Comparative Proteomic Analysis Reveals the Effects of Exogenous Calcium against Acid Rain Stress in Liquidambar formosana Hance Leaves.

PubMed

Hu, Wen-Jun; Wu, Qian; Liu, Xiang; Shen, Zhi-Jun; Chen, Juan; Liu, Ting-Wu; Chen, Juan; Zhu, Chun-Quan; Wu, Fei-Hua; Chen, Lin; Wei, Jia; Qiu, Xiao-Yun; Shen, Guo-Xin; Zheng, Hai-Lei

2016-01-04

Acid rain (AR) impacts forest health by leaching calcium (Ca) away from soils and plants. Ca is an essential element and participates in various plant physiological responses. In the present study, the protective role of exogenous Ca in alleviating AR stress in Liquidambar formosana Hance at the physiological and proteomic levels was examined. Our results showed that low Ca condition resulted in the chlorophyll content and photosynthesis decreasing significantly in L. formosana leaves; however, these effects could be reversed by high Ca supplementation. Further proteomic analyses successfully identified 81 differentially expressed proteins in AR-treated L. formosana under different Ca levels. In particular, some of the proteins are involved in primary metabolism, photosynthesis, energy production, antioxidant defense, transcription, and translation. Moreover, quantitative real time polymerase chain reaction (qRT-PCR) results indicated that low Ca significantly increased the expression level of the investigated Ca-related genes, which can be reversed by high Ca supplementation under AR stress. Further, Western blotting analysis revealed that exogenous Ca supply reduced AR damage by elevating the expression of proteins involved in the Calvin cycle, reactive oxygen species (ROS) scavenging system. These findings allowed us to better understand how woody plants respond to AR stress at various Ca levels and the protective role of exogenous Ca against AR stress in forest tree species.

Identification and Levels of 2′-Carboxyarabinitol in Leaves 1

PubMed Central

Moore, Brandon d.; Sharkey, Thomas D.; Kobza, John; Seemann, Jeffrey R.

1992-01-01

2′-Carboxyarabinitol 1-phosphate (CA1P) is a naturally occurring inhibitor of ribulose-1,5 bisphosphate carboxylase/oxygenase activity. A chloroplast phosphatase has previously been identified that degrades CA1P in vitro to carboxyarabinitol (CA) plus phosphate, but CA has not yet been detected in plants. Here, we detail procedures to isolate and assay CA from leaves and utilize mass spectrometry to demonstrate for the first time that CA is present in plants. CA was present in leaves of all 13 species examined, including those of C3, C4, and Crassulacean acid metabolism photosynthetic subgroups. CA was present both in species with high levels of CA1P (e.g. Phaseolus vulgaris, Lycopersicon esculentum, Beta vulgaris) as well as in species with low levels of CA1P (e.g. Spinacea oleracea, Triticum aestivum). CA levels in the light were sometimes greater than those in the dark. Bean leaves had the most CA of any species tested, with levels in the light approaching 1 micromole per milligram of chlorophyll. In illuminated bean leaves, about 63% of the CA is located outside the chloroplast. CA is one of only a few branched chain sugar acids to be identified from plants. PMID:16669072

HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant.

PubMed

Growdon, Whitfield B; Groeneweg, Jolijn; Byron, Virginia; DiGloria, Celeste; Borger, Darrell R; Tambouret, Rosemary; Foster, Rosemary; Chenna, Ahmed; Sperinde, Jeff; Winslow, John; Rueda, Bo R

2015-04-01

Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000 and 2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest®), HER2 fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag® testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8RF/mm2 was observed in 53% (n=54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p<0.001). These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Bioelements in hair of children with selected neurological disorders.

PubMed

Józefczuk, Jan; Kasprzycka, Wiktoria; Czarnecki, Rafał; Graczyk, Alfreda; Józefczuk, Paweł; Krzysztof, Magda; Lampart, Urszula; Mrozowska-Ząbek, Ewa; Surdy, Weronika; Kwiatkowska-Graczyk, Róża

2017-01-01

We have analyzed concentrations of magnesium (Mg), calcium (Ca), copper (Cu), zinc (Zn) and iron (Fe) in hair of a group of 82 children with mental retardation, in which 9 patients suffered from epilepsy, 18 from the Down's syndrome and 55 from cerebral palsy. Girls comprised little over 50% of the patients. In the group of boys with epilepsy, we found Mg, Ca, Cu and Fe deficiency, and normal level of Zn. In the group of girls with epilepsy, apart from low Fe concentration, a high level of Ca, Mg, Zn, and Cu was noted. For girls with the Down's syndrome, a high or normal level of Ca, Mg, Zn and Cu was found, whereas the Fe concentration varied and presented itself in a non-characteristic way. Both groups of children with cerebral palsy, i.e. boys and girls, displayed low Fe concentration in their hair; low Cu level was found in older patients as well. In this group of patients, we also noted high concentrations of Ca, Mg and Zn in girls and normal in boys. A high concentration of Ca in girls with cerebral palsy requires separate analysis. The obtained results could be useful as guidance in the direction and determination of the amount of possible patient nutritional supplementation.

Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.

PubMed

Uharcek, P; Mlyncek, M; Ravinger, J

2007-01-01

Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.

Ionic regulation of the cardiac sodium-calcium exchanger.

PubMed

Reeves, John P; Condrescu, Madalina

2008-01-01

The Na(+)-Ca(2+) exchanger (NCX) links transmembrane movements of Ca(2+) ions to the reciprocal movement of Na(+) ions. It normally functions primarily as a Ca(2+) efflux mechanism in excitable tissues such as the heart, but it can also mediate Ca(2+) influx under certain conditions. Na(+) and Ca(2+) ions exert complex regulatory effects on NCX activity. Ca(2+) binds to two regulatory sites in the exchanger's central hydrophilic domain, and this interaction is normally essential for activation of exchange activity. High cytosolic Na(+) concentrations, however, can induce a constitutive activity that by-passes the need for allosteric Ca(2+) activation. Constitutive NCX activity can also be induced by high levels of phopshotidylinositol-4,5-bisphosphate (PIP₂) and by mutations affecting the regulatory calcium binding domains. In addition to promoting constitutive activity, high cytosolic Na(+) concentrations also induce an inactivated state of the exchanger (Na(+)-dependent inactivation) that becomes dominant when cytosolic pH and PIP₂ levels fall. Na(+)-dependent inactivation may provide a means of protecting cells from Ca(2+) overload due to NCX-mediated Ca(2+) influx during ischemia.

Identifying and predicting subgroups of information needs among cancer patients: an initial study using latent class analysis.

PubMed

Neumann, Melanie; Wirtz, Markus; Ernstmann, Nicole; Ommen, Oliver; Längler, Alfred; Edelhäuser, Friedrich; Scheffer, Christian; Tauschel, Diethard; Pfaff, Holger

2011-08-01

Understanding how the information needs of cancer patients (CaPts) vary is important because met information needs affect health outcomes and CaPts' satisfaction. The goals of the study were to identify subgroups of CaPts based on self-reported cancer- and treatment-related information needs and to determine whether subgroups could be predicted on the basis of selected sociodemographic, clinical and clinician-patient relationship variables. Three hundred twenty-three CaPts participated in a survey using the "Cancer Patients Information Needs" scale, which is a new tool for measuring cancer-related information needs. The number of information need subgroups and need profiles within each subgroup was identified using latent class analysis (LCA). Multinomial logistic regression was applied to predict class membership. LCA identified a model of five subgroups exhibiting differences in type and extent of CaPts' unmet information needs: a subgroup with "no unmet needs" (31.4% of the sample), two subgroups with "high level of psychosocial unmet information needs" (27.0% and 12.0%), a subgroup with "high level of purely medical unmet information needs" (16.0%) and a subgroup with "high level of medical and psychosocial unmet information needs" (13.6%). An assessment of sociodemographic and clinical characteristics revealed that younger CaPts and CaPts' requiring psychological support seem to belong to subgroups with a higher level of unmet information needs. However, the most significant predictor for the subgroups with unmet information needs is a good clinician-patient relationship, i.e. subjective perception of high level of trust in and caring attention from nurses together with high degree of physician empathy seems to be predictive for inclusion in the subgroup with no unmet information needs. The results of our study can be used by oncology nurses and physicians to increase their awareness of the complexity and heterogeneity of information needs among CaPts and of clinically significant subgroups of CaPts. Moreover, regression analyses indicate the following association: Nurses and physicians seem to be able to reduce CaPts' unmet information needs by establishing a relationship with the patient, which is trusting, caring and empathic.

Evaluation of CA125 and NT-proBNP values in patients undergoing transcatheter aortic valve implantation

PubMed Central

Ayhan, Hüseyin; Kasapkara, Hacı Ahmet; Durmaz, Tahir; Keleş, Telat; Sarı, Cenk; Baştuğ, Serdal; Erdoğan, Kemal Eşref; Bayram, Nihal Akar; Bilen, Emine; Akçay, Murat; Bozkurt, Engin

2015-01-01

Background Transcatheter aortic valve implantation (TAVI) is a minimally invasive, emerging therapy in surgically high risk, or inoperable patients. Parameters used for risk classification have some deficiencies in the selection of patients. The objective of this study is to evaluate the impact of TAVI on carbohydrate antigen 125 (CA125) and N-Terminal pro Brain-type Natriuretic Peptide (NT-proBNP) as biomarkers that have been used frequently in recent years, and also the relationship of these biomarkers to prognosis. Methods & Results Transcatheter aortic valve implantation was practiced on 31 patients in this study. Then, CA125 and NT-proBNP levels studied in patients prior to and after the TAVI were evaluated. The patients were also grouped in accordance with their left ventricular ejection fraction (LVEF) and CA125 levels (LVEF ≥ 40% and < 40%; CA125 ≤ 35 U/L and > 35 U/L). The TAVI operation was successfully performed in all patients. There was no in-hospital mortality and substantial improvement in functional capacity was detected at follow ups. In addition, a statistically significant decrease was detected in post-TAVI CA125 and NT-proBNP levels of all patients (CA125 83.8 ± 18.1 U/L vs. 64.3 ± 14.2 U/L, P = 0.008; NT-proBNP: 4633.6 ± 627.6 pg/mL vs. 2866.3 ± 536.8 pg/mL, P < 0.001). In groups divided according to the CA125 levels, there was also statistically significant post-TAVI decline in CA125 levels. Within CA125 > 35 U/L and LVEF < 40% groups, the permanent need for a pacemaker was required in one (3.2%) patient and mortality was observed in two (6.4%) patients after TAVI at follow up. Conclusions The results show that TAVI can be performed effectively and reliably in patients with high baseline levels of CA125 and NT-proBNP. These biomarkers are reduced substantially with TAVI, while high biomarker levels are associated with undesired events, and certainly, these biomarkers can be used for risk classifications in patient selection for TAVI. PMID:25870611

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

PubMed

Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

2018-02-12

Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

Calcium sources and their interaction with the different levels of non-phytate phosphorus affect performance and bone mineralization in broiler chickens.

PubMed

Hamdi, M; Solà-Oriol, D; Davin, R; Perez, J F

2015-09-01

An experiment was conducted to evaluate the influence of different Ca sources (limestone, Ca chloride, and Lipocal, a fat-encapsulated tricalcium phosphate, TCP) in conjunction with 4 dietary levels of non-phytate P (NPP) on performance, ileal digestibility of Ca and P, and bone mineralization in broiler chickens. Calcium sources were also evaluated in vitro to measure acid-binding capacity (ABC) and Ca solubility at different pH values. Ca chloride showed the highest solubility of Ca, with TCP showing the highest ABC. Ross male broiler-chicks were sorted by BW at 1 d post-hatch and assigned to 5 cages per diet with 5 birds per cage. Twelve diets were arranged in a 3×4 factorial of the 3 Ca sources and 4 levels of NPP (0.3%, 0.35%, 0.4% or 0.45%) consisting of 4 added P levels (Ca(H2PO4)2) with a high dose of phytase (1,150 U/kg) in all diets. On d 14 post-hatch, 3 birds were euthanized, and ileal digesta and the right tibia were collected to determine ileal Ca and P digestibility and bone mineralization, respectively. Feed intake (FI) and weight gain (WG) on d 14 was higher (P<0.01) with TCP and limestone than with Ca chloride. Added P increased the tibia weight and tibia ash content in chicks fed TCP up to 0.4% NPP and limestone up to 0.35% NPP. Calcium ileal digestibility was higher (P<0.01) with Ca chloride (73.7%) than with limestone (67.1%) or TCP (66.8%), which increased (P<0.05) with added levels of P from monocalcium phosphate. Phosphorus ileal digestibility was not affected by the Ca source and increased (P<0.001) with added levels of NPP. It can be concluded that starting broilers responded better to low-soluble Ca sources compared to high-soluble sources. A level of 0.35%-0.40% NPP with a high dose of phytase (1,150 U/kg) in diets including limestone or TCP is sufficient to guarantee performance and bone formation for broiler chickens from d 0 to d 14. © 2015 Poultry Science Association Inc.

Identification and functional characterization of the pepper CaDRT1 gene involved in the ABA-mediated drought stress response.

PubMed

Baek, Woonhee; Lim, Sohee; Lee, Sung Chul

2016-05-01

Plants are constantly challenged by various environmental stresses, including high salinity and drought, and they have evolved defense mechanisms to counteract the deleterious effects of these stresses. The plant hormone abscisic acid (ABA) regulates plant growth and developmental processes and mediates abiotic stress responses. Here, we identified the Capsicum annuum DRought Tolerance 1 (CaDRT1) gene from pepper leaves treated with ABA. CaDRT1 was strongly expressed in pepper leaves in response to environmental stresses and after ABA treatment, suggesting that the CaDRT1 protein functions in the abiotic stress response. Knockdown expression of CaDRT1 via virus-induced gene silencing resulted in a high level of drought susceptibility, and this was characterized by increased transpirational water loss via decreased stomatal closure. CaDRT1-overexpressing (OX) Arabidopsis plants exhibited an ABA-hypersensitive phenotype during the germinative, seedling, and adult stages. Additionally, these CaDRT1-OX plants exhibited a drought-tolerant phenotype characterized by low levels of transpirational water loss, high leaf temperatures, increased stomatal closure, and enhanced expression levels of drought-responsive genes. Taken together, our results suggest that CaDRT1 is a positive regulator of the ABA-mediated drought stress response.

Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy

PubMed Central

Javadzadeh, Alireza; Ghorbanihaghjo, Amir; Adl, Farzad Hami; Andalib, Dima; Khojasteh-Jafari, Hassan

2013-01-01

Purpose To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). Methods In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120–200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. Results The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69±0.32 pg/ml in the CaD group and 0.86±0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). Conclusions Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients. PMID:23335852

Calcium deficiency and CaCO/sub 3/ on micronutrient status of plants grown in solution culture. [Lycopersicon esculentum, Phaseolus vulgaris

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

Wallace, A.; Cha, J.W.; Alexander, G.V.

Plants were grown in solution culture with different levels of Ca to further evaluate Ca relationships to trace metal uptake and to toxicity of trace metals. When tomato plants (Lycopersicon esculentum L., Tropic) were grown at a low level of Ca, the Zn, Cu, Fe, Mn, Al, and Ti concentrations of leaves, stