaustein, Mordecai P

2018-01-01

Two prescient 1953 publications set the stage for the elucidation of a novel endocrine system: Schatzmann's report that cardiotonic steroids (CTSs) are all Na + pump inhibitors, and Szent-Gyorgi's suggestion that there is an endogenous "missing screw" in heart failure that CTSs like digoxin may replace. In 1977 I postulated that an endogenous Na + pump inhibitor acts as a natriuretic hormone and simultaneously elevates blood pressure (BP) in salt-dependent hypertension. This hypothesis was based on the idea that excess renal salt retention promoted the secretion of a CTS-like hormone that inhibits renal Na + pumps and salt reabsorption. The hormone also inhibits arterial Na + pumps, elevates myocyte Na + and promotes Na/Ca exchanger-mediated Ca 2+ gain. This enhances vasoconstriction and arterial tone-the hallmark of hypertension. Here I describe how those ideas led to the discovery that the CTS-like hormone is endogenous ouabain (EO), a key factor in the pathogenesis of hypertension and heart failure. Seminal observations that underlie the still-emerging picture of the EO-Na + pump endocrine system in the physiology and pathophysiology of multiple organ systems are summarized. Milestones include: 1) cloning the Na + pump isoforms and physiological studies of mutated pumps in mice; 2) discovery that Na + pumps are also EO-triggered signaling molecules; 3) demonstration that ouabain, but not digoxin, is hypertensinogenic; 4) elucidation of EO's roles in kidney development and cardiovascular and renal physiology and pathophysiology; 5) discovery of "brain ouabain", a component of a novel hypothalamic neuromodulatory pathway; and 6) finding that EO and its brain receptors modulate behavior and learning.

Adenylyl cyclase A mRNA localized at the back of cells is actively translated in live chemotaxing Dictyostelium.

PubMed

Wang, Weiye; Chen, Song; Das, Satarupa; Losert, Wolfgang; Parent, Carole A

2018-05-04

Dictyostelium discoideum cells transport adenylyl cyclase A (ACA)-containing vesicles to the back of polarized cells to relay exogenous cAMP signals during chemotaxis. Fluorescence in situ hybridization (FISH) experiments showed that ACA mRNA is also asymmetrically distributed at the back of polarized cells. By using the MS2 bacteriophage system, we now visualize the distribution of ACA mRNA in live chemotaxing cells. We found that the ACA mRNA localization is not dependent on the translation of the protein product and requires multiple cis-acting elements within the ACA-coding sequence. We show that ACA mRNA is associated with actively translating ribosomes and is transported along microtubules towards the back of cells. By monitoring the recovery of ACA-YFP after photobleaching, we observed that local translation of ACA-YFP occurs at the back of cells. These data represent a novel functional role for localized translation in the relay of chemotactic signals during chemotaxis. © 2018. Published by The Company of Biologists Ltd.

New saliva secretion model based on the expression of Na+-K+ pump and K+ channels in the apical membrane of parotid acinar cells.

PubMed

Almássy, János; Siguenza, Elias; Skaliczki, Marianna; Matesz, Klara; Sneyd, James; Yule, David I; Nánási, Péter P

2018-04-01

The plasma membrane of parotid acinar cells is functionally divided into apical and basolateral regions. According to the current model, fluid secretion is driven by transepithelial ion gradient, which facilitates water movement by osmosis into the acinar lumen from the interstitium. The osmotic gradient is created by the apical Cl - efflux and the subsequent paracellular Na + transport. In this model, the Na + -K + pump is located exclusively in the basolateral membrane and has essential role in salivary secretion, since the driving force for Cl - transport via basolateral Na + -K + -2Cl - cotransport is generated by the Na + -K + pump. In addition, the continuous electrochemical gradient for Cl - flow during acinar cell stimulation is maintained by the basolateral K + efflux. However, using a combination of single-cell electrophysiology and Ca 2+ -imaging, we demonstrate that photolysis of Ca 2+ close to the apical membrane of parotid acinar cells triggered significant K + current, indicating that a substantial amount of K + is secreted into the lumen during stimulation. Nevertheless, the K + content of the primary saliva is relatively low, suggesting that K + might be reabsorbed through the apical membrane. Therefore, we investigated the localization of Na + -K + pumps in acinar cells. We show that the pumps appear evenly distributed throughout the whole plasma membrane, including the apical pole of the cell. Based on these results, a new mathematical model of salivary fluid secretion is presented, where the pump reabsorbs K + from and secretes Na + to the lumen, which can partially supplement the paracellular Na + pathway.

The pure rotational spectrum of CaNC

NASA Astrophysics Data System (ADS)

Scurlock, C. T.; Steimle, T. C.; Suenram, R. D.; Lovas, F. J.

1994-03-01

The pure rotational spectrum of calcium isocyanide, CaNC, in its (0,0,0) X 2Σ+ vibronic state was measured using a combination of Fourier transform microwave (FTMW) and pump/probe microwave-optical double resonance (PPMODR) spectroscopy. Gaseous CaNC was generated using a laser ablation/supersonic expansion source. The determined spectroscopic parameters are (in MHz), B=4048.754 332 (29); γ=18.055 06 (23); bF=12.481 49 (93); c=2.0735 (14); and eQq0=-2.6974 (11). The hyperfine parameters are qualitatively interpreted in terms of a plausible molecular orbital descriptions and a comparison with the alkaline earth monohalides and the alkali monocyanides is given.

Microchip Yb:CaLnAlO4 lasers with up to 91% slope efficiency.

PubMed

Loiko, Pavel; Serres, Josep Maria; Mateos, Xavier; Xu, Xiaodong; Xu, Jun; Jambunathan, Venkatesan; Navratil, Petr; Lucianetti, Antonio; Mocek, Tomas; Zhang, Xuzhao; Griebner, Uwe; Petrov, Valentin; Aguiló, Magdalena; Díaz, Francesc; Major, Arkady

2017-07-01

Multi-watt continuous-wave (CW) operation of tetragonal rare-earth calcium aluminate Yb:CaLnAlO 4 (Ln=Gd,Y)) crystals in plano-plano microchip lasers was demonstrated with an almost quantum-defect-limited slope efficiency. Pumped at 978 nm by an InGaAs laser diode, a 3.4 mm long 8 at. % Yb:CaGdAlO 4 laser generated 7.79 W at 1057-1065 nm with a slope efficiency of η=84% (with respect to the absorbed pump power). An even higher η=91% was achieved with a 2.5 mm long 3 at. % Yb:CaYAlO 4 laser, from which 5.06 W were extracted at 1048-1056 nm. Both lasers produced linearly polarized output (σ-polarization) with an almost circular diffraction-limited beam (Mx,y2<1.1). The output performance of the developed lasers was modeled, yielding an internal loss coefficient as low as 0.004-0.007  cm -1 . In addition, their spectroscopic properties were revisited.

Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro.

PubMed

Prasanna, Vaddi K; Venkatesh, Yeldur P

2015-06-01

Onion (Allium cepa), a bulb crop of economic importance, is known to have many health benefits. The major objective of the present study is to address the immunomodulatory properties of onion lectin (A. cepa agglutinin; ACA). ACA was purified from onion extract by D-mannose-agarose chromatography (yield: ~1 mg/kg). ACA is non-glycosylated and showed a molecular mass of ~12 kDa under reducing/non-reducing SDS-PAGE; glutaraldehyde cross-linking indicated that ACA is a non-covalent tetramer of ~12 kDa subunits. Its N-terminal sequence (RNVLLNNEGL; UniProt KB Accn. C0HJM8) showed 70-90% homology to mannose-specific Allium agglutinins. ACA showed specific hemagglutination activity of 8200 units/mg and is stable in the pH range 6-10 and up to 45° C. The immunomodulatory activity of ACA was assessed using the macrophage cell line, RAW264.7 and rat peritoneal macrophages; at 0.1 μg/well, it showed a significant increase (6-8-fold vs. control) in the production of nitric oxide at 24h, and significantly stimulated (2-4-fold vs. control) the production of pro-inflammatory cytokines (TNF-α and IL-12) at 24h. ACA (0.1 μg/well) enhanced the proliferation of murine thymocytes by ~4 fold (vs. control) at 24h; however, ACA does not proliferate B cell-enriched rat splenocytes. Further, it significantly elevated the expression levels of cytokines (IFN-γ and IL-2) over the control in murine thymocytes. Taken together, purified ACA induces a Th1-type immune response in vitro. Though present in low amounts, ACA may contribute to the immune-boosting potential of the popular spice onion since considerable amounts are consumed on a daily basis universally. Copyright © 2015 Elsevier B.V. All rights reserved.

Ionization studies in laser-excited alkaline-earth vapors.

PubMed

Hermann, J P; Wynne, J J

1980-06-01

We report on the time behavior of ionization signals produced by laser excitation of Ca and Ba atomic vapor to high-Rydberg states. A space-charge-limited thermionic diode detector shows a long-lived (>I-msec) ionization signal. However, optical detection of atomic ions (Ca+, Ba+) shows that these species live for much shorter times (<100 microsec). These results, in conjunction with published results on mass-spectrometric studies of high-density atomic beams, suggest that our ionization signal is primarily due to molecular species (Ca2+, Ba2+). We also observed optically pumped amplified spontaneous emission and stimulated electronic Raman scattering in Ca+ and Ba+.

1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

PubMed

Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

2016-09-25

1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Insulin pump therapy with automated insulin suspension in response to hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk.

PubMed

Choudhary, Pratik; Shin, John; Wang, Yongyin; Evans, Mark L; Hammond, Peter J; Kerr, David; Shaw, James A M; Pickup, John C; Amiel, Stephanie A

2011-09-01

To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients.

Lvad pump speed increase is associated with increased peak exercise cardiac output and vo2, postponed anaerobic threshold and improved ventilatory efficiency.

PubMed

Vignati, Carlo; Apostolo, Anna; Cattadori, Gaia; Farina, Stefania; Del Torto, Alberico; Scuri, Silvia; Gerosa, Gino; Bottio, Tomaso; Tarzia, Vincenzo; Bejko, Jonida; Sisillo, Erminio; Nicoli, Flavia; Sciomer, Susanna; Alamanni, Francesco; Paolillo, Stefania; Agostoni, Piergiuseppe

2017-03-01

Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VO 2 ), provided that arteriovenous O 2 difference [Δ(Ca-Cv)O 2 ] does not decrease. At anaerobic threshold, VO 2 , is related to CO. We tested the hypothesis that, in heart failure (HF) patients with left ventricular assistance device (LVAD), an acute increase of CO obtained through changes in LVAD pump speed is associated with peak exercise and anaerobic threshold VO 2 increase. Fifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4. Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p=0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p<0.01) at rest and peak exercise, respectively. Similarly, VO 2 increased from 788±169 to 841±152mL/min (ΔVO 2 52±76mL/min, p=0.01) and from 568±116 to 619±124mL/min (ΔVO 2 69±96mL/min, p=0.02) at peak exercise and at anaerobic threshold, respectively. Δ(Ca-Cv)O 2 did not change significantly, while ventilatory efficiency improved (VE/VCO 2 slope from 39.9±5.4 to 34.9±8.3, ΔVE/VCO 2 -5.0±6.4, p<0.01). In HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO 2 , postponed anaerobic threshold, and improved ventilatory efficiency. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Differences in the Stimulus Accommodative Convergence/Accommodation Ratio using Various Techniques and Accommodative Stimuli.

PubMed

Satou, Tsukasa; Ito, Misae; Shinomiya, Yuma; Takahashi, Yoshiaki; Hara, Naoto; Niida, Takahiro

2018-04-04

To investigate differences in the stimulus accommodative convergence/accommodation (AC/A) ratio using various techniques and accommodative stimuli, and to describe a method for determining the stimulus AC/A ratio. A total of 81 subjects with a mean age of 21 years (range, 20-23 years) were enrolled. The relationship between ocular deviation and accommodation was assessed using two methods. Ocular deviation was measured by varying the accommodative requirement using spherical plus/minus lenses to create an accommodative stimulus of 10.00 diopters (D) (in 1.00 D steps). Ocular deviation was assessed using the alternate prism cover test in method 1 at distance (5 m) and near (1/3 m), and the major amblyoscope in method 2. The stimulus AC/A ratios obtained using methods 1 and 2 were calculated and defined as the stimulus AC/A ratios with low and high accommodation, respectively, using the following analysis method. The former was calculated as the difference between the convergence response to an accommodative stimulus of 3 D and 0 D, divided by 3. The latter was calculated as the difference between the convergence response to a maximum (max) accommodative stimulus with distinct vision of the subject and an accommodative stimulus of max minus 3.00 D, divided by 3. The median stimulus AC/A ratio with low accommodation (1.0 Δ/D for method 1 at distance, 2.0 Δ/D for method 1 at near, and 2.7 Δ/D for method 2) differed significantly among the measurement methods (P < 0.01). Differences in the median stimulus AC/A ratio with high accommodation (4.0 Δ/D for method 1 at distance, 3.7 Δ/D for method 1 at near, and 4.7 Δ/D for method 2) between method 1 at distance and method 2 were statistically significant (P < 0.05), while method 1 at near was not significantly different compared with other methods. Differences in the stimulus AC/A ratio value were significant according to measurement technique and accommodative stimuli. However, differences caused by measurement technique may be reduced by using a high accommodative stimulus during measurements.

Thermoelectric Mechanism and Interface Characteristics of Cyanide-Free Nanogold-Coated Silver Wire

NASA Astrophysics Data System (ADS)

Tseng, Yi-Wei; Hung, Fei-Yi; Lui, Truan-Sheng

2016-01-01

Traditional bath-plated gold contains a cyanide complex, which is an environmental hazard. In response, our study used a green plating process to produce cyanide-free gold-coated silver (cyanide-free ACA) bonding wire that has been proven to be a feasible alternative to gold bonding wire in semiconductor packaging. In this work, ACA wire annealed at 550°C was found to have stable microstructure and superior mechanical properties. Intermetallic compounds Ag2Al and AuAl2 grew from Ag-Au balls and Al pads after aging at 175°C for 500 h. After current testing, ACA wire was found to have improved electrical properties due to equiaxed grain growth. The gold nanolayer on the Ag surface increased the oxidation resistance. These results provide insights regarding the reliability of ACA wire in advanced bonding processes.

Polyaniline-Coated Activated Carbon Aerogel/Sulfur Composite for High-performance Lithium-Sulfur Battery

NASA Astrophysics Data System (ADS)

Tang, Zhiwei; Jiang, Jinglin; Liu, Shaohong; Chen, Luyi; Liu, Ruliang; Zheng, Bingna; Fu, Ruowen; Wu, Dingcai

2017-12-01

An activated carbon aerogel (ACA-500) with high surface area (1765 m2 g-1), pore volume (2.04 cm3 g-1), and hierarchical porous nanonetwork structure is prepared through direct activation of organic aerogel (RC-500) with a low potassium hydroxide ratio (1:1). Based on this substrate, a polyaniline (PANi)-coated activated carbon aerogel/sulfur (ACA-500-S@PANi) composite is prepared via a simple two-step procedure, including melt-infiltration of sublimed sulfur into ACA-500, followed by an in situ polymerization of aniline on the surface of ACA-500-S composite. The obtained ACA-500-S@PANi composite delivers a high reversible capacity up to 1208 mAh g-1 at 0.2C and maintains 542 mAh g-1 even at a high rate (3C). Furthermore, this composite exhibits a discharge capacity of 926 mAh g-1 at the initial cycle and 615 mAh g-1 after 700 cycles at 1C rate, revealing an extremely low capacity decay rate (0.48‰ per cycle). The excellent electrochemical performance of ACA-500-S@PANi can be attributed to the synergistic effect of hierarchical porous nanonetwork structure and PANi coating. Activated carbon aerogels with high surface area and unique three-dimensional (3D) interconnected hierarchical porous structure offer an efficient conductive network for sulfur, and a highly conductive PANi-coating layer further enhances conductivity of the electrode and prevents the dissolution of polysulfide species.

Spectroscopic, luminescent and laser properties of nanostructured CaF2:Tm materials

NASA Astrophysics Data System (ADS)

Lyapin, A. A.; Fedorov, P. P.; Garibin, E. A.; Malov, A. V.; Osiko, V. V.; Ryabochkina, P. A.; Ushakov, S. N.

2013-08-01

The laser quality transparent СаF2:Tm fluoride ceramics has been prepared by hot forming. Comparative study of absorption and emission spectra of СаF2:Tm (4 mol.% TmF3) ceramic and single crystal samples demonstrated that these materials possess almost identical spectroscopic properties. Laser oscillations of СаF2:Tm ceramics were obtained at 1898 nm under diode pumping, with the slope efficiency of 5.5%. Also, the continuous-wave (CW) laser have been obtained for СаF2:Tm single crystal at 1890 nm pumped by a diode laser was demonstrated.

Dual-wavelength Nd:CaLnAlO4 lasers at 1.365 and 1.390 μm

NASA Astrophysics Data System (ADS)

Loiko, Pavel; Maria Serres, Josep; Mateos, Xavier; Xu, Xiaodong; Xu, Jun; Griebner, Uwe; Petrov, Valentin; Aguiló, Magdalena; Díaz, Francesc; Major, Arkady

2018-02-01

Tetragonal calcium rare-earth aluminates, CaLnAlO4, are attractive laser host crystals. The emission of Nd3+ ions at 1.3- 1.4 μm due to the 4F3/2 -> 4I13/2 transition is of interest for medicine, fiber optics, and light conversion. We report on compact Nd:CaLnAlO4 lasers using a plane-plane cavity. With an a-cut 0.8 at.% Nd:CaYAlO4 crystal diode-pumped at 802 nm, a maximum continuous-wave output power of 365 mW was achieved at 1.365 & 1.390 μm corresponding to the σ-polarization. The 4F3/2 -> 4I13/2 laser performance of the Nd:CaLnAlO4 crystals was compared to that from a monoclinic Nd:KGd(WO4)2. At the 4F3/2-> 4I11/2 transition (1.08 μm), a Nd:CaYAlO4 micro-laser generated multi-watt output (>4 W) with a slope efficiency of 39%.

Solid state proton and electron mediating membrane and use in catalytic membrane reactors

DOEpatents

White, James H.; Schwartz, Michael; Sammells, Anthony F.

2001-01-01

Mixed electron- and proton-conducting metal oxide materials are provided. These materials are useful in fabrication of membranes for use in catalytic membrane reactions, particularly for promoting dehydrogenation of hydrocarbons, oligomerization of hydrocarbons and for the decomposition of hydrogen-containing gases. Membrane materials are perovskite compounds of the formula: AB.sub.1-x B'.sub.x O.sub.3-y where A=Ca, Sr, or Ba; B=Ce, Tb, Pr or Th; B'=Ti, V, Cr, Mn, Fe, Co, Ni or Cu; 0.2.ltoreq.x.ltoreq.0.5, and y is a number sufficient to neutralize the charge in the mixed metal oxide material.

Solid state proton and electron mediating membrane and use in catalytic membrane reactors

DOEpatents

White, James H.; Schwartz, Michael; Sammells, Anthony F.

2000-01-01

Mixed electron- and proton-conducting metal oxide materials are provided. These materials are useful in fabrication of membranes for use in catalytic membrane reactions, particularly for promoting dehydrogenation of hydrocarbons, oligomerization of hydrocarbons and for the decomposition of hydrogen-containing gases. Membrane materials are perovskite compounds of the formula: AB.sub.1-x B'.sub.x O.sub.3-y where A=Ca, Sr, or Ba; B=Ce, Tb, Pr or Th; B'=Ti, V, Cr, Mn, Fe, Co, Ni or Cu; 0.2

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles.

PubMed

Barclay, C J

2012-12-01

The aims of this study were to quantify the Ca(2+) release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca(2+) release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca(2+) release was quantified from the amount of ATP used to remove Ca(2+) from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca(2+) pump ATP turnover. At 20°C, Ca(2+) release in response to a single stimulus was 34 and 84 μmol (kg muscle)(-1) for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg(-1); EDL, 168 μmol kg(-1)). Delivery of another stimulus within 100 ms of the first produced a smaller Ca(2+) release. The maximum magnitude of the decrease in Ca(2+) release was greater in EDL than soleus. Ca(2+) release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca(2+) released and crossbridge cycles performed are consistent with a scheme in which Ca(2+) binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles

PubMed Central

Barclay, C J

2012-01-01

The aims of this study were to quantify the Ca2+ release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca2+ release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca2+ release was quantified from the amount of ATP used to remove Ca2+ from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca2+ pump ATP turnover. At 20°C, Ca2+ release in response to a single stimulus was 34 and 84 μmol (kg muscle)−1 for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg−1; EDL, 168 μmol kg−1). Delivery of another stimulus within 100 ms of the first produced a smaller Ca2+ release. The maximum magnitude of the decrease in Ca2+ release was greater in EDL than soleus. Ca2+ release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca2+ released and crossbridge cycles performed are consistent with a scheme in which Ca2+ binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles. PMID:23027818

Real-time Recording of Cytosolic Calcium Levels in Arabidopsis thaliana Cell Cultures during Parabolic Flights

NASA Astrophysics Data System (ADS)

Neef, Maren; Ecke, Margret; Hampp, Rüdiger

2015-07-01

In plants, like in other organisms, calcium (Ca2+) is an important second messenger which participates in the conversion of environmental signals into molecular responses. There is increasing evidence, that sensing of changes in gravitation or reorientation of tissues is an example for such signaling cascades in which Ca2+ is involved. In order to determine g-dependent changes in the cytosolic calcium (Ca^{2+}_{ {cyt}}) concentration of plant cells, semisolid transgenic callus cell cultures of Arabidopsis thaliana (A.t.), expressing the calcium sensor YC3.6 (cameleon), were exposed to g-forces between 1.8 g and μ g during parabolic flights. Using such cells, intracellular calcium transients can be monitored by FRET in vivo and in real-time. Interestingly we observed a slight decrease of the Ca^{2+}_{ {cyt}} level during the hypergravity phases of a parabola but a significant increase of the Ca^{2+}_{ {cyt}} concentration during microgravity. Application of known Ca2+ inhibitors and antagonists yielded the following effects: nifedipine (Ca2+ channel blocker) showed no effect, whereas LaCl3, GdCl3 (both inhibitors of uptake at the plasma membrane), DPI (inhibitor of NADP oxidase), and DMSO (solvent) diminished the gravity-alteration-related Ca^{2+}_{ {cyt}} response. EGTA (binding of Ca2+) and eosin yellow (inhibitor of a plasma membrane-located Ca2+ pump) suppressed the respective Ca^{2+}_{ {cyt}} changes entirely. We thus conclude that the significant increase in Ca^{2+}_{ {cyt}} under microgravity is largely due to extracellular Ca2+ sources.

Secretory pathway Ca2+ -ATPases promote in vitro microcalcifications in breast cancer cells.

PubMed

Dang, Donna; Prasad, Hari; Rao, Rajini

2017-11-01

Calcification of the breast is often an outward manifestation of underlying molecular changes that drive carcinogenesis. Up to 50% of all non-palpable breast tumors and 90% of ductal carcinoma in situ present with radiographically dense mineralization in mammographic scans. However, surprisingly little is known about the molecular pathways that lead to microcalcifications in the breast. Here, we report on a rapid and quantitative in vitro assay to monitor microcalcifications in breast cancer cell lines, including MCF7, MDA-MB-231, and Hs578T. We show that the Secretory Pathway Ca 2+ -ATPases SPCA1 and SPCA2 are strongly induced under osteogenic conditions that elicit microcalcifications. SPCA gene expression is significantly elevated in breast cancer subtypes that are associated with microcalcifications. Ectopic expression of SPCA genes drives microcalcifications and is dependent on pumping activity. Conversely, knockdown of SPCA expression significantly attenuates formation of microcalcifications. We propose that high levels of SPCA pumps may initiate mineralization in the secretory pathway by elevating luminal Ca 2+ . Our new findings offer mechanistic insight and functional implications on a widely observed, yet poorly understood radiographic signature of breast cancer. © 2017 Wiley Periodicals, Inc.

Effects of diltiazem or verapamil on calcium uptake and release from chicken skeletal muscle sarcoplasmic reticulum.

PubMed

Paydar, Mehrak Javadi; Pousti, Abbas; Farsam, Hasan; Amanlou, Massoud; Mehr, Shahram Ejtemaei; Dehpour, Ahmad Reza

2005-11-01

The purpose of this study was to determine the effects of 2 Ca2+ channel blockers, verapamil and diltiazem, on calcium loading (active Ca2+ uptake) and the following Ca2+ release induced by silver ion (Ag+) and Ca2+ from the membrane of heavy sarcoplasmic reticulum (SR) of chicken skeletal muscle. A fluorescent probe technique was employed to determine the calcium movement through the SR. Pretreatment of the medium with diltiazem and verapamil resulted in a significant decrease in the active Ca2+ uptake, with IC50 of about 290 micromol/L for verapamil and 260 micromol/L for diltiazem. Inhibition of Ca2+ uptake was not due to the development of a substantial drug-dependent leak of Ca2+ from the SR. It might, in part, have been mediated by a direct inhibitory effect of these drugs on the Ca2+ ATPase activity of the SR Ca2+ pump. We confirmed that Ca2+ channel blockers, administered after SR Ca2+ loading and before induction of Ca2+ release, caused a dose-dependent inhibition of both Ca2+- and Ag+-induced Ca2+ release rate. Moreover, if Ca2+ channel blockers were administered prior to SR Ca2+ loading, in spite of Ca2+ uptake inhibition the same reduction in Ca2+- and Ag+-induced Ca2+ release rate was seen. We showed that the inhibition of Ag+-induced Ca2+ release by L-channel blockers is more sensitive than Ca2+-induced Ca2+ release inhibition, so the IC50 for Ag+- and Ca2+-induced Ca2+ release was about 100 and 310 micromol/L for verapamil and 79 and 330 micromol/L for diltiazem, respectively. Our results support the evidence that Ca2+ channel blockers affect muscle microsome of chicken skeletal muscle by 2 independent mechanisms: first, reduction of Ca2+ uptake rate and Ca2+-ATPase activity inhibition, and second, inhibition of both Ag+- and Ca2+-induced Ca2+ release by Ca2+ release channels. These findings confirm the direct effect of Ca2+ channel blockers on calcium release channels. Our results suggest that even if the SR is incompletely preloaded with Ca2+ because of inhibition of Ca2+ uptake by verapamil and diltiazem, no impairment in Ca2+ release occurs.

Black phosphorus saturable absorber for a diode-pumped passively Q-switched Er:CaF2 mid-infrared laser

NASA Astrophysics Data System (ADS)

Li, Chun; Liu, Jie; Guo, Zhinan; Zhang, Han; Ma, Weiwei; Wang, Jingya; Xu, Xiaodong; Su, Liangbi

2018-01-01

A multilayer black phosphorus, as a novel two dimensional saturable absorber, has superb saturable absorption properties for a Er:CaF2 solid-state pulse laser. The pulse laser is realized at mid-infrared region with the passively Q-switched technology by a diode-pumping. The high-quality black phosphorus saturable absorber is fabricated by liquid phase exfoliation method. The pulse laser generates the pulses operation with the pulse duration of 954.8 ns, the repetition rate of 41.93 kHz, the pulse energy of 4.25 μJ and the peak power of 4.45 W. Our work demonstrates that black phosphorus could be used as a kind of efficient mid-infrared region optical absorber for ultrafast photonics.

Energy dissipation in slipping biological pumps.

PubMed

Kjelstrup, Signe; Rubi, J Miguel; Bedeaux, Dick

2005-12-07

We describe active transport in slipping biological pumps, using mesoscopic nonequilibrium thermodynamics. The pump operation is characterised by its stochastic nature and energy dissipation. We show how heating as well as cooling effects can be associated with pump operation. We use as an example the well studied active transport of Ca2+ across a biological membrane by means of its ATPase, and use published data to find values for the transport coefficients of the pump under various conditions. Most of the transport coefficients of the pump, including those that relate ATP hydrolysis or synthesis to thermal effects, are estimated. This can give a quantitative description of thermogenesis. We show by calculation that all of these coupling coefficients are significant.

Carbonic Anhydrase Activity Associated with the Cyanobacterium Synechococcus PCC7942 1

PubMed Central

Badger, Murray R.; Price, G. Dean

1989-01-01

Intact cells and crude homogenates of high (1% CO2) and low dissolved inorganic carbon (Ci) (30-50 microliters per liter of CO2) grown Synechococcus PCC7942 have carbonic anhydrase (CA)-like activity, which enables them to catalyze the exchange of 18O from CO2 to H2O. This activity was studied using a mass spectrometer coupled to a cuvette with a membrane inlet system. Intact high and low Ci cells were found to contain CA activity, separated from the medium by a membrane which is preferentially permeable to CO2. This activity is most apparent in the light, where 18O-labeled CO2 species are being taken up by the cells but the effluxing CO2 has lost most of its label to water. In the dark, low Ci cells catalyze the depletion of the 18O enrichment of CO2 and this activity is inhibited by both ethoxyzolamide and 2-(trifluoromethoxy)carbonyl cyanide. This may occur via a common inhibition of the Ci pump and the Ci pump is proposed as a potential site for the exchange of 18O. CA activity was measurable in homogenates of both cell types but was 5- to 10-fold higher in low Ci cells. This was inhibited by ethoxyzolamide with an I50 of 50 to 100 micromolar in both low and high Ci cells. A large proportion of the internal CA activity appears to be pelletable in nature. This pelletability is increased by the presence of Mg2+ in a manner similar to that of ribulose bisphosphate carboxylase-oxygenase activity and chlorophyll (thylakoids) and may be the result of nonspecific aggregation. Separation of crude homogenates on sucrose gradients is consistent with the notion that CA and ribulose bisphosphate carboxylase-oxygenase activity may be associated with the same pelletable fraction. However, we cannot unequivocally establish that CA is located within the carboxysome. The sucrose gradients show the presence of separate soluble and pelletable CA activity. This may be due to the presence of separate forms of the enzyme or may arise from the same pelletable association which is unstable during extraction. PMID:16666546

Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts

PubMed Central

Itoh, Hideki; Oyama, Kotaro; Suzuki, Madoka; Ishiwata, Shin’ichi

2014-01-01

Temperature-sensitive Ca2+ dynamics occur primarily through transient receptor potential channels, but also by means of Ca2+ channels and pumps on the endoplasmic reticulum membrane. As such, cytoplasmic Ca2+ concentration ([Ca2+]cyt) is re-equilibrated by changes in ambient temperature. The present study investigated the effects of heat pulses (heating duration: 2 s or 150 s) on [Ca2+]cyt in single WI-38 fibroblasts, which are considered as normal cells. We found that Ca2+ burst occurred immediately after short (2 s) heat pulse, which is similar to our previous report on HeLa cells, but with less thermosensitivity. The heat pulses originated from a focused 1455-nm infrared laser light were applied in the vicinity of cells under the optical microscope. Ca2+ bursts induced by the heat pulse were suppressed by treating cells with inhibitors for sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) or inositol trisphosphate receptor (IP3R). Long (150 s) heat pulses also induced Ca2+ bursts after the onset of heating and immediately after re-cooling. Cells were more thermosensitive at physiological (37°C) than at room (25°C) temperature; however, at 37°C, cells were responsive at a higher temperature (ambient temperature+heat pulse). These results strongly suggest that the heat pulse-induced Ca2+ burst is caused by a transient imbalance in Ca2+ flow between SERCA and IP3R, and offer a potential new method for thermally controlling Ca2+-regulated cellular functions. PMID:27493505

Comparative effectiveness of epsilon-aminocaproic acid and tranexamic acid on postoperative bleeding following cardiac surgery during a national medication shortage.

PubMed

Blaine, Kevin P; Press, Christopher; Lau, Ken; Sliwa, Jan; Rao, Vidya K; Hill, Charles

2016-12-01

The aim of this study was to compare the effectiveness of epsilon-aminocaproic acid (εACA) and tranexamic acid (TXA) in contemporary clinical practice during a national medication shortage. A retrospective cohort study. The study was performed in all consecutive cardiac surgery patients (n=128) admitted to the cardiac-surgical intensive care unit after surgery at a single academic center immediately before and during a national medication shortage. Demographic, clinical, and outcomes data were compared by descriptive statistics using χ 2 and t test. Surgical drainage and transfusions were compared by multivariate linear regression for patients receiving εACA before the shortage and TXA during the shortage. In multivariate analysis, no statistical difference was found for surgical drain output (OR 1.10, CI 0.97-1.26, P=.460) or red blood cell transfusion requirement (OR 1.79, CI 0.79-2.73, P=.176). Patients receiving εACA were more likely to receive rescue hemostatic medications (OR 1.62, CI 1.02-2.55, P=.041). Substitution of εACA with TXA during a national medication shortage produced equivalent postoperative bleeding and red cell transfusions, although patients receiving εACA were more likely to require supplemental hemostatic agents. Published by Elsevier Inc.

NMR measurements of Ca2+ and H+ transport mediated by A23187 and reconstituted plasma membrane Ca(2+)-ATPase.

PubMed

Waldeck, A R; Xu, A S; Roufogalis, B D; Kuchel, P W

1998-01-01

NMR-based assays for measuring the fluxes of Ca2+, H+, and ATP in liposomal systems are presented. The 19F NMR Ca(2+)-chelating molecule 5,5-difluoro-1,2-bis(o-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA) was trapped inside large unilamellar vesicles and used to monitor passive and A23187-mediated Ca2+ transport into them. The data were analyzed using progress curves of the transport reaction. They demonstrated the general applicability of 5FBAPTA as a 19F NMR probe of active Ca2+ transport. 31P NMR time-courses were used to monitor simultaneously the ATP hydrolysing activity of the reconstituted human erythrocyte Ca(2+)-ATPase and the concomitant acidification of the reaction medium in a suspension of small unilamellar vesicles. Using an estimate of the extraliposomal buffering capacity, the H+/ATP coupling stoichiometry, in the presence of A23187, was estimated from the NMR-derived data at steady state; it amounted to 1.4 +/- 0.3. This result is discussed with respect to the issue of molecular 'slip' in the context of a non-equilibrium thermodynamics model of the pump (accompanying paper in this issue). Importantly, NMR, in contrast to optical detection methods, can potentially register all fluxes and (electro)chemical gradients involved in the Ca(2+)-ATPase-mediated H+/Ca2+ counterport, in a single experiment.

Performance analysis of solar-assisted chemical heat-pump dryer

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

Fadhel, M.I.; Faculty of Engineering and Technology, Multimedia University, Jalan Ayer Keroh Lama, 75450, Melaka; Sopian, K.

2010-11-15

A solar-assisted chemical heat-pump dryer has been designed, fabricated and tested. The performance of the system has been studied under the meteorological conditions of Malaysia. The system consists of four main components: solar collector (evacuated tubes type), storage tank, solid-gas chemical heat pump unit and dryer chamber. A solid-gas chemical heat pump unit consists of reactor, condenser and evaporator. The reaction used in this study (CaCl2-NH{sub 3}). A simulation has been developed, and the predicted results are compared with those obtained from experiments. The maximum efficiency for evacuated tubes solar collector of 80% has been predicted against the maximum experimentmore » of 74%. The maximum values of solar fraction from the simulation and experiment are 0.795 and 0.713, respectively, whereas the coefficient of performance of chemical heat pump (COP{sup h}) maximum values 2.2 and 2 are obtained from simulation and experiments, respectively. The results show that any reduction of energy at condenser as a result of the decrease in solar radiation will decrease the coefficient of performance of chemical heat pump as well as decrease the efficiency of drying. (author)« less

A search for chemical laser action in low pressure metal vapor flames. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Zwillenberg, M. L.

1975-01-01

Optical emissions were studied from low pressure (approximately 1 torr) dilute diffusion flames of Ca and Mg vapor with O2, N2O and mixtures of CCl4 and O2. The Ca flames with O2 and N2O revealed high vibrational excitation of the product CaO molecule (up to v=30). The flames with CCl4 revealed extreme nonequilibrium metal atom electronic excitation, up to the metal atom ionization limit (6.1 eV for Ca, 7.6 eV for Mg). The metal atom excited electronic state populations did not follow a Boltzmann distribution, but the excitation rates ('pumping rate') were found to obey an Arrhenius-type expression, with the electronic excitation energy playing the role of activation energy and a temperature of about 5000 K for triplet excited states and 2500 K for singlets (vs. approximately 500 K translational temperature).

Modulation of Gardos channel activity by oxidants and oxygen tension: effects of 1-chloro-2,4-dinitrobenzene and phenazine methosulphate.

PubMed

Gibson, John S; Muzyamba, Morris C

2004-05-01

We compare the effects of 1-chloro-2,4-dinitrobenzene (CDNB) and phenazine methosulphate (PMS) on Gardos channel activity in normal human red cells. Both stimulate channel activity, both are dependent on the presence of extracellular Ca2+, and neither is affected by inhibitors of protein (de)phosphorylation. Of the two, PMS has a considerably greater effect. In addition, a major difference is that whilst CDNB has a greater stimulatory effect in oxygenated cells, by contrast, PMS is more effective in deoxygenated cells. These actions are correlated with ca. 30% inhibition of the plasma membrane Ca2+ pump (PMCA) and an increased sensitivity of the Gardos channel to Ca2+ (EC50 falling to about 150 nM). These findings are important in understanding how oxidants alter red cell cation permeability and may be relevant to the abnormal permeability phenotype shown by deoxygenated sickle cells.

Subpopulation of store-operated Ca2+ channels regulate Ca2+-induced Ca2+ release in non-excitable cells.

PubMed

Yao, Jian; Li, Qin; Chen, Jin; Muallem, Shmuel

2004-05-14

Ca2+-induced Ca2+ release (CICR) is a well characterized activity in skeletal and cardiac muscles mediated by the ryanodine receptors. The present study demonstrates CICR in the non-excitable parotid acinar cells, which resembles the mechanism described in cardiac myocytes. Partial depletion of internal Ca2+ stores leads to a minimal activation of Ca2+ influx. Ca2+ influx through this pathway results in an explosive mobilization of Ca2+ from the majority of the stores by CICR. Thus, stimulation of parotid acinar cells in Ca2+ -free medium with 0.5 microm carbachol releases approximately 5% of the Ca2+ mobilizable by 1 mm carbachol. Addition of external Ca2+ induced the same Ca2+ release observed in maximally stimulated cells. Similar results were obtained by a short treatment with 2.5-10 microm cyclopiazonic acid, an inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase pump. The Ca2+ release induced by the addition of external Ca2+ was largely independent of IP(3)Rs because it was reduced by only approximately 30% by the inhibition of the inositol 1,4,5-trisphosphate receptors with caffeine or heparin. Measurements of Ca2+ -activated outward current and [Ca2+](i) suggested that most CICR triggered by Ca2+ influx occurred away from the plasma membrane. Measurement of the response to several concentrations of cyclopiazonic acid revealed that Ca2+ influx that regulates CICR is associated with a selective portion of the internal Ca2+ pool. The minimal activation of Ca2+ influx by partial store depletion was confirmed by the measurement of Mn2+ influx. Inhibition of Ca2+ influx with SKF96365 or 2-aminoethoxydiphenyl borate prevented activation of CICR observed on addition of external Ca2+. These findings provide evidence for activation of CICR by Ca2+ influx in non-excitable cells, demonstrate a previously unrecognized role for Ca2+ influx in triggering CICR, and indicate that CICR in non-excitable cells resembles CICR in cardiac myocytes with the exception that in cardiac cells Ca2+ influx is mediated by voltage-regulated Ca2+ channels whereas in non-excitable cells Ca2+ influx is mediated by store-operated channels.

ACUTE EFFECT OF ETHANOL ON HEPATIC RETICULAR G6Pase AND Ca2+ POOL

PubMed Central

Jacobs-Harper, Amy; Crumbly, Ashlee; Romani, Andrea

2012-01-01

Background Hydrolysis of glucose 6-phosphate via glucose 6-phosphatase enlarges the reticular Ca2+ pool of the hepatocyte. Exposure of liver cells to ethanol impairs reticular Ca2+ homeostasis. The present study investigated the effect of acute ethanol administration on glucose 6-phosphate supported Ca2+ accumulation in liver cells. Methods Total microsomes were isolated from rat livers acutely perfused with varying doses of ethanol (0.01%, 0.1%, or 1% v/v) for 8 minutes. Calcium uptake was assessed by 45Ca redistribution. Inorganic phosphate (Pi) formation was measured as an indicator of glucose 6-phosphatase hydrolytic activity. Results Glucose 6-phosphate-supported Ca2+ uptake decreased in a manner directly proportional to the dose of ethanol infused in the liver whereas Ca2+ uptake via SERCA pumps was decreased by ~25% only at the highest dose of alcohol administered. The reduced accumulation of Ca2+ within the microsomes resulted in a smaller IP3-induced Ca2+ release. Kinetic assessment of IP3 and passive Ca2+ release indicated a faster mobilization in microsomes from ethanol-treated livers, suggesting alcohol-induced alteration of Ca2+ releasing mechanisms. Pre-treatment of livers with chloromethiazole or dithio-threitol, but not 4-methyl-pyrazole prevented the inhibitory effect of ethanol on glucose 6-phosphatase activity and Ca2+ homeostasis. Conclusions Liver glucose 6-phosphatase activity and IP3-mediated Ca2+ release are rapidly inhibited following acute (8 min) exposure to ethanol, thus compromising the ability of the endoplasmic reticulum to dynamically modulate Ca2+ homeostasis in the hepatocyte. The protective effect of chloromethiazole and di-thio-threitol suggests that the inhibitory effect of ethanol is mediated through its metabolism via reticular cyP4502E1 and consequent free radicals formation. PMID:22958133

Low-temperature magnetic ordering in the perovskites Pr 1-xA xCoO 3 (A=Ca, Sr)

NASA Astrophysics Data System (ADS)

Deac, Iosif G.; Tetean, Romulus; Balasz, Istvan; Burzo, Emil

2010-05-01

The magnetic and electrical properties of polycrystalline Pr 1-xA xCoO 3 cobaltites with A=Ca, Sr and 0≤ x≤0.5 were studied in the temperature range 4 K≤ T≤1000 K and field up to 7 T. The X-ray analyses show the presence of only one phase having monoclinic or orthorhombic symmetry. The magnetic measurements indicate that the Ca-doped samples have at low temperatures, similar properties to the frustrated magnetic materials. PrCoO 3 is a paramagnetic insulator in the range from 4 to 1000 K. The Sr-doped cobaltites exhibit two phase transitions: a paramagnetic-ferromagnetic (or magnetic phase separated state) phase transition at about 240 K and a second one at about 100 K. The magnetic measurements suggest the presence of magnetic clusters and a change in the nature of magnetic coupling between Co ions at low temperatures. A semiconducting type behavior and high negative magnetoresistance was found for the Ca-doped samples, while the Sr-doped ones were metallic and with negligible magnetoresistance. The results are analyzed in the frame of a phase separation scenario in the presence of the spin-state transitions of Co ions.

Up-to-Date on Preventive Care Services Under Affordable Care Act: A Trend Analysis From MEPS 2007-2014.

PubMed

Hong, Young-Rock; Jo, Ara; Mainous, Arch G

2017-08-01

The utilization of preventive care services has been less than optimal. As part of an effort to address this, the Affordable Care Act (ACA) mandated that private health insurance plans cover evidence-based preventive services. To evaluate whether the provisions of ACA have increased being up-to-date on recommended preventive care services among privately insured individuals aged 18-64. Multivariate linear regression models were used to examine trends in prevalence of being up-to-date on selected preventive services, diagnosis of health conditions, and health expenditures between pre-ACA (2007-2010) and post-ACA (2011-2014). Adjusted difference-in-difference analyses were used to estimate changes in those outcomes in the privately insured that differed from changes in the uninsured (control group). After the passage of ACA, up-to-date rates of routine checkup (2.7%; 95% confidence interval, 0.8%-4.7%; P=0.007) and flu vaccination (5.9%; 95% confidence interval, 4.2%-7.6%; P<0.001) increased among those with private insurance, as compared with the control group. Changes in blood pressure check, cholesterol check and cancer screening (pap smear test, mammography, and colorectal cancer screening) were not associated with the ACA. Prevalence in diagnosis of health conditions remained constant. Slower uptrends in adjusted total health care expenditures and downtrends in adjusted out-of-pocket costs were observed during the study period. The provisions of the ACA have resulted in trivial increases in being up-to-date on selected preventive care services. Additional efforts may be required to take full advantage of the elimination of cost-sharing under the ACA.

Barriers to Homeless Persons Acquiring Health Insurance Through the Affordable Care Act.

PubMed

Fryling, Lauren R; Mazanec, Peter; Rodriguez, Robert M

2015-11-01

Medicaid expansion under the Affordable Care Act (ACA) is intended to provide a framework for increasing health care access for vulnerable populations, including the 1.2 million who experience homelessness each year in the United States. We sought to characterize homeless persons' knowledge of the ACA, identify barriers to their ACA enrollment, and determine access to various forms of communication that could be used to facilitate enrollment. At an urban county Level I trauma center, we interviewed all noncritically ill adults who presented to the emergency department (ED) during daytime hours and were able to provide consent. We assessed access to communication, awareness of the ACA, insurance status, and barriers preventing subjects from enrolling in health insurance and compared homeless persons' responses with concomitantly enrolled housed individuals. Of the 650 enrolled subjects, 134 (20.2%) were homeless. Homeless subjects were more likely to have never heard of the ACA (26% vs. 10%). "Not being aware if they qualify for Medicaid" was the most common (70%) and most significant (30%) barrier to enrollment reported by uninsured homeless persons. Of homeless subjects who were unsure if they qualified for Medicaid, 91% reported an income < 138% of the federal poverty level, likely qualifying them for enrollment. Although 99% of housed subjects reported access to either phone or internet, only 74% of homeless subjects reported access. Homeless persons report having less knowledge of the ACA than their housed counterparts, poor understanding of ACA qualification criteria, and limited access to phone and internet. ED-based outreach and education regarding ACA eligibility may increase their enrollment. Copyright © 2015 Elsevier Inc. All rights reserved.

Childhood Cancer Survivor Study participants' perceptions and understanding of the Affordable Care Act.

PubMed

Park, Elyse R; Kirchhoff, Anne C; Perez, Giselle K; Leisenring, Wendy; Weissman, Joel S; Donelan, Karen; Mertens, Ann C; Reschovsky, James D; Armstrong, Gregory T; Robison, Leslie L; Franklin, Mariel; Hyland, Kelly A; Diller, Lisa R; Recklitis, Christopher J; Kuhlthau, Karen A

2015-03-01

The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown. Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study. Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered "very important" are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as "very important" (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees. Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits. © 2015 by American Society of Clinical Oncology.

Childhood Cancer Survivor Study Participants' Perceptions and Understanding of the Affordable Care Act

PubMed Central

Park, Elyse R.; Kirchhoff, Anne C.; Perez, Giselle K.; Leisenring, Wendy; Weissman, Joel S.; Donelan, Karen; Mertens, Ann C.; Reschovsky, James D.; Armstrong, Gregory T.; Robison, Leslie L.; Franklin, Mariel; Hyland, Kelly A.; Diller, Lisa R.; Recklitis, Christopher J.; Kuhlthau, Karen A.

2015-01-01

Purpose The Patient Protection and Affordable Care Act (ACA) established provisions intended to increase access to affordable health insurance and thus increase access to medical care and long-term surveillance for populations with pre-existing conditions. However, childhood cancer survivors' coverage priorities and familiarity with the ACA are unknown. Methods Between May 2011 and April 2012, we surveyed a randomly selected, age-stratified sample of 698 survivors and 210 siblings from the Childhood Cancer Survivor Study. Results Overall, 89.8% of survivors and 92.1% of siblings were insured. Many features of insurance coverage that survivors considered “very important” are addressed by the ACA, including increased availability of primary care (94.6%), no waiting period before coverage initiation (79.0%), and affordable premiums (88.1%). Survivors were more likely than siblings to deem primary care physician coverage and choice, protections from costs due to pre-existing conditions, and no start-up period as “very important” (P < .05 for all). Only 27.3% of survivors and 26.2% of siblings reported familiarity with the ACA (12.1% of uninsured v 29.0% of insured survivors; odds ratio, 2.86; 95% CI, 1.28 to 6.36). Only 21.3% of survivors and 18.9% of siblings believed the ACA would make it more likely that they would get quality coverage. Survivors' and siblings' concerns about the ACA included increased costs, decreased access to and quality of care, and negative impact on employers and employees. Conclusion Although survivors' coverage preferences match many ACA provisions, survivors, particularly uninsured survivors, were not familiar with the ACA. Education and assistance, perhaps through cancer survivor navigation, are critically needed to ensure that survivors access coverage and benefits. PMID:25646189

Human Papillomavirus Vaccination Uptake before and after the Affordable Care Act: Variation According to Insurance Status, Race, and Education (NHANES 2006-2014).

PubMed

Corriero, Rosemary; Gay, Jennifer L; Robb, Sara Wagner; Stowe, Ellen W

2018-02-01

The purpose of the study was to compare human papillomavirus (HPV) vaccination rates before and after Affordable Care Act (ACA) implementation among women, and examine differences according to insurance status and other sociodemographic variables. This was a cross-sectional analysis of the National Health and Nutrition Examination Survey questionnaire data. Participants (n = 4599) were from a random sample of the United States population. HPV vaccination status and number of doses received according to age, income, education, race, and insurance coverage. Over time, the proportion of women reporting HPV vaccination increased from 16.4% to 27.6%, and reporting vaccination completion (3 doses) increased from 56.8% to 67.2%. After ACA implementation, respondents were 3.3 times more likely to be vaccinated compared with before ACA implementation (95% confidence interval [CI], 2.0-5.5) adjusting for age, race, and insurance coverage. Similarly, respondents were more likely to have received 2 (odds ratio, 2.8; 95% CI, 1.5-5.3) or 3 doses (odds ratio, 5.8; 95% CI, 2.5-13.6). Vaccination uptake increased in a comparison of waves of data from before and after ACA implementation. This increase in vaccination coverage could be related to the increased preventative service coverage, which includes vaccines, required by the ACA. Future studies might focus on the role insurance has on vaccination uptake, and meeting Healthy People 2020 objectives for vaccination coverage. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Histopathology and immunophenotype of acrodermatitis chronica atrophicans correlated with ospA and ospC genotypes of Borrelia species.

PubMed

Brandt, Friederike C; Ertas, Beyhan; Falk, Thomas M; Metze, Dieter; Böer-Auer, Almut

2015-10-01

Chronic cutaneous borreliosis (acrodermatitis chronica atrophicans, ACA) is a relatively rare manifestation of borreliosis attributed mainly to Borrelia afzelii. Chronic borreliosis has been associated with ospA and ospC genotypes. Literature on molecular investigations of Borrelia in lesions of ACA is scant. Histopathological and immmunohistochemical features in 22 biopsies of ACA (16 patients) were examined. Paraffin-embedded biopsies were analyzed with polymerase chain reaction (PCR) assays targeting ospA and ospC genes, sequencing and phylogenetic analysis. Genotyping of ospA identified B. afzelii, serotype 2, in 12 of 16 patients. ospC-PCR was positive in seven patients revealing genotypes Af5 (n = 4), Af2 (n = 2) and Af6 (n = 1). Histopathologically, interstitial granulomatous infiltrates (CD68 positive) were common, combined with thickened collagen bundles and band-like infiltrates of CD4 positive T lymphocytes. Plasma cells were sparse/absent in 9 of 22 specimens even on staining with CD138. On CD34-staining, interstitial fibroblasts were often reduced akin to the situation in morphea. With assays targeting ospA and ospC genes we confirmed from paraffin-embedded biopsies that B. afzelii, serotype 2, osp C groups Af5, Af2 and Af6 is the main cause of ACA. Specimens commonly showed a combination of band-like T-cell-rich infiltrates with interstitial granulomatous features, a pattern previously under-recognized in ACA. This finding was particularly typical for lesions infected with ospC genotype Af5. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytosolic acidification and intracellular zinc release in hippocampal neurons

PubMed Central

Kiedrowski, Lech

2012-01-01

In neurons exposed to glutamate, Ca2+ influx triggers intracellular Zn2+ release via an as yet unclear mechanism. Since glutamate induces a Ca2+-dependent cytosolic acidification, the present work tested the relationships among intracellular Ca2+ concentration ([Ca2+]i), intracellular pH (pHi), and [Zn2+]i. Cultured hippocampal neurons were exposed to glutamate and glycine (Glu/Gly), while [Zn2+]i, [Ca2+]i and pHi were monitored using FluoZin-3, Fura2-FF, and 2′,7′-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. Glu/Gly applications decreased pHi to 6.1 and induced intracellular Zn2+ release in a Ca2+-dependent manner, as expected. The pHi drop reduced the affinity of FluoZin-3 and Fura-2-FF for Zn2+. The rate of Glu/Gly-induced [Zn2+]i increase was not correlated with the rate of [Ca2+]i increase. Instead, the extent of [Zn2+]i elevations corresponded well to the rate of pHi drop. Namely, [Zn2+]i increased more in more highly acidified neurons. Inhibiting the mechanisms responsible for the Ca2+-dependent pHi drop (plasmalemmal Ca2+ pump and mitochondria) counteracted the Glu/Gly-induced intracellular Zn2+ release. Alkaline pH (8.5) suppressed Glu/Gly-induced intracellular Zn2+ release whereas acidic pH (6.0) enhanced it. A pHi drop to 6.0 (without any Ca2+ influx or glutamate receptor activation) led to intracellular Zn2+ release; the released Zn2+ (free Zn2+ plus Zn2+ bound to Fura-2FF and FluoZin-3) reached 1 μM. PMID:22339672

A rice tonoplastic calcium exchanger, OsCCX2 mediates Ca2+/cation transport in yeast

PubMed Central

Yadav, Akhilesh K.; Shankar, Alka; Jha, Saroj K.; Kanwar, Poonam; Pandey, Amita; Pandey, Girdhar K.

2015-01-01

In plant cell, cations gradient in cellular compartments is maintained by synergistic action of various exchangers, pumps and channels. The Arabidopsis exchanger family members (AtCCX3 and AtCCX5) were previously studied and belong to CaCA (calcium cation exchangers) superfamily while none of the rice CCXs has been functionally characterized for their cation transport activities till date. Rice genome encode four CCXs and only OsCCX2 transcript showed differential expression under abiotic stresses and Ca2+ starvation conditions. The OsCCX2 localized to tonoplast and suppresses the Ca2+ sensitivity of K667 (low affinity Ca2+ uptake deficient) yeast mutant under excess CaCl2 conditions. In contrast to AtCCXs, OsCCX2 expressing K667 yeast cells show tolerance towards excess Na+, Li+, Fe2+, Zn2+ and Co2+ and suggest its ability to transport both mono as well as divalent cations in yeast. Additionally, in contrast to previously characterized AtCCXs, OsCCX2 is unable to complement yeast trk1trk2 double mutant suggesting inability to transport K+ in yeast system. These finding suggest that OsCCX2 having distinct metal transport properties than previously characterized plant CCXs. OsCCX2 can be used as potential candidate for enhancing the abiotic stress tolerance in plants as well as for phytoremediation of heavy metal polluted soil. PMID:26607171

Antihypertensive and vasorelaxant effects of aqueous extract of Artemisia campestris L. from Eastern Morocco.

PubMed

Dib, Ikram; Tits, Monique; Angenot, Luc; Wauters, Jean Noel; Assaidi, Asmae; Mekhfi, Hassane; Aziz, Mohammed; Bnouham, Mohammed; Legssyer, Abdelkhaleq; Frederich, Michel; Ziyyat, Abderrahim

2017-07-12

Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice. The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10 -2 -2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl 2 did not alter this effect. The oral administration of AcAE (0-6g/kg) reveals no mortality or toxicity. our study proved that AcAE possess an important antihypertensive, hypotensive and vasorelaxant effect, which is mediated via calmodulin-NO-cGC-PKG pathway, and via inhibition of calcium influx through voltage-operated calcium channels and activation of intracellular calcium mobilization into sarcoplasmic reticulum. Therefore, our findings give first evidence about the traditional use of A. campestris L. as antihypertensive plant. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Effects of adrenalectomy on the alpha-adrenergic regulation of cytosolic free calcium in hepatocytes

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

Freudenrich, C.C.; Borle, A.B.

1988-06-25

We have previously published that bilateral adrenalectomy in the rat reduces the Ca2+-mediated alpha-adrenergic activation of hepatic glycogenolysis, while it increases the cellular calcium content of hepatocytes. In the experiments presented here, the concentration of cytosolic free calcium (Ca2+i) at rest and in response to epinephrine was measured in aequorin-loaded hepatocytes isolated from sham and adrenalectomized male rats. We found that in adrenalectomized rats the resting Ca2+i was elevated, the rise in Ca2+i evoked by epinephrine was reduced, and the rise in /sup 45/Ca efflux that follows such stimulation was depressed. Furthermore, the slope of the relationship between Ca2+i andmore » calcium efflux was decreased 60% in adrenalectomized. Adrenalectomy did not change Ca2+ release from intracellular calcium pools in response to IP3 in saponin-permeabilized hepatocytes. The EC50 for inositol 1,4,5-triphosphate and the maximal Ca2+ released were similar in both sham and adrenalectomized animals. Finally, the liver calmodulin content determined by radioimmunoassay was not significantly different between sham and adrenalectomized rats. These results suggest that 1) adrenalectomy reduces calcium efflux from the hepatocyte, probably by an effect on the plasma membrane (Ca2+-Mg2+)-ATPase-dependent Ca2+ pump and thus alters cellular calcium homeostasis; 2) adrenalectomy decreases the rise in Ca2+i in response to epinephrine; 3) this decreased rise in Ca2+i is not due to defects in the intracellular Ca2+ storage and mobilization processes; and 4) the effects of adrenalectomy on cellular calcium metabolism and on alpha-adrenergic activation of glycogenolysis are not caused by a reduction in soluble calmodulin.« less

Polyamines Interact with Hydroxyl Radicals in Activating Ca2+ and K+ Transport across the Root Epidermal Plasma Membranes1[W

PubMed Central

Zepeda-Jazo, Isaac; Velarde-Buendía, Ana María; Enríquez-Figueroa, René; Bose, Jayakumar; Shabala, Sergey; Muñiz-Murguía, Jesús; Pottosin, Igor I.

2011-01-01

Reactive oxygen species (ROS) are integral components of the plant adaptive responses to environment. Importantly, ROS affect the intracellular Ca2+ dynamics by activating a range of nonselective Ca2+-permeable channels in plasma membrane (PM). Using patch-clamp and noninvasive microelectrode ion flux measuring techniques, we have characterized ionic currents and net K+ and Ca2+ fluxes induced by hydroxyl radicals (OH•) in pea (Pisum sativum) roots. OH•, but not hydrogen peroxide, activated a rapid Ca2+ efflux and a more slowly developing net Ca2+ influx concurrent with a net K+ efflux. In isolated protoplasts, OH• evoked a nonselective current, with a time course and a steady-state magnitude similar to those for a K+ efflux in intact roots. This current displayed a low ionic selectivity and was permeable to Ca2+. Active OH•-induced Ca2+ efflux in roots was suppressed by the PM Ca2+ pump inhibitors eosine yellow and erythrosine B. The cation channel blockers gadolinium, nifedipine, and verapamil and the anionic channel blockers 5-nitro-2(3-phenylpropylamino)-benzoate and niflumate inhibited OH•-induced ionic currents in root protoplasts and K+ efflux and Ca2+ influx in roots. Contrary to expectations, polyamines (PAs) did not inhibit the OH•-induced cation fluxes. The net OH•-induced Ca2+ efflux was largely prolonged in the presence of spermine, and all PAs tested (spermine, spermidine, and putrescine) accelerated and augmented the OH•-induced net K+ efflux from roots. The latter effect was also observed in patch-clamp experiments on root protoplasts. We conclude that PAs interact with ROS to alter intracellular Ca2+ homeostasis by modulating both Ca2+ influx and efflux transport systems at the root cell PM. PMID:21980172

Direct and indirect organogenesis of Alpinia galanga and the phytochemical analysis.

PubMed

Rao, Kiranmayee; Chodisetti, Bhuvaneswari; Gandi, Suryakala; Mangamoori, Lakshmi Narasu; Giri, Archana

2011-11-01

Alpinia galanga is a rhizomatous herb rich in essential oils and various other significant phytoconstituents. Rapid direct regeneration was obtained from the rhizome explants (15.66 ± 0.57 shoots) on MS media supplemented with zeatin at a concentration of 2 mg/l. The callus cultures of A. galanga were initiated from the rhizome explants on MS media supplemented with 2 mg/l each of BAP, 2,4-D, and NAA. The callus was analyzed for the presence of a vital phytoconstituent--acetoxychavicol acetate (ACA) associated with various biological properties. ACA was detected in the young friable callus as well as the stationary phase callus. Moreover, the induction of morphogenetic response in callus resulted in higher accumulation of ACA. The phytohormone withdrawal from the propagation media and the subsequent transfer of callus to BAP (2 mg/l) containing MS media has resulted in multiple shoot induction. The regenerated (indirect) plants have shown 1.6-fold higher ACA content (1.253%) when compared to the control plant (0.783%). Micropropagation of such conventionally propagated plants is very essential to meet the commercial demand as well as to ensure easy storage and transportation of disease free stocks.

Lipid peroxidation in sarcoplasmic reticulum membranes: effect on functional and biophysical properties.

PubMed

Dinis, T C; Almeida, L M; Madeira, V M

1993-03-01

The fluorescent polyunsaturated parinaric acid (PnA) incorporated in sarcoplasmic reticulum membranes (SR) was used to probe the initial stages of membrane lipid peroxidation. The experimental set up of the PnA assay was investigated by means of several peroxidation initiators to ascertain peroxidation conditions. This assay in SR is particularly useful to evaluate the membrane susceptibility to peroxidation and to ascertain suitable conditions (concentration of initiators and cofactors) to challenge peroxidation in each preparation under study. On the basis of the PnA assay, Fe2+/ascorbate was selected among the different initiator systems to assess the effect of lipid peroxidation upon biochemical and biophysical parameters of SR membranes. Under mildly controlled conditions at 25 degrees C, the lipid degradative process, as detected by fatty acid analysis, decreases the Ca2+ uptake (up to about 50% of control) and reduces the Ca2+ pump efficiency (Ca2+/ATP ratio) up to about 58% of control, without inactivation the ATPase enzyme turnover. The effect of lipid peroxidation on the SR bilayer organization is dependent either on the extent of lipid peroxidation or on the depth of the bilayer as probed by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene and by intramolecular excimerization of 1,3-di(1-pyrenyl)propane. It is concluded that the effect of mild lipid peroxidation on Ca2+ pump activity is partially exerted through the alteration of physical properties in the lipid phase or lipid-protein interfaces.

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

PubMed Central

Greenstein, Joseph L; Winslow, Raimond L

2002-01-01

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

Are Press Depictions of Affordable Care Act Beneficiaries Favorable to Policy Durability?

PubMed

Chattopadhyay, Jacqueline

2015-01-01

If successfully implemented and enduring, the Affordable Care Act (ACA) stands to expand health insurance access in absolute terms, reduce inter-group disparities in that access, and reduce exposure to the financial vulnerabilities illness entails. Its durability--meaning both avoidance of outright retrenchment and fidelity to its policy aims--is thus of scholarly interest. Past literature suggests that social constructions of a policy's beneficiaries may impact durability. This paper first describes media portrayals of ACA beneficiaries with an eye toward answering three descriptive questions: (1) Do portrayals depict beneficiaries as economically heterogeneous? (2) Do portrayals focus attention on groups that have acquired new political relevance due to the ACA, such as young adults? (3) What themes that have served as messages about beneficiary "deservingness" in past social policy are most frequent in ACA beneficiary portrayals? The paper then assesses how the portrayal patterns that these questions uncover may work both for and against the ACA's durability, finding reasons for confidence as well as caution. Using manual and automated methods, this paper analyzes newspaper text from August 2013 through January 2014 to trace portrayals of two ACA "target populations" before and during the new law's first open-enrollment period: those newly eligible for Medicaid, and those eligible for subsidies to assist in the purchase of private health insurance under the ACA. This paper also studies newspaper text portrayals of two groups informally crafted by the ACA in this timeframe: those gaining health insurance and those losing it. The text data uncover the following answers to the three descriptive questions for the timeframe studied: (1) Portrayals may underplay beneficiaries' economic heterogeneity. (2) Portrayals pay little attention to young adults. (3) Portrayals emphasize themes of workforce participation, economic self-sufficiency, and insider status. Health status, age, gender, and race/ethnicity appear to receive little attention. Existing literature suggests that these portrayal patterns may both support and limit ACA durability. In favor of durability is that ACA beneficiaries are depicted in terms that have been associated with deservingness in past American social policy--particularly being cast as workers and insiders. Yet, the results also give three reasons for caution. First, ACA insurance-losers are also portrayed as deserving. Second, it is unclear how the portrayal patterns found may impact the durability of the ACA's efforts to cut insurance disparities by age, health status, and especially race/ethnicity. Third, portrayals' strong casting of beneficiaries as workers, and limited attention to beneficiaries' economic heterogeneity and to young adults, may do little to help cultivate beneficiary political engagement around the ACA.

Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime.

PubMed

McBrayer, MaryKate; Nixon, Ralph A

2013-12-01

Early-onset FAD (familial Alzheimer's disease) is caused by mutations of PS1 (presenilin 1), PS2 (presenilin 2) and APP (amyloid precursor protein). Beyond the effects of PS1 mutations on proteolytic functions of the γ-secretase complex, mutant or deficient PS1 disrupts lysosomal function and Ca2+ homoeostasis, both of which are considered strong pathogenic factors in FAD. Loss of PS1 function compromises assembly and proton-pumping activity of the vacuolar-ATPase on lysosomes, leading to defective lysosomal acidification and marked impairment of autophagy. Additional dysregulation of cellular Ca2+ by mutant PS1 in FAD has been ascribed to altered ion channels in the endoplasmic reticulum; however, rich stores of Ca2+ in lysosomes are also abnormally released in PS1-deficient cells secondary to the lysosomal acidification defect. The resultant rise in cytosolic Ca2+ activates Ca2+-dependent enzymes, contributing substantially to calpain overactivation that is a final common pathway leading to neurofibrillary degeneration in all forms of AD (Alzheimer's disease). In the present review, we discuss the close inter-relationships among deficits of lysosomal function, autophagy and Ca2+ homoeostasis as a pathogenic process in PS1-related FAD and their relevance to sporadic AD.

Cancer preventive services, socioeconomic status, and the Affordable Care Act.

PubMed

Cooper, Gregory S; Kou, Tzuyung Doug; Dor, Avi; Koroukian, Siran M; Schluchter, Mark D

2017-05-01

Out-of-pocket expenditures are thought to be an important barrier to the receipt of cancer preventive services, especially for those of a lower socioeconomic status (SES). The Affordable Care Act (ACA) eliminated out-of-pocket expenditures for recommended services, including mammography and colonoscopy. The objective of this study was to determine changes in the uptake of mammography and colonoscopy among fee-for-service Medicare beneficiaries before and after ACA implementation. Using Medicare claims data, this study identified women who were 70 years old or older and had not undergone mammography in the previous 2 years and men and women who were 70 years old or older, were at increased risk for colorectal cancer, and had not undergone colonoscopy in the past 5 years. The receipt of procedures in the 2-year period before the ACA's implementation (2009-2010) and after its implementation (2011 to September 2012) was also identified. Multivariate generalized estimating equation models were used to determine the independent association and county-level quartile of median income and education with the receipt of testing. For mammography, a lower SES quartile was associated with less uptake, but the post-ACA disparities were smaller than those in the pre-ACA period. In addition, mammography rates increased from the pre-ACA period to the post-ACA period in all SES quartiles. For colonoscopy, in both the pre- and post-ACA periods, there was an association between uptake and educational level and, to some extent, income. However, there were no appreciable changes in colonoscopy and SES after implementation of the ACA. The removal of out-of-pocket expenditures may overcome a barrier to the receipt of recommended preventive services, but for colonoscopy, other procedural factors may remain as deterrents. Cancer 2017;123:1585-1589. © 2017 American Cancer Society. © 2017 American Cancer Society.

Functional effects of uridine triphosphate on human skinned skeletal muscle fibers.

PubMed

Vianna-Jorge, R; Oliveira, C F; Mounier, Y; Suarez-Kurtz, G

1998-02-01

Chemically skinned human skeletal muscle fibers were used to study the effects of uridine triphosphate (UTP) on the tension-pCa relationship and on Ca2+ uptake and release by the sarcoplasmic reticulum (SR). Total replacement (2.5 mM) of adenosine triphosphate (ATP) with UTP (i) displaced the tension-pCa relationship to the left along the abcissae and increased maximum Ca(2+)-activated tension, both effects being larger in slow- than in fast-type fibers; (ii) markedly reduced Ca2+ uptake by the SR (evaluated by the caffeine-evoked tension) in both fiber types; (iii) had no effect on the rate of depletion of caffeine-sensitive Ca2+ stores during soaking in relaxing solutions; (iv) induced tension in slow- but not in fast-type fibers. The effects on the SR functional properties are consistent with the notion that UTP is a poor substitute for ATP as a substrate for the Ca ATPase pump and as an agonist of the ryanodine-sensitive Ca(2+)-release channel. The UTP-induced tension in human slow-type fibers is attributed to effect(s) of the nucleotide on the tension-pCa relationship of the contractile machinery. The present data reveal important differences between the effects of UTP on human versus rat muscle fibers.

OGLE-IV Transient Search report 31 December 2016, part 2

NASA Astrophysics Data System (ADS)

Wyrzykowski, L.; Hamanowicz, A.; Kostrzewa-Rutkowska, Z.; Klencki, J.; Sitek, M.; Udalski, A.; Kozlowski, S.; Ulaczyk, K.; Soszynski, I.; Mroz, P.; Szymanski, M. K.; Poleski, R.; Pietrukowicz, P.; Pawlak, M.; Skowron, J.

2016-12-01

The OGLE-IV Transient Detection System (Wyrzykowski et al. 2014, AcA,64,197; Kozlowski et al. 2013; Klencki et al. 2016, AcA, 66,15) announces discovery of 46 transients discovered in last three months.

Dissecting blue light signal transduction pathway in leaf epidermis using a pharmacological approach.

PubMed

Živanović, Branka D; Shabala, Lana I; Elzenga, Theo J M; Shabala, Sergey N

2015-10-01

Blue light signalling pathway in broad bean leaf epidermal cells includes key membrane transporters: plasma- and endomembrane channels and pumps of H (+) , Ca (2+) and K (+) ions, and plasma membrane redox system. Blue light signalling pathway in epidermal tissue isolated from the abaxial side of fully developed Vicia faba leaves was dissected by measuring the effect of inhibitors of second messengers on net K(+), Ca(2+) and H(+) fluxes using non-invasive ion-selective microelectrodes (the MIFE system). Switching the blue light on-off caused transient changes of the ion fluxes. The effects of seven groups of inhibitors were tested in this study: CaM antagonists, ATPase inhibitors, Ca(2+) anatagonists or chelators, agents affecting IP3 formation, redox system inhibitors, inhibitors of endomembrane Ca(2+) transport systems and an inhibitor of plasma membrane Ca(2+)-permeable channels. Most of the inhibitors had a significant effect on steady-state (basal) net fluxes, as well as on the magnitude of the transient ion flux responses to blue light fluctuations. The data presented in this study suggest that redox signalling and, specifically, plasma membrane NADPH oxidase and coupled Ca(2+) and K(+) fluxes play an essential role in blue light signal transduction.

Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn’s disease

PubMed Central

Sipeki, Nora; Davida, Laszlo; Palyu, Eszter; Altorjay, Istvan; Harsfalvi, Jolan; Antal Szalmas, Peter; Szabo, Zoltan; Veres, Gabor; Shums, Zakera; Norman, Gary L; Lakatos, Peter L; Papp, Maria

2015-01-01

AIM: To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients. METHODS: About 458 consecutive patients [Crohn’s disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients’ medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed. RESULTS: Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis. CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course. PMID:26078573

8111/8116 Security Police Staff Officers 8121/8124 Security Police Officers AFSC: 81XX

DTIC Science & Technology

1992-02-01

c 6I4 .1 4 6 5 . 5 6 -6 0 m 0 60 . 0.. C afa 0 -6 0 1 0 .4 L 0 CL & f6 C 6.4 6%. 4 040E .~ ~ a 0 0.41.ft i 0 a 0w m a 2m 2 0 0. Mv 0U 4 0. L.~ 0 0ty...m ~ SC 6& Ct D0 CC Z~C)d Ř-66 64 I Ř.64C0 Ř E~ L 𔄀 6660 LO U64 W . .0 C 𔄀 -4 0L 6 0 L 1- 4 0ŘC C #.4 f6 ൶ 0 151 6W ~ )d6I.ILC E 11 .4 6.4...L - - R~ . ( *U # ACCa .4 % 40 a - 4- 1 4 4-L 0 *-46.40 50 a .40C CL 0 Ŕ 1 0. 0 OUUCC>CU.U0C4-LSa LC .CaC CW~ift-4C .4,4f L .4 -S(( a-..CA a COC *-. 4

Pulmonary microsomes contain a Ca(2+)-transport system sensitive to oxidative stress.

PubMed

Menshikova, E V; Ritov, V B; Shvedova, A A; Elsayed, N; Karol, M H; Kagan, V E

1995-03-14

A variety of events, including inhalation of atmospheric chemicals, trauma, and ischemia-reperfusion, may cause generation of reactive oxygen species in the lung and result in airways constriction. The specific metabolic mechanisms that translate oxygen radical production into airways constriction are yet to be identified. In the lung, calcium homeostasis is central to release of bronchoactive and vasoactive chemical mediators and to regulation of smooth muscle cell contractility, i.e., airway constriction. In the present work, we characterized Ca(2+)-transport in the microsomal fraction of mouse lungs, and determined how reactive oxygen species, generated by Fe2+/ascorbate and H2O2/hemoglobin, affected Ca2+ transport. The microsomal fraction of pulmonary tissue accumulated 90 +/- 5 nmol Ca2+/mg protein by an ATP-dependent process in the presence of 15 mM oxalate, and 16 +/- 2 nmol Ca2+ in its absence. In the presence of oxalate, the rate of Ca2+ uptake was 50 +/- 5 nmol Ca2+/min per mg protein at pCa 5.9 (37 degrees C). The Ca(2+)-ATPase activity was 50-60 nmol Pi/min per mg protein (pCa 5.9, 37 degrees C) in the presence of alamethicin. Inhibitors of mitochondrial H(+)-ATPase had no effect on the Ca2+ transport. Half-maximal activation of Ca2+ transport was produced by 0.4-0.5 microM Ca2+. Endoplasmic reticulum Ca(2+)-pump (SERC-ATPase) was found to be predominantly responsible for the Ca(2+)-accumulating capacity of the pulmonary microsomes. Incubation of the microsomes in the presence of either Fe2+/ascorbate or H2O2/hemoglobin resulted in a time-dependent accumulation of peroxidation products (TBARS) and in inhibition of the Ca2+ transport. The inhibitory effect of Fe2+/ascorbate on Ca2+ transport strictly correlated with the inhibition of the Ca(2+)-ATPase activity. These results are the first to indicate a highly active microsomal Ca2+ transport system in murine lungs which is sensitive to endogenous oxidation products. The importance of this system to pulmonary disorders exacerbated by oxidative chemicals remains to be studied.

PLCζ Induced Ca2+ Oscillations in Mouse Eggs Involve a Positive Feedback Cycle of Ca2+ Induced InsP3 Formation From Cytoplasmic PIP2

PubMed Central

Sanders, Jessica R.; Ashley, Bethany; Moon, Anna; Woolley, Thomas E.; Swann, Karl

2018-01-01

Egg activation at fertilization in mammalian eggs is caused by a series of transient increases in the cytosolic free Ca2+ concentration, referred to as Ca2+ oscillations. It is widely accepted that these Ca2+ oscillations are initiated by a sperm derived phospholipase C isoform, PLCζ that hydrolyses its substrate PIP2 to produce the Ca2+ releasing messenger InsP3. However, it is not clear whether PLCζ induced InsP3 formation is periodic or monotonic, and whether the PIP2 source for generating InsP3 from PLCζ is in the plasma membrane or the cytoplasm. In this study we have uncaged InsP3 at different points of the Ca2+ oscillation cycle to show that PLCζ causes Ca2+ oscillations by a mechanism which requires Ca2+ induced InsP3 formation. In contrast, incubation in Sr2+ media, which also induces Ca2+ oscillations in mouse eggs, sensitizes InsP3-induced Ca2+ release. We also show that the cytosolic level Ca2+ is a key factor in setting the frequency of Ca2+ oscillations since low concentrations of the Ca2+ pump inhibitor, thapsigargin, accelerates the frequency of PLCζ induced Ca2+ oscillations in eggs, even in Ca2+ free media. Given that Ca2+ induced InsP3 formation causes a rapid wave during each Ca2+ rise, we use a mathematical model to show that InsP3 generation, and hence PLCζ's substate PIP2, has to be finely distributed throughout the egg cytoplasm. Evidence for PIP2 distribution in vesicles throughout the egg cytoplasm is provided with a rhodamine-peptide probe, PBP10. The apparent level of PIP2 in such vesicles could be reduced by incubating eggs in the drug propranolol which also reversibly inhibited PLCζ induced, but not Sr2+ induced, Ca2+ oscillations. These data suggest that the cytosolic Ca2+ level, rather than Ca2+ store content, is a key variable in setting the pace of PLCζ induced Ca2+ oscillations in eggs, and they imply that InsP3 oscillates in synchrony with Ca2+ oscillations. Furthermore, they support the hypothesis that PLCζ and sperm induced Ca2+ oscillations in eggs requires the hydrolysis of PIP2 from finely spaced cytoplasmic vesicles. PMID:29666796

Annexin II Dependent Mechanism of Breast Cancer Progression

DTIC Science & Technology

2009-06-01

Sashida, T., Yoshida, M., Miyashita, T., and Nakamura, A. Treatment of advanced ovarian cancer with fibrinolytic inhibitor ( tranexamic acid ). Acta Obstet...from Calbiochem, (La Jolla, CA). Lysine–Sepharose and ε-aminocaproic acid (ε-ACA) were procured from Sigma (St. Louis, MO). Chromatography and

Total internal reflection-based side-pumping configuration for terawatt ultraviolet amplifier and laser oscillator development

NASA Astrophysics Data System (ADS)

Cadatal-Raduban, Marilou; Pham, Minh Hong; Pham, Duong Van; Bui, Duong Thi Thuy; Yamanoi, Kohei; Takeda, Kohei; Empizo, Melvin John F.; Mui, Luong Viet; Shimizu, Toshihiko; Nguyen, Hung Dai; Sarukura, Nobuhiko; Fukuda, Tsuguo

2018-06-01

A two-side-pumping scheme that is based on total internal reflection in a diamond-cut Ce3+:LiCaAlF6 crystal suitable for the development of an ultraviolet laser and femtosecond amplifier system is proposed. Experimental fluorescence images and lasing results that demonstrate total internal reflection of the excitation beam using this diamond-cut crystal are presented. Calculations for the optimized crystal geometry that facilitate high extraction efficiency and homogeneity of the absorbed excitation beam are also discussed. About 50% increase in extraction efficiency compared to previously reported chirped-pulse femtosecond ultraviolet amplifier operating at 50-GW peak power is expected using this total internal reflection-based two-side-pumping configuration and a diamond-cut Ce3+:LiCaAlF6 crystal with a geometry of {φ _1} = 103°, {φ _2} = {φ _4} = 82°, {φ _3} = 93°, a length of 1.23 cm, a height of 2 cm, and an absorption coefficient of 1.5 cm-1. Our results can be used as a guide during the crystal growth process by providing the appropriate crystal geometry and size for a particular absorption coefficient to achieve high extraction efficiency. With the appropriate crystal combined with multiple-beam pumping afforded by the side-pumping scheme, the development of an all-solid-state ultraviolet laser operating at terawatt level would be within reach.

Detection and quantification of RNA 2′-O-methylation and pseudouridylation

PubMed Central

Karijolich, John

2016-01-01

RNA-guided RNA modification is a naturally occurring process that introduces 2′-O-methylation and pseudouridylation into rRNA, spliceosomal snRNA and several other types of RNA. The Box C/D ribonucleoproteins (RNP) and Box H/ACA RNP, each containing one unique guide RNA (Box C/D RNA or Box H/ACA RNA) and a set of core proteins, are responsible for 2′-O-methylation and pseudouridylation respectively. Box C/D RNA and Box H/ACA RNA provide the modification specificity through base pairing with their RNA substrate. These post-transcriptional modifications could profoundly alter the properties and functions of substrate RNAs. Thus it is desirable to establish reliable and standardized modification methods to study biological functions of modified nucleotides in RNAs. Here, we present several sensitive and efficient methods and protocols for detecting and quantifying post-transcriptional 2′-O-methylation and pseudouridylation. PMID:26853326

Hydrogen sulphide inhibits carbachol-induced contractile responses in β-escin permeabilized guinea-pig taenia caecum.

PubMed

Denizalti, Merve; Durlu-Kandilci, N Tugba; Bozkurt, T Emrah; Sahin-Erdemli, Inci

2011-05-11

Hydrogen sulphide (H(2)S) is an endogenous mediator producing a potent relaxation response in vascular and non-vascular smooth muscles. While ATP-sensitive potassium channels are mainly involved in this relaxant effect in vascular smooth muscle, the mechanism in other smooth muscles has not been revealed yet. In the present study, we investigated how H(2)S relaxes non-vascular smooth muscle by using intact and β-escin permeabilized guinea-pig taenia caecum. In intact tissues, concentration-dependent relaxation response to H(2)S donor NaHS in carbachol-precontracted preparations did not change in the presence of a K(ATP) channel blocker glibenclamide, adenylate cyclase inhibitor SQ-22536, guanylate cyclase inhibitor ODQ, protein kinase A inhibitor KT-5720, protein kinase C inhibitor H-7, tetrodotoxin, apamin/charybdotoxin, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin. We then studied how H(2)S affected carbachol- or Ca(2+)-induced contractions in permeabilized tissues. When Ca(2+) was clamped to a constant value (pCa6), a further contraction could be elicited by carbachol that was decreased by NaHS. This decrease in contraction was reversed by catalase but not by superoxide dismutase or N-acetyl cysteine. The sarcoplasmic reticulum Ca(2+)-ATPase pump inhibitor, cyclopiazonic acid, also decreased the carbachol-induced contraction that was further inhibited by NaHS. Mitochondrial proton pump inhibitor carbonyl cyanide p-trifluromethoxyphenylhydrazone also decreased the carbachol-induced contraction but this was not additionally changed by NaHS. The carbachol-induced Ca(2+) sensitization, calcium concentration-response curves, IP(3)- and caffeine-induced contractions were not affected by NaHS. In conclusion, we propose that hydrogen peroxide and mitochondria may have a role in H(2)S-induced relaxation response in taenia caecum. Copyright © 2011 Elsevier B.V. All rights reserved.

Pump-induced phase aberrations in Yb3+-doped materials(Conference Presentation)

NASA Astrophysics Data System (ADS)

Keppler, Sebastian; Tamer, Issa; Hornung, Marco; Körner, Jörg; Liebetrau, Hartmut; Hein, Joachim; Kaluza, Malte C.

2017-05-01

Optical pumping of laser materials is an effective way to create a population inversion necessary for laser operation. However, a fraction of the pump energy is always transfered as heat into the laser material, which is mainly caused by the quantum defect. For Yb3+-doped materials, the small energy difference between the pump level and the laser level and the pumping with narrowband high-power laser diodes result in a quantum defect of approx. 9%, which is significantly lower compared to other dopants e.g. Ti3+ (33%) or Nd3+ (24%). Due to the low heat introduction, high optical-to-optical efficiency and high repetition rate laser systems based on diode-pumping are well-suited for a number of applications. Here, however, laser beam quality is of crucial importance. Phase distortions and beam profile modulations can lead to optical damages as well as a significant reduction of the focal spot intensity. Pump-induced phase aberrations are the main cause for phase distortions of the amplified laser beam. The heat transferred to the material causes a change of the refractive index (dn/dT), thermal expansion and stress within the laser material, eventually leading to spatial phase aberrations (also called `thermal lens'). However, the spatially dependent distribution of the population inversion itself also leads to spatial phase aberrations. Since electron excitation directly leads to a change in the charge distribution of the laser active ions, the dynamic response of the material to external fields changes. These electronic phase aberrations (also called `population lens') are described by a change in the polarizability of the material. Due to the low quantum defect of Yb3+-doped materials, this effect becomes more important. We show the first comprehensive spatio-temporal characterization of the pump-induced phase aberration including both effects. A high-resolution interference measurement was carried out with time steps of 50µs for times during the pump period and the cooling period between subsequent pump pulses. We found that both phase effects significantly contribute to the overall phase distortions. Since the temporal characteristic of the electronic phase depends on the fluorescence lifetime and the thermal phase on the thermal diffusivity, both phase effects could be distinguished by their different lifetimes. The measurements were carried out for Yb:YAG, Yb:CaF2 and Yb:glass, and are in excellent agreement to our detailed, COMSOL-based, spatio-temporal phase simulations. Since Yb:CaF2 and Yb:glass provide a negative dn/dT, the electronic phase change becomes even more important and, in case of Yb:CaF2, almost completely compensates the thermal phase imprint of a pump pulse during the time frame of laser pulse amplification.

Kinetics of Ca2+ binding to parvalbumin in bovine chromaffin cells: implications for [Ca2+] transients of neuronal dendrites

PubMed Central

Lee, Suk-Ho; Schwaller, Beat; Neher, Erwin

2000-01-01

The effect of parvalbumin (PV) on [Ca2+] transients was investigated by perfusing adrenal chromaffin cells with fura-2 and fluorescein isothiocyanate (FITC)-labelled PV. As PV diffused into cells, the decay of [Ca2+] transients was transformed from monophasic into biphasic. The proportion of the initial fast decay phase increased in parallel with the fluorescence intensity of FITC, indicating that PV is responsible for the initial fast decay phase.The relationship between the fast decay phase and the [Ca2+] level was investigated using depolarizing trains of stimuli. Within a train the relative amplitude of the fast decay phase was inversely dependent on the [Ca2+] level preceding a given stimulus.Based on these observations, we estimated the Ca2+ binding ratio of PV (κP), the apparent dissociation constant of PV for Ca2+ (Kdc,app), and the unbinding rate constant of Ca2+ from PV (kc-) in the cytosol of chromaffin cells. Assuming free [Mg2+] to be 0.14 mm, we obtained values of 51.4 ± 2.0 nm (n = 3) and 0.95 ± 0.026 s−1 (n = 3), for Kdc,app and kc-, respectively.With the parameters obtained in the perfusion study, we simulated [Ca2+] transients, using two different Ca2+ extrusion rates (γ) – 20 and 300 s−1– which represent typical values for chromaffin cells and neuronal dendrites, respectively. The simulation indicated that Ca2+ is pumped out before it is equilibrated with PV, when γ is comparable to the equilibration rates between PV and Ca2+, resulting in the fast decay phase of a biexponential [Ca2+] transient.From these results we conclude that Ca2+ buffers with slow kinetics, such as PV, may cause biexponential decays in [Ca2+] transients, thereby complicating the analysis of endogenous Ca2+ binding ratios (κS) based on time constants. Nevertheless, estimates of κS based on Ca2+ increments provide reasonable estimates for Ca2+ binding ratios before equilibration with PV. PMID:10835044

Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

PubMed Central

Babick, Andrea; Chapman, Donald; Zieroth, Shelley; Elimban, Vijayan; Dhalla, Naranjan S

2012-01-01

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI-induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca2+-pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca2+-stimulated ATPase activity and α-myosin heavy chain mRNA levels were depressed, whereas β-myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca2+-release activity and mRNA levels for SR Ca2+-pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca2+-release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions. PMID:22947202

Photocopy of drawing located at National Archives, Sand Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, Sand Bruno, California (Navy # 110-A-1 2 of 5. Scofiled Construction Company Mare Island Office, Mare Island Cal. Plan of operating floor, September 2, 1908. - Mare Island Naval Shipyard, Pump House, California Avenue, east side between Dry Dock 1 & Dry Dock 2, near Ninth Street, Vallejo, Solano County, CA

Variable stoichiometry in active ion transport: theoretical analysis of physiological consequences.

PubMed

Johnson, E A; Tanford, C; Reynolds, J A

1985-08-01

Active ion transport systems with fixed stoichiometry are subject to a thermodynamic limit on the ion concentration gradients that they can generate and maintain, and their net rates of transport must inevitably decrease as this limit is approached. The capability to vary stoichiometry might thus be physiologically advantageous: a shift to lower stoichiometry (fewer ions pumped per reaction cycle) at increasing thermodynamic load could increase the limit on the supportable concentration gradient and could accelerate the rate of transport under high-load conditions. Here we present a theoretical and numerical analysis of this possibility, using the sarcoplasmic reticulum ATP-driven Ca pump as the example. It is easy to introduce alternate pathways into the reaction cycle for this system to shift the stoichiometry (Ca2+/ATP) from the normal value of 2:1 to 1:1, but it cannot be done without simultaneous generation of a pathway for uncoupled leak of Ca2+ across the membrane. This counteracts the advantageous effect of the change in transport stoichiometry and a physiologically useful rate acceleration cannot be obtained. This result is likely to be generally applicable to most active transport systems.

Variable stoichiometry in active ion transport: theoretical analysis of physiological consequences.

PubMed Central

Johnson, E A; Tanford, C; Reynolds, J A

1985-01-01

Active ion transport systems with fixed stoichiometry are subject to a thermodynamic limit on the ion concentration gradients that they can generate and maintain, and their net rates of transport must inevitably decrease as this limit is approached. The capability to vary stoichiometry might thus be physiologically advantageous: a shift to lower stoichiometry (fewer ions pumped per reaction cycle) at increasing thermodynamic load could increase the limit on the supportable concentration gradient and could accelerate the rate of transport under high-load conditions. Here we present a theoretical and numerical analysis of this possibility, using the sarcoplasmic reticulum ATP-driven Ca pump as the example. It is easy to introduce alternate pathways into the reaction cycle for this system to shift the stoichiometry (Ca2+/ATP) from the normal value of 2:1 to 1:1, but it cannot be done without simultaneous generation of a pathway for uncoupled leak of Ca2+ across the membrane. This counteracts the advantageous effect of the change in transport stoichiometry and a physiologically useful rate acceleration cannot be obtained. This result is likely to be generally applicable to most active transport systems. PMID:3860866

Neuronal calcium wave propagation varies with changes in endoplasmic reticulum parameters: a computer model

PubMed Central

Neymotin, Samuel A.; McDougal, Robert A.; Sherif, Mohamed A.; Fall, Christopher P.; Hines, Michael L.; Lytton, William W.

2015-01-01

Calcium (Ca2+) waves provide a complement to neuronal electrical signaling, forming a key part of a neuron’s second messenger system. We developed a reaction-diffusion model of an apical dendrite with diffusible inositol triphosphate (IP3), diffusible Ca2+, IP3 receptors (IP3Rs), endoplasmic reticulum (ER) Ca2+ leak, and ER pump (SERCA) on ER. Ca2+ is released from ER stores via IP3Rs upon binding of IP3 and Ca2+. This results in Ca2+-induced-Ca2+-release (CICR) and increases Ca2+ spread. At least two modes of Ca2+ wave spread have been suggested: a continuous mode based on presumed relative homogeneity of ER within the cell; and a pseudo-saltatory model where Ca2+ regeneration occurs at discrete points with diffusion between them. We compared the effects of three patterns of hypothesized IP3R distribution: 1. continuous homogeneous ER, 2. hotspots with increased IP3R density (IP3R hotspots), 3. areas of increased ER density (ER stacks). All three modes produced Ca2+ waves with velocities similar to those measured in vitro (~50–90µm /sec). Continuous ER showed high sensitivity to IP3R density increases, with time to onset reduced and speed increased. Increases in SERCA density resulted in opposite effects. The measures were sensitive to changes in density and spacing of IP3R hotspots and stacks. Increasing the apparent diffusion coefficient of Ca2+ substantially increased wave speed. An extended electrochemical model, including voltage gated calcium channels and AMPA synapses, demonstrated that membrane priming via AMPA stimulation enhances subsequent Ca2+ wave amplitude and duration. Our modeling suggests that pharmacological targeting of IP3Rs and SERCA could allow modulation of Ca2+ wave propagation in diseases where Ca2+ dysregulation has been implicated. PMID:25734493

Energy transfer in M₅(PO₄)₃  F:Eu²⁺,Ce³⁺ (M = Ca and Ba) phosphors.

PubMed

Shinde, K N; Dhoble, S J

2014-08-01

M5(PO4)3F:Eu(2+) (M = Ca and Ba) co-doped with Ce(3+) phosphors were successfully prepared by the combustion synthesis method. The introduction of co-dopant (Ce(3+)) into the host enhanced the luminescent intensity of the M5(PO4)3F:Eu(2+) (M = Ca and Ba) efficiently. Previously, we have reported the synthesis and photoluminescence properties of same phosphors. The aim of this article is to report energy transfer mechanism between Ce(3+) ➔Eu(2+) ions in M5(PO4)3F:Eu(2+) (M = Ca and Ba) phosphors, where Ce(3+) ions act as sensitizers and Eu(2+) ions act as activators. The M5(PO4)3F:Eu(2+) (M = Ca and Ba) co-doped with Ce(3+) phosphor exhibits great potential for use in white ultraviolet (UV) light-emitting diode applications to serve as a single-phased phosphor that can be pumped with near-UV or UV light-emitting diodes. Copyright © 2013 John Wiley & Sons, Ltd.

Frequency of distracting tasks people do while driving : an analysis of the ACAS FOT data.

DOT National Transportation Integrated Search

2007-06-01

This report describes further analysis of data from the advanced collision avoidance system (ACAS) field operational test, a naturalistic driving study. To determine how distracted and nondistracted driving differ, a stratified sample of 2,914 video ...

OGLE-IV Transient Search report 25 September 2017 part 2

NASA Astrophysics Data System (ADS)

Wyrzykowski, L.; Gromadzki, M.; Hamanowicz, A.; Rybicki, K.; Klencki, J.; Kozlowski, S.; Udalski, A.; Poleski, R.; Szymanski, M. K.; Skowron, J.; Ulaczyk, K.; Pawlak, M.; Mroz, P.; Soszynski, I.; Pietrukowicz, P.; Sitek, M.; Ihanec, N.

2017-09-01

The OGLE-IV Transient Detection System (Wyrzykowski et al. 2014, AcA,64,197; Kozlowski et al. 2013; Klencki et al. 2016, AcA, 66,15) announces discovery of 49 new on-going and recently finished transients discovered since Jan 2017.

Influence of accommodative lag upon the far-gradient measurement of accommodative convergence to accommodation ratio in strabismic patients.

PubMed

Miyata, Manabu; Hasebe, Satoshi; Ohtsuki, Hiroshi

2006-01-01

To determine the influence of the lag of accommodation (LOA) on the accommodative convergence to accommodation (AC/A) ratio measured by the far-gradient method in strabismic patients. The AC/A ratio was measured with a distance target viewed with and without -3.00 diopter (D) addition lenses in 63 patients with different types of strabismus (age range, 7-34 years; range of strabismic angle, -60 to +40 prism diopters; refractive error range, -7.33 to +6.63 D). The LOA for the same lens was measured with an open-view-type autorefractometer. The stimulus AC/A ratio and the AC/A ratio adjusted by the individually measured LOA (adjusted AC/A ratio) were compared. The mean +/- SD of the LOA to the -3.00 D lenses was 1.06 +/- 0.43 D. The mean adjusted AC/A ratio was 41% greater than the stimulus AC/A ratio. The LOA differed widely among patients (0.13 to 2.14 D), and a large LOA tended to appear in myopic or young patients. The AC/A ratio obtained using the conventional far-gradient method is significantly biased by the LOA, and thus does not always represent the actual relationship between accommodation and vergence control systems. Copyright Japanese Ophthalmological Society 2006.

Perceived Impacts of the Affordable Care Act: Perspectives of Buprenorphine Prescribers

PubMed Central

Knudsen, Hannah K.; Studts, Jamie L.

2017-01-01

The Affordable Care Act (ACA) has been heralded as a major policy change that is expected to transform the delivery of substance use disorder (SUD) treatment. Few studies have reported on the perceived impacts of ACA from the perspectives of SUD treatment providers, such as physicians who prescribe buprenorphine to patients with opioid use disorder. The present study describes buprenorphine prescribers’ perceptions regarding impacts of the ACA on the delivery of buprenorphine and examines whether state-level approaches to implementing ACA are associated with its perceived impacts. Data are drawn from a national sample of current buprenorphine prescribers (n=1,174) who were surveyed by mail. On average, buprenorphine prescribers reported ambivalence regarding the impacts of the ACA, as indicated by a mean of 2.75 (SD=0.69) on a scale that ranged from 1 (“strongly disagree”) to 5 (“strongly agree”). A multi-level mixed effects regression model indicated that physicians practicing in states that were supportive of ACA, as indicated by adopting both the Medicaid expansion and implementing a state-based health insurance exchange, had more positive perceptions of the ACA than physicians in states that had declined both of these policies. This study suggests that state approaches to ACA may be associated with varied impacts. PMID:28296579

Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implication in Fracture Repair and Wound Healing in Humans

DTIC Science & Technology

2008-04-01

designed in this study: Mg4718-F: 5’-GCA TTT TGA TCC CTT ATA ATA CA-3’ Mg4718-R: 5’- GTG GAA GAC CCT TGA ATG G-3’ Mg4723-F: 5’-GCA TAG CCA ACA AAA...GAA ATC TAA TG-3’ Mg4723-R: 5’-GCA GTG TAG CTC AGT GGT AGA TCA C-3’ After each cross, the progenies were genotyped as described above. We have also...mutant F2 mice. PPD is a likelihood statistic that gives rise to the 95% confidence intervals, which is indicated by gray horizontal bars. cM

Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus.

PubMed

Bayer, A; Önol, M

2017-04-01

PurposeTo evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS).Patients and methodsIn this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS.ResultsThere were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05).ConclusionsThe use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group.

Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus

PubMed Central

Bayer, A; Önol, M

2017-01-01

Purpose To evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS). Patients and methods In this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS. Results There were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05). Conclusions The use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group. PMID:27983734

The effect of pharmacologic pupillary dilatation on anterior segment parameters in patients with exfoliation syndrome.

PubMed

Mocan, Mehmet Cem; Ustunel, Saim; Dikmetas, Ozlem; Bozkurt, Banu; Irkec, Murat

2014-01-01

The purpose of this study was to evaluate the effect of pharmacologic pupillary dilatation on anterior chamber depth (ACD) and anterior chamber angle (ACA) in eyes with exfoliation syndrome (XFS). Thirty-six eyes of 36 patients with XFS were evaluated with slit-lamp examination, Goldmann applanation tonometry and ultrasound biomicroscopy (UBM) under standard light conditions. Primary outcome parameters were defined as the change in ACD and ACA measured before and 40 min after instillation of a single drop of either 1% cyclopentolate (Group I; n=12), 2.5% phenylephrine (Group II; n=12) or 1% tropicamide (Group III; n=12). Change in intraocular pressure (IOP) during the same time interval was included as a secondary outcome measure. The average predilatation ACD, ACA and IOP values in the study subjects were 2.54±0.40 mm, 27.9±6.3° and 14.9±3.1 mmHg, respectively. There were no significant differences in the mean age (p=0.461), the female/male ratio (p=0.232), baseline ACD (p=0.841), ACA (p=0.761) or IOP (p=0.070) within the three groups. Differences in dilation induced changes in ACD (p=0.108), ACA (p=0.636) and IOP (p=0.160) between the three groups were not statistically significant. Pupillary dilatation with a single drop of 1.0% cyclopentolate, 2.5% phenylephrine or 1% tropicamide is not associated with shallowing of the anterior chamber or narrowing of the ACA in patients with XFS who present with open angles. Copyright © 2013 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Regulation of Endoplasmic Reticulum-Mitochondria Ca2+ Transfer and Its Importance for Anti-Cancer Therapies.

PubMed

Pedriali, Gaia; Rimessi, Alessandro; Sbano, Luigi; Giorgi, Carlotta; Wieckowski, Mariusz R; Previati, Maurizio; Pinton, Paolo

2017-01-01

Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca 2+ concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca 2+ among several compartments. The resulting highly defined spatial and temporal patterns of Ca 2+ movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins. PM and ER organize specialized junctions. Here, many components of the receptor-dependent Ca 2+ signals are clustered, including the ORAI1-stromal interaction molecule 1 complex. This complex constitutes a primary mechanism for Ca 2+ entry into non-excitable cells, modulated by intracellular Ca 2+ . Several contact sites between the ER and mitochondria, termed mitochondria-associated membranes, show a very complex and specialized structure and host a wide number of proteins that regulate Ca 2+ transfer. In this review, we summarize current knowledge of the particular action of several oncogenes and tumor suppressors at these specialized check points and analyze anti-cancer therapies that specifically target Ca 2+ flow at the inter-organelle contacts to alter the metabolism and fate of the cancer cell.

Ca2+-stores in sperm: their identities and functions

PubMed Central

Costello, Sarah; Michelangeli, Francesco; Nash, Kate; Lefievre, Linda; Morris, Jennifer; Machado-Oliveira, Gisela; Barratt, Christopher; Kirkman-Brown, Jackson; Publicover, Stephen

2013-01-01

Intracellular Ca2+ stores play a central role in the regulation of cellular [Ca2+]i and the generation of complex [Ca2+] signals such as oscillations and waves. Ca2+ signalling is of particular significance in sperm cells, where it is a central regulator in many key activities (including capacitation, hyperactivation, chemotaxis and acrosome reaction) yet mature sperm lack endoplasmic reticulum and several other organelles which serve as Ca2+ stores in somatic cells. Here we review (i) the evidence for the expression in sperm of the molecular components (pumps and channels) which are functionally significant in the activity of Ca2+ stores of somatic cells and (ii) the evidence for the existence of functional Ca2+ stores in sperm. This evidence supports the existence of at least two storage organelles in mammalian sperm, one in the acrosomal region and another in the region of the sperm neck and midpiece. We then go on to discuss the likely identity of these organelles and their discrete functions: regulation by the acrosome of its own secretion and regulation by membranous organelles at the sperm neck (and possibly by the mitochondria) of flagellar activity and hyperactivation. Finally we consider the ability of the sperm discretely to control mobilisation of these stores and the functional interaction of stored Ca2+ at the sperm neck/midpiece with CatSper channels in the principal piece in regulation of the activities of mammalian sperm. PMID:19542252

Alternatives to the ACA's Affordability Firewall.

PubMed

Nowak, Sarah A; Saltzman, Evan; Cordova, Amado

2016-05-09

The Affordable Care Act (ACA) was designed to increase health insurance coverage while limiting the disruption to individuals with existing sources of insurance coverage, particularly those with employer-sponsored insurance (ESI). To limit disruption to those with coverage, the ACA implements the employer mandate, which requires firms with more than 50 employees to offer health insurance or face penalties, and the individual "affordability firewall," which limits subsidies to individuals lacking access to alternative sources of coverage that are "affordable." This article examines the policy impacts of the affordability firewall and investigates two potential modifications. Option 1, which is the "entire family" scenario, involves allowing an exception to the firewall for anyone in a family where the family ESI premium contribution exceeds 9.5 percent of the worker's household income. In Option 2, the "dependents only" scenario, only dependents (and not the worker) become eligible for Marketplace subsidies when the ESI premium contribution exceeds 9.5 percent of the worker's household income. Relative to the ACA, RAND researchers estimate that nongroup enrollment will increase by 4.1 million for Option 1 and by 1.4 million for Option 2. However, the number without insurance only declines by 1.5 million in Option 1 and 0.7 million in Option 2. The difference between the increase in nongroup enrollment and the decrease in uninsurance is primarily due to ESI crowd-out, which is more pronounced for Option 1. Researchers also estimated that about 1.3 million families who have ESI and unsubsidized nongroup coverage under current ACA policy would receive Marketplace subsidies under the alternative affordability firewall scenarios. For these families, health insurance coverage would become substantially more affordable; these families' risk of spending at least 20 percent of income on health care would drop by more than two thirds. We additionally estimated that federal spending will increase by $8.9 billion and $3.9 billion for Options 1 and 2, respectively, relative to the ACA.

Signaling mechanisms that link salt retention to hypertension: endogenous ouabain, the Na(+) pump, the Na(+)/Ca(2+) exchanger and TRPC proteins.

PubMed

Blaustein, Mordecai P; Hamlyn, John M

2010-12-01

Salt retention as a result of chronic, excessive dietary salt intake, is widely accepted as one of the most common causes of hypertension. In a small minority of cases, enhanced Na(+) reabsorption by the kidney can be traced to specific genetic defects of salt transport, or pathological conditions of the kidney, adrenal cortex, or pituitary. Far more frequently, however, salt retention may be the result of minor renal injury or small genetic variation in renal salt transport mechanisms. How salt retention actually leads to the increase in peripheral vascular resistance (the hallmark of hypertension) and the elevation of blood pressure remains an enigma. Here we review the evidence that endogenous ouabain (an adrenocortical hormone), arterial smooth muscle α2 Na(+) pumps, type-1 Na/Ca exchangers, and receptor- and store-operated Ca(2+) channels play key roles in the pathway that links salt to hypertension. We discuss cardenolide structure-function relationships in an effort to understand why prolonged administration of ouabain, but not digoxin, induces hypertension, and why digoxin is actually anti-hypertensive. Finally, we summarize recent observations which indicate that ouabain upregulates arterial myocyte Ca(2+) signaling mechanisms that promote vasoconstriction, while simultaneously downregulating endothelial vasodilator mechanisms. In sum, the reports reviewed here provide novel insight into the molecular mechanisms by which salt retention leads to hypertension. Copyright © 2010 Elsevier B.V. All rights reserved.

The Slow Dynamics of Intracellular Sodium Concentration Increase the Time Window of Neuronal Integration: A Simulation Study

PubMed Central

Zylbertal, Asaph; Yarom, Yosef; Wagner, Shlomo

2017-01-01

Changes in intracellular Na+ concentration ([Na+]i) are rarely taken into account when neuronal activity is examined. As opposed to Ca2+, [Na+]i dynamics are strongly affected by longitudinal diffusion, and therefore they are governed by the morphological structure of the neurons, in addition to the localization of influx and efflux mechanisms. Here, we examined [Na+]i dynamics and their effects on neuronal computation in three multi-compartmental neuronal models, representing three distinct cell types: accessory olfactory bulb (AOB) mitral cells, cortical layer V pyramidal cells, and cerebellar Purkinje cells. We added [Na+]i as a state variable to these models, and allowed it to modulate the Na+ Nernst potential, the Na+-K+ pump current, and the Na+-Ca2+ exchanger rate. Our results indicate that in most cases [Na+]i dynamics are significantly slower than [Ca2+]i dynamics, and thus may exert a prolonged influence on neuronal computation in a neuronal type specific manner. We show that [Na+]i dynamics affect neuronal activity via three main processes: reduction of EPSP amplitude in repeatedly active synapses due to reduction of the Na+ Nernst potential; activity-dependent hyperpolarization due to increased activity of the Na+-K+ pump; specific tagging of active synapses by extended Ca2+ elevation, intensified by concurrent back-propagating action potentials or complex spikes. Thus, we conclude that [Na+]i dynamics should be considered whenever synaptic plasticity, extensive synaptic input, or bursting activity are examined. PMID:28970791

Ultralow-threshold Raman lasing with CaF2 resonators.

PubMed

Grudinin, Ivan S; Maleki, Lute

2007-01-15

We demonstrate efficient Raman lasing with CaF2 whispering-gallery-mode resonators. Continuous-wave emission threshold is shown to be possible below 1 microW with a 5mm cavity, which is to our knowledge orders of magnitude lower than in any other Raman source. Low-threshold lasing is made possible by the ultrahigh optical quality factor of the cavity, of the order of Q=5x10(10). Stokes components of up to the fifth order were observed at a pump power of 160 microW, and up to the eighth order at 1 mW. A lasing threshold of 15 microW was also observed in a 100 microm CaF2 microcavity. Potential applications are discussed.

Asymmetric conjugate addition of Grignard reagents to pyranones.

PubMed

Mao, Bin; Fañanás-Mastral, Martín; Feringa, Ben L

2013-01-18

An efficient enantioselective synthesis of lactones was developed based on the catalytic asymmetric conjugate addition (ACA) of alkyl Grignard reagents to pyranones. The use of 2H-pyran-2-one for the first time in the ACA with Grignard reagents allows for a variety of further transformations to access highly versatile building blocks such as β-alkyl substituted aldehydes or β-bromo-γ-alkyl substituted alcohols with excellent regio- and stereoselectivity.

A bio-injectable algin-aminocaproic acid thixogel with tri-stimuli responsiveness.

PubMed

Chejara, Dharmesh R; Mabrouk, Mostafa; Badhe, Ravindra V; Mulla, Jameel A S; Kumar, Pradeep; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-01-01

In this article a novel bio-injectable algin-aminocaproic acid (Alg-ACA) tri-stimuli responsive thixogel system is reported. The designed soft thixotrophic hydrogel (thixogel) was characterized using various analytical techniques such as FT-IR, NMR, SEM, AFM and DSC. The soft thixogel system was further investigated for stress responsiveness using different rheological studies which confirmed the thixotropic nature of the gel [Thixotropic area (Ar) of Alg-ACA (1:0.5), Alg-ACA (1:1) and Alg-ACA (1:2), were 23.5%, 43.1%, and 27.59%, respectively, which were higher than that of Na-Alg (2.08%)]. The thixogel also demonstrated temperature and ultrasonication responsiveness. This tri-stimuli responsive soft thixogel system was rendered flowable (fluid) on applying the described physical stimuli and recovered its "rigid" gel structure upon removal of the applied stimuli. This approach of synthesizing a thixogels may be applicable to a broad variety of other natural polymers and has the potential for use in biomedical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Health Care Sharing Ministries and Their Exemption From the Individual Mandate of the Affordable Care Act.

PubMed

Galarneau, Charlene

2015-06-01

The U.S. 2010 Patient Protection and Affordable Care Act (ACA) exempts members of health care sharing ministries (HCSMs) from the individual mandate to have minimum essential insurance coverage. Little is generally known about these religious organizations and even less critical attention has been brought to bear on them and their ACA exemption. Both deserve close scrutiny due to the exemption's less than clear legislative justification, their potential influence on the ACA's policy and ethical success, and their salience to current religious liberty debates surrounding the expansion of religious exemptions from ACA responsibilities for both individuals and corporations. Analyzing documents of the United States' three largest health care sharing ministries and related material, I examine these organizations and their ACA exemption with particular consideration of their ethical dimensions. Here a thick description of the nature and workings of health care sharing ministries precedes a similar account of the ACA exemption. From these empirical analyses, five ethical and policy concerns emerge: (1) the charity versus insurance status of these ministries; (2) the conflation of two ACA religious exemptions; (3) the tension between the values of religious liberty and of justice; (4) the potential undermining of ACA policy goals; and (5) the questionable compliance of health care sharing ministries with ACA exemption requirements.  An accurate and informed understanding of HCSMs is required for policymakers and others to justify the ACA exemption of health care sharing ministry members. A sufficient justification would address at least the five ethical and policy concerns raised here.

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad.

PubMed

Kabbara, A A; Allen, D G

2001-07-01

1. Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 degrees C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (K(Ca) 90 microM). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. 2. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. 3. To establish the site of loading, fibres were exposed to 30 mM caffeine in the presence of 20 microM 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca(2+) from the SR; this procedure reduced the fluorescence to 46 +/- 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 microg ml(-1) saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 +/- 2 % of the control value. 4. During maximally activated tetani (100 Hz stimulation rate, 22 degrees C) the component of signal from the SR declined by 33 +/- 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 +/- 0.14 s and 10.1 +/- 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca(2+) pump inhibitor TBQ slowed the rate of recovery of the SR signal. 5. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca(2+) signal was eventually reduced to 71 +/- 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 +/- 0.2 s so that by 20 s of recovery the SR Ca(2+) signal was 86 +/- 7 % of control; the second phase was slower and by 5 min the SR Ca(2+) signal was back to control values (98 +/- 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Delta[Ca(2+)](SR)) declined monotonically throughout fatigue and returned to control after 5 min recovery. 6. This approach can monitor the SR Ca(2+) concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca(2+) available for release in the SR declines during fatigue. This reduction in [Ca(2+)](SR) will contribute to the failure of Ca(2+) delivery to the myofilaments which is an important cause of muscle fatigue.

Mechanosensitive Ca²⁺-permeable channels in human leukemic cells: pharmacological and molecular evidence for TRPV2.

PubMed

Pottosin, Igor; Delgado-Enciso, Iván; Bonales-Alatorre, Edgar; Nieto-Pescador, María G; Moreno-Galindo, Eloy G; Dobrovinskaya, Oxana

2015-01-01

Mechanosensitive channels are present in almost every living cell, yet the evidence for their functional presence in T lymphocytes is absent. In this study, by means of the patch-clamp technique in attached and inside-out modes, we have characterized cationic channels, rapidly activated by membrane stretch in Jurkat T lymphoblasts. The half-activation was achieved at a negative pressure of ~50mm Hg. In attached mode, single channel currents displayed an inward rectification and the unitary conductance of ~40 pS at zero command voltage. In excised inside-out patches the rectification was transformed to an outward one. Mechanosensitive channels weakly discriminated between mono- and divalent cations (PCa/PNa~1) and were equally permeable for Ca²⁺ and Mg²⁺. Pharmacological analysis showed that the mechanosensitive channels were potently blocked by amiloride (1mM) and Gd³⁺ (10 μM) in a voltage-dependent manner. They were also almost completely blocked by ruthenium red (1 μM) and SKF 96365 (250 μM), inhibitors of transient receptor potential vanilloid 2 (TRPV2) channels. At the same time, the channels were insensitive to 2-aminoethoxydiphenyl borate (2-APB, 100 μM) or N-(p-amylcinnamoyl)anthranilic acid (ACA, 50 μM), antagonists of transient receptor potential canonical (TRPC) or transient receptor potential melastatin (TRPM) channels, respectively. Human TRPV2 siRNA virtually abolished the stretch-activated current. TRPV2 are channels with multifaceted functions and regulatory mechanisms, with potentially important roles in the lymphocyte Ca²⁺ signaling. Implications of their regulation by mechanical stress are discussed in the context of lymphoid cells functions. Copyright © 2014 Elsevier B.V. All rights reserved.

A cross-jurisdictional evaluation of insurance coverage among HIV care patients following the Affordable Care Act.

PubMed

Hood, Julia E; Buskin, Susan E; Anderson, Bridget J; Gagner, Alexandra; Kienzle, Jennifer; Maggio, David; Markey, Katie; Reuer, Jennifer; Benbow, Nanette; Wortley, Pascale

2017-04-01

The impact of the Affordable Care Act (ACA) on HIV care patients, aged 18-64, was evaluated in three jurisdictions with Medicaid expansion (Chicago, New York State, and Washington) and three jurisdictions without Medicaid expansion (Georgia, Texas, and Virginia) using data from the Medical Monitoring Project. Multivariate regression models were used to evaluate insurance status that was reported pre- and post-ACA; self-reported impact of ACA on HIV care was explored with descriptive statistics. The likelihood of having insurance was significantly greater post-ACA compared to pre-ACA in Chicago (aRR = 1.33, 95%CI = 1.20, 1.47), Washington (aRR = 1.15, 95%CI = 1.08, 1.22), and Virginia (aRR = 1.14, 95%CI = 1.00, 1.29). In Washington and Chicago, the likelihood of being Medicaid-insured was greater post-ACA compared to pre-ACA implementation (Chicago: aRR = 1.25, 95%CI = 1.03,1.53; Washington: aRR = 1.66 95% CI = 1.30, 2.13). No other significant differences were observed. Only a subset of HIV care patients (range: 15-35%) reported a change in insurance that would have coincided with the implementation of ACA; and within this subset, a change in medical care costs was the most commonly noted issue. In conclusion, the influence of ACA on insurance coverage and other factors affecting HIV care likely varies by jurisdiction.

Ca²⁺-pumping impairment during repetitive fatiguing contractions in single myofibers: role of cross-bridge cycling.

PubMed

Nogueira, Leonardo; Shiah, Amy A; Gandra, Paulo G; Hogan, Michael C

2013-07-15

The energy cost of contractions in skeletal muscle involves activation of both actomyosin and sarcoplasmic reticulum (SR) Ca²⁺-pump (SERCA) ATPases, which together determine the overall ATP demand. During repetitive contractions leading to fatigue, the relaxation rate and Ca²⁺ pumping become slowed, possibly because of intracellular metabolite accumulation. The role of the energy cost of cross-bridge cycling during contractile activity on Ca²⁺-pumping properties has not been investigated. Therefore, we inhibited cross-bridge cycling by incubating isolated Xenopus single fibers with N-benzyl-p-toluene sulfonamide (BTS) to study the mechanisms by which SR Ca²⁺ pumping is impaired during fatiguing contractions. Fibers were stimulated in the absence (control) and presence of BTS and cytosolic calcium ([Ca²⁺]c) transients or intracellular pH (pHi) changes were measured. BTS treatment allowed normal [Ca²⁺]c transients during stimulation without cross-bridge activation. At the time point that tension was reduced to 50% in the control condition, the fall in the peak [Ca²⁺]c and the increase in basal [Ca²⁺]c did not occur with BTS incubation. The progressively slower Ca²⁺ pumping rate and the fall in pHi during repetitive contractions were reduced during BTS conditions. However, when mitochondrial ATP supply was blocked during contractions with BTS present (BTS + cyanide), there was no further slowing in SR Ca²⁺ pumping during contractions compared with the BTS-alone condition. Furthermore, the fall in pHi was significantly less during the BTS + cyanide condition than in the control conditions. These results demonstrate that factors related to the energetic cost of cross-bridge cycling, possibly the accumulation of metabolites, inhibit the Ca²⁺ pumping rate during fatiguing contractions.

Synthesis and Characterization of Nd(3+)-Doped CaF2 Nanoparticles.

PubMed

Yuan, Dan; Li, Weiwei; Mei, Bingchu; Song, Jinghong

2015-12-01

The Ca(1-x)F(2+x):Nd(x) nanoparticles were synthesized by chemical direct precipitation method. X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Image analyzer, absorption spectrum and transmittance were taken to characterization the phases, morphologies, sizes, size distribution and optical properties of the samples. The results indicate that the Ca(1-x)F(2+x):Nd(x) samples can be rationally modified in size and morphology by altering the Nd3+ ions doping concentration. With increasing concentration of Nd3+ ions, the particle size decreased from 24 to 14 nm, the intensity of the diffraction peaks decreased, the Ca(1-x)F(2+x):Nd(x) particles aggregated ion of the formed clusters which should have an effect on both speed and orientation of the particles growth. The transmittance of ceramics with a thickness of 2 mm showed that the transmittance can reach 90% when the doping concentration was 5%, which should be profitable for LD pumping.

Efficient continuous-wave, broadly tunable and passive Q-switching lasers based on a Tm3+:CaF2 crystal

NASA Astrophysics Data System (ADS)

Liu, Jingjing; Zhang, Cheng; Zu, Yuqian; Fan, Xiuwei; Liu, Jie; Guo, Xinsheng; Qian, Xiaobo; Su, Liangbi

2018-04-01

Laser operations in the continuous-wave as well as in the pulsed regime of a 4 at.% Tm3+:CaF2 crystal are reported. For the continuous-wave operation, a maximum average output power of 1.15 W was achieved, and the corresponding slope efficiency was more than 64%. A continuous tuning range of about 160 nm from 1877-2036 nm was achieved using a birefringent filter. Using Argentum nanorods as a saturable absorber, the significant pulsed operation of a passively Q-switched Tm3+:CaF2 laser was observed at 1935.4 nm for the first time, to the best of our knowledge. A maximum output power of 385 mW with 41.4 µJ pulse energy was obtained under an absorbed pump power of 2.04 W. The present results indicate that the Tm3+:CaF2 lasers could be promising laser sources to operate in the eye-safe spectral region.

Ion transport regulation by prostaglandins in mouse macrophages.

PubMed

Braquet, P; Diez, J; Garay, R

1985-01-01

Although the prostaglandins PGE1, PGE2 and PGF2 alpha had no effect on ion transport in isolated human erythrocytes, they modulated ion transport in isolated mouse macrophages, apparently through the mediation of cAMP, by inhibiting the NA+, K+ cotransport system, stimulating the Na+, K+ pump, and stimulating the Na+: Ca++ exchange mechanism.

The development, distribution and density of the PMCA2 calcium pump in rat cochlear hair cells

PubMed Central

Chen, Qingguo; Mahendrasingam, Shanthini; Tickle, Jacqueline A.; Hackney, Carole M.; Furness, David N.; Fettiplace, Robert

2012-01-01

Calcium is tightly regulated in cochlear outer hair cells (OHCs). It enters mainly via mechanotransducer (MT) channels and is extruded by the PMCA2 isoform of the plasma membrane calcium ATPase, mutations in which cause hearing loss. To assess how pump expression matches the demands of Ca2+ homeostasis, the distribution of PMCA2 at different cochlear locations during development was quantified using immunofluorescence and post-embedding immunogold labeling. The PMCA2 isoform was confined to stereociliary bundles, first appearing at the base of the cochlea around post-natal day 0 (P0) followed by the middle and then the apex by P3, and was unchanged after P8. The developmental appearance matches maturation of the MT channels in rat OHCs. High-resolution immunogold labeling in adult rats showed PMCA2 was distributed along the membranes of all three rows of OHC stereocilia at similar densities and at about a quarter the density in IHC stereocilia. The difference between OHCs and inner hair cells (IHCs) is similar to the ratio of their MT channel resting open probabilities. Gold particle counts revealed no difference in PMCA2 density between low- and high-frequency OHC bundles despite larger MT currents in high-frequency OHCs. The PMCA2 density in OHC stereocilia was determined in low- and high-frequency regions from calibration of immunogold particle counts as 2200/μm2 from which an extrusion rate of ~200 ions·s−1 per pump was inferred. The limited ability of PMCA2 to extrude the Ca2+ load through MT channels may constitute a major cause of OHC vulnerability and high-frequency hearing loss. PMID:22672315

1′-Acetoxychavicol Acetate Isolated from Alpinia galanga Ameliorates Ovalbumin-Induced Asthma in Mice

PubMed Central

Park, Sang-Joon; Lee, Eun-Ji; Lee, Jong-Hwa; Han, Sang-Seop; Pyo, Byeong Sik; Park, Dae-Hun; Kim, Bong-Hee

2013-01-01

The World Health Organization reports that 235 million people are currently affected by asthma. This disease is associated with an imbalance of Th1 and Th2 cells, which results in the upregulation of cytokines that promote chronic inflammation of the respiratory system. The inflammatory response causes airway obstruction and can ultimately result in death. In this study we evaluated the effect of 1′-acetoxychavicol acetate (ACA) isolated from Alpinia galanga rhizomes in a mouse model of ovalbumin (OVA)-induced asthma. To generate the mouse model, BALB/c mice were sensitized by intraperitoneal injection of OVA and then challenged with OVA inhalation for 5 days. Mice in the vehicle control group were sensitized with OVA but not challenged with OVA. Treatment groups received dexamethasone, 25 mg/kg/day ACA, or 50 mg/kg/day ACA for 5 days. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. Our results showed that ACA reduced the infiltration of white blood cells (especially eosinophils) and the level of IgE in the lungs of mice challenged with OVA and suppressed histopathological changes such as airway remodeling, goblet-cell hyperplasia, eosinophil infiltration, and glycoprotein secretion. In addition, ACA inhibited expression of the Th2 cytokines interleukin (IL)-4 and IL-13, and Th1 cytokines IL-12α and interferon-γ. Because asthmatic reactions are mediated by diverse immune and inflammatory pathways, ACA shows promise as an antiasthmatic drug candidate. PMID:23451048

Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via regulating RSU1.

PubMed

Phuah, Neoh Hun; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

2017-01-01

Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1'S-1'-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera , induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells. The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA. Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression. Overexpression of RSU1 augmented antiproliferative and apoptosis-inducing effects of ACA. Our findings showed that combination of ACA with miR-629 and RSU1 may provide a potential strategy in treating cervical cancer.

Milrinone and thyroid hormone stimulate myocardial membrane Ca2+-ATPase activity and share structural homologies.

PubMed Central

Mylotte, K M; Cody, V; Davis, P J; Davis, F B; Blas, S D; Schoenl, M

1985-01-01

We have recently shown that thyroid hormone in physiological concentrations stimulates sarcolemma-enriched rabbit-myocardial-membrane Ca2+-ATPase in vitro. In this study, milrinone [2-methyl-5-cyano-(3,4'-bipyridin)-6(1H)-one], a cardiac inotropic agent, was thyromimetic in the same system. At clinically achievable concentrations (50-500 nM), milrinone significantly stimulated membrane Ca2+-ATPase in vitro. This action was antagonized by W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], an agent that also blocks thyroid hormone action on the Ca2+-ATPase, at concentrations as low as 5 microM. Progressive additions of milrinone to membranes incubated with a fixed concentration of thyroxine (0.10 nM) or triiodothyronine resulted in a progressive obliteration of the thyroid hormone effect on Ca2+-ATPase. Amrinone [5-amino-(3,4'-bipyridin)-6(1H)-one], the parent bipyridine of milrinone, had no effect on myocardial Ca2+-ATPase activity. X-ray crystallographic analysis of milrinone and amrinone revealed structural homologies between the phenolic ring of thyroxine and the substituted ring of milrinone, whereas amrinone did not share these homologies. The mechanism(s) of the inotropic actions of thyroxine and of milrinone is not clearly understood, but these observations implicate Ca2+-ATPase, a calcium pump-associated enzyme, as one mediator of the effects on the heart of these two compounds. PMID:2933747

Ho3+ doped fluoroaluminate glass fibers for 2.9 µm lasing

NASA Astrophysics Data System (ADS)

Jia, S. J.; Jia, Z. X.; Yao, C. F.; Wang, S. B.; Jiang, H. W.; Zhang, L.; Feng, Y.; Qin, G. S.; Ohishi, Y.; Qin, W. P.

2018-01-01

Ho3+ doped fluoroaluminate glass fibers based on chemically durable AlF3-BaF2-YF3-PbF2-MgF2-CaF2 glasses are fabricated by using a rod-in-tube method. By using an 84 cm long Ho3+-doped fluoroaluminate glass fiber as the gain medium and a 1120 nm fiber laser as the pump source, lasing at 2868 nm is obtained, the maximum unsaturated power is about 57 mW for a pump power of 1224 mW, and the corresponding slope efficiency is ~5.1%. The effect of the fiber length on lasing at 2868 nm is also investigated. Our results show that Ho3+-doped fluoroaluminate glass fibers are promising gain media for 2.9 µm laser applications.

Scattering and Propagation in Random Media

DTIC Science & Technology

1988-01-01

courts porno C~r) module Au champ darns Is pupille A,Ca)4 amplitude complex* Au chomp danms 1. plan focal OMf fouction As tranefert longue point do...instantenie N nosbre minimum d~imagem A utilimer doen les algorithmasm I noabre As taveluros prisontos darns V image courts porno N) noabre do moum

Overview of the Affordable Care Act's impact on military and veteran mental health services: nine implications for significant improvements in care.

PubMed

Russell, Mark C; Figley, Charles R

2014-01-01

On March 23, 2010, President Barack Obama signed the Affordable Care Act (ACA) into law. Implications of the ACA on mental health care for 9.7 million military active-duty, reserve, and family members and 22.2 million veterans, as well as 1.3 uninsured veterans, is reviewed in light of a major crisis. The authors trace historical roots of the ACA to the World War II generation and efforts to transform the mental health care system by implementing hard-won war trauma lessons. The authors posit 9 principles reflected in the ACA that represent unfulfilled generational war trauma lessons and potential transformation of the military and national mental health care systems.

Intraoperative trans-fontanellar cerebral ultrasonography in infants during cardiac surgery under cardiopulmonary bypass: an observational study.

PubMed

Park, Yong-Hee; Song, In-Kyung; Lee, Ji-Hyun; Kim, Hee-Soo; Kim, Chong-Sung; Kim, Jin-Tae

2017-02-01

This study was performed to evaluate the feasibility of intraoperative point-of-care trans-fontanellar cerebral ultrasonography (TFCU) to obtain blood flow velocity (BFV) reference values at the internal carotid arteries (ICAs) and peri-callosal part of the anterior cerebral artery (pACA) during pediatric cardiac surgery under cardiopulmonary bypass (CPB). TFCU was performed at three time points (after induction of anesthesia, during CPB, after CPB) in 35 infants. BFV was measured at both ICAs and pACA through the anterior fontanelle with an ultrasound sector probe. We divided patients into Group S (<5 kg, n = 16) and Group L (≥5 kg, n = 19) for comparisons according to weight. We also analyzed BFV in low cerebral regional oxygen saturation (rSO 2 ) data. All measurements of the BFV at both the ICAs and the pACA were possible. BFVs at the ICAs were lower in Group S than in Group L at all three time points. BFVs at the pACA were similar in both groups except higher value in Group L after CPB. When the rSO 2 was <50, most BFVs (14 of 15 measurements) were lower than the median BFV value during CPB. However, a low rSO 2 did not always reflect low BFV before and after CPB. Point-of-care TFCU can determine BFV at the ICAs and pACA during pediatric cardiac surgery. BFV differs according to the patient's size and CPB application. TFCU can be a practical cerebral blood flow monitoring method when rSO 2 changes without any specific reason in infants.ClinicalTrials.gov NCT01996020.

Diode pumped Yb:CN laser at 1082 nm and intracavity doubling to the green spectral range

NASA Astrophysics Data System (ADS)

Liu, B.; Li, Y. L.; Jiang, H. L.

2011-08-01

A diode pumped Yb:CaNb2O6 (Yb:CN) laser at 1082 nm with a maximum output of 1.35 W at 13.3 W pump power has been demonstrated. The slope efficiency was 12.4%. Moreover, intracavity second-harmonic generation (SHG) has also been achieved with a maximum green power of 374 mW by using a LiB3O5 (LBO) nonlinear crystal. To the best of our knowledge, this is the first report on continuous wave (CW) green generation by intracavity frequency doubling Yb:CN laser.

The use of the indicator fluo-5N to measure sarcoplasmic reticulum calcium in single muscle fibres of the cane toad

PubMed Central

Kabbara, Akram A; Allen, David G

2001-01-01

Single fibres from the lumbrical muscles of the cane toad (Bufo marinus) were incubated in fluo-5N AM for 2 h at 35 °C in order to load the indicator into the sarcoplasmic reticulum. Fluo-5N is a low-affinity calcium indicator (KCa 90 μm). Successful sarcoplasmic reticulum (SR) loading was indicated by a fluorescence signal that declined during contraction. Confocal microscopy showed that the dye loaded principally in lines perpendicular to the long axis of the fibre that repeated each sarcomere. This is consistent with much of the dye residing in the SR. To establish the site of loading, fibres were exposed to 30 mm caffeine in the presence of 20 μm 2,5-di(tert-butyl)1,4-hydroquinone (TBQ, an SR pump inhibitor) which should release most Ca2+ from the SR; this procedure reduced the fluorescence to 46 ± 4 % of the control value. To determine how much indicator was in the myoplasm, fibres were exposed to 100 μg ml−1 saponin which permeabilizes the surface membrane; saponin treatment reduced the fluorescence to 51 ± 2 % of the control value. During maximally activated tetani (100 Hz stimulation rate, 22 °C) the component of signal from the SR declined by 33 ± 4 %. During relaxation the SR signal recovered in two phases with time constants of 0.38 ± 0.14 s and 10.1 ± 1.7 s. Partially activated tetani (30 Hz stimulation rate) showed a smaller SR signal. Application of the SR Ca2+ pump inhibitor TBQ slowed the rate of recovery of the SR signal. Muscle fatigue was produced by repeated short tetani until tension was reduced to 50 %. The SR signal during the periods between tetani declined steadily and the SR Ca2+ signal was eventually reduced to 71 ± 8 % of the control signal. This signal recovered in two phases when the muscle was rested. An initial phase had a time constant of 1.7 ± 0.2 s so that by 20 s of recovery the SR Ca2+ signal was 86 ± 7 % of control; the second phase was slower and by 5 min the SR Ca2+ signal was back to control values (98 ± 5 % control). In addition the magnitude of the SR signal decline associated with each tetanus (Δ[Ca2+]SR) declined monotonically throughout fatigue and returned to control after 5 min recovery. This approach can monitor the SR Ca2+ concentration in normally functioning muscle fibres with good time resolution. The method confirms other approaches that show that the free Ca2+ available for release in the SR declines during fatigue. This reduction in [Ca2+]SR will contribute to the failure of Ca2+ delivery to the myofilaments which is an important cause of muscle fatigue. PMID:11432994

DOE ZERH Case Study: Mutual Housing California, Mutual Housing at Spring Lake, Woodland, CA

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

none,

2015-09-01

Case study of a DOE 2015 Housing Innovation Award winning multifamily project of 62 affordable-housing apartment home in the hot-dry climate that exceeded CA Title 24-2008 by 35%, with 2x4 16” on center walls with R-21 fiberglass bass walls, uninsulated salb on grade foundation; vented attic with R-44 blown fiberglass; air to water heat pumps.

Specialty, political affiliation, and perceived social responsibility are associated with U.S. physician reactions to health care reform legislation.

PubMed

Antiel, Ryan M; James, Katherine M; Egginton, Jason S; Sheeler, Robert D; Liebow, Mark; Goold, Susan Dorr; Tilburt, Jon C

2014-02-01

Little is known about how U.S. physicians’ political affiliations, specialties, or sense of social responsibility relate to their reactions to health care reform legislation. To assess U.S. physicians’ impressions about the direction of U.S. health care under the Affordable Care Act (ACA), whether that legislation will make reimbursement more or less fair, and examine how those judgments relate to political affiliation and perceived social responsibility. A cross-sectional, mailed, self-reported survey. Simple random sample of 3,897 U.S.physicians. Views on the ACA in general, reimbursement under the ACA in particular, and perceived social responsibility. Among 2,556 physicians who responded (RR2: 65 %), approximately two out of five (41 %) believed that the ACA will turn U.S. health care in the right direction and make physician reimbursement less fair (44 %). Seventy-two percent of physicians endorsed a general professional obligation to address societal health policy issues, 65 % agreed that every physician is professionally obligated to care for the uninsured or underinsured, and half (55 %) were willing to accept limits on coverage for expensive drugs and procedures for the sake of expanding access to basic health care. In multivariable analyses, liberals and independents were both substantially more likely to endorse the ACA (OR 33.0 [95 % CI, 23.6–46.2]; OR 5.0 [95 % CI, 3.7–6.8], respectively), as were physicians reporting a salary (OR 1.7 [95 % CI, 1.2–2.5])or salary plus bonus (OR 1.4 [95 % CI, 1.1–1.9)compensation type. In the same multivariate models, those who agreed that addressing societal health policy issues are within the scope of their professional obligations (OR 1.5 [95 % CI, 1.0–2.0]), who believe physicians are professionally obligated to care for the uninsured / under-insured (OR 1.7 [95 % CI,1.3–2.4]), and who agreed with limiting coverage for expensive drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8–3.0]), were all significantly more likely to endorse the ACA. Surgeons and procedural specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4–0.7], OR 0.6 [95 %CI, 0.5–0.9], respectively). Significant subsets of U.S. physicians express concerns about the direction of U.S. health care under recent health care reform legislation. Those opinions appear intertwined with political affiliation,type of medical specialty, as well as perceived social responsibility.

Systolic [Ca2+]i regulates diastolic levels in rat ventricular myocytes

PubMed Central

Sankaranarayanan, Rajiv; Kistamás, Kornél; Greensmith, David J.; Venetucci, Luigi A.

2017-01-01

Key points For the heart to function as a pump, intracellular calcium concentration ([Ca2+]i) must increase during systole to activate contraction and then fall, during diastole, to allow the myofilaments to relax and the heart to refill with blood.The present study investigates the control of diastolic [Ca2+]i in rat ventricular myocytes.We show that diastolic [Ca2+]i is increased by manoeuvres that decrease sarcoplasmic reticulum function. This is accompanied by a decrease of systolic [Ca2+]i such that the time‐averaged [Ca2+]i remains constant.We report that diastolic [Ca2+]i is controlled by the balance between Ca2+ entry and Ca2+ efflux during systole.The results of the present study identify a novel mechanism by which changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i. Abstract The intracellular Ca concentration ([Ca2+]i) must be sufficently low in diastole so that the ventricle is relaxed and can refill with blood. Interference with this will impair relaxation. The factors responsible for regulation of diastolic [Ca2+]i, in particular the relative roles of the sarcoplasmic reticulum (SR) and surface membrane, are unclear. We investigated the effects on diastolic [Ca2+]i that result from the changes of Ca cycling known to occur in heart failure. Experiments were performed using Fluo‐3 in voltage clamped rat ventricular myocytes. Increasing stimulation frequency increased diastolic [Ca2+]i. This increase of [Ca2+]i was larger when SR function was impaired either by making the ryanodine receptor leaky (with caffeine or ryanodine) or by decreasing sarco/endoplasmic reticulum Ca‐ATPase activity with thapsigargin. The increase of diastolic [Ca2+]i produced by interfering with the SR was accompanied by a decrease of the amplitude of the systolic Ca transient, such that there was no change of time‐averaged [Ca2+]i. Time‐averaged [Ca2+]i was increased by β‐adrenergic stimulation with isoprenaline and increased in a saturating manner with increased stimulation frequency; average [Ca2+]i was a linear function of Ca entry per unit time. Diastolic and time‐averaged [Ca2+]i were decreased by decreasing the L‐type Ca current (with 50 μm cadmium chloride). We conclude that diastolic [Ca2+]i is controlled by the balance between Ca entry and efflux during systole. Furthermore, manoeuvres that decrease the amplitude of the Ca transient (without decreasing Ca influx) will therefore increase diastolic [Ca2+]i. This identifies a novel mechanism by which changes of the amplitude of the systolic Ca transient control diastolic [Ca2+]i. PMID:28617952

New members of the A2 M ‧ M2″ structure family (A=Ca, Sr, Yb, La; M ‧ = In , Sn , Pb; M ″ = Si , Ge)

NASA Astrophysics Data System (ADS)

Jehle, Michael; Dürr, Ines; Fink, Saskia; Lang, Britta; Langenmaier, Michael; Steckhan, Julia; Röhr, Caroline

2015-01-01

The new mixed tetrelides Sr2PbGe2 and Yb2SnGe2, several mixed Ca/Sr (AII) germanides A2II (Sn, Pb)Ge2 and two polymorphs of La2 InSi2 represent new members of the general structure family of ternary alkaline-earth/lanthanoid main group silicides/germanides A2 M ‧ M2″ (M ‧ = In , Sn , Pb ; M ″ = Si , Ge). All compounds were synthesized from melts of the elements and their crystal structures have been determined by means of single crystal X-ray diffraction. Sr2PbGe2 (Cmmm, a=402.36(11), b=1542.3(4), c=463.27(10) pm) crystallizes with the Mn2AlB2 -type structure. In exhibiting infinite planar Ge zig-zag chains, it represents one border of the compound series. The other borderline case, where only [Ge2 ] dumbbells are left as Ge building units, is represented by the Ca/Yb tin germanides Ca2SnGe2 and Yb2SnGe2 (Mo2FeB2 -type; P4/mbm, a=748.58(13)/740.27(7), c=445.59(8)/435.26(5) pm). In between these two border structures compounds with variable Si/Ge chain lengths could be obtained by varying the averaged size of the AII cations: Ca0.45Sr1.55PbGe2 (new structure type; Pbam, a=791.64(5), b=2311.2(2), c=458.53(3) pm) contains planar six-membered chain segments [Ge6 ]. Tetrameric pieces [Ge4 ] are the conspicuous structure elements in Ca1.16Sr0.84SnGe2 and La2 InSi2 (La2InNi2 -type; Pbam, a=781.01(2)/762.01(13), b=1477.95(3)/1494.38(6), c=457.004(9)/442.1(3) pm). The tetragonal form of 'La2 In Si2‧ (exact composition: La2In1.07Si1.93, P4/mbm, a=1309.11(12), c=443.32(4) pm) also crystallizes in a new structure type, containing only [Si3 ] trimers as cutouts of the planar chains. In all structures the Si/Ge zig-zag chains/chain segments are connected by In/Sn/Pb atoms to form planar M layers, which are separated by pure A layers. Band structure calculations within the FP-LAPW DFT approach together with the Zintl formalism, extended by the presence of hypervalent bonding of the heavier M ‧ elements, give insight into the chemical bonding of this series of p-block metallides. An analysis of the band structure for the border phases Sr2PbGe2 and Ca2SnGe2 shows the considerable π bonding contributions within the Ge building units, which also become apparent from the short Ge-Ge bond lengths.

Patient Protection and Affordable Care Act of 2010 and children and youth with special health care needs.

PubMed

Feldman, Heidi M; Buysse, Christina A; Hubner, Lauren M; Huffman, Lynne C; Loe, Irene M

2015-04-01

The Patient Protection and Affordable Care Act (ACA) was designed to (1) decrease the number of uninsured Americans, (2) make health insurance and health care affordable, and (3) improve health outcomes and performance of the health care system. During the design of ACA, children in general and children and youth with special health care needs and disabilities (CYSHCN) were not a priority because before ACA, a higher proportion of children than adults had insurance coverage through private family plans, Medicaid, or the State Children's Health Insurance Programs (CHIP). ACA benefits CYSHCN through provisions designed to make health insurance coverage universal and continuous, affordable, and adequate. Among the limitations of ACA for CYSHCN are the exemption of plans that had been in existence before ACA, lack of national standards for insurance benefits, possible elimination or reductions in funding for CHIP, and limited experience with new delivery models for improving care while reducing costs. Advocacy efforts on behalf of CYSHCN must track implementation of ACA at the federal and the state levels. Systems and payment reforms must emphasize access and quality improvements for CYSHCN over cost savings. Developmental-behavioral pediatrics must be represented at the policy level and in the design of new delivery models to assure high quality and cost-effective care for CYSHCN.

Early Impacts of the Affordable Care Act on Health Insurance Coverage in Medicaid Expansion and Non-Expansion States.

PubMed

Courtemanche, Charles; Marton, James; Ukert, Benjamin; Yelowitz, Aaron; Zapata, Daniela

2017-01-01

The Affordable Care Act (ACA) aimed to achieve nearly universal health insurance coverage in the United States through a combination of insurance market reforms, mandates, subsidies, health insurance exchanges, and Medicaid expansions, most of which took effect in 2014. This paper estimates the causal effects of the ACA on health insurance coverage in 2014 using data from the American Community Survey. We utilize difference-in-difference-in-differences models that exploit cross-sectional variation in the intensity of treatment arising from state participation in the Medicaid expansion and local area pre-ACA uninsured rates. This strategy allows us to identify the effects of the ACA in both Medicaid expansion and non-expansion states. Our preferred specification suggests that, at the average pre-treatment uninsured rate, the full ACA increased the proportion of residents with insurance by 5.9 percentage points compared to 2.8 percentage points in states that did not expand Medicaid. Private insurance expansions from the ACA were due to increases in both employer-provided and non-group coverage. The coverage gains from the full ACA were largest for those without a college degree, non-whites, young adults, unmarried individuals, and those without children in the home. We find no evidence that the Medicaid expansion crowded out private coverage.

Divalent europium doped and un-doped calcium iodide scintillators: Scintillator characterization and single crystal growth

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

Boatner, L. A.; Ramey, J. O.; Kolopus, J. A.

2015-02-21

Initially, the alkaline-earth scintillator, CaI 2:Eu 2+, was discovered around 1964 by Hofstadter, Odell, and Schmidt. Serious practical problems quickly arose, however, that were associated with the growth of large monolithic single crystals of this material due to its lamellar, mica-like structure. As a result of its theoretically higher light yield, CaI 2:Eu 2+ has the potential to exceed the excellent scintillation performance of SrI 2:Eu 2+. In fact, theoretical predictions for the light yield of CaI2:Eu 2+ scintillators suggested that an energy resolution approaching 2% at 662 keV could be achievable. Like the early SrI 2:Eu 2+ scintillator, themore » performance of CaI 2:Eu 2+ scintillators has traditionally suffered due, at least in part, to outdated materials synthesis, component stoichiometry/purity, and single-crystal-growth techniques. Based on our recent work on SrI 2:Eu 2+ scintillators in single-crystal form, we have developed new techniques that are applied here to CaI 2:Eu 2+ and pure CaI 2 with the goal of growing large un-cracked crystals and, potentially, realizing the theoretically predicted performance of the CaI 2:Eu 2+ form of this material. Calcium iodide does not adhere to modern glassy carbon Bridgman crucibles - so there should be no differential thermal-contraction-induced crystal/crucible stresses on cooling that would result in crystal cracking of the lamellar structure of CaI 2. Here we apply glassy carbon crucible Bridgman growth, high-purity growth-charge compounds, our molten salt processing/filtration technique, and extended vacuum-melt-pumping methods to the growth of both CaI 2:Eu 2+ and un-doped CaI 2. Moreover, large scintillating single crystals were obtained, and detailed characterization studies of the scintillation properties of CaI 2:Eu 2+ and pure CaI 2 single crystals are presented that include studies of the effects of plastic deformation of the crystals on the scintillator performance.« less

A novel mechanism of tandem activation of ryanodine receptors by cytosolic and SR luminal Ca2+ during excitation-contraction coupling in atrial myocytes.

PubMed

Maxwell, Joshua T; Blatter, Lothar A

2017-06-15

In atrial myocytes excitation-contraction coupling is strikingly different from ventricle because atrial myocytes lack a transverse tubule membrane system: Ca 2+ release starts in the cell periphery and propagates towards the cell centre by Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum (SR) Ca 2+ store. The cytosolic Ca 2+ sensitivity of the ryanodine receptor (RyRs) Ca 2+ release channel is low and it is unclear how Ca 2+ release can be activated in the interior of atrial cells. Simultaneous confocal imaging of cytosolic and intra-SR calcium revealed a transient elevation of store Ca 2+ that we termed 'Ca 2+ sensitization signal'. We propose a novel paradigm of atrial ECC that is based on tandem activation of the RyRs by cytosolic and luminal Ca 2+ through a 'fire-diffuse-uptake-fire' (or FDUF) mechanism: Ca 2+ uptake by SR Ca 2+ pumps at the propagation front elevates Ca 2+ inside the SR locally, leading to luminal RyR sensitization and lowering of the cytosolic Ca 2+ activation threshold. In atrial myocytes Ca 2+ release during excitation-contraction coupling (ECC) is strikingly different from ventricular myocytes. In many species atrial myocytes lack a transverse tubule system, dividing the sarcoplasmic reticulum (SR) Ca 2+ store into the peripheral subsarcolemmnal junctional (j-SR) and the much more abundant central non-junctional (nj-SR) SR. Action potential (AP)-induced Ca 2+ entry activates Ca 2+ -induced Ca 2+ release (CICR) from j-SR ryanodine receptor (RyR) Ca 2+ release channels. Peripheral elevation of [Ca 2+ ] i initiates CICR from nj-SR and sustains propagation of CICR to the cell centre. Simultaneous confocal measurements of cytosolic ([Ca 2+ ] i ; with the fluorescent Ca 2+ indicator rhod-2) and intra-SR ([Ca 2+ ] SR ; fluo-5N) Ca 2+ in rabbit atrial myocytes revealed that Ca 2+ release from j-SR resulted in a cytosolic Ca 2+ transient of higher amplitude compared to release from nj-SR; however, the degree of depletion of j-SR [Ca 2+ ] SR was smaller than nj-SR [Ca 2+ ] SR . Similarly, Ca 2+ signals from individual release sites of the j-SR showed a larger cytosolic amplitude (Ca 2+ sparks) but smaller depletion (Ca 2+ blinks) than release from nj-SR. During AP-induced Ca 2+ release the rise of [Ca 2+ ] i detected at individual release sites of the nj-SR preceded the depletion of [Ca 2+ ] SR , and during this latency period a transient elevation of [Ca 2+ ] SR occurred. We propose that Ca 2+ release from nj-SR is activated by cytosolic and luminal Ca 2+ (tandem RyR activation) via a novel 'fire-diffuse-uptake-fire' (FDUF) mechanism. This novel paradigm of atrial ECC predicts that Ca 2+ uptake by sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA) at the propagation front elevates local [Ca 2+ ] SR , leading to luminal RyR sensitization and lowering of the activation threshold for cytosolic CICR. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Estimation of Distributed Groundwater Pumping Rates in Yolo County,CA—Intercomparison of Two Modeling Frameworks

NASA Astrophysics Data System (ADS)

Maples, S.; Fogg, G. E.; Harter, T.

2015-12-01

Accurate estimation of groundwater (GW) budgets and effective management of agricultural GW pumping remains a challenge in much of California's Central Valley (CV) due to a lack of irrigation well metering. CVHM and C2VSim are two regional-scale integrated hydrologic models that provide estimates of historical and current CV distributed pumping rates. However, both models estimate GW pumping using conceptually different agricultural water models with uncertainties that have not been adequately investigated. Here, we evaluate differences in distributed agricultural GW pumping and recharge estimates related to important differences in the conceptual framework and model assumptions used to simulate surface water (SW) and GW interaction across the root zone. Differences in the magnitude and timing of GW pumping and recharge were evaluated for a subregion (~1000 mi2) coincident with Yolo County, CA, to provide similar initial and boundary conditions for both models. Synthetic, multi-year datasets of land-use, precipitation, evapotranspiration (ET), and SW deliveries were prescribed for each model to provide realistic end-member scenarios for GW-pumping demand and recharge. Results show differences in the magnitude and timing of GW-pumping demand, deep percolation, and recharge. Discrepancies are related, in large part, to model differences in the estimation of ET requirements and representation of soil-moisture conditions. CVHM partitions ET demand, while C2VSim uses a bulk ET rate, resulting in differences in both crop-water and GW-pumping demand. Additionally, CVHM assumes steady-state soil-moisture conditions, and simulates deep percolation as a function of irrigation inefficiencies, while C2VSim simulates deep percolation as a function of transient soil-moisture storage conditions. These findings show that estimates of GW-pumping demand are sensitive to these important conceptual differences, which can impact conjunctive-use water management decisions in the CV.

Degraded Operational Environment: Integration of Social Network Infrastructure Concept in a Traditional Military C2 System

DTIC Science & Technology

2013-06-01

Communication Applet) UNIGE – D.I.M.E. Using a free application as “MIT APP Inventor” Android Software Development Kit DEGRADED C2 ICCRTS 2013...operate on an Android operating system up-gradable on which will be developed a simplified ACA ( Android Communication Applet) that will call C24U...Server) IP number . . . Portable COTS Devices ACA - C24U ( Android Communication Applet) Sending/receiving SEFL (Simple Exchange

G2(+)M study on N-alkylamino cation affinities of neutral main-group element hydrides: trends across the periodic table.

PubMed

Geng, Song; Wu, Ding-Lu; Yang, Jing; Wei, Xi-Guang; Zhu, Jun; Zhang, Hai-Bo; Ren, Yi; Lau, Kai-Chung

2014-05-08

We have made an extensive theoretical exploration of gas-phase N-alkylamino cation affinities (NAAMCA), including amino cation affinities (AMCA) and N-dimethylamino cation affinities (NDMAMCA), of neutral main-group element hydrides of groups 15-17 and periods 2-4 in the periodic table by using the G2(+)M method. Some similarities and differences are found between NAAMCA and the corresponding alkyl cation affinities (ACA) of H(n)X. Our calculations show that the AMCA and NDMAMCA are systematically lower than the corresponding proton affinities (PA) for H(n)X. In general, there is no linear correlation between NAAMCA and PA of H(n)X. Instead, the correlations exist only within the central elements X in period 2, or periods 3-4, which is significantly different from the reasonable correlations between ACA and PA for all H(n)X. NAAMCA (H(n)X) are weaker than NAAMCA (H(n-1)X(-)) by more than 700 kJ/mol and generally stronger than ACA (H(n)X), with three exceptions: H2ONR2(+)(R = H, Me) and HFNH2(+). These new findings can be rationalized by the negative hyperconjugation and Pauli repulsion.

Synthesis of novel Eu(III) luminescent probe based on 9- acridinecarboxylic acid skelton for sensing of ds-DNA.

PubMed

Azab, Hassan A; Hussein, Belal H M; El-Falouji, Abdullah I

2012-03-01

Eu(III)-9-acridinecarboxylate (9-ACA) complex was synthesized and characterized by elemental analysis, conductivity measurement, IR spectroscopy, thermal analysis, mass spectroscopy, (1)H-NMR, fluorescence and ultraviolet spectra. The results indicated that the composition of this complex is [Eu(III)-(9-ACA)(2)(NCS)(C(2)H(5)OH)(2)] 2.5 H(2)O and the oxygen of the carbonyl group coordinated to Eu(III). The interaction between the complex with nucleotides guanosine 5'- monophosphate (5'-GMP), adenosine 5'-diphosphates (5'-ADP), inosine (5'-IMP) and CT-DNA was studied by fluorescence spectroscopy. The fluorescence intensity of Eu(III)-9-acridinecarboxylate complex was enhanced with the addition of CT-DNA. The effect of pH values on the fluorescence intensity of Eu(III) complex was investigated. Under experimental conditions, the linear range was 9-50 ng mL(-1) for calf thymus DNA (CT- DNA) and the corresponding detection limit was 5 ng mL(-1). The results showed that Eu(III)-(9-ACA)(2) complex binds to CT-DNA with stability constant of 2.41 × 10(4) M.

Ca2+-regulated-cAMP/PKA signaling in cardiac pacemaker cells links ATP supply to demand.

PubMed

Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E; Spurgeon, Harold A; Sollott, Steven J; Lakatta, Edward G

2011-11-01

In sinoatrial node cells (SANC), Ca(2+) activates adenylate cyclase (AC) to generate a high basal level of cAMP-mediated/protein kinase A (PKA)-dependent phosphorylation of Ca(2+) cycling proteins. These result in spontaneous sarcoplasmic-reticulum (SR) generated rhythmic Ca(2+) oscillations during diastolic depolarization, that not only trigger the surface membrane to generate rhythmic action potentials (APs), but, in a feed-forward manner, also activate AC/PKA signaling. ATP is consumed to pump Ca(2+) to the SR, to produce cAMP, to support contraction and to maintain cell ionic homeostasis. Since feedback mechanisms link ATP-demand to ATP production, we hypothesized that (1) both basal ATP supply and demand in SANC would be Ca(2+)-cAMP/PKA dependent; and (2) due to its feed-forward nature, a decrease in flux through the Ca(2+)-cAMP/PKA signaling axis will reduce the basal ATP production rate. O(2) consumption in spontaneous beating SANC was comparable to ventricular myocytes (VM) stimulated at 3 Hz. Graded reduction of basal Ca(2+)-cAMP/PKA signaling to reduce ATP demand in rabbit SANC produced graded ATP depletion (r(2)=0.96), and reduced O(2) consumption and flavoprotein fluorescence. Neither inhibition of glycolysis, selectively blocking contraction nor specific inhibition of mitochondrial Ca(2+) flux reduced the ATP level. Feed-forward basal Ca(2+)-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca(2+)-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes. Published by Elsevier Ltd.

Photocopy of drawing located at National Archives, San Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, San Bruno, California (Navy # 110-A-14 of 5. Scofiled Construction Company Mare Island office, Mare Island Cal. Louvers details; September 2, 1908. - Mare Island Naval Shipyard, Pump House, California Avenue, east side between Dry Dock 1 & Dry Dock 2, near Ninth Street, Vallejo, Solano County, CA

Interaction of cardiac troponin with cardiotonic drugs: a structural perspective.

PubMed

Li, Monica X; Robertson, Ian M; Sykes, Brian D

2008-04-25

Over the 40 years since its discovery, many studies have focused on understanding the role of troponin as a myofilament based molecular switch in regulating the Ca(2+)-dependent activation of striated muscle contraction. Recently, studies have explored the role of cardiac troponin as a target for cardiotonic agents. These drugs are clinically useful for treating heart failure, a condition in which the heart is no longer able to pump enough blood to other organs. These agents act via a mechanism that modulates the Ca(2+)-sensitivity of troponin; such a mode of action is therapeutically desirable because intracellular Ca(2+) concentration is not perturbed, preserving the regulation of other Ca(2+)-based signaling pathways. This review describes molecular details of the interaction of cardiac troponin with a variety of cardiotonic drugs. We present recent structural work that has identified the docking sites of several cardiotonic drugs in the troponin C-troponin I interface and discuss their relevance in the design of troponin based drugs for the treatment of heart disease.

The Affordable Care Act and Diabetes Diagnosis and Care: Exploring the Potential Impacts

PubMed Central

Laiteerapong, Neda

2016-01-01

This article reviews available data on the implications of the Affordable Care Act (ACA) for the diagnosis and care of type 2 diabetes. We provide a general overview of the major issues for diabetes diagnosis and care, and describe the policies in the ACA that affect diabetes diagnosis and care. We also estimate that approximately 2.3 million of the 4.6 million people in the USA with undiagnosed diabetes aged 18–64 in 2009–2010 may have gained access to free preventive care under the ACA, which could increase diabetes detection. In addition, we note two factors that may limit the success of the ACA for improving access to diabetes care. First, many states with the highest diabetes prevalence have not expanded Medicaid eligibility, and second, primary care providers may not adequately meet the increase in Medicaid patients because federal funding to increase provider reimbursement for Medicaid visits recently expired. We close by discussing current gaps in the literature and future directions for research on the ACA’s impact on diabetes diagnosis, care, and health outcomes. PMID:26892908

Ca2+ handling remodeling and STIM1L/Orai1/TRPC1/TRPC4 upregulation in monocrotaline-induced right ventricular hypertrophy.

PubMed

Jessica, Sabourin; Angèle, Boet; Catherine, Rucker-Martin; Mélanie, Lambert; Ana-Maria, Gomez; Jean-Pierre, Benitah; Frédéric, Perros; Marc, Humbert; Fabrice, Antigny

2018-05-01

Right ventricular (RV) function is the most important prognostic factor for pulmonary arterial hypertension (PAH) patients. The progressive increase of pulmonary vascular resistance induces RV hypertrophy (RVH) and at term RV failure (RVF). However, the molecular mechanisms of RVH and RVF remain understudied. In this study, we gained insights into cytosolic Ca 2+ signaling remodeling in ventricular cardiomyocytes during the pathogenesis of severe pulmonary hypertension (PH) induced in rats by monocrotaline (MCT) exposure, and we further identified molecular candidates responsible for this Ca 2+ remodeling. After PH induction, hypertrophied RV myocytes presented longer action potential duration, higher and faster [Ca 2+ ] i transients and increased sarcoplasmic reticulum (SR) Ca 2+ content, whereas no changes in these parameters were detected in left ventricular (LV) myocytes. These modifications were associated with increased P-Ser 16 -phospholamban pentamer expression without altering SERCA2a (Sarco/Endoplasmic Reticulum Ca 2+ -ATPase) pump abundance. Moreover, after PH induction, Ca 2+ sparks frequency were higher in hypertrophied RV cells, while total RyR2 (Ryanodine Receptor) expression and phosphorylation were unaffected. Together with cellular hypertrophy, the T-tubules network was disorganized. Hypertrophied RV cardiomyocytes from MCT-exposed rats showed decreased expression of classical STIM1 (Stromal Interaction molecule) associated with increased expression of muscle-specific STIM1 Long isoform, glycosylated-Orai1 channel form, and TRPC1 and TRPC4 channels, which was correlated with an enhanced Ca 2+ -release-activated Ca 2+ (CRAC)-like current. Pharmacological inhibition of TRPCs/Orai1 channels in hypertrophied RV cardiomyocytes normalized [Ca 2+ ] i transients amplitude, the SR Ca 2+ content and cell contractility to control levels. Finally, we showed that most of these changes did not appear in LV cardiomyocytes. These new findings demonstrate RV-specific cellular Ca 2+ cycling remodeling in PH rats with maladaptive RVH and that the STIM1L/Orai1/TRPC1/C4-dependent Ca 2+ current participates in this Ca 2+ remodeling in RVH secondary to PH. Copyright © 2018 Elsevier Ltd. All rights reserved.

Elimination of cost-sharing and receipt of screening for colorectal and breast cancer.

PubMed

Fedewa, Stacey A; Goodman, Michael; Flanders, W Dana; Han, Xuesong; Smith, Robert A; M Ward, Elizabeth; Doubeni, Chyke A; Sauer, Ann Goding; Jemal, Ahmedin

2015-09-15

The aim of the cost-sharing provision of the Patient Protection and Affordable Care Act (ACA) was to reduce financial barriers for preventive services, including screening for colorectal cancer (CRC) and breast cancer (BC) among privately and Medicare-insured individuals. Whether the provision has affected CRC and BC screening prevalence is unknown. The current study investigated whether CRC and BC screening prevalence among privately and Medicare-insured adults by socioeconomic status (SES) changed before and after the ACA. Data obtained from the National Health Interview Survey pertaining to privately and Medicare-insured adults from 2008 (before the ACA) and 2013 (after the ACA) were used. There were 15,786 adults aged 50 to 75 years in the CRC screening analysis and 14,530 women aged ≥40 years in the BC screening analysis. Changes in guideline-recommended screening between 2008 and 2013 by SES were expressed as the prevalence difference (PD) and 95% confidence interval (95% CI) adjusted for demographics, insurance, income, education, body mass index, and having a usual provider. Overall, CRC screening prevalence increased from 57.3% to 61.2% between 2008 and 2013 (P<.001). Adjusted CRC screening prevalence during the corresponding period increased in low-income (PD, 5.9; 95% CI, 1.8 to 10.2), least-educated (PD, 7.2; 95% CI, 0.9 to 13.5), and Medicare-insured (PD, 6.2; 95% CI, 1.7 to 10.7) individuals, but not in high-income, most-educated, and privately insured respondents. BC screening remained unchanged overall (70.5% in 2008 vs 70.2% in 2013) and in the low SES groups. Increases in CRC screening prevalence between 2008 and 2013 were confined to respondents with low SES. These findings may in part reflect the ACA's removal of financial barriers. © 2015 American Cancer Society.

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

Cancer Preventive Services, Socioeconomic Status and the Affordable Care Act

PubMed Central

Cooper, Gregory S; Kou, Tzuyung Doug; Dor, Avi; Koroukian, Siran M; Schluchter, Mark D

2016-01-01

Background Out of pocket expenditures are thought to be an important barrier to receipt of cancer preventive services, especially among lower socioeconomic status (SES). The Affordable Care Act (ACA) eliminated out-of-pocket expenditures for recommended services, including mammography and colonoscopy. Our objective was to determine changes in uptake of mammography and colonoscopy among fee-for-service Medicare beneficiaries before and after ACA implementation. Methods Using Medicare claims data, we identified women ≥ 70 without mammography in the previous 2 years, and men and women ≥ 70 at increased risk for colorectal cancer without colonoscopy in the past 5 years. We identified procedure receipt in the two-year period prior to ACA implementation (2009-2010) and after implementation (2011-September 2012). Multivariable generalized estimating equation models determine the independent association of and county-level quartile of median income and education with receipt of testing. Results For mammography, lower SES quartile was associated with less uptake but the post-ACA disparities were smaller compared to the pre-ACA period. In addition, mammography rates increased from pre- to post-ACA in all SES quartiles. For colonoscopy, in both the pre- and post-ACA periods, there was an association between uptake and educational level and to some extent, income. However, there were no appreciable changes with colonoscopy and SES following the ACA. Conclusions Removal of out-of-pocket expenditures may overcome a barrier to receipt of recommended preventive services but for colonoscopy, other procedural factors may remain as deterrents. PMID:28067955

Combining native MS approaches to decipher archaeal box H/ACA ribonucleoprotein particle structure and activity.

PubMed

Saliou, Jean-Michel; Manival, Xavier; Tillault, Anne-Sophie; Atmanene, Cédric; Bobo, Claude; Branlant, Christiane; Van Dorsselaer, Alain; Charpentier, Bruno; Cianférani, Sarah

2015-08-01

Site-specific isomerization of uridines into pseudouridines in RNAs is catalyzed either by stand-alone enzymes or by box H/ACA ribonucleoprotein particles (sno/sRNPs). The archaeal box H/ACA sRNPs are five-component complexes that consist of a guide RNA and the aCBF5, aNOP10, L7Ae, and aGAR1 proteins. In this study, we performed pairwise incubations of individual constituents of archaeal box H/ACA sRNPs and analyzed their interactions by native MS to build a 2D-connectivity map of direct binders. We describe the use of native MS in combination with ion mobility-MS to monitor the in vitro assembly of the active H/ACA sRNP particle. Real-time native MS was used to monitor how box H/ACA particle functions in multiple-turnover conditions. Native MS also unambiguously revealed that a substrate RNA containing 5-fluorouridine (f(5) U) was hydrolyzed into 5-fluoro-6-hydroxy-pseudouridine (f(5) ho(6) Ψ). In terms of enzymatic mechanism, box H/ACA sRNP was shown to catalyze the pseudouridylation of a first RNA substrate, then to release the RNA product (S22 f(5) ho(6) ψ) from the RNP enzyme and reload a new substrate RNA molecule. Altogether, our native MS-based approaches provide relevant new information about the potential assembly process and catalytic mechanism of box H/ACA RNPs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cation interdependency in acute stressor states.

PubMed

Khan, M Usman; Komolafe, Babatunde O; Weber, Karl T

2013-05-01

Acute stressor states are inextricably linked to neurohormonal activation which includes the adrenergic nervous system. Consequent elevations in circulating epinephrine and norepinephrine unmask an interdependency that exists between K+, Mg2+ and Ca2+. Catecholamines, for example, regulate the large number of Mg2+-dependent Na/K ATPase pumps present in skeletal muscle. A hyperadrenergic state accounts for a sudden translocation of K+ into muscle and rapid appearance of hypokalemia. In the myocardium, catecholamines promote Mg2+ efflux from cardiomyocytes, whereas intracellular Ca2+ influx and overloading account for the induction of oxidative stress and necrosis of these cells with leakage of their contents, including troponins. Accordingly, acute stressor states can be accompanied by nonischemic elevations in serum troponins, together with the concordant appearance of hypokalemia, hypomagnesemia and ionized hypocalcemia, causing a delay in myocardial repolarization and electrocardiographic QTc prolongation raising the propensity for arrhythmias, including atrial fibrillation and polymorphic ventricular tachycardia. In this review, we focus on the interdependency between K+, Mg2+ and Ca2+ which are clinically relevant to acute stressor states.

Predictors of anonymous cyber aggression: the role of adolescents' beliefs about anonymity, aggression, and the permanency of digital content.

PubMed

Wright, Michelle F

2014-07-01

Little attention has been given to whether adolescents' beliefs about anonymity and their normative beliefs about cyber aggression jointly increase their perpetration of cyber aggression. To this end, the present longitudinal study examined the moderating influence of these variables on the relationships among adolescents' attitudes toward the permanency of digital content, confidence with not getting caught, and anonymous cyber aggression (ACA) assessed 1 year later (Time 2). These associations were examined among 274 7th and 8th graders and through five technologies, including social networking sites (SNS), e-mail, instant messenger (IM), mobile phones, and chatrooms. Findings indicated that increases in Time 2 ACA and attitudes toward the permanency of digital content were more strongly related when adolescents reported greater confidence with not getting caught and higher normative beliefs concerning cyber aggression through SNS and mobile phones. In addition, higher levels of attitudes toward the permanency of digital content, confidence with not getting caught, beliefs about anonymity, and normative beliefs regarding cyber aggression were related to greater Time 2 ACA through e-mail, IM, and chatrooms. All findings are discussed in the context of adolescents' positive attitudes toward ACA, and an appeal for additional research is made to understand more about anonymity in cyberspace.

The role of East Asian monsoon system in shaping population divergence and dynamics of a constructive desert shrub Reaumuria soongarica

PubMed Central

Yin, Hengxia; Yan, Xia; Shi, Yong; Qian, Chaoju; Li, Zhonghu; Zhang, Wen; Wang, Lirong; Li, Yi; Li, Xiaoze; Chen, Guoxiong; Li, Xinrong; Nevo, Eviatar; Ma, Xiao-Fei

2015-01-01

Both of the uplift of Qinghai-Tibet Plateau (QTP) and the development of East Asian monsoon system (EAMS) could have comprehensively impacted the formation and evolution of Arid Central Asia (ACA). To understand how desert plants endemic to ACA responded to these two factors, we profiled the historical population dynamics and distribution range shift of a constructive desert shrub Reaumuria soongarica (Tamaricaceae) based on species wide investigation of sequence variation of chloroplast DNA and nuclear ribosomal ITS. Phylogenetic analysis uncovered a deep divergence occurring at ca. 2.96 Mya between the western and eastern lineages of R. soongarica, and ecological niche modeling analysis strongly supported that the monsoonal climate could have fragmented its habitats in both glacial and interglacial periods and impelled its intraspecific divergence. Additionally, the population from the east monsoonal zone expanded rapidly, suggesting that the local monsoonal climate significantly impacted its population dynamics. The isolation by distance tests supported strong maternal gene flow along the direction of the East Asian winter monsoon, whose intensification induced the genetic admixture along the latitudinal populations of R. soongarica. Our results presented a new case that the development of EAMS had prominently impacted the intraspecific divergence and population dynamics of this desert plant. PMID:26510579

Characterization of NAADP-mediated calcium signaling in human spermatozoa

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

Sánchez-Tusie, A.A.; Vasudevan, S.R.; Churchill, G.C.

Highlights: •Human sperm cells synthesize NAADP. •NAADP-AM mediates [Ca{sup 2+}]{sub i} increases in human sperm in the absence of [Ca{sup 2+}]{sub o}. •Human sperm have two acidic compartments located in the head and midpiece. -- Abstract: Ca{sup 2+} signaling in spermatozoa plays a crucial role during processes such as capacitation and release of the acrosome, but the underlying molecular mechanisms still remain unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca{sup 2+}-releasing second messenger in a variety of cellular processes. The presence of a NAADP synthesizing enzyme in sea urchin sperm has been previously reported, suggesting a possiblemore » role of NAADP in sperm Ca{sup 2+} signaling. In this work we used in vitro enzyme assays to show the presence of a novel NAADP synthesizing enzyme in human sperm, and to characterize its sensitivity to Ca{sup 2+} and pH. Ca{sup 2+} fluorescence imaging studies demonstrated that the permeable form of NAADP (NAADP-AM) induces intracellular [Ca{sup 2+}] increases in human sperm even in the absence of extracellular Ca{sup 2+}. Using LysoTracker®, a fluorescent probe that selectively accumulates in acidic compartments, we identified two such stores in human sperm cells. Their acidic nature was further confirmed by the reduction in staining intensity observed upon inhibition of the endo-lysosomal proton pump with Bafilomycin, or after lysosomal bursting with glycyl-L-phenylalanine-2-naphthylamide. The selective fluorescent NAADP analog, Ned-19, stained the same subcellular regions as LysoTracker®, suggesting that these stores are the targets of NAADP action.« less

Intracellular Ca2+ regulation by the leech giant glial cell.

PubMed

Nett, W; Deitmer, J W

1998-02-15

1. We have measured the intracellular Ca2+ concentration, [Ca2+]i, and the intracellular Na+ concentration, [Na+]i, with the fluorescent dyes fura-2 (for Ca2+) and SBFI (for Na+) in situ in giant glial cells of the central nervous system of the leech Hirudo medicinalis. 2. The basal [Ca2+]i was 79 +/- 35 nM (n = 27) in cells voltage clamped at -70 to -80 mV, and 75 +/- 29 nM (mean +/- S.D., n = 82) in unclamped cells at a mean membrane potential of -67 +/- 6 mV. 3. Removal of external Na+ evoked a small reversible [Ca2+]i increase of 29 +/- 21 nM (n = 27) in cells voltage clamped at -70 to -80 mV, and of 35 +/- 18 nM (n = 37) in unclamped cells. This [Ca2+]i increase, and the time constant of the subsequent [Ca2+]i recovery after Na+ re-addition, did not change significantly with the holding potential between -110 and -60 mV. 4. The basal [Na+]i was 5.6 +/- 1.3 mM (n = 18). Increasing [Na+]i by inhibiting the Na+-K+ pump with 100 microM ouabain had no effect on the [Ca2+]i rise upon removal of external Na+. 5. The time course of recovery from a [Ca2+]i load mediated by voltage-dependent Ca2+ influx during depolarization in high K+ was unaffected by the removal of external Na+. 6. Cyclopiazonic acid (10 muM), an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a transient increase in [Ca2+]i of 28 +/- 11 nM (n = 5), and significantly slowed the recovery from imposed [Ca2+]i loads. 7. Iontophoretic injection of orthovanadate, an inhibitor of P-type ATPases including the plasma membrane Ca2+-ATPase, caused a persistent increase in the basal [Ca2+]i of 163 +/- 101 nM (n = 5) in standard saline, and of 427 +/- 338 nM in Na+-free saline (n = 5). Vanadate injection significantly slowed the recovery from [Ca2+]i loads. Removal of external Na+ during vanadate injection induced an additional, reversible [Ca2+]i increase of 254 +/- 64 nM (n = 3). 8. The results suggest that the low basal [Ca2+]i in these glial cells is predominantly maintained by a Ca2+-ATPase in the plasma membrane. This ATPase is also the main Ca2+ extruder after an intracellular Ca2+ load, while intracellular stores appear to contribute little to this recovery. A Na+-Ca2+ exchanger seems to play a minor role in the maintenance of basal [Ca2+]i in these cells, but becomes prominent when the plasma membrane Ca2+-ATPase is blocked.

1. Credit USAF, ca. 1942. Original housed in the Muroc ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Credit USAF, ca. 1942. Original housed in the Muroc Flight Test Base, Unit History, 1 September 1942 - 30 June 1945. Alfred F. Simpson Historical Research Agency. United States Air Force. Maxwell AFB, Alabama. Historical view looks west southwest at construction of Building 4317, Deluge Water Pumping Station (then designated Pump House No. 3). This in-ground structure houses fire pumps which draw water from an in-ground reservoir, Building 4316 (See HAER photos CA-170-I). Pumping station was built in-ground to take advantage of gravity, since water flows from reservoir to prime the pumps, and fire system piping is underground. Opening in far wall is to stairs leading up to ground level. Earth mound in background is part of water reservoir construction (Building 4316). - Edwards Air Force Base, North Base, Deluge Water Pumping Station, Near Second & D Streets, Boron, Kern County, CA

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

Nakata, Kouhei; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp

Purpose: This study was designed to compare the strength among bone marrow nails created to treat long bone fractures using interventional procedures. Methods: Twelve resected intact tibiae of healthy swine were used. A circumferential bone fracture was made in nine tibiae and restored with the following created bone marrow nails: acrylic cement alone (ACA) (n = 3), acrylic-cement-filled bare metallic stent (AC-FBMS) (n = 3), and acrylic-cement-filled covered metallic (AC-FCMS) stent (n = 3). The remaining intact tibiae (n = 3) were used as controls. Results: A bone marrow nail was successfully achieved within 30 min in all swine. Themore » maximum injection volume of acrylic cement for creating ACA, AC-FBMS, and AC-FCMS was 1.7 {+-} 0.3, 3.2 {+-} 0.4, and 2.9 {+-} 0.4 mL, respectively. The thickness of bone marrow nail created in the ACA, AC-FBMS, and AC-FCMS groups was 3.6 {+-} 1.0, 10.3 {+-} 0.26, and 9.6 {+-} 0.32 mm, respectively (AC-FBMS group versus AC-FCMS group, p = 0.038), probably because of leakage of acrylic cement surrounding the interstices. The maximum bending power (kilonewton) and bending strength (newton/mm{sup 2}) in the normal long bone, ACA, AC-FBMS, and AC-FCMS groups were: 1.70 {+-} 0.25 and 79.2 {+-} 16.1; 0.21 {+-} 0.11 and 8.8 {+-} 2.8; 0.46 {+-} 0.06 and 18.2 {+-} 1.6; and 0.18 {+-} 0.04 and 7.8 {+-} 2.7, respectively. Conclusions: Although the maximum bending power and bending strength of AC-FBMS were not satisfactory, it was the most robust of the three marrow nails for restoring fractured long bone.« less

Function of a STIM1 Homologue in C. elegans: Evidence that Store-operated Ca2+ Entry Is Not Essential for Oscillatory Ca2+ Signaling and ER Ca2+ Homeostasis

PubMed Central

Yan, Xiaohui; Xing, Juan; Lorin-Nebel, Catherine; Estevez, Ana Y.; Nehrke, Keith; Lamitina, Todd; Strange, Kevin

2006-01-01

1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling regulates gonad function, fertility, and rhythmic posterior body wall muscle contraction (pBoc) required for defecation in Caenorhabditis elegans. Store-operated Ca2+ entry (SOCE) is activated during endoplasmic reticulum (ER) Ca2+ store depletion and is believed to be an essential and ubiquitous component of Ca2+ signaling pathways. SOCE is thought to function to refill Ca2+ stores and modulate Ca2+ signals. Recently, stromal interaction molecule 1 (STIM1) was identified as a putative ER Ca2+ sensor that regulates SOCE. We cloned a full-length C. elegans stim-1 cDNA that encodes a 530–amino acid protein with ∼21% sequence identity to human STIM1. Green fluorescent protein (GFP)–tagged STIM-1 is expressed in the intestine, gonad sheath cells, and spermatheca. Knockdown of stim-1 expression by RNA interference (RNAi) causes sterility due to loss of sheath cell and spermatheca contractile activity required for ovulation. Transgenic worms expressing a STIM-1 EF-hand mutant that constitutively activates SOCE in Drosophila and mammalian cells are sterile and exhibit severe pBoc arrhythmia. stim-1 RNAi dramatically reduces STIM-1∷GFP expression, suppresses the EF-hand mutation–induced pBoc arrhythmia, and inhibits intestinal store-operated Ca2+ (SOC) channels. However, stim-1 RNAi surprisingly has no effect on pBoc rhythm, which is controlled by intestinal oscillatory Ca2+ signaling, in wild type and IP3 signaling mutant worms, and has no effect on intestinal Ca2+ oscillations and waves. Depletion of intestinal Ca2+ stores by RNAi knockdown of the ER Ca2+ pump triggers the ER unfolded protein response (UPR). In contrast, stim-1 RNAi fails to induce the UPR. Our studies provide the first detailed characterization of STIM-1 function in an intact animal and suggest that SOCE is not essential for certain oscillatory Ca2+ signaling processes and for maintenance of store Ca2+ levels in C. elegans. These findings raise interesting and important questions regarding the function of SOCE and SOC channels under normal and pathophysiological conditions. PMID:16966474

Function of a STIM1 homologue in C. elegans: evidence that store-operated Ca2+ entry is not essential for oscillatory Ca2+ signaling and ER Ca2+ homeostasis.

PubMed

Yan, Xiaohui; Xing, Juan; Lorin-Nebel, Catherine; Estevez, Ana Y; Nehrke, Keith; Lamitina, Todd; Strange, Kevin

2006-10-01

1,4,5-trisphosphate (IP(3))-dependent Ca(2+) signaling regulates gonad function, fertility, and rhythmic posterior body wall muscle contraction (pBoc) required for defecation in Caenorhabditis elegans. Store-operated Ca(2+) entry (SOCE) is activated during endoplasmic reticulum (ER) Ca(2+) store depletion and is believed to be an essential and ubiquitous component of Ca(2+) signaling pathways. SOCE is thought to function to refill Ca(2+) stores and modulate Ca(2+) signals. Recently, stromal interaction molecule 1 (STIM1) was identified as a putative ER Ca(2+) sensor that regulates SOCE. We cloned a full-length C. elegans stim-1 cDNA that encodes a 530-amino acid protein with approximately 21% sequence identity to human STIM1. Green fluorescent protein (GFP)-tagged STIM-1 is expressed in the intestine, gonad sheath cells, and spermatheca. Knockdown of stim-1 expression by RNA interference (RNAi) causes sterility due to loss of sheath cell and spermatheca contractile activity required for ovulation. Transgenic worms expressing a STIM-1 EF-hand mutant that constitutively activates SOCE in Drosophila and mammalian cells are sterile and exhibit severe pBoc arrhythmia. stim-1 RNAi dramatically reduces STIM-1GFP expression, suppresses the EF-hand mutation-induced pBoc arrhythmia, and inhibits intestinal store-operated Ca(2+) (SOC) channels. However, stim-1 RNAi surprisingly has no effect on pBoc rhythm, which is controlled by intestinal oscillatory Ca(2+) signaling, in wild type and IP(3) signaling mutant worms, and has no effect on intestinal Ca(2+) oscillations and waves. Depletion of intestinal Ca(2+) stores by RNAi knockdown of the ER Ca(2+) pump triggers the ER unfolded protein response (UPR). In contrast, stim-1 RNAi fails to induce the UPR. Our studies provide the first detailed characterization of STIM-1 function in an intact animal and suggest that SOCE is not essential for certain oscillatory Ca(2+) signaling processes and for maintenance of store Ca(2+) levels in C. elegans. These findings raise interesting and important questions regarding the function of SOCE and SOC channels under normal and pathophysiological conditions.

Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban.

PubMed

Fechner, H; Suckau, L; Kurreck, J; Sipo, I; Wang, X; Pinkert, S; Loschen, S; Rekittke, J; Weger, S; Dekkers, D; Vetter, R; Erdmann, V A; Schultheiss, H-P; Paul, M; Lamers, J; Poller, W

2007-02-01

Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.

Higgs Mode in the d -Wave Superconductor Bi2Sr2CaCu2O8 +x Driven by an Intense Terahertz Pulse

NASA Astrophysics Data System (ADS)

Katsumi, Kota; Tsuji, Naoto; Hamada, Yuki I.; Matsunaga, Ryusuke; Schneeloch, John; Zhong, Ruidan D.; Gu, Genda D.; Aoki, Hideo; Gallais, Yann; Shimano, Ryo

2018-03-01

We investigate the terahertz (THz)-pulse-driven nonlinear response in the d -wave cuprate superconductor Bi2Sr2CaCu2O8 +x (Bi2212) using a THz pump near-infrared probe scheme in the time domain. We observe an oscillatory behavior of the optical reflectivity that follows the THz electric field squared and is markedly enhanced below Tc . The corresponding third-order nonlinear effect exhibits both A1 g and B1 g symmetry components, which are decomposed from polarization-resolved measurements. A comparison with a BCS calculation of the nonlinear susceptibility indicates that the A1 g component is associated with the Higgs mode of the d -wave order parameter.

Higgs Mode in the d -Wave Superconductor Bi 2 Sr 2 CaCu 2 O 8 + x Driven by an Intense Terahertz Pulse

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

Katsumi, Kota; Tsuji, Naoto; Hamada, Yuki I.

We investigated the terahertz (THz)-pulse driven nonlinear response in the d-wave cuprate superconductor Bi 2Sr 2CaCu 2O 8+x (Bi2212) using a THz pump near-infrared probe scheme in the time domain. We have observed an oscillatory behavior of the optical reflectivity that follows the THz electric field squared and is strongly enhanced below Tc. The corresponding third-order nonlinear effect exhibits both A 1g and B 1g symmetry components, which are decomposed from polarization-resolved measurements. Comparison with a BCS calculation of the nonlinear susceptibility indicates that the A 1g component is associated with the Higgs mode of the d-wave order parameter.

Higgs Mode in the d -Wave Superconductor Bi 2 Sr 2 CaCu 2 O 8 + x Driven by an Intense Terahertz Pulse

DOE PAGES

Katsumi, Kota; Tsuji, Naoto; Hamada, Yuki I.; ...

2018-03-14

We investigated the terahertz (THz)-pulse driven nonlinear response in the d-wave cuprate superconductor Bi 2Sr 2CaCu 2O 8+x (Bi2212) using a THz pump near-infrared probe scheme in the time domain. We have observed an oscillatory behavior of the optical reflectivity that follows the THz electric field squared and is strongly enhanced below Tc. The corresponding third-order nonlinear effect exhibits both A 1g and B 1g symmetry components, which are decomposed from polarization-resolved measurements. Comparison with a BCS calculation of the nonlinear susceptibility indicates that the A 1g component is associated with the Higgs mode of the d-wave order parameter.

Multiple effects of ryanodine on intracellular free Ca2+ in smooth muscle cells from bovine and porcine coronary artery: modulation of sarcoplasmic reticulum function.

PubMed

Wagner-Mann, C; Hu, Q; Sturek, M

1992-04-01

1. The effects of ryanodine and caffeine on intracellular free Ca2+ concentration ([Ca2+]i) were studied by use of fura-2 microfluorometry in single smooth muscle cells freshly dispersed from bovine and porcine coronary artery. 2. Bovine and porcine cells demonstrated similar sensitivities to 10 min of exposure to ryanodine in physiological salt solution (PSS), as determined by comparable dose-dependent decreases in the subsequent [Ca2+]i transient induced by 5 mM caffeine. 3. Ryanodine (10 microM) caused a significant increase in [Ca2+]i to a plateau level 27 +/- 3% and 38 +/- 4% above baseline [Ca2+]i (baseline [Ca2+]i = [Ca2+]i at 0 min) in porcine and bovine cells, respectively, when bathed in PSS. In bovine cells the time required to reach 1/2 the plateau level was only 3 min versus 6 min for porcine cells. 4. The ryanodine-induced plateau increase in [Ca2+]i was 35 +/- 5% above baseline for bovine cells bathed in 0 Ca PSS (PSS including 10 microM EGTA with no added Ca2+), but only 7 +/- 3% above baseline in porcine cells during 10 min exposure to 10 microM ryanodine. In bovine cells [Ca2+]i showed proportional increases when extracellular Ca2+ was increased from the normal 2 mM Ca2+ PSS to 5 and 10 mM. 5. Cells pretreated with caffeine in 0 Ca PSS, which depleted the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, showed no increase in [Ca2+]i when challenged with 10 microM ryanodine. The ryanodine-associated increase in [Ca2+]i, which was sustained in 0 Ca PSS during the 10 min ryanodine exposure in cells not pretreated with caffeine, suggests that ryanodine releases Ca2+ from the sarcoplasmic reticulum, but also inhibits Ca2+ efflux.6. Intracellular free Ba2+ ([Ba24],) was measured with fura-2 microfluorometry to define further the Ca2" efflux pathway inhibited by ryanodine; specifically, Ba2+ is not transported by the Ca2" pump, but will substitute for Ca2" in Na+-Ca24 exchange. In porcine cells pretreated with caffeine in 0 Ca PSS to deplete the caffeine-sensitive sarcoplasmic reticulum Ca2+ store, depolarization with 80 mM K4 in 2 mM external Ba24 caused a 100 +/- 6% increase in fura-2 fluorescence ([Ba2+]j). During the 17.5 min 0 Ca PSS recovery from depolarization, exposure to 10 microM ryanodine inhibited the removal of [Ba24]i by 69 + 3% when compared with control (0 Ca PSS without ryanodine).7. It was concluded that in bovine and porcine smooth muscle cells: (a) ryanodine (> 10 microM) releases Ca24 from the sarcoplasmic reticulum; (b) ryanodine ( 10O microM) decreases Ca24 efflux, probably by inhibition of Na+-Ca2+ exchange; (c) the sarcoplasmic reticulum Ca24 store may be larger in bovine than in porcine smooth muscle cells; thus, porcine cells have a relatively greater reliance on Ca24 influx to increase [Ca2+]i.

Cinnamic acid shortens the period of the circadian clock in mice.

PubMed

Oishi, Katsutaka; Yamamoto, Saori; Oike, Hideaki; Ohkura, Naoki; Taniguchi, Masahiko

2017-03-01

Cinnamic acid (CA) derivatives have recently received focus due to their anticancer, antioxidant, and antidiabetic properties. The present study aimed to determine the effects of cinnamic acid on the circadian clock, which is a cell-autonomous endogenous system that generates circadian rhythms that govern the behavior and physiology of most organisms. Cinnamic acid significantly shortened the circadian period of PER2::LUC expression in neuronal cells that differentiated from neuronal progenitor cells derived from PER2::LUC mouse embryos. Cinnamic acid did not induce the transient mRNA expression of clock genes such as Per1 and Per2 in neuronal cells, but significantly shortened the half-life of PER2::LUC protein in neuronal cells incubated with actinomycin D, suggested that CA post-transcriptionally affects the molecular clock by decreasing Per2 mRNA stability. A continuous infusion of CA into mice via an Alzet osmotic pump under constant darkness significantly shortened the free-running period of wheel-running rhythms. These findings suggest that CA shortens the circadian period of the molecular clock in mammals.

Growth, spectroscopic properties and laser output of Er : Ca 4YO(BO 3) 3 and Er : Yb : Ca 4YO(BO 3) 3 crystals

NASA Astrophysics Data System (ADS)

Zhang, Huaijin; Meng, Xianlin; Wang, Changqing; Wang, Pu; Zhu, Li; Liu, Xuesong; Dong, Chunming; Yang, Yuyong; Cheng, Ruiping; Dawes, Judith; Piper, Jim; Zhang, Shaojun; Sun, Lianke

2000-09-01

In this paper, Er : Ca 4YO(BO 3) 3 (Er : YCOB) and Er : Yb : Ca 4YO(BO 3) 3 (Er : Yb : YCOB) crystals with large size and excellent quality have been grown by the Czochralski method. The absorption and emission spectra of Er : YCOB and Er : Yb : YCOB crystals have been measured; the emission spectrum of Er : Yb : YCOB crystal shows that the strongest emission peak is located at 1537 nm. An output power of about 2 mW at the wavelength of 1553 nm has been obtained under the pumping power of a fiber-coupled laser diode (LD) of 1600 mW at 976 nm, using a Y direction cut 2.5 mm thick Er : Yb : YCOB crystal sample.

Dispersed-fluorescence spectroscopy of jet-cooled calcium ethoxide radical (CaOC2H5)

NASA Astrophysics Data System (ADS)

Paul, Anam C.; Reza, Md. Asmaul; Liu, Jinjun

2016-12-01

Dispersed fluorescence (DF) spectra of the calcium ethoxide radical (CaOC2H5) have been obtained by pumping the A˜1 2 A‧ ←X˜2A‧ and the A˜2 2 A‧‧ ←X˜2A‧ origin bands in its laser-induced fluorescence spectrum. Dominant transitions in the vibrationally resolved DF spectra are well reproduced using Franck-Condon factors predicted by complete active space self-consistent field (CASSCF) calculations. Collision-induced population transfer between the A˜1 2 A‧ and the A22 A‧‧ states results in additional peaks in the experimental DF spectra. Differences between the intensities of vibronic bands in the A˜1 2 A‧ →X˜2A‧ and the A˜2 2 A‧‧ →X˜2A‧ DF spectra are attributed to different symmetries of the two excited electronic states.

Patient Protection and Affordable Care Act of 2010 and Children and Youth With Special Health Care Needs

PubMed Central

Buysse, Christina A.; Hubner, Lauren M.; Huffman, Lynne C.; Loe, Irene M.

2015-01-01

ABSTRACT: The Patient Protection and Affordable Care Act (ACA) was designed to (1) decrease the number of uninsured Americans, (2) make health insurance and health care affordable, and (3) improve health outcomes and performance of the health care system. During the design of ACA, children in general and children and youth with special health care needs and disabilities (CYSHCN) were not a priority because before ACA, a higher proportion of children than adults had insurance coverage through private family plans, Medicaid, or the State Children's Health Insurance Programs (CHIP). ACA benefits CYSHCN through provisions designed to make health insurance coverage universal and continuous, affordable, and adequate. Among the limitations of ACA for CYSHCN are the exemption of plans that had been in existence before ACA, lack of national standards for insurance benefits, possible elimination or reductions in funding for CHIP, and limited experience with new delivery models for improving care while reducing costs. Advocacy efforts on behalf of CYSHCN must track implementation of ACA at the federal and the state levels. Systems and payment reforms must emphasize access and quality improvements for CYSHCN over cost savings. Developmental-behavioral pediatrics must be represented at the policy level and in the design of new delivery models to assure high quality and cost-effective care for CYSHCN. PMID:25793891

Antioxidant, antibacterial, anti-inflammatory and wound healing effects of Artemisia campestris aqueous extract in rat.

PubMed

Ghlissi, Zohra; Sayari, Nadhim; Kallel, Rim; Bougatef, Ali; Sahnoun, Zouheir

2016-12-01

This study investigated some biological properties of Artemisia campestris aqueous extract (ACAE) as well its global chemical compositions. Twenty four rats were excised on the posterior neck skin area and divided into 4 groups, treated respectively with: sterile saline, glycerol, CICAFLORA and ACAE. The wound closure rate, histopathology evolution and the superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) level in skin tissue were evaluated. Anti-inflammatory activity was studied by carrageenan-induced rat paw edema. Animals were divided into 3 groups pre-treated respectively with sterile saline, acetylsalicylic acid (AA) and ACAE. The antibacterial activity was tested against six bacteria and the antioxidant activity was estimated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and β-carotene activities. Our results demonstrated a significant improvement in wound healing progression and in oxidative stress damage in the wounds tissues of ACAE-treated rats, compared to control. ACAE-treated rats revealed also a significant inhibition of carrageenan-induced hind paws edema as confirmed by the histological analysis. In addition to the antioxidant activity, ACAE showed considerable antibacterial activities. ACAE exhibited important wound healing effect probably due to the anti-inflammatory, antibacterial and antioxidant activities of its phytochemical contents. Therefore, this study confirms its popular use and highlights its promise in the development of new drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Photocopy of drawing located at National Archives, San Bruno, California ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing located at National Archives, San Bruno, California (Navy # 110-A-1 3 of 5). Scofiled Construction Company Mare Island Office, Mare Island Cal, details of doors windows and terra cotta, September 2, 1908. - Mare Island Naval Shipyard, Pump House, California Avenue, east side between Dry Dock 1 & Dry Dock 2, near Ninth Street, Vallejo, Solano County, CA

Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

PubMed

Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

2017-10-01

Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Lactate-H+ Transport Is a Significant Component of the In Vivo Corneal Endothelial Pump

PubMed Central

Nguyen, Tracy T.; Bonanno, Joseph A.

2012-01-01

Purpose. To confirm the expression of monocarboxylate transporters (MCT) 1, 2, and 4 in rabbit CE and to test the hypothesis that cellular buffering contributed by HCO3−, NBCe1, and carbonic anhydrase (CA) activity facilitates lactate-H+ efflux thereby controlling corneal hydration in vivo. Methods. MCT1–4 expression of rabbit endothelium was examined by Western blotting and immunofluorescence staining. Lactate-induced acidification (LIA) was measured in perfused CE in the presence and absence of HCO3− and acetazolamide (ACTZ) using tissue treated with siRNA specific to MCT1, 2, and 4. Corneal thickness and lactate concentration were measured in New Zealand White rabbits treated with the topical CA inhibitor Azopt, and from eyes that were injected intracamerally with ouabain, disodium 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS), and shRNA specific to the 1Na+:2HCO3− cotransporter NBCe1. Results. MCT1 and MCT4 are localized to the lateral membrane, while MCT2 is apical. Cell pH measurements showed LIA in response to 40 mM lactate in bicarbonate free (BF) Ringer's that was inhibited by niflumic acid and by MCT siRNA knockdown, and significantly reduced in the presence of HCO3−. Lactate-dependent proton flux in vitro was not significantly greater in the presence of HCO3− or reduced by ACTZ. However, when active transport, NBCe1, or CA activity was disrupted in vivo, corneal edema ensued and was associated with significant corneal lactate accumulation. Conclusions. MCT1, 2, and 4 are expressed in rabbit CE on both the apical and basolateral surfaces and function to transport lactate-H+. Lactate-H+ flux is facilitated by active transport, HCO3− transport and CA activity, disruption of which causes corneal edema in vivo and indicates that facilitation of lactate efflux is a component of the endothelial pump. PMID:22410572

Alleviation of cyclophosphamide-induced immunosuppression in Wistar rats by onion lectin (Allium cepa agglutinin).

PubMed

Kumar, Vaddi P; Venkatesh, Yeldur P

2016-06-20

In various traditional medicines, onion has been classified as an immune-boosting food. Recent studies have claimed this property due to the presence of bioactive organosulfur compounds, prebiotic fructo-oligosaccharides and an immunomodulatory protein, lectin (Allium cepa agglutinin; ACA) (Prasanna and Venkatesh, 2015. Characterization of onion lectin (Allium cepa agglutinin) as an immunomodulatory protein inducing Th1-type immune response in vitro. Int. Immunopharmacol. vol. 26, pp. 304-313). The aim of this study was to evaluate the immunoprotective properties of ACA in normal and cyclophosphamide (CP; 100μg/kg)-induced immunosuppressed Wistar rats. Wistar rats were administrated different doses of ACA (1, 10, and 100μg) to respective groups in normal as well as immunosuppressed animals. The effect of ACA on the status of immune organs was assessed by examining the splenic and thymic indices, and histopathological changes. The biomarkers for humoral immunity (serum IgG and IgA levels) and serum pro-inflammatory markers (COX-2, TNF-α and IL-10) were measured by ELISA. ACA showed immunoprotective properties by significantly promoting the restoration of lymphoid cell count by ~6 fold vs. model control (immunosuppressed animals) and promotes the immune response significantly (~1.5-fold) in CP-induced immunosuppressed animals compared to model control; production of pro-inflammatory molecules (COX-2 and nitric oxide) and expression levels of immune regulatory molecule (TNF-α) were elevated in a dose-dependent manner. The observed in vivo results suggest that ACA has the potential to be used as a nutritional therapeutic to boost the immune status of immunosuppressed subjects brought about by CP administration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Revascularization of the anterior cerebral artery by Y-shaped superficial temporal artery interposition graft for the treatment of a de novo aneurysm arising at the site of A3-A3 bypass: technical case report.

PubMed

Endo, Hidenori; Sugiyama, Shin-Ichiro; Endo, Toshiki; Fujimura, Miki; Shimizu, Hiroaki; Tominaga, Teiji

2017-12-22

The most frequently used option to reconstruct the anterior cerebral artery (ACA) is an ACA-ACA side-to-side anastomosis. The long-term outcome and complications of this technique are unclear. The authors report a case of a de novo aneurysm arising at the site of A 3 -A 3 anastomosis. A 53-year-old woman underwent A 3 -A 3 side-to-side anastomosis for the treatment of a ruptured right A 2 dissecting aneurysm. At 44 months after surgery, a de novo aneurysm developed at the site of anastomosis. The aneurysm developed in the front wall of the anastomosis site, and projected to the anterosuperior direction. A computational fluid dynamics (CFD) study showed the localized region with high wall shear stress coincident with the pulsation in the front wall of the anastomosis site, where the aneurysm developed. A Y-shaped superficial temporal artery (STA) interposition graft was used successfully to reconstruct both ACAs, and then the aneurysm was trapped. To the authors' knowledge, this is the first case of a de novo aneurysm that developed at the site of an ACA-ACA side-to-side anastomosis. A CFD study showed that hemodynamic stress might be an underlying cause of the aneurysm formation. A Y-shaped STA interposition graft is a useful option to treat this aneurysm. Long-term follow-up is necessary to detect this rare complication after ACA-ACA anastomosis.

Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

PubMed

Gómez-Hurtado, Nieves; Domínguez-Rodríguez, Alejandro; Mateo, Philippe; Fernández-Velasco, María; Val-Blasco, Almudena; Aizpún, Rafael; Sabourin, Jessica; Gómez, Ana María; Benitah, Jean-Pierre; Delgado, Carmen

2017-07-01

Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart. Controversy exists regarding the adverse and beneficial effects of leptin on the heart We analysed the effect of a non-hypertensive dose of leptin on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction. We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype. These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca 2+ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca 2+ handling parameters. Leptin, is a 16 kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca 2+ ] i handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure-overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36 mg kg -1  day -1 ) or vehicle via osmotic minipumps for 3 weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca 2+ ] i transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin-treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca 2+ waves. These proarrhythmic manifestations, related to Ca 2+ /calmodulin-dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Specialty, Political Affiliation, and Perceived Social Responsibility Are Associated with U.S. Physician Reactions to Health Care Reform Legislation.

PubMed

Antiel, Ryan M; James, Katherine M; Egginton, Jason S; Sheeler, Robert D; Liebow, Mark; Goold, Susan Dorr; Tilburt, Jon C

2013-06-25

Little is known about how U.S. physicians' political affiliations, specialties, or sense of social responsibility relate to their reactions to health care reform legislation. To assess U.S. physicians' impressions about the direction of U.S. health care under the Affordable Care Act (ACA), whether that legislation will make reimbursement more or less fair, and examine how those judgments relate to political affiliation and perceived social responsibility. A cross-sectional, mailed, self-reported survey. Simple random sample of 3,897 U.S. physicians. Views on the ACA in general, reimbursement under the ACA in particular, and perceived social responsibility. Among 2,556 physicians who responded (RR2: 65 %), approximately two out of five (41 %) believed that the ACA will turn U.S. health care in the right direction and make physician reimbursement less fair (44 %). Seventy-two percent of physicians endorsed a general professional obligation to address societal health policy issues, 65 % agreed that every physician is professionally obligated to care for the uninsured or underinsured, and half (55 %) were willing to accept limits on coverage for expensive drugs and procedures for the sake of expanding access to basic health care. In multivariable analyses, liberals and independents were both substantially more likely to endorse the ACA (OR 33.0 [95 % CI, 23.6-46.2]; OR 5.0 [95 % CI, 3.7-6.8], respectively), as were physicians reporting a salary (OR 1.7 [95 % CI, 1.2-2.5]) or salary plus bonus (OR 1.4 [95 % CI, 1.1-1.9) compensation type. In the same multivariate models, those who agreed that addressing societal health policy issues are within the scope of their professional obligations (OR 1.5 [95 % CI, 1.0-2.0]), who believe physicians are professionally obligated to care for the uninsured / under-insured (OR 1.7 [95 % CI, 1.3-2.4]), and who agreed with limiting coverage for expensive drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8-3.0]), were all significantly more likely to endorse the ACA. Surgeons and procedural specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4-0.7], OR 0.6 [95 % CI, 0.5-0.9], respectively). Significant subsets of U.S. physicians express concerns about the direction of U.S. health care under recent health care reform legislation. Those opinions appear intertwined with political affiliation, type of medical specialty, as well as perceived social responsibility.

Generation, Analysis and Functional Annotation of Expressed Sequence Tags from the Sheepshead Minnow (Cyprinodon variegatus)

DTIC Science & Technology

2010-01-01

any other provision of law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a...CA) were cloned using the pGEM-T Easy Vector System (Promega, Madison, WI) and Electromax DH10B T1 Phage Resistant Cells (Invitrogen, Carlsbad, CA...reactions were performed using 75ng of plasmid DNA template and a M13 (-40) forward primer according to the manufac- turer’s protocol for DNA sequencing of

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.

Box H/ACA snoRNAs are preferred substrates for the trimethylguanosine synthase in the divergent unicellular eukaryote Trichomonas vaginalis

PubMed Central

Simoes-Barbosa, Augusto; Chakrabarti, Kausik; Pearson, Michael; Benarroch, Delphine; Shuman, Stewart; Johnson, Patricia J.

2012-01-01

The 2,2,7-trimethylguanosine caps of eukaryal snRNAs and snoRNA are formed by the enzyme Tgs1, which catalyzes sequential guanine-N2 methylations of m7G caps. Atypically, in the divergent unicellular eukaryote Trichomonas vaginalis, spliceosomal snRNAs lack a guanosine cap and the recombinant T. vaginalis trimethylguanosine synthase (TvTgs) produces only m2,7G in vitro. Here, we show by direct metabolic labeling that endogenous T. vaginalis RNAs contain m7G, m2,7G, and m2,2,7G caps. Immunodepletion of TvTgs from cell extracts and TvTgs add-back experiments demonstrate that TvTgs produces m2,7G and m2,2,7G caps. Expression of TvTgs in yeast tgs1Δ cells leads to the formation of m2,7G and m2,2,7G caps and complementation of the lethality of a tgs1Δ mud2Δ strain. Whereas TvTgs is present in the nucleus and cytosol of T. vaginalis cells, TMG-containing RNAs are localized primarily in the nucleolus. Molecular cloning of anti-TMG affinity-purified T. vaginalis RNAs identified 16 box H/ACA snoRNAs, which are implicated in guiding RNA pseudouridylation. The ensemble of new T. vaginalis H/ACA snoRNAs allowed us to predict and partially validate an extensive map of pseudouridines in T. vaginalis rRNA. PMID:22847815

Gain in Insurance Coverage and Residual Uninsurance Under the Affordable Care Act: Texas, 2013-2016.

PubMed

Pickett, Stephen; Marks, Elena; Ho, Vivian

2017-01-01

To examine the effects of the Affordable Care Act's (ACA's) Marketplace on Texas residents and determine which population subgroups benefited the most and which the least. We analyzed insurance coverage rates among nonelderly Texas adults using the Health Reform Monitoring Survey-Texas from September 2013, just before the first open enrollment period in the Marketplace, through March 2016. Texas has experienced a roughly 6-percentage-point increase in insurance coverage (from 74.7% to 80.6%; P = .012) after implementation of the major insurance provisions of the ACA. The 4 subgroups with the largest increases in adjusted insurance coverage between 2013 and 2016 were persons aged 50 to 64 years (12.1 percentage points; P = .002), Hispanics (10.9 percentage points; P = .002), persons reporting fair or poor health status (10.2 percentage points; P = .038), and those with a high school diploma as their highest educational attainment (9.2 percentage points; P = .023). Many population subgroups have benefited from the ACA's Marketplace, but approximately 3 million Texas residents still lack health coverage. Adopting the ACA's Medicaid expansion is a means to address the lack of coverage.

Evaluation of Tests for Determining the Pumpability of Concrete Mixtures.

DTIC Science & Technology

1981-10-01

mixture No. 4 21 MIXTURE NO. 5 (Pumped) CHARACTERISTIC DESIRED RANGE ACTUALI NG ? OKIADJUSLTHENT CA/TARATIO50% LI.RGER MSA CA/T RATUMO TO IMORE RD AGG 65 ...CA/TA RATIO TO MORE RD AGG (BY VOLUME) 65 % LOW FM OF FA 50%. N. WT. 2.4 - . FM OF FA LT". . -- - #k0 SIEVE 15-30% 18 X CUM 7 FA PASSI ___ IVE 5 --, T...Chief of Engineers, U. S. Army EL E C LU Washington, D. C. 20314 S L~w Under CWIS Work Unit 31138 D -34 Destroy this report when no longer needed. Do

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2013-06-01

AGA GAG GGA GAT GCT CAG TGT TGG M32599 18S AGT GCG GGT CAT AAG CTT GC GGG CCT CAC TAA AC CAT CCA V00851 β-actin GTT TGA GAC CTT CAA CAC CCC GTG ...GCC ATC TCC TGC TCG AAG TC Meredith et al 2011* Mstn ACT GGA CCT CTC GAT AGA ACA CTC ACT TAG TGC TGT GTG TGT GGA GAT NM_010834.2 IGF-1 CAG...ACA GGA GCC CAG GAA AG AAG TGC CGT ATC CCA GAG GA NM_184052 MHC ACA GTC AGA GGT GTG ACTC AGC CG CCG ACT TGC GGA GGA AAG GTG C NM_001099635 Murf1

Acid stress mediated adaptive divergence in ion channel function during embryogenesis in Rana arvalis

PubMed Central

Shu, Longfei; Laurila, Anssi; Räsänen, Katja

2015-01-01

Ion channels and pumps are responsible for ion flux in cells, and are key mechanisms mediating cellular function. Many environmental stressors, such as salinity and acidification, are known to severely disrupt ionic balance of organisms thereby challenging fitness of natural populations. Although ion channels can have several vital functions during early life-stages (e.g. embryogenesis), it is currently not known i) how developing embryos maintain proper intracellular conditions when exposed to environmental stress and ii) to what extent environmental stress can drive intra-specific divergence in ion channels. Here we studied the moor frog, Rana arvalis, from three divergent populations to investigate the role of different ion channels and pumps for embryonic survival under acid stress (pH 4 vs 7.5) and whether populations adapted to contrasting acidities differ in the relative role of different ion channel/pumps. We found that ion channels that mediate Ca2+ influx are essential for embryonic survival under acidic pH, and, intriguingly, that populations differ in calcium channel function. Our results suggest that adaptive divergence in embryonic acid stress tolerance of amphibians may in part be mediated by Ca2+ balance. We suggest that ion flux may mediate adaptive divergence of natural populations at early life-stages in the face of environmental stress. PMID:26381453

Modulation of Diabetes-Induced Oxidative Stress, Apoptosis, and Ca2+ Entry Through TRPM2 and TRPV1 Channels in Dorsal Root Ganglion and Hippocampus of Diabetic Rats by Melatonin and Selenium.

PubMed

Kahya, Mehmet Cemal; Nazıroğlu, Mustafa; Övey, İshak Suat

2017-04-01

Neuropathic pain and hippocampal injury can arise from the overload of diabetes-induced calcium ion (Ca 2+ ) entry and oxidative stress. The transient receptor potential (TRP) melastatin 2 (TRPM2) and TRP vanilloid type 1 (TRPV1) are expressed in sensory neurons and hippocampus. Moreover, activations of TRPM2 and TRPV1 during oxidative stress have been linked to neuronal death. Melatonin (MEL) and selenium (Se) have been considered potent antioxidants that detoxify a variety of reactive oxygen species (ROS) in neurological diseases. In order to better characterize the actions of MEL and Se in diabetes-induced peripheral pain and hippocampal injury through modulation of TRPM2 and TRPV1, we tested the effects of MEL and Se on apoptosis and oxidative stress in the hippocampal and dorsal root ganglion (DRG) neurons of streptozotocin (STZ)-induced diabetic rats. Fifty-eight rats were divided into six groups. The first group was used as control. The second group was used as the diabetic group. The third and fourth groups received Se and MEL, respectively. Intraperitoneal Se and MEL were given to diabetic rats in the fifth and sixth groups. On the 14th day, hippocampal and DRG neuron samples were freshly taken from all animals. The neurons were stimulated with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We observed a modulator role of MEL and Se on intracellular free Ca 2+ concentrations, current densities of TRPM2 and TRPV1 channels, apoptosis, caspase 3, caspase 9, mitochondrial depolarization, reduced glutathione, glutathione peroxidase, lipid peroxidation, and intracellular ROS production values in the neurons. In addition, procaspase 3 and 9 activities in western blot analyses of the brain cortex were also decreased by MEL and Se treatments. In conclusion, in our diabetes experimental model, TRPM2 and TRPV1 channels are involved in the Ca 2+ entry-induced neuronal death and modulation of this channel activity by MEL and Se treatment may account for their neuroprotective activity against apoptosis and Ca 2+ entry. Graphical Abstract Possible molecular pathways of involvement of melatonin and selenium in diabetes-induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus and DRG neurons of rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin and it is blocked by capsazepine (CPZ). Diabetes can result in augmented ROS release in hippocampal and DRG neurons through polyol reactions, leading to Ca 2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca 2+ provided intracellular Ca 2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Melatonin and selenium reduce TRPM2 and TRPV1 channel activation through the modulation of polyol oxidative reactions and selenium-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Accommodation, accommodative convergence, and response AC/A ratios before and at the onset of myopia in children.

PubMed

Gwiazda, Jane; Thorn, Frank; Held, Richard

2005-04-01

The purpose of this study was to investigate accommodation, accommodative convergence, and AC/A ratios before and at the onset of myopia in children. Refractive error, accommodation, and phorias were measured annually over a period of 3 years in 80 6- to 18-year-old children (mean age at first visit = 11.1 years), including 26 who acquired myopia of at least -0.50 D and 54 who remained emmetropic (-0.25 to + 0.75 D). Refraction was measured by noncycloplegic distance retinoscopy. Concomitant measures of accommodation and phorias were taken for letter targets at 4.0 m and 0.33 m using the Canon R-1 open field-of-view autorefractor with an attached motorized Risley prism and Maddox rod. The accommodation and phoria measurements were used to calculate response AC/A ratios. Compared with children who remained emmetropic, those who became myopic had elevated response AC/A ratios at 1 and 2 years before the onset of myopia, in addition to at onset and 1 year later (t's = -2.97 to -4.04, p < 0.01 at all times). The significantly higher AC/A ratios in the children who became myopic are a result of significantly reduced accommodation. Accommodative convergence was significantly greater in myopes only at onset. These findings suggest that the abnormal oculomotor factors found before the onset of myopia may contribute to myopigenesis by producing hyperopic retinal defocus when a child is engaged in near-viewing tasks.

Phospholamban, a predicted candidate for early cardiac problem detection using signal processing techniques.

PubMed

Hejase de Trad, C

2005-01-01

Heart failure has been identified as a serious international problem, in particular for aging groups, posing both an increasing number of patients on waiting lists in countries susceptible with Medicare systems and increasing financial burdens. It may be imperative to develop a marker that can identify such problems at an early stage. It is believed that certain proteins have crucial roles in early detection of cardiovascular disease, the number one killer in United Arab Emirates. This might be accomplished by recognition of unusual features in protein candidates. Phospholamban (PLB) is a 52 amino acid phosphoprotein which regulates the calcium pump of cardiac sarcoplasmic reticulum (SR). During muscle contraction, PLB inhibits the Ca⁺⁺ pump. During muscle relaxation, it can be phosphorylated, removing the inhibition and allowing Ca⁺⁺ to be pumped back into SR. With the calcium pump disrupted, the heart muscle is probably weakened, resulting in congestive heart failure. Interleukin 6 (IL-6) is considered as a better predictor of heart attack in elderly people. It could serve as an early warning sign since its level increases early in the inflammatory process. Also, it has been established that myocyte enhancer factor 2A (MEF2A) plays a vital role in the development of cardiovascular problems like atherosclerosis and restenosis after angioplasty inflammation. In this paper, the resonance recognition method (RRM) has been employed to determine the characteristic frequencies of the above-mentioned proteins. It has been found that phospholamban and IL-6 share the same characteristic frequency, 0.3320 plusmn 0.0002 suggesting their common probable contribution to heart failure. Myocyte enhancer factor 2A does not share the same characteristic frequency. Hence, phospholamban is suggested as a highly probable early marker for cardiac problem detection.

Voltage activation and hysteresis of the non-selective voltage-dependent channel in the intact human red cell.

PubMed

Bennekou, Poul; Barksmann, Trine L; Jensen, Lars R; Kristensen, Berit I; Christophersen, Palle

2004-05-01

Suspension of intact human red cells in media with low chloride and sodium concentrations (isotonic sucrose substitution) results in strongly inside positive membrane potentials, which activate the voltage-dependent non-selective cation (NSVDC) channel. By systematic variation of the initial Nernst potentials for chloride (degree of ion substitution) as well as the chloride conductance (block by NS1652), and by exploiting the interplay between the Ca(2+)-permeable NSVDC channel, the Ca(2+)-activated K+ channel (the Gárdos channel) and the Ca(2+)-pump, a graded activation of the NSVDC channel was achieved. Under these conditions, it was shown that the NSVDC channels exist in two states of activation depending on the initial conditions for the activation. The hysteretic behaviour, which in patch clamp experiments has been found for the individual channel unit, is thus retained at the cellular level and can be demonstrated with red cells in suspension.

Dispersed-Fluorescence Spectroscopy of Jet-Cooled Calcium Ethoxide Radical (CaOC_2H_5)

NASA Astrophysics Data System (ADS)

Paul, Anam C.; Reza, Md Asmaul; Liu, Jinjun

2016-06-01

Metal-containing free radicals are important intermediates in metal-surface reactions and in the interaction between metals and organic molecules. In the present work, dispersed fluorescence (DF) spectra of the calcium ethoxide radical (CaOC_2H_5) have been obtained by pumping the {tilde A^2}{A}' ← {tilde X^2}{A}' and the {tilde B^2}{A}'' ← {tilde X^2}{A}' origin bands in its laser-induced fluorescence (LIF) spectrum. CaOC_2H_5 radicals were produced by 1064 nm laser ablation of calcium grains in the presence of ethanol under jet-cooled conditions. Dominant transitions in the vibrationally resolved DF spectra are well reproduced using Franck-Condon factors predicted by complete active space self-consistent (CASSCF) calculations. Differences in transition intensities between the {tilde A^2}{A}' → {tilde X^2}{A}' and the {tilde B^2}{A}'' → {tilde X^2}{A}' DF spectra are attributed to the pseudo-Jahn-Teller interaction between the tilde A ^2 A' and the tilde B ^2 A'' states. Collision-induced population transfer between these two excited electronic states results in additional peaks in the DF spectra.

Credit BG. Interior view of the building displays temporary wooden ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Credit BG. Interior view of the building displays temporary wooden building construction, pump, and water piping arrangements. The well is currently used as an observation post for changes in ground water levels - Edwards Air Force Base, North Base, Well No. 2, East of Second Street, Boron, Kern County, CA

Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

PubMed Central

Maltsev, Alexander V.; Maltsev, Victor A.; Stern, Michael D.

2017-01-01

Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates. PMID:28792496

Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

PubMed

ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Zhang, Mei Luo; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

2008-01-01

Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac muscle. These Ca2+ waves can reversibly be induced in muscle with non-uniform excitation contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating Ca2+ waves and reversibly induced arrhythmias. We hypothesize that rapid force loss by sarcomeres in the border zone during relaxation causes Ca2+ release from Tn-C and initiates Ca2+ waves propagated by the sarcoplasmic reticulum (SR). These observations suggest the unifying hypothesis that force feedback to Ca2+ binding by Tn-C is responsible for Starling's Law and the ESPVR in uniform myocardium and leads in non-uniform myocardium to a surge of Ca2+ released by the myofilaments during relaxation, which initiates arrhythmogenic propagating Ca2+ release by the SR.

Calcium carbonate as ikaite crystals in Antarctic sea ice

NASA Astrophysics Data System (ADS)

Dieckmann, Gerhard S.; Nehrke, Gernot; Papadimitriou, Stathys; Göttlicher, Jörg; Steininger, Ralph; Kennedy, Hilary; Wolf-Gladrow, Dieter; Thomas, David N.

2008-04-01

We report on the discovery of the mineral ikaite (CaCO3.6H2O) in sea-ice from the Southern Ocean. The precipitation of CaCO3 during the freezing of seawater has previously been predicted from thermodynamic modelling, indirect measurements, and has been documented in artificial sea ice during laboratory experiments but has not been reported for natural sea-ice. It is assumed that CaCO3 formation in sea ice may be important for a sea ice-driven carbon pump in ice-covered oceanic waters. Without direct evidence of CaCO3 precipitation in sea ice, its role in this and other processes has remained speculative. The discovery of CaCO3.6H2O crystals in natural sea ice provides the necessary evidence for the evaluation of previous assumptions and lays the foundation for further studies to help elucidate the role of ikaite in the carbon cycle of the seasonally sea ice-covered regions

Mutation tryptophan to leucine at position 222 of haemagglutinin could facilitate H3N2 influenza A virus infection in dogs

PubMed Central

Yang, Guohua; Li, Shoujun; Blackmon, Sherry; Ye, Jianqiang; Bradley, Konrad C.; Cooley, Jim; Smith, Dave; Hanson, Larry; Cardona, Carol; Steinhauer, David A.; Webby, Richard; Liao, Ming

2013-01-01

An avian-like H3N2 influenza A virus (IAV) has recently caused sporadic canine influenza outbreaks in China and Korea, but the molecular mechanisms involved in the interspecies transmission of H3N2 IAV from avian to canine species are not well understood. Sequence analysis showed that residue 222 in haemagglutinin (HA) is predominantly tryptophan (W) in the closely related avian H3N2 IAV, but was leucine (L) in canine H3N2 IAV. In this study, reassortant viruses rH3N2-222L (canine-like) and rH3N2-222W (avian-like) with HA mutation L222W were generated using reverse genetics to evaluate the significance of the L222W mutation on receptor binding and host tropism of H3N2 IAV. Compared with rH3N2-222W, rH3N2-222L grew more rapidly in MDCK cells and had significantly higher infectivity in primary canine tracheal epithelial cells. Tissue-binding assays demonstrated that rH3N2-222L had a preference for canine tracheal tissues rather avian tracheal tissues, whereas rH3N2-222W favoured slightly avian rather canine tracheal tissues. Glycan microarray analysis suggested both rH3N2-222L and rH3N2-222W bound preferentially to α2,3-linked sialic acids. However, the rH3N2-222W had more than twofold less binding affinity than rH3N2-222L to a set of glycans with Neu5Aca2–3Galb1–4(Fuca-)-like or Neu5Aca2–3Galb1–3(Fuca-)-like structures. These data suggest the W to L mutation at position 222 of the HA could facilitate infection of H3N2 IAV in dogs, possibly by increasing the binding affinities of the HA to specific receptors with Neu5Aca2–3Galb1–4(Fuca-) or Neu5Aca2–3Galb1–3(Fuca-)-like structures that are present in dogs. PMID:23994833

Surface Second Harmonic Generation Studies of Stepped Ag(111) Electrode Surfaces

DTIC Science & Technology

1993-05-27

Surface Warfare Center China Lake, CA 93555-6001 Carderock Division Detachment Annapolis, MD 21402-1198 Dr. Elek Lindner (1) Naval Command, Contrl and...polarized pump beam at frequency (t. (2,W) (,( d) sin(3)p)qS’ , ,si ,p Eq. 3 with dj" =FXzf f, 10 d3 sin(3(p) Eq.4 with d = F1z)fkfk where the...electrodes at an applied potential of -0.5 V as a function of azimuthal angle for s-polarized SHG and s-polarized pump beam. Shown are measurements on

Disproportionate-share hospital payment reductions may threaten the financial stability of safety-net hospitals.

PubMed

Neuhausen, Katherine; Davis, Anna C; Needleman, Jack; Brook, Robert H; Zingmond, David; Roby, Dylan H

2014-06-01

Safety-net hospitals rely on disproportionate-share hospital (DSH) payments to help cover uncompensated care costs and underpayments by Medicaid (known as Medicaid shortfalls). The Affordable Care Act (ACA) anticipates that insurance expansion will increase safety-net hospitals' revenues and will reduce DSH payments accordingly. We examined the impact of the ACA's Medicaid DSH reductions on California public hospitals' financial stability by estimating how total DSH costs (uncompensated care costs and Medicaid shortfalls) will change as a result of insurance expansion and the offsetting DSH reductions. Decreases in uncompensated care costs resulting from the ACA insurance expansion may not match the act's DSH reductions because of the high number of people who will remain uninsured, low Medicaid reimbursement rates, and medical cost inflation. Taking these three factors into account, we estimate that California public hospitals' total DSH costs will increase from $2.044 billion in 2010 to $2.363-$2.503 billion in 2019, with unmet DSH costs of $1.381-$1.537 billion. Project HOPE—The People-to-People Health Foundation, Inc.

ACA dependent coverage provision reduced high out-of-pocket health care spending for young adults.

PubMed

Busch, Susan H; Golberstein, Ezra; Meara, Ellen

2014-08-01

Since September 2010 the Affordable Care Act (ACA) has required that insurers allow children to remain as dependents on their parents' private insurance plans until age twenty-six. Studies have shown that this provision increased coverage rates among young adults. In this article we analyze whether the provision also protected young adults from large and uncertain out-of-pocket expenses. We found that the policy was associated with a statistically significant reduction in the share of young adults facing annual out-of-pocket expenditures greater than $1,500 (decreasing from 4.2 percent to 2.9 percent), compared to an increase in the proportion of their slightly older peers facing such expenditures (increasing from 4.4 percent to 5.4 percent), a net difference of -2.4 percentage points, or 57 percent. We conclude that the dependent coverage provision in the ACA provides financial protection for young adults at a time when they often face high debt burden but low wages. Project HOPE—The People-to-People Health Foundation, Inc.

Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

DTIC Science & Technology

2013-03-01

tissue have been optimized • Optimization of flow cytometry-based analyses to characterize co- incident expression of multiple MSC-related markers on a...CA). Mouse anti-human vimentin (clone LN-6) was purchased from Sigma-Aldrich (St. Louis, MO). Goat anti-mouse Alexa Fluor 488, Roswell Park

Perception and Confusion of Speech Sounds by Adults with a Cochlear Implant

ERIC Educational Resources Information Center

Rodvik, Arne K.

2008-01-01

The aim of this pilot study was to identify the most common speech sound confusions of 5 Norwegian cochlear implanted post-lingually deafened adults. We played recorded nonwords, aCa, iCi and bVb, to our informants, asked them to repeat what they heard, recorded their repetitions and transcribed these phonetically. We arranged the collected data…

Identification and characterization of a calmodulin binding domain in the plasma membrane Ca2+-ATPase from Trypanosoma equiperdum.

PubMed

Ramírez-Iglesias, José Rubén; Pérez-Gordones, María Carolina; Del Castillo, Jesús Rafael; Mijares, Alfredo; Benaim, Gustavo; Mendoza, Marta

2018-05-09

The plasma membrane Ca 2+ -ATPase (PMCA) from trypanosomatids lacks a classical calmodulin (CaM) binding domain, although CaM stimulated activities have been detected by biochemical assays. Recently we proposed that the Trypanosoma equiperdum CaM-sensitive PMCA (TePMCA) contains a potential 1-18 CaM-binding motif at the C-terminal region of the pump. In the present study, we evaluated the potential CaM-binding motifs using CaM from Trypanosoma cruzi and either the recombinant full length TePMCA C-terminal sequence (P14) or synthetic peptides comprising different regions of the C-terminal domain. We demonstrated that P14 and a synthetic peptide corresponding to residues 1037-1062 (which contains the predicted 1-18 binding motif) competed efficiently for binding to TcCaM, exhibiting similar IC 50 s of 200 nM. A stable complex of this peptide and TcCaM was formed in the presence of Ca 2+ , as determined by native-polyacrylamide gel electrophoresis. A predicted structure obtained by molecular docking showed an interaction of the 1-18 binding motif with the Ca 2+ /CaM complex. Moreover, when the peptide was incubated with CaM and Ca 2+ , a blue shift in the tryptophan fluorescence spectrum (from 350 to 329 nm) was observed. Substitutions at W 1039 and F 1056 , strongly decreased both CaM-peptide interaction and the complex assembly. Our results demonstrated the presence of a functional 1-18 motif at the TePMCA C-terminal domain. Furthermore, on the basis of spectrofluorometric assays and the resulting structure modeled by docking we propose that the L 1042 and W 1060 residues might also participate as anchors to form a 1-4-18-22 motif. Copyright © 2018 Elsevier B.V. All rights reserved.

Droplet Size and Liquid Water Characteristics of the USAAEFA (CH-47) Helicopter Spray System and Natural Clouds as Sampled by a JUH-1H Helicopter.

DTIC Science & Technology

1980-08-01

o080Atalea Cal lolna 9" C’ lelephone 121 3) 79, .I 9" lee f6 5A2i A S.,&,osa’fr o MC CALIBRAT ION REPORT Date: 1/8/80 Instrument: ASSP-l 00-1 Size Size...c% c l a a 0 -1 a*’ ac e a***cca *a c a am a*ca c acca =aac ca~ac caaa U𔃺 C C C C0 C C C C C C C C Q C C C C C C C> C C C C C C C CD C C C C CD 0 a C...C C atI 0 l C 0 .C C 0 0 QC 0 0 0 c CD C c 0 C C 0 Q 0 CIC C C0 C 0 C C> C go 1 C 0j C C C QC 0 QQO0COQC=C0c 00CC =1C Q0c cC aCCa CSQ --- -V -, -7

Osteopathic medical students' understanding of the Patient Protection and Affordable Care Act: a first step toward a policy-informed curriculum.

PubMed

Beverly, Elizabeth Ann; Skinner, Daniel; Bianco, Joseph A; Ice, Gillian H

2015-03-01

Current osteopathic medical students will play an important role in implementing, modifying, and advocating for or against the Patient Protection and Affordable Care Act (ACA) of 2010. Accordingly, medical educators will need to address curricular gaps specific to the ACA and medical practice. Research that gauges osteopathic medical students' level of understanding of the ACA is needed to inform an evidence-based curriculum. To assess first- and second-year osteopathic medical students' beliefs about the ACA. In this descriptive cross-sectional survey-based study, first- and second-year students were recruited because their responses would be indicative of what, if any, information about the ACA was being covered in the preclinical curriculum. A 30-item survey was distributed in November 2013, after the health insurance exchanges launched on October 1, 2013. A total of 239 first- and second-year osteopathic medical students completed the survey. One hundred ten students (46%) disagreed and 103 (43.1%) agreed that the ACA would provide health insurance coverage for all US citizens. The ACA was predicted to lead to lower wages and fewer jobs (73 students [30.5%]), as well as small business bankruptcy because of employees' health insurance costs (96 [40.2%]). Regarding Medicare recipients, 113 students (47.3%) did not know whether these individuals would be required to buy insurance through the health insurance exchanges. The majority of students knew that the ACA would require US citizens to pay a penalty if they did not have health insurance (198 [82.8%]) and understood that not everyone would be required to purchase health insurance through health insurance exchanges (137 [57.3%]). Although students took note of certain clinical benefits for patients offered by the ACA, they remained concerned about the ACA's impact on their professional prospects, particularly in the area of primary care. These findings build on the existing literature that emphasize the need for incorporating into the osteopathic medical curriculum knowledge of the dynamics of health care policy and reform and for creating opportunities for students to follow health policy developments as they evolve in real time. © 2015 The American Osteopathic Association.

Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy.

PubMed

Haaß, Wiltrud; Kleiner, Helga; Weiß, Christel; Haferlach, Claudia; Schlegelberger, Brigitte; Müller, Martin C; Hehlmann, Rüdiger; Hofmann, Wolf-Karsten; Fabarius, Alice; Seifarth, Wolfgang

2015-01-01

Unbalanced (major route) additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukemia (CML) indicate an increased risk of progression and shorter survival. Moreover, newly arising ACA under imatinib treatment and clonal evolution are considered features of acceleration and define failure of therapy according to the European LeukemiaNet (ELN) recommendations. On the basis of 1151 Philadelphia chromosome positive chronic phase patients of the randomized CML-study IV, we examined the incidence of newly arising ACA under imatinib treatment with regard to the p210BCR-ABL breakpoint variants b2a2 and b3a2. We found a preferential acquisition of unbalanced ACA in patients with b3a2 vs. b2a2 fusion type (ratio: 6.3 vs. 1.6, p = 0.0246) concurring with a faster progress to blast crisis for b3a2 patients (p = 0.0124). ESPL1/Separase, a cysteine endopeptidase, is a key player in chromosomal segregation during mitosis. Separase overexpression and/or hyperactivity has been reported from a wide range of cancers and cause defective mitotic spindles, chromosome missegregation and aneuploidy. We investigated the influence of p210BCR-ABL breakpoint variants and imatinib treatment on expression and proteolytic activity of Separase as measured with a specific fluorogenic assay on CML cell lines (b2a2: KCL-22, BV-173; b3a2: K562, LAMA-84). Despite a drop in Separase protein levels an up to 5.4-fold increase of Separase activity under imatinib treatment was observed exclusively in b3a2 but not in b2a2 cell lines. Mimicking the influence of imatinib on BV-173 and LAMA-84 cells by ESPL1 silencing stimulated Separase proteolytic activity in both b3a2 and b2a2 cell lines. Our data suggest the existence of a fusion type-related feedback mechanism that posttranslationally stimulates Separase proteolytic activity after therapy-induced decreases in Separase protein levels. This could render b3a2 CML cells more prone to aneuploidy and clonal evolution than b2a2 progenitors and may therefore explain the cytogenetic results of CML patients.

UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells.

PubMed

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca 2+ -dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca 2+ imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca 2+ oscillations in BON. UTP evoked a biphasic concentration-dependent Ca 2+ response. Cells responded in the order of UTP, ATP > UTPγS > UDP > MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y 4 , 50% cells), UDP (P2Y 6 , 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca 2+ responses were blocked with inhibitors of PLC, IP3R, SERCA Ca 2+ pump, La 3+ sensitive Ca 2+ channels or chelation of intracellular free Ca 2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca 2+ pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca 2+ currents (I Ca ), V m -depolarization and inhibited I K (not I A ) currents. An I Kv 7.2/7.3 K + channel blocker XE-991 mimicked UTP-induced V m -depolarization and blocked UTP-responses. XE-991 blocked I K and UTP caused further reduction. La 3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca 2+ buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y 4 /P2Y 6 R. Zero-Ca 2+ buffer augmented Ca 2+ responses and 5-HT release. Conclusion: UTP activates a predominant P2Y 4 R pathway to trigger Ca 2+ oscillations via internal Ca 2+ mobilization through a PLC/IP 3 /IP3R/SERCA Ca 2+ signaling pathway to stimulate 5-HT release; Ca 2+ influx is inhibitory. UTP-induced V m -depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca 2+ oscillations or I ca /VOCC). UTP-gated signaling pathways triggered by activation of P2Y 4 R stimulate 5-HT release.

TRPV2 is critical for the maintenance of cardiac structure and function in mice

PubMed Central

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-01-01

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. PMID:24874017

TRPV2 is critical for the maintenance of cardiac structure and function in mice.

PubMed

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-05-29

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.

[Protective effect of indirect activator of calcium pump on noise-induced hearing loss].

PubMed

Liu, Jun; Yu, Ning; Han, Dongyi; Yang, Weiyan; Li, Xingqi

2002-12-01

To investigate the possible protective effect of phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C (PKC) and indirect activator of Ca2+ pump, on noise-induced hearing loss (NIHL). Twenty guinea pigs were divided randomly into two groups, and then perfused with artificial perilymph solutions in one group and with artificial perilymph solutions containing 3 mumol/L PMA in the other one, respectively. All animals were exposed with 100 dB SPL white noise for 2 hours. Cochlear microphonics (CM) and compound action potential (CAP) were recorded from the round window (RW) before noise exposure and 2 hours after noise exposure. There was no significant difference in CAP threshold and CM amplitude between two groups before noise exposure. A significant difference was observed in CAP threshold and CM amplitude between two groups after noise exposure. The amplitude of CM decreased and the threshold of CAP increased in both group after noise exposure, but in the PMA group the decrease of the amplitude of CM was higher while the increase of threshold of CAP lower than that in control (P < 0.05). PMA might have partly protective effect on NIHL. These findings indirectly proved that intracellular Ca2+ overload might involve in the mechanism of NIHL.

Tunable blue-green emission and energy transfer properties in β-Ca3(PO4)2:Eu(2+), Tb(3+) phosphors with high quantum efficiencies for UV-LEDs.

PubMed

Li, Kai; Zhang, Yang; Li, Xuejiao; Shang, Mengmeng; Lian, Hongzhou; Lin, Jun

2015-03-14

A series of Eu(2+) and Tb(3+) singly-doped and co-doped β-Ca3(PO4)2 phosphors have been synthesized via the high-temperature solid-state reaction method. Thermogravimetric (TG) analysis, fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD) patterns and Rietveld refinements, photoluminescence (PL) spectra including temperature-dependent PL and quantum efficiency, and fluorescence decay lifetimes have been used to characterise the as-prepared samples. Under UV excitation, β-Ca3(PO4)2:Eu(2+) presents a broad emission band centered at 415 nm, which can be decomposed into five symmetrical bands peaking at 390, 408, 421, 435 and 511 nm based on the substitution of five kinds of Ca(2+) sites by Eu(2+) ions. β-Ca3(PO4)2:Tb(3+) shows characteristic emission lines under Tb(3+) 4f-5d transition excitation around 223 nm. In β-Ca3(PO4)2:Eu(2+), Tb(3+) phosphors, similar excitation spectra monitored at 415 and 547 nm have been observed, which illustrates the possibility of energy transfer from Eu(2+) to Tb(3+) ions. The variations in the emission spectra and decay lifetimes further demonstrate the existence of energy transfer from Eu(2+) to Tb(3+) ions under UV excitation. The energy transfer mechanism has been confirmed to be dipole-quadrupole, which can be validated via the agreement of critical distances obtained from the concentration quenching (12.11 Å) and spectrum overlap methods (9.9-13.2 Å). The best quantum efficiency can reach 90% for the β-Ca3(PO4)2:0.01Eu(2+), 0.15Tb(3+) sample under 280 nm excitation. These results show that the developed phosphors may possess potential applications in UV-pumped white light-emitting diodes.

The Role of Cell Compartmentalization and Cell Differentiation in Cyanobacterial Excavation of Miineral Carbonates

NASA Astrophysics Data System (ADS)

Garcia-Pichel, F.; Guida, B. S.; Couradeau, E.

2015-12-01

The bioerosion of coastal limestones and biogenic carbonates by boring filamentous or pseudo-filamentous cyanobacteria is not only a geomicrobial phenomenon of global proportions, but also plays an important role in the demise of coral reefs, and affects significantly human enterprises like bivalve fisheries. In spite of its importance, the mechanism by which cyanobacteria excavate carbonates constitutes an apparent paradox, in that their metabolism will tend to precipitate carbonates, not dissolved them. We have previously advanced, and obtained evidence for, a mechanism of excavation that relies on the uptake of Ca2+ by cells at the boring front, its trans-cellular transport along the filaments, and its eventual active excretion at the solid/liquid interface. It was postulated that the mechanism involved the strategically organized deployment of Ca2+ transport enzymes like P-type Ca2+ ATPases and Ca2+ channels. Here we present evidence that confirms this basic mechanism, but also reveals that it is based on an unexpected level of cellular complexity. The model organism Mastigocoleus testarum BC008, transports Ca2+ from the mineral to the external medium using a repetitive, polar arrangement of Ca2+ ATPases, localized preferentially on one cellular pole, in a ring conformation on the cell membrane adjacent to the trans-cellular septum, pumping Ca2+ locally towards the periplasmic space, from which it passively enters the next cell. This strain also develops specialized groups of cells, which we named calcicytes, often but not exclusively located at the ends of filaments, that accumulate large concentrations of Ca2+, some 40-fold higher than typical in microbes, and seem to act as sinks or capacitors in the trans-cellular Ca2+ transport. Calcicytes are also characterized by a lack of photosynthetic pigments, and a very high intracellular pH. These cellular adaptations can also be found in evolutionary distant euendoliths such as the pseudofilamentous Hyella sp.

The Affordable Care Act, Accountable Care Organizations, and Mental Health Care for Older Adults: Implications and Opportunities.

PubMed

Bartels, Stephen J; Gill, Lydia; Naslund, John A

2015-01-01

The Patient Protection and Affordable Care Act (ACA) represents the most significant legislative change in the United States health care system in nearly half a century. Key elements of the ACA include reforms aimed at addressing high-cost, complex, vulnerable patient populations. Older adults with mental health disorders are a rapidly growing segment of the population and are among the most challenging subgroups within health care, and they account for a disproportionate amount of costs. What does the ACA mean for geriatric mental health? We address this question by highlighting opportunities for reaching older adults with mental health disorders by leveraging the diverse elements of the ACA. We describe nine relevant initiatives: (1) accountable care organizations, (2) patient-centered medical homes, (3) Medicaid-financed specialty health homes, (4) hospital readmission and health care transitions initiatives, (5) Medicare annual wellness visit, (6) quality standards and associated incentives, (7) support for health information technology and telehealth, (8) Independence at Home and 1915(i) State Plan Home and Community-Based Services program, and (9) Medicare-Medicaid Coordination Office, Center for Medicare and Medicaid Innovation, and the Patient-Centered Outcomes Research Institute. We also consider potential challenges to full implementation of the ACA and discuss novel solutions for advancing geriatric mental health in the context of projected workforce shortages and the opportunities afforded by the ACA.

The Affordable Care Act, Accountable Care Organizations, and Mental Health Care for Older Adults: Implications and Opportunities

PubMed Central

Bartels, Stephen J.; Gill, Lydia; Naslund, John A.

2015-01-01

Abstract The Patient Protection and Affordable Care Act (ACA) represents the most significant legislative change in the United States health care system in nearly half a century. Key elements of the ACA include reforms aimed at addressing high-cost, complex, vulnerable patient populations. Older adults with mental health disorders are a rapidly growing segment of the population and are among the most challenging subgroups within health care, and they account for a disproportionate amount of costs. What does the ACA mean for geriatric mental health? We address this question by highlighting opportunities for reaching older adults with mental health disorders by leveraging the diverse elements of the ACA. We describe nine relevant initiatives: (1) accountable care organizations, (2) patient-centered medical homes, (3) Medicaid-financed specialty health homes, (4) hospital readmission and health care transitions initiatives, (5) Medicare annual wellness visit, (6) quality standards and associated incentives, (7) support for health information technology and telehealth, (8) Independence at Home and 1915(i) State Plan Home and Community-Based Services program, and (9) Medicare-Medicaid Coordination Office, Center for Medicare and Medicaid Innovation, and the Patient-Centered Outcomes Research Institute. We also consider potential challenges to full implementation of the ACA and discuss novel solutions for advancing geriatric mental health in the context of projected workforce shortages and the opportunities afforded by the ACA. PMID:25811340

Loss of Ca2+-mediated ion transport during colitis correlates with reduced ion transport responses to a Ca2+-activated K+ channel opener

PubMed Central

Hirota, Christina L; McKay, Derek M

2009-01-01

Background and purpose: Epithelial surface hydration is critical for proper gut function. However, colonic tissues from individuals with inflammatory bowel disease or animals with colitis are hyporesponsive to Cl− secretagogues. The Cl− secretory responses to the muscarinic receptor agonist bethanechol are virtually absent in colons of mice with dextran sodium sulphate (DSS)-induced colitis. Our aim was to define the mechanism underlying this cholinergic hyporesponsiveness. Experimental approach: Colitis was induced by 4% DSS water, given orally. Epithelial ion transport was measured in Ussing chambers. Colonic crypts were isolated and processed for mRNA expression via RT-PCR and protein expression via immunoblotting and immunolocalization. Key results: Expression of muscarinic M3 receptors in colonic epithelium was not decreased during colitis. Short-circuit current (ISC) responses to other Ca2+-dependent secretagogues (histamine, thapsigargin, cyclopiazonic acid and calcium ionophore) were either absent or severely attenuated in colonic tissue from DSS-treated mice. mRNA levels of several ion transport molecules (a Ca2+-regulated Cl− channel, the intermediate-conductance Ca2+-activated K+ channel, the cystic fibrosis transmembrane conductance regulator, the Na+/K+-ATPase pump or the Na+/K+/2Cl− co-transporter) were not reduced in colonic crypts from DSS-treated mice. However, protein expression of Na+/K+-ATPase α1 subunits was decreased twofold during colitis. Activation of Ca2+-activated K+ channels increased ISC significantly less in DSS colons compared with control, as did the protein kinase C activator, phorbol 12-myristate 13-acetate. Conclusions and implications: Decreased Na+/K+-ATPase expression probably contributes to overall epithelial hyporesponsiveness during colitis, while dysfunctional K+ channels may account, at least partially, for lack of epithelial secretory responses to Ca2+-mediated secretagogues. PMID:19298254

The plasma membrane Ca2+ pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells.

PubMed

Hegedũs, Luca; Garay, Tamás; Molnár, Eszter; Varga, Karolina; Bilecz, Ágnes; Török, Szilvia; Padányi, Rita; Pászty, Katalin; Wolf, Matthias; Grusch, Michael; Kállay, Enikõ; Döme, Balázs; Berger, Walter; Hegedũs, Balázs; Enyedi, Agnes

2017-06-15

Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca 2+ signaling is a well-known regulator of tumor progression, the crosstalk between Ca 2+ signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca 2+ ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi. The MEK inhibitor selumetinib-similarly to that of the BRAF-specific inhibitor-also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. The increased abundance of PMCA4b in the plasma membrane enhances [Ca 2+ ] i clearance from cells after Ca 2+ entry. Moreover we show that both vemurafenib treatment and PMCA4b overexpression induce marked inhibition of migration of BRAF mutant melanoma cells. Importantly, reduced migration of PMCA4b expressing BRAF mutant cells is associated with a marked decrease in their metastatic potential in vivo. Taken together, our data reveal an important crosstalk between Ca 2+ signaling and the MAPK pathway through the regulation of PMCA4b expression and suggest that PMCA4b is a previously unrecognized metastasis suppressor. © 2016 UICC.

Program Implementation Approaches to Build and Sustain Health Care Coordination for Type 2 Diabetes.

PubMed

Fitzgerald, Tania M; Williams, Pam A; Dodge, Julia A; Quinn, Martha; Heminger, Christina L; Moultrie, Rebecca; Taylor, Olivia; Nelson, Belinda W; Lewis, Megan A

2017-03-01

As more people enter the U.S. health care system under the Affordable Care Act (ACA), it is increasingly critical to deliver coordinated, high-quality health care. The ACA supports implementation and sustainability of efficient health care models, given expected limits in available resources. This article highlights implementation strategies to build and sustain care coordination, particularly ones consistent with and reinforced by the ACA. It focuses on disease self-management programs to improve the health of patients with type 2 diabetes, exemplified by grantees of the Alliance to Reduce Disparities in Diabetes. We conducted interviews with grantee program representatives throughout their 5-year programs and conducted a qualitative framework analysis of data to identify key themes related to care coordination. The most promising care coordination strategies that grantee programs described included establishing clinic-community collaborations, embedding community health workers within care management teams, and sharing electronic data. Establishing provider buy-in was crucial for these strategies to be effective. This article adds new insights into strategies promoting effective care coordination. The strategies that grantees implemented throughout the program align with ACA requirements, underscoring their relevance to the changing U.S. health care environment and the likelihood of further support for program sustainability.

Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction.

PubMed

Hu, Zhenyu; Li, Guang; Wang, Jiong-Wei; Chong, Suet Yen; Yu, Dejie; Wang, Xiaoyuan; Soon, Jia Lin; Liang, Mui Cheng; Wong, Yuk Peng; Huang, Na; Colecraft, Henry M; Liao, Ping; Soong, Tuck Wah

2018-04-12

Background -L-type Ca V 1.2 channels play crucial roles in regulation of blood pressure. Galectin-1 (Gal-1), has been reported to bind to the I-II loop of Ca V 1.2 channels to reduce their current density. However, the mechanistic understanding for the down-regulation of Ca V 1.2 channels by Gal-1, and whether Gal-1 plays a direct role in blood pressure regulation remain unclear. Methods - In vitro experiments involving co-IP, western blot, patch-clamp recordings, immunohistochemistry and pressure myography were used to evaluate the molecular mechanisms by which Gal-1 down-regulates Ca V 1.2 channel in transfected HEK 293 cells, smooth muscle cells, arteries from Lgasl1 -/- mice, rat and human patients. In vivo experiments involving delivery of Tat-e9c peptide and AAV5-Gal-1 into rats were performed to investigate the effect of targeting Ca V 1.2-Gal-1 interaction on blood pressure monitored by tail cuff or telemetry methods. Results -Our study reveals that Gal-1 is a key regulator for proteasomal degradation of Ca V 1.2 channels. Gal-1 competed allosterically with Ca V β subunit for binding to the I-II loop of Ca V 1.2 channel. This competitive disruption of Ca V β binding led to Ca V 1.2 degradation by exposing the channels to poly-ubiquitination. Notably, we demonstrated that the inverse relationship of reduced Gal-1 and increased Ca V 1.2 protein levels in arteries was associated with hypertension in hypertensive rats and patients, and Gal-1 deficiency induces higher blood pressure in mice due to up-regulated Ca V 1.2 protein level in arteries. To directly regulate blood pressure by targeting the Ca V 1.2-Gal-1 interaction, we administered Tat-e9c, a peptide that competed for binding of Gal-1, by a mini-osmotic pump and this specific disruption of Ca V 1.2-Gal-1 coupling increased smooth muscle Ca V 1.2 currents, induced larger arterial contraction and caused hypertension in rats. In contrasting experiments, over-expression of Gal-1 in smooth muscle by a single bolus of AAV5-Gal-1 significantly reduced blood pressure in spontaneously hypertensive rats. Conclusions -We have defined molecularly that Gal-1 promotes Ca V 1.2 degradation by replacing Ca V β and thereby exposing specific lysines for poly-ubiquitination, and by masking I-II loop ER export signals. This mechanistic understanding provided the basis for targeting Ca V 1.2-Gal-1 interaction to demonstrate clearly the modulatory role Gal-1 plays in regulating blood pressure, and offering a potential approach for therapeutic management of hypertension.

Na/Ca exchange in the basolateral membrane of the A6 cell monolayer: role in Cai homeostasis.

PubMed

Brochiero, E; Raschi, C; Ehrenfeld, J

1995-05-01

The presence of a Na/Ca exchanger in A6 cells was investigated by measuring intracellular calcium (Cai) fluctuations and the 45Ca fluxes through the basolateral membranes (blm) of the cell monolayer. Removal of Na+ from the medium produced a transient increase in Cai followed by a regulatory phase returning Cai to control levels in 3-4 min, this phase being greatly accelerated (< 60 s) by NaCl addition (apparent Km of approximately 5 mM Na+). The Cai increase was only found with the Na(+)-free medium on the basolateral side of the cell monolayer. A twofold increase in the 45Ca influx was observed under these conditions. In Ca(2+)- depleted cells, the initial Cai increase after Ca2+ addition to the medium was greater when the putative Na/Ca exchanger was not functioning (i.e. in a Na(+)-free medium). 45Ca effluxes through the blm of the monolayer were greatly and transiently increased by a Na(+)-free medium on the serosal side and blocked by orthovanadate (1 mM). The Cai increased induced by a hypo-osmotic shock was greater in cells bathed in a Na(+)-medium, conditions expected to block the activity of the Na/Ca exchanger. These findings support the hypothesis that a Na/Ca exchanger is present on the blm of A6 cells and affirm its role in Cai homeostasis in steady-state conditions and following osmotic shock. In addition, a Ca2+ pump also located on the blm and Ca2+ stores sensitive to inositol 1,4,5-trisphosphate were found to be implicated in Cai homeostasis.

UTP – Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells

PubMed Central

Liñán-Rico, Andromeda; Ochoa-Cortes, Fernando; Zuleta-Alarcon, Alix; Alhaj, Mazin; Tili, Esmerina; Enneking, Josh; Harzman, Alan; Grants, Iveta; Bergese, Sergio; Christofi, Fievos L.

2017-01-01

Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca2+-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well. We tested the hypothesis that UTP is a regulator of 5-HT release in human EC cells. Methods: UTP signaling mechanisms were studied in BON cells, a human EC model, using Fluo-4/Ca2+imaging, patch-clamp, pharmacological analysis, immunohistochemistry, western blots and qPCR. 5-HT release was monitored in BON or EC isolated from human gut surgical specimens (hEC). Results: UTP, UTPγS, UDP or ATP induced Ca2+oscillations in BON. UTP evoked a biphasic concentration-dependent Ca2+response. Cells responded in the order of UTP, ATP > UTPγS > UDP >> MRS2768, BzATP, α,β-MeATP > MRS2365, MRS2690, and NF546. Different proportions of cells activated by UTP and ATP also responded to UTPγS (P2Y4, 50% cells), UDP (P2Y6, 30%), UTPγS and UDP (14%) or MRS2768 (<3%). UTP Ca2+responses were blocked with inhibitors of PLC, IP3R, SERCA Ca2+pump, La3+sensitive Ca2+channels or chelation of intracellular free Ca2+ by BAPTA/AM. Inhibitors of L-type, TRPC, ryanodine-Ca2+pools, PI3-Kinase, PKC or SRC-Kinase had no effect. UTP stimulated voltage-sensitive Ca2+currents (ICa), Vm-depolarization and inhibited IK (not IA) currents. An IKv7.2/7.3 K+ channel blocker XE-991 mimicked UTP-induced Vm-depolarization and blocked UTP-responses. XE-991 blocked IK and UTP caused further reduction. La3+ or PLC inhibitors blocked UTP depolarization; PKC inhibitors, thapsigargin or zero Ca2+buffer did not. UTP stimulated 5-HT release in hEC expressing TPH1, 5-HT, P2Y4/P2Y6R. Zero-Ca2+buffer augmented Ca2+responses and 5-HT release. Conclusion: UTP activates a predominant P2Y4R pathway to trigger Ca2+oscillations via internal Ca2+mobilization through a PLC/IP3/IP3R/SERCA Ca2+signaling pathway to stimulate 5-HT release; Ca2+influx is inhibitory. UTP-induced Vm-depolarization depends on PLC signaling and an unidentified K channel (which appears independent of Ca2+oscillations or Ica/VOCC). UTP-gated signaling pathways triggered by activation of P2Y4R stimulate 5-HT release. PMID:28751862

Synthesis, crystal structures, and physical properties of the new Zintl phases A{sub 21}Zn{sub 4}Pn{sub 18} (A=Ca, Eu; Pn=As, Sb)—Versatile arrangements of [ZnPn{sub 4}] tetrahedra

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

Suen, Nian-Tzu; Wang, Yi; Bobev, Svilen, E-mail: bobev@udel.edu

Four new Zintl phases, Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18} and Eu{sub 21}Zn{sub 4}Sb{sub 18} have been synthesized by metal flux reactions. Their structures have been established from single-crystal X-ray diffraction. Despite the similar chemical makeup and the identical formulae, the structures of the four compounds are not the same—Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18} and Eu{sub 21}Zn{sub 4}As{sub 18} crystallize in the monoclinic space group C2/m (No. 12, Z=4) with the β-Ca{sub 21}Mn{sub 4}Sb{sub 18} structure type, while Eu{sub 21}Zn{sub 4}Sb{sub 18} adopts the Ba{sub 21}Cd{sub 4}Sb{sub 18} structure type withmore » the orthorhombic space group Cmce (No. 64, Z=8). Both structures are based on ZnAs{sub 4} or ZnSb{sub 4} tetrahedra, linked in slightly different ways, and Ca{sup 2+} and Eu{sup 2+} cations that fill the space between them. The structural relationships between the title compounds and other known ternary phases with intricate structures are discussed. Electrical resistivity measurement on single-crystalline Eu{sub 21}Zn{sub 4}Sb{sub 18} suggests an intrinsic semiconductor behavior with a band gap of ca. 0.2 eV. The temperature dependent DC magnetization measurement on the same material indicates Curie–Weiss paramagnetism in the high-temperature regime, and a spontaneous antiferromagnetic ordering below 8 K. The calculated effective moments of Eu confirm the divalent Eu{sup 2+} ground state, as expected from the Zintl–Klemm concept. - Graphical abstract: The four new Zintl phases—Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18}, and Eu{sub 21}Zn{sub 4}Sb{sub 18}—crystallize in two structure types, showing the versatility in the arrangements of ZnAs{sub 4} and ZnSb{sub 4} tetrahedra. - Highlights: • Ca{sub 21}Zn{sub 4}As{sub 18}, Ca{sub 21}Zn{sub 4}Sb{sub 18}, Eu{sub 21}Zn{sub 4}As{sub 18}, and Eu{sub 21}Zn{sub 4}Sb{sub 18} are new compounds in the respective ternary phase diagrams. • They form with structure types, showing the versatility in the arrangements of ZnAs{sub 4} and ZnSb{sub 4} tetrahedra. • For both structures, the valence electron count follows the Zintl–Klemm rules.« less

Measurement and simulation of myoplasmic calcium transients in mouse slow-twitch muscle fibres.

PubMed

Hollingworth, Stephen; Kim, Michele M; Baylor, Stephen M

2012-02-01

Bundles of intact fibres from soleus muscles of adult mice were isolated by dissection and one fibre within a bundle was micro-injected with either furaptra or mag-fluo-4, two low-affinity rapidly responding Ca(2+) indicators. Fibres were activated by action potentials to elicit changes in indicator fluorescence (ΔF), a monitor of the myoplasmic free Ca(2+) transient ([Ca(2+)]), and changes in fibre tension. All injected fibres appeared to be slow-twitch (type I) fibres as inferred from the time course of their tension responses. The full-duration at half-maximum (FDHM) of ΔF was found to be essentially identical with the two indicators; the mean value was 8.4 ± 0.3 ms (±SEM) at 16°C and 5.1 ± 0.3 ms at 22°C. The value at 22°C is about one-third that reported previously in enzyme-dissociated slow-twitch fibres that had been AM-loaded with mag-fluo-4: 12.4 ± 0.8 ms and 17.2 ± 1.7 ms. We attribute the larger FDHM in enzyme-dissociated fibres either to an alteration of fibre properties due to the enzyme treatment or to some error in the measurement of ΔF associated with AM loading. ΔF in intact fibres was simulated with a multi-compartment reaction-diffusion model that permitted estimation of the amount and time course of Ca(2+) release from the sarcoplasmic reticulum (SR), the binding and diffusion of Ca(2+) in the myoplasm, the re-uptake of Ca(2+) by the SR Ca(2+) pump, and Δ[Ca(2+)] itself. In response to one action potential at 16°C, the following estimates were obtained: 107 μm for the amount of Ca(2+) release; 1.7 ms for the FDHM of the release flux; 7.6 μm and 4.9 ms for the peak and FDHM of spatially averaged Δ[Ca(2+)]. With five action potentials at 67 Hz, the estimated amount of Ca(2+) release is 186 μm. Two important unknown model parameters are the on- and off-rate constants of the reaction between Ca(2+) and the regulatory sites on troponin; values of 0.4 × 10(8) m(-1) s(-1) and 26 s(-1), respectively, were found to be consistent with the ΔF measurements.

The influence of managed versus natural hydrologic regimes on the hydrochemical patterns in a constructed wetland in the Athabasca oil sands region, Canada.

NASA Astrophysics Data System (ADS)

Biagi, K.; Oswald, C.; Nicholls, E.; Carey, S.

2017-12-01

Bitumen extraction via surface mining in the Athabasca Oil Sands Region (AOSR) results in permanent alteration of the landscape once rich in boreal forest and wetlands. As part of their legal requirements, oil companies must reclaim disturbed landscapes into functioning ecosystems, and to date only two pilot wetland-peatland systems have been constructed. Peatland reclamation is challenging as they must be completely reconstructed with few guidelines or previous work in this region. Furthermore, the variable sub-humid climate and salinity of waste-materials are obstacles to the success of peatland creation. In 2012, Syncrude Canada Ltd. constructed a 52 ha upland-wetland system, the Sandhill Fen Watershed (SFW), which was designed with a pump and underdrain system to provide freshwater and enhance drainage to limit salinization from underlying waste materials that have elevated electrical conductivity (EC) and Na+. The objective of this research is to understand the hydrochemical response of a constructed wetland to variations in hydrological management with respect to sources, flow pathways and major chemical transformations of water in the three years following commissioning. EC, major ions and stable isotopes were collected using a combination of high frequency and discrete water sampling from 2013-2015. Results indicate that high activity of both inflow and outflow pumps in 2013 kept the EC relatively low, with most wetland sites <1000 µS/cm. Ca+2 was the dominant cation in 2013, averaging 105 mg/L in the wetland while Na+ averaged 56 mg/L. With limited pump activity in 2014 and 2015, the EC and ion concentrations increased considerably with EC in the wetland >1000 µS/cm in 2014 and >2000 µS/cm in 2015. Most wetland sites remained Ca+2 dominant where Ca+2 and Na+ averaged 200 and 130 mg/L, respectively. However, the most notable change in 2014 and 2015 was the emergence of several Na+ "hotspots" in the margins where Na+ concentrations averaged 450 mg/L while Ca+2 averaged 250 mg/L. Stable isotope data confirm that the "hotspots" match the underlying waste water and provide evidence of its upward transport and seepage under a natural hydrologic regime. Minimizing salinization is critical for reclamation in the AOSR, and lessons learned from SFW will guide both current and future peatland creation efforts.

Uptake of CO2, SO2, HNO3 and HCl on calcite (CaCO3) at 300 K: mechanism and the role of adsorbed water.

PubMed

Santschi, Ch; Rossi, M J

2006-06-01

All experimental observations of the uptake of the four title compounds on calcite are consistent with the presence of a reactive bifunctional surface intermediate Ca(OH)(HCO3) that has been proposed in the literature. The uptake of CO2 and SO2 occurs on specific adsorption sites of crystalline CaCO3(s) rather than by dissolution in adsorbed water, H2O(ads). SO2 primarily interacts with the bicarbonate moiety whereas CO2, HNO3 and HCl all react first with the hydroxyl group of the surface intermediate. Subsequently, the latter two react with the bicarbonate group to presumably form Ca(NO3)2 and CaCl2.2H2O. The effective equilibrium constant of the interaction of CO2 with calcite in the presence of H2O(ads) is kappa = deltaCO2/(H2O(ads)[CO2]) = 1.62 x 10(3) bar(-1), where CO2 is the quantity of CO2 adsorbed on CaCO3. The reaction mechanism involves a weakly bound precursor species that is reversibly adsorbed and undergoes rate-controlling concurrent reactions with both functionalities of the surface intermediate. The initial uptake coefficients gamma0 on calcite powder depend on the abundance of H2O(ads) under the present experimental conditions and are on the order of 10(-4) for CO2 and 0.1 for SO2, HNO3 and HCl, with gamma(ss) being significantly smaller than gamma0 for HNO3 and HCl, thus indicating partial saturation of the uptake. At 33% relative humidity and 300 K there are 3.5 layers of H2O adsorbed on calcite that reduce to a fraction of a monolayer of weakly and strongly bound water upon pumping and/or heating.

Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.

PubMed

Heck, Dorothee; Wortmann, Sebastian; Kraus, Luitgard; Ronchi, Cristina L; Sinnott, Richard O; Fassnacht, Martin; Sbiera, Silviu

2015-12-01

Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

STAR FORMATION AND FEEDBACK: A MOLECULAR OUTFLOW–PRESTELLAR CORE INTERACTION IN L1689N

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

Lis, D. C.; Pagani, L.; Wootten, H. A.

2016-08-20

We present Herschel ,{sup 11} ALMA Compact Array (ACA), and Caltech Submillimeter Observatory observations of the prestellar core in L1689N, which has been suggested to be interacting with a molecular outflow driven by the nearby solar-type protostar IRAS 16293-2422. This source is characterized by some of the highest deuteration levels observed in the interstellar medium. The change in the NH{sub 2}D line velocity and width across the core provides clear evidence of an interaction with the outflow, traced by the high-velocity water emission. Quiescent, cold gas characterized by narrow line widths is seen in the NE part of the core,more » while broader, more disturbed line profiles are seen in the W/SW part. Strong N{sub 2}D{sup +} and ND{sub 3} emission is detected with ACA extending S/SW from the peak of the single-dish NH{sub 2}D emission. The ACA data also reveal the presence a compact dust continuum source with a mean size of ∼1100 au, a central density of (1–2) × 10{sup 7} cm{sup −3}, and a mass of 0.2–0.4 M {sub ⊙}. The dust emission peak is displaced ∼5″ to the south with respect to the N{sub 2}D{sup +} and ND{sub 3} emission, as well as the single-dish dust continuum peak, suggesting that the northern, quiescent part of the core is characterized by spatially extended continuum emission, which is resolved out by the interferometer. We see no clear evidence of fragmentation in this quiescent part of the core, which could lead to a second generation of star formation, although a weak dust continuum source is detected in this region in the ACA data.« less

Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium.

PubMed

Decker, Keith F; Heijman, Jordi; Silva, Jonathan R; Hund, Thomas J; Rudy, Yoram

2009-04-01

Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I(to1)), the slow component of the delayed rectifier K(+) current (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump current (I(NaK)) fit to data from canine ventricular myocytes. We found that I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic reticulum Ca(2+) release for propagated APs but modulates the time course of APD restitution. I(Ks) plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I(Ca,L) plays a critical role in APD accommodation and rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn increases Na(+) extrusion via outward I(NaK). APD accommodation results from this increased outward I(NaK). Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.

Readmissions, Observation, and the Hospital Readmissions Reduction Program.

PubMed

Zuckerman, Rachael B; Sheingold, Steven H; Orav, E John; Ruhter, Joel; Epstein, Arnold M

2016-04-21

The Hospital Readmissions Reduction Program, which is included in the Affordable Care Act (ACA), applies financial penalties to hospitals that have higher-than-expected readmission rates for targeted conditions. Some policy analysts worry that reductions in readmissions are being achieved by keeping returning patients in observation units instead of formally readmitting them to the hospital. We examined the changes in readmission rates and stays in observation units over time for targeted and nontargeted conditions and assessed whether hospitals that had greater increases in observation-service use had greater reductions in readmissions. We compared monthly, hospital-level rates of readmission and observation-service use within 30 days after hospital discharge among Medicare elderly beneficiaries from October 2007 through May 2015. We used an interrupted time-series model to determine when trends changed and whether changes differed between targeted and nontargeted conditions. We assessed the correlation between changes in readmission rates and use of observation services after adoption of the ACA in March 2010. We analyzed data from 3387 hospitals. From 2007 to 2015, readmission rates for targeted conditions declined from 21.5% to 17.8%, and rates for nontargeted conditions declined from 15.3% to 13.1%. Shortly after passage of the ACA, the readmission rate declined quickly, especially for targeted conditions, and then continued to fall at a slower rate after October 2012 for both targeted and nontargeted conditions. Stays in observation units for targeted conditions increased from 2.6% in 2007 to 4.7% in 2015, and rates for nontargeted conditions increased from 2.5% to 4.2%. Within hospitals, there was no significant association between changes in observation-unit stays and readmissions after implementation of the ACA. Readmission trends are consistent with hospitals' responding to incentives to reduce readmissions, including the financial penalties for readmissions under the ACA. We did not find evidence that changes in observation-unit stays accounted for the decrease in readmissions.

Glaucoma anterior chamber morphometry based on optical Scheimpflug images.

PubMed

Alonso, Ruiz Simonato; Ambrósio Junior, Renato; Paranhos Junior, Augusto; Sakata, Lisandro Massanori; Ventura, Marcelo Palis

2010-01-01

To compare the performance of gonioscopy and noncontact morphometry with anterior chamber tomography (High Resolution Pentacam - HR) using optical Scheimpflug images in the evaluation of the anterior chamber angle (ACA). Transversal study. 112 eyes from 74 subjects evaluated at the Glaucoma Department, Fluminense Federal University, underwent gonioscopy and Pentacam HR. Using gonioscopy, the ACA was graded using the Shaffer Classification (SC) by a single experienced examiner masked to the Pentacam HR findings. Narrow angle was determined in eyes in which the posterior trabecular meshwork could not be seen in two or more quadrants on non-indentation gonioscopy (SC Grade 2 or less). Pentacam HR images of the nasal and temporal quadrants were evaluated by custom software to automatically obtain anterior chamber measurements, such as: anterior chamber angle (ACA), anterior chamber volume (ACV) and anterior chamber depth (ACD). Based on gonioscopy results, 74 (60.07%) eyes of patients classified as open-angle (SC 3 and 4) and 38 (33.93%) eyes of patients classified as narrow-angle (SC 1 and 2). Noncontact morphometry with Scheimpflug images revealed a mean ACA of 39.20 ± 5.31 degrees for open-angle and 21.18 ± 7.98 degrees for narrow-angle. The open-angle group showed significant greater ACV and ACD values when compared to narrow-angle group (ACV of 193 ± 36 mm³ vs. 90 ± 25 mm³, respectively, p<0.001; and ACD of 3,09 ± 0,42 mm vs. 1,55 ± 0,64 mm, respectively, p<0.0001.). In screening eyes with open-angle and narrow-angle with the Pentacam ACA of 20º (SC Grade 2) using the ROC curves, the analysis showed 52.6% of sensitivity and 100% of specificity. The Pentacam showed ability in detecting eyes at risk for angle closure analyzing ACV and ACD.

Glucose acutely decreases pH of secretory granules in mouse pancreatic islets. Mechanisms and influence on insulin secretion.

PubMed

Stiernet, Patrick; Guiot, Yves; Gilon, Patrick; Henquin, Jean-Claude

2006-08-04

Glucose-induced insulin secretion requires a rise in beta-cell cytosolic Ca2+ ([Ca2+]c) that triggers exocytosis and a mechanistically unexplained amplification of the action of [Ca2+]c. Insulin granules are kept acidic by luminal pumping of protons with simultaneous Cl- uptake to maintain electroneutrality. Experiments using patched, dialyzed beta-cells prompted the suggestion that acute granule acidification by glucose underlies amplification of insulin secretion. However, others found glucose to increase granular pH in intact islets. In this study, we measured islet granular pH with Lysosensor DND-160, a fluorescent dye that permits ratiometric determination of pH < 6 in acidic compartments. Stimulation of mouse islets with glucose reversibly decreased granular pH by mechanisms that are dependent on metabolism and Cl- ions but independent of changes in [Ca2+]c and protein kinase A or C activity. Granular pH was increased by concanamycin (blocker of the vesicular type H+-ATPase) > methylamine (weak base) > Cl- omission. Concanamycin and methylamine did not alter glucose-induced [Ca2+]c increase in islets but strongly inhibited the two phases of insulin secretion. Omission of Cl- did not affect the first phase but decreased the second phase of both [Ca2+]c and insulin responses. Neither experimental condition affected the [Ca2+]c rise induced by 30 mM KCl, but the insulin responses were inhibited by concanamycin > methylamine and not affected by Cl- omission. The amplification of insulin secretion by glucose was not suppressed. We conclude that an acidic granular pH is important for insulin secretion but that the acute further acidification produced by glucose is not essential for the augmentation of secretion via the amplifying pathway.

Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores

PubMed Central

Kochan, Travis J.; Kaiser, Alyssa M.; Hastie, Jessica L.; Giordano, Nicole P.; Smith, Ashley D.

2017-01-01

Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI. PMID:28704538

Separation of High Order Harmonics with Fluoride Windows

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

Allison, Tom; van Tilborg, Jeroen; Wright, Travis

2010-08-02

The lower orders produced in high order harmonic generation can be effciently temporally separated into monochromatic pulses by propagation in a Fluoride window while still preserving their femtosecond pulse duration. We present calculations for MgF2, CaF2, and LiF windows for the third, fifth, and seventh harmonics of 800 nm. We demonstrate the use of this simple and inexpensive technique in a femtosecond pump/probe experiment using the fifth harmonic.

Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation.

PubMed

Betzer, Cristine; Lassen, Louise Berkhoudt; Olsen, Anders; Kofoed, Rikke Hahn; Reimer, Lasse; Gregersen, Emil; Zheng, Jin; Calì, Tito; Gai, Wei-Ping; Chen, Tong; Moeller, Arne; Brini, Marisa; Fu, Yuhong; Halliday, Glenda; Brudek, Tomasz; Aznar, Susana; Pakkenberg, Bente; Andersen, Jens Peter; Jensen, Poul Henning

2018-05-01

Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca 2+ and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced cytosolic Ca 2+ levels followed by a later Ca 2+ increase. Aggregated but not monomeric α-synuclein binds to and activates SERCA in vitro , and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase in cytosolic Ca 2+ CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and in Caenorhabditis elegans in vivo Proximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies. We conclude that α-synuclein aggregates bind SERCA and stimulate its activity. Reducing SERCA activity is neuroprotective, indicating that SERCA and down-stream processes may be therapeutic targets for treating α-synucleinopathies. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Effects of Fuel Temperature on Injection Process and Combustion of Dimethyl Ether Engine.

PubMed

Guangxin, Gao; Zhulin, Yuan; Apeng, Zhou; Shenghua, Liu; Yanju, Wei

2013-12-01

To investigate the effects of fuel temperature on the injection process in the fuel-injection pipe and the combustion characteristics of compression ignition (CI) engine, tests on a four stroke, direct injection dimethyl ether (DME) engine were conducted. Experimental results show that as the fuel temperature increases from 20 to 40 °C, the sound speed is decreased by 12.2%, the peak line pressure at pump and nozzle sides are decreased by 7.2% and 5.6%, respectively. Meanwhile, the injection timing is retarded by 2.2 °CA and the injection duration is extended by 0.8 °CA. Accordingly, the ignition delay and the combustion duration are extended by 0.7 °CA and 4.0 °CA, respectively. The cylinder peak pressure is decreased by 5.4%. As a result, the effective thermal efficiency is decreased, especially for temperature above 40 °C. Before beginning an experiment, the fuel properties of DME, including the density, the bulk modulus, and the sound speed were calculated by "ThermoData." The calculated result of sound speed is consistent with the experimental results.

The Protective Role of Selenium on Scopolamine-Induced Memory Impairment, Oxidative Stress, and Apoptosis in Aged Rats: The Involvement of TRPM2 and TRPV1 Channels.

PubMed

Balaban, Hasan; Nazıroğlu, Mustafa; Demirci, Kadir; Övey, İshak Suat

2017-05-01

Inhibition of Ca 2+ entry into the hippocampus and dorsal root ganglion (DRG) through inhibition of N-methyl-D-aspartate (NMDA) receptor antagonist drugs is the current standard of care in neuronal diseases such as Alzheimer's disease, dementia, and peripheral pain. Oxidative stress activates Ca 2+ -permeable TRPM2 and TRPV1, and recent studies indicate that selenium (Se) is a potent TRPM2 and TRPV1 channel antagonist in the hippocampus and DRG. In this study, we investigated the neuroprotective properties of Se in primary hippocampal and DRG neuron cultures of aged rats when given alone or in combination with scopolamine (SCOP). Thirty-two aged (18-24 months old) rats were divided into four groups. The first and second groups received a placebo and SCOP (1 mg/kg/day), respectively. The third and fourth groups received intraperitoneal Se (1.5 mg/kg/ over day) and SCOP + Se, respectively. The hippocampal and DRG neurons also were stimulated in vitro with a TRPV1 channel agonist (capsaicin) and a TRPM2 channel agonist (cumene hydroperoxide). We found that Se was fully effective in reversing SCOP-induced TRPM2 and TRPV1 current densities as well as errors in working memory and reference memory. In addition, Se completely reduced SCOP-induced oxidative toxicity by modulating lipid peroxidation, reducing glutathione and glutathione peroxidase. The Se and SCOP + Se treatments also decreased poly (ADP-ribose) polymerase activity, intracellular free Ca 2+ concentrations, apoptosis, and caspase 3, caspase 9, and mitochondrial membrane depolarization values in the hippocampus. In conclusion, the current study reports on the cellular level for SCOP and Se on the different endocytotoxic cascades for the first time. Notably, the research indicates that Se can result in remarkable neuroprotective and memory impairment effects in the hippocampal neurons of rats. Graphical abstract Possible molecular pathways of involvement of selenium (Se) in scopolamine (SCOP) induced apoptosis, oxidative stress, and calcium accumulation through TRPM2 and TRPV1 channels in the hippocampus neurons of aged rats. The TRPM2 channel is activated by ADP-ribose and oxidative stress, although it is inhibited by ACA. The TRPV1 channel is activated by oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). The beta-amyloid plaque induces oxidative stress in hippocampus. SCOP can result in augmented ROS release in hippocampal neurons, leading to Ca 2+ uptake through TRPM2 and TRPV1 channels. Mitochondria were reported to accumulate Ca 2+ provided that intracellular Ca 2+ rises, thereby leading to the depolarization of mitochondrial membranes and release of apoptosis-inducing factors such as caspase 3 and caspase 9. Se reduced TRPM2 and TRPV1 channel activation through the modulation of aging oxidative reactions and Se-dependent glutathione peroxidase (GSH-Px) antioxidant pathways.

Accurate and Precise Bottom Water Paleotemperatures from Aragonitic Benthic Foraminiferal Li/Mg: Calibration, Theory, and Application

NASA Astrophysics Data System (ADS)

Marchitto, T. M., Jr.; Valley, S.; Lynch-Stieglitz, J.

2015-12-01

While great progress has been made in reconstructing past sea surface temperatures, reliable bottom water paleotemperature measurements are not routinely available. We suggest that Li/Mg ratios in biogenic aragonites, particularly in the cosmopolitan benthic foraminifer Hoeglundina elegans, have the potential to bridge this gap. Core top calibration shows that H. elegans Li/Mg decreases by 5.5% per °C (r2 = 0.91), with a relationship that is nearly identical to that displayed by a wide range of corals (r2 = 0.95). The fact that such disparate organisms behave so similarly suggests to us that thermodynamics are shining through the 'vital effects' that so often plague paleoceanographic proxies. We hypothesize that Ca2+ pumping causes Li/Ca and Mg/Ca ratios in the organisms' calcification pools to decline, while Li/Mg remains constant. Rayleigh fractionation has the opposite effect on calcification pool Li/Ca and Mg/Ca (they rise), while Li/Mg still remains essentially constant. Hence any environmental influences on Ca2+ pumping and/or Rayleigh fractionation, such as seawater carbonate chemistry, have no measurable effects on aragonite Li/Mg. Our first downcore test of the Li/Mg proxy is performed in core KNR166-2-26JPC from 546 m water depth in the Florida Straits. Benthic foraminiferal δ18O was previously used to document decreased seawater density during both Heinrich Stadial 1 (HS1) and the Younger Dryas (YD), consistent with flattening of isopycnals across the Florida Current caused by slowdown of the AMOC. Here we show striking agreement between H. elegans Li/Mg and ice-volume-corrected δ18O temperatures since ~17 ka (in both absolute values and temporal changes), confirming that bottom waters abruptly warmed during HS1 and the YD. The YD, which is better-resolved, was ~2°C warmer than the Holocene. Li/Mg indicates that Last Glacial Maximum bottom waters were ~2-3°C, or ~5°C colder than during the Holocene. If these glacial temperatures are accurate, they require a similar seawater δ18O to today, which suggests relative freshening in the face of higher mean ocean δ18O. Overall the Li/Mg paleotemperature reproducibility is very good, with a median five-depth running standard deviation of <0.6°C (even before omitting apparent outliers), a number which certainly includes real temporal variability.

Involvement of plasma membrane Ca2+ channels, IP3 receptors, and ryanodine receptors in the generation of spontaneous rhythmic contractions of the cricket lateral oviduct.

PubMed

Tamashiro, Hirotake; Yoshino, Masami

2014-12-01

In the present study, the isolated cricket (Gryllus bimaculatus) lateral oviduct exhibited spontaneous rhythmic contractions (SRCs) with a frequency of 0.29±0.009 Hz (n=43) and an amplitude of 14.6±1.25 mg (n=29). SRCs completely disappeared following removal of extracellular Ca2+ using a solution containing 5mM EGTA. Application of the non-specific Ca2+ channel blockers Co2+, Ni2+, and Cd2+ also decreased both the frequency and amplitude of SRCs in dose-dependent manners, suggesting that Ca2+ entry through plasma membrane Ca2+ channels is essential for the generation of SRCs. Application of ryanodine (30 μM), which depletes intracellular Ca2+ by locking ryanodine receptor (RyR)-Ca2+ channels in an open state, gradually reduced the frequency and amplitude of SRCs. A RyR antagonist, tetracaine, reduced both the frequency and amplitude of SRCs, whereas a RyR activator, caffeine, increased the frequency of SRCs with a subsequent increase in basal tonus, indicating that RyRs are essential for generating SRCs. To further investigate the involvement of phospholipase C (PLC) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in SRCs, we examined the effect of a PLC inhibitor, U73122, and an IP3R antagonist, 2-aminoethoxydiphenyl borate (2-APB), on SRCs. Separately, U73122 (10 μM) and 2-APB (30-50 μM) both significantly reduced the amplitude of SRCs with little effect on their frequency, further indicating that the PLC/IP3R signaling pathway is fundamental to the modulation of the amplitude of SRCs. A hypotonic-induced increase in the frequency and amplitude of SRCs and a hypertonic-induced decrease in the frequency and amplitude of SRCs indicated that mechanical stretch of the lateral oviduct is involved in the generation of SRCs. The sarcoplasmic reticulum Ca2+-pump ATPase inhibitors thapsigargin and cyclopiazonic acid impaired or suppressed the relaxation phase of SRCs. Taken together, the present results indicate that Ca2+ influx through plasma membrane Ca2+ channels and Ca2+ release from RyRs play an essential role in pacing SRCs and that Ca2+ release from IP3Rs may play a role in modulating the amplitude of SRCs, probably via activation of PLC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

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

Faddy, Helen M.; Smart, Chanel E.; Xu, Ren

2008-04-09

The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold duringmore » lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.« less

1'-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations.

PubMed

In, Lionel L A; Arshad, Norhafiza M; Ibrahim, Halijah; Azmi, Mohamad Nurul; Awang, Khalijah; Nagoor, Noor Hasima

2012-10-09

Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-κB through suppression of IKKα/β activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-κB regulated gene (FasL and Bim), including proinflammatory (NF-κB and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger.

1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

PubMed Central

2012-01-01

Background Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1’S-1’-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes. Methods Whether ACA can inhibit the growth of oral squamous cell carcinoma (SCC) cells alone or in combination with cisplatin (CDDP), was explored both in vitro using MTT assays and in vivo using Nu/Nu mice. Occurrence of apoptosis was assessed using PARP and DNA fragmentation assays, while the mode of action were elucidated through global expression profiling followed by Western blotting and IHC assays. Results We found that ACA alone inhibited the growth of oral SCC cells, induced apoptosis and suppressed its migration rate, while minimally affecting HMEC normal cells. ACA further enhanced the cytotoxic effects of CDDP in a synergistic manner as suggested by combination index studies. We also found that ACA inhibited the constitutive activation of NF-κB through suppression of IKKα/β activation. Human oral tumor xenografts studies in mice revealed that ACA alone was as effective as CDDP in reducing tumor volume, and further potentiated CDDP effects when used in combination with minimal body weight loss. The effects of ACA also correlated with a down-regulation of NF-κB regulated gene (FasL and Bim), including proinflammatory (NF-κB and COX-2) and proliferative (cyclin D1) biomarkers in tumor tissue. Conclusion Overall, our results suggest that ACA inhibits the growth of oral SCC and further potentiates the effect of standard CDDP treatment by modulation of proinflammatory microenvironment. The current preclinical data could form the basis for further clinical trials to improve the current standards for oral cancer care using this active component from the Malaysian ginger. PMID:23043547

In vitro evaluation of encapsulated primary rat hepatocytes pre- and post-cryopreservation at -80°C and in liquid nitrogen.

PubMed

Durkut, Serap; Elçin, A Eser; Elçin, Y Murat

2015-02-01

Encapsulation techniques have the potential to protect hepatocytes from cryoinjury. In this study, we comparatively evaluated the viability and metabolic function of primary rat hepatocytes encapsulated in calcium alginate microbeads, in chitosan tripolyphosphate beads, and in three-layered alginate-chitosan-alginate (ACA) microcapsules, before and after cryopreservation at -80°C and in liquid nitrogen (LN2) for 1 and 3 months. Findings demonstrated that LN2 was atop of -80°C in regard to preservation of viability (> 90%) and hepatic functions. LN2-cryopreserved hepatocytes encapsulated in ACA microcapsules retained metabolic function post-thawing, with > 90% of the albumin, total protein and urea syntheses activities, and > 80% of oxidative function.

Non-linearity of the response accommodative convergence to accommodation ratio.

PubMed

Johnston, Miriam S; Firth, Alison Y

2013-09-01

Previous studies have reported variation in stimulus accommodative convergence to accommodation (AC/A) ratio across differing accommodative stimuli. Response AC/A ratio was assessed across 4 accommodative demands to determine if these differences could be due to accommodative inaccuracies to stimuli. Twenty-three student participants aged 18 to 26 years (mean age 20.3 ± 1.7 years) successfully completed all testing conditions. The modified Thorington technique was used at 4 m to measure heterophoria. The Shin Nippon SRW 5000 infrared autorefractor was used to determine accommodative change to -1.50, -3.00, -4.50, and -6.00D lens stimuli. Significant differences were found in response AC/A ratio between different minus lens stimulated accommodative demands (p < 0.001). Mean AC/A ratio values were 3.11 ± 1.29 with the -1.50D lens stimulus; 4.03 ± 2.11 with -3.00D; 4.14 ± 1.40 with -4.50D; and 4.48 ± 1.56 with -6.00D. No differences in linearity were noted between myopes and non-myopic participants, but myopes tended to have higher response AC/A ratios than non-myopes, mean 4.88 ± 1.89 for myopes vs 3.61 ± 1.47 for non-myopes (p = 0.045). Response AC/A ratio did not display linearity across 4 minus lens accommodative stimuli, but tended to increase with accommodative demand. Significant variability in response AC/A ratio was found, both within individuals to different accommodative demands, and between individuals across the data set.

Characteristics of Posterior Corneal Astigmatism in Different Stages of Keratoconus.

PubMed

Aslani, Fereshteh; Khorrami-Nejad, Masoud; Aghazadeh Amiri, Mohammad; Hashemian, Hesam; Askarizadeh, Farshad; Khosravi, Bahram

2018-01-01

To evaluate the magnitudes and axis orientation of anterior corneal astigmatism (ACA) and posterior corneal astigmatism (PCA), the ratio of ACA to PCA, and the correlation between ACA and PCA in the different stages of keratoconus (KCN). This retrospective case series comprised 161 eyes of 161 patients with KCN (104 men, 57 women; mean age, 22.35 ± 6.10 years). The participants were divided into four subgroups according to the Amsler-Krumeich classification. A Scheimpflug imaging system was used to measure the magnitude and axis orientation of ACA and PCA. The posterior-anterior corneal astigmatism ratio was also calculated. The results were compared among different subgroups. The average amounts of anterior, posterior, and total corneal astigmatism were 4.08 ± 2.21 diopters (D), 0.86 ± 0.46 D, and 3.50 ± 1.94 D, respectively. With-the-rule, against-the-rule, and oblique astigmatisms of the posterior surface of the cornea were found in 61 eyes (37.9%), 67 eyes (41.6%), and 33 eyes (20.5%), respectively; corresponding figures in the anterior corneal surface were 55 eyes (32.4%), 56 eyes (34.8%), and 50 eyes (31.1%), respectively. A strong correlation ( P ≤ 0.001, r = 0.839) was found between ACA and PCA in the different stages of KCN; the correlation was weaker in eyes with grade 3 ( P ≤ 0.001, r = 0.711) and grade 4 ( P ≤ 0.001, r = 0.717) KCN. The maximum posterior-anterior corneal astigmatism ratio (PCA/ACA, 0.246) was found in patients with stage 1 KCN. Corneal astigmatism in anterior surface was more affected than posterior surface by increasing in the KCN severity, although PCA was more affected than ACA in an early stage of KCN.

Impacts of the Affordable Care Act's Medicaid Expansion on Women of Reproductive Age: Differences by Parental Status and State Policies.

PubMed

Johnston, Emily M; Strahan, Andrea E; Joski, Peter; Dunlop, Anne L; Adams, E Kathleen

We use data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2012 to 2015 to estimate the effects of the Affordable Care Act's (ACA) Medicaid expansions on insurance coverage and access to care for low-income women of reproductive age (19-44). We use two-way fixed effects difference-in-differences models to estimate the effects of Medicaid expansions on low-income (<100% of the Federal Poverty Level) women of reproductive age. Additional models are stratified to estimate effects based on women's parental status, pre-ACA state Medicaid eligibility levels, and the presence of a state Medicaid family planning waiver. ACA Medicaid expansions decreased uninsurance among low-income women of reproductive age by 13.2 percentage points. This decrease was driven by a decrease of 27.4 percentage points for women without dependent children, who also experienced a decrease in the likelihood of not having a personal doctor (13.3 percentage points). We find a 3.8-percentage point reduction in the likelihood of experiencing a cost barrier to care among all women, but no significant effects for other access measures or subgroups. When stratified by state policies, decreases in uninsurance were greater in states expanding from pre-ACA eligibility levels of less than 50% of Federal Poverty Level (19.4 percentage points) and in states without a Medicaid family planning waiver (17.6 percentage points). The ACA Medicaid expansion increased insurance coverage for low-income women of reproductive age, with the greatest effects for women without dependent children and women residing in states with relatively lower pre-ACA Medicaid eligibility levels or with no family planning waiver before the ACA. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Changes in premiums of cancelled nongroup plans under the Affordable Care Act.

PubMed

Maeda, Jared Lane L K; Chen, Jersey; Plemons, Brent R

2016-07-01

To examine the effect of the Affordable Care Act (ACA) on changes in premiums for subscribers of nongrandfathered, nongroup insurance plans that were "cancelled." Retrospective multivariate analyses. Changes in annual premiums post ACA were evaluated across subgroups of subscriber and health plan characteristics. Data was derived from databases containing information on premiums, plan benefit, and demographics for subscribers aged 18 to 64 years within Kaiser Permanente of the Mid-Atlantic States. A linear regression model was used to examine the independent association between subscriber and health plan characteristics on the relative change in premiums. In 2013, 4169 nongroup subscribers were enrolled in plans that were cancelled as a result of the ACA. The median pre-ACA premium was $3240 (range = $780-$39,492), which increased by a median of 21.3% (range = -77.4% to 193.6%), or $685 (range = -$27,464 to $8676), post ACA in 2014. Premiums increased more for high-deductible plans (median = 63.7%) than standard-deductible plans (median = 8.4%). Due to shifts in the age curve, premiums decreased for more than half of women aged 18 to 44 years, but increased by 35.2% for women aged 55 to 64 years. Premiums fell by 15.5% for subscribers who did not pass standard medical underwriting due to preexisting conditions. Changes in premiums in the nongroup market post ACA, varied substantially across subgroups, primarily due to differences in the amount of coverage, changes in rating criteria, shifts in the age curve, and anticipated differences in risk selection and composition of the risk pool. Given the extent of this variation, it would be incorrect to conclude the ACA as being uniformly beneficial or detrimental to subscribers of these cancelled plans.

An anti-steroidogenic inhibitory primer pheromone in male sea lamprey (Petromyzon marinus)

USGS Publications Warehouse

Chung-Davidson, Yu-Wen; Wang, Huiyong; Bryan, Mara B.; Wu, Hong; Johnson, Nicholas S.; Li, Weiming

2013-01-01

Reproductive functions can be modulated by both stimulatory and inhibitory primer pheromones released by conspecifics. Many stimulatory primer pheromones have been documented, but relatively few inhibitory primer pheromones have been reported in vertebrates. The sea lamprey male sex pheromone system presents an advantageous model to explore the stimulatory and inhibitory primer pheromone functions in vertebrates since several pheromone components have been identified. We hypothesized that a candidate sex pheromone component, 7α, 12α-dihydroxy-5α-cholan-3-one-24-oic acid (3 keto-allocholic acid or 3kACA), exerts priming effects through the hypothalamic-pituitary-gonadal (HPG) axis. To test this hypothesis, we measured the peptide concentrations and gene expressions of lamprey gonadotropin releasing hormones (lGnRH) and the HPG output in immature male sea lamprey exposed to waterborne 3kACA. Exposure to waterborne 3kACA altered neuronal activation markers such as jun and jun N-terminal kinase (JNK), and lGnRH mRNA levels in the brain. Waterborne 3kACA also increased lGnRH-III, but not lGnRH-I or -II, in the forebrain. In the plasma, 3kACA exposure decreased all three lGnRH peptide concentrations after 1 h exposure. After 2 h exposure, 3kACA increased lGnRHI and -III, but decreased lGnRH-II peptide concentrations in the plasma. Plasma lGnRH peptide concentrations showed differential phasic patterns. Group housing condition appeared to increase the averaged plasma lGnRH levels in male sea lamprey compared to isolated males. Interestingly, 15α-hydroxyprogesterone (15α-P) concentrations decreased after prolonged 3kACA exposure (at least 24 h). To our knowledge, this is the only known synthetic vertebrate pheromone component that inhibits steroidogenesis in males.

Metallogeny of precious and base metal mineralization in the Murchison Greenstone Belt, South Africa: indications from U-Pb and Pb-Pb geochronology

NASA Astrophysics Data System (ADS)

Jaguin, J.; Poujol, M.; Boulvais, P.; Robb, L. J.; Paquette, J. L.

2012-10-01

The 3.09 to 2.97 Ga Murchison Greenstone Belt is an important metallotect in the northern Kaapvaal Craton (South Africa), hosting several precious and base metal deposits. Central to the metallotect is the Antimony Line, striking ENE for over 35 km, which hosts a series of structurally controlled Sb-Au deposits. To the north of the Antimony Line, hosted within felsic volcanic rocks, is the Copper-Zinc Line where a series of small, ca. 2.97 Ga Cu-Zn volcanogenic massive sulfide (VMS)-type deposits occur. New data are provided for the Malati Pump gold mine, located at the eastern end of the Antimony Line. Crystallizations of a granodiorite in the Malati Pump Mine and of the Baderoukwe granodiorite are dated at 2,964 ± 7 and 2,970 ± 7 Ma, respectively (zircon U-Pb), while pyrite associated with gold mineralization yielded a Pb-Pb age of 2,967 ± 48 Ma. Therefore, granodiorite emplacement, sulfide mineral deposition and gold mineralization all happened at ca. 2.97 Ga. It is, thus, suggested that the major styles of orogenic Au-Sb and the Cu-Zn VMS mineralization in the Murchison Greenstone Belt are contemporaneous and that the formation of meso- to epithermal Au-Sb mineralization at fairly shallow levels was accompanied by submarine extrusion of felsic volcanic rocks to form associated Cu-Zn VMS mineralization.

Imbalance of plasma membrane ion leak and pump relationship as a new aetiological basis of certain disease states.

PubMed

Ronquist, G; Waldenström, A

2003-12-01

The basis for life is the ability of the cell to maintain ion gradients across biological membranes. Such gradients are created by specific membrane-bound ion pumps [adenosine triphosphatases (ATPases)]. According to physicochemical rules passive forces equilibrate (dissipate) ion gradients. The cholesterol/phospholipid ratio of the membrane and the degree of saturation of phospholipid fatty acids are important factors for membrane molecular order and herewith a determinant of the degree of non-specific membrane leakiness. Other operative principles, i.e. specific ion channels can be opened and closed according to mechanisms that are specific to the cell. Certain compounds called ionophores can be integrated in the plasma membrane and permit specific inorganic ions to pass. Irrespective of which mechanism ions leak across the plasma membrane the homeostasis may be kept by increasing ion pumping (ATPase activity) in an attempt to restore the physiological ion gradient. The energy source for this work seems to be glycolytically derived ATP formation. Thus an increase in ion pumping is reflected by increased ATP hydrolysis and rate of glycolysis. This can be measured as an accumulation of breakdown products of ATP and end-products of anaerobic glycolysis (lactate). In certain disease entities, the balance between ATP formation and ion pumping may be disordered resulting in a decrease in inter alia (i.a.) cellular energy charge, and an increase in lactate formation and catabolites of adenylates. Cardiac syndrome X is proposed to be due to an excessive leakage of potassium ions, leading to electrocardiographic (ECG) changes, abnormal Tl-scintigraphy of the heart and anginal pain (induced by adenosine). Cocksackie B3 infections, a common agent in myocarditis might also induce an ionophore-like effect. Moreover, Alzheimer's disease is characterized by the formation of extracellular amyloid deposits in the brain of patients. Perturbation of cellular membranes by the amyloid peptide during the development of Alzheimer's disease is one of several mechanisms proposed to account for the toxicity of this peptide on neuronal membranes. We have studied the effects of the peptide and fragments thereof on 45Ca2+-uptake in human erythrocytes and the energetic consequences. Treatment of erythrocytes with the beta 1-40 peptide, results in qualitatively similar nucleotide pattern and decrease of energy charge as the treatment with Ca2+-ionophore A23187. Finally, in recent studies we have revealed and published in this journal that a rare condition, Tarui's disease or glycogenosis type VII, primarily associated with a defect M-subunit of phosphofructokinase, demonstrates as a cophenomenon an increased leak of Ca2+ into erythrocytes.

Alterations in expression of senescence marker protein-30 gene by 3,3',5-triiodo-L-thyronine (T3).

PubMed

Sar, Pranati; Rath, Bandita; Subudhi, Umakanta; Chainy, Gagan Bihari Nityananda; Supakar, Prakash Chandra

2007-09-01

Thyroid hormone (T3) is essential for normal development, differentiation, and metabolic balance of the body. A toxic dose of T(3) in animals increases the basal metabolic rate and reactive oxygen species production, resulting more oxidative stress through Ca(2+) influx to cytoplasm. Senescence Marker Protein-30 (SMP30) is preferentially expressed in the liver and protects cells against various injuries by enhancement of Ca(2+) efflux to either extra cellular space or intraorganellar spaces through membrane Ca(2+) pump activity. In this paper we report an alteration in the level of SMP30 gene expression using RT-PCR and western blot analysis in T(3) treated female Wistar rats. The results indicate that there is an induction of SMP30 expression during early hours of T(3 )treatment and it declines in severe hyperthyroidism. Therefore, we speculate that SMP30 is regulated by T(3) and might play a protective role in hyperthyroidism.

Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria.

PubMed

Kaur, Harparkash; Allan, Elizabeth Louise; Mamadu, Ibrahim; Hall, Zoe; Ibe, Ogochukwu; El Sherbiny, Mohamed; van Wyk, Albert; Yeung, Shunmay; Swamidoss, Isabel; Green, Michael D; Dwivedi, Prabha; Culzoni, Maria Julia; Clarke, Siân; Schellenberg, David; Fernández, Facundo M; Onwujekwe, Obinna

2015-01-01

Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. ACAs were purchased using three sampling approaches--convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained.

From syncitium to regulated pump: a cardiac muscle cellular update

PubMed Central

2011-01-01

The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca2+ microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca2+ cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca2+ from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca2+ homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca2+-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle. PMID:21385997

Role of H(+)-pyrophosphatase activity in the regulation of intracellular pH in a scuticociliate parasite of turbot: Physiological effects.

PubMed

Mallo, Natalia; Lamas, Jesús; de Felipe, Ana-Paula; Sueiro, Rosa-Ana; Fontenla, Francisco; Leiro, José-Manuel

2016-10-01

The scuticociliatosis is a very serious disease that affects the cultured turbot, and whose causal agent is the anphizoic and marine euryhaline ciliate Philasterides dicentrarchi. Several protozoans possess acidic organelles that contain high concentrations of pyrophosphate (PPi), Ca(2+) and other elements with essential roles in vesicular trafficking, pH homeostasis and osmoregulation. P. dicentrarchi possesses a pyrophosphatase (H(+)-PPase) that pumps H(+) through the membranes of vacuolar and alveolar sacs. These compartments share common features with the acidocalcisomes described in other parasitic protozoa (e.g. acid content and Ca(2+) storage). We evaluated the effects of Ca(2+) and ATP on H (+)-PPase activity in this ciliate and analyzed their role in maintaining intracellular pH homeostasis and osmoregulation, by the addition of PPi and inorganic molecules that affect osmolarity. Addition of PPi led to acidification of the intracellular compartments, while the addition of ATP, CaCl2 and bisphosphonates analogous of PPi and Ca(2+) metabolism regulators led to alkalinization and a decrease in H(+)-PPase expression in trophozoites. Addition of NaCl led to proton release, intracellular Ca(2+) accumulation and downregulation of H(+)-PPase expression. We conclude that the regulation of the acidification of intracellular compartments may be essential for maintaining the intracellular pH homeostasis necessary for survival of ciliates and their adaptation to salt stress, which they will presumably face during the endoparasitic phase, in which the salinity levels are lower than in their natural environment. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma membrane calcium ATPase 4 (PMCA4) co-ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity.

PubMed

Olli, Kristine E; Li, Kun; Galileo, Deni S; Martin-DeLeon, Patricia A

2018-01-01

Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca 2+ -ATPase 4 (Pmca4) gene which encodes the highly conserved Ca 2+ efflux pump, PMCA4. This is the major Ca 2+ clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased. Using co-immunoprecipitation (Co-IP) and Fluorescence Resonance Energy Transfer (FRET), we show an association of PMCA4 with the NOSs in elevated cytosolic [Ca 2+ ] in capacitated and Ca 2+ ionophore-treated sperm and with neuronal (nNOS) at basal [Ca 2+ ] (ucapacitated sperm). FRET efficiencies for PMCA4-eNOS were 35% and 23% in capacitated and uncapacitated sperm, significantly (p < 0.01) different, with the molecules being <10 nm apart. For PMCA4-nNOS, this interaction was seen only for capacitated sperm where FRET efficiency was 24%, significantly (p < 0.05) higher than in uncapacitated sperm (6%). PMCA4 and the NOSs were identified as interacting partners in a quaternary complex that includes Caveolin1, which co-immunoprecipitated with eNOS in a Ca 2+ -dependent manner. In Pmca4 -/- sperm NOS activity was elevated twofold in capacitated/uncapacitated sperm (vs. wild-type), accompanied by a twofold increase in peroxynitrite levels and significantly (p < 0.001) increased numbers of apoptotic germ cells. The data support a quaternary complex model in which PMCA4 co-ordinates Ca 2+ and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4 -/- males. They suggest the involvement of PMCA4 mutations in human asthenospermia, with diagnostic relevance. © 2017 Wiley Periodicals, Inc.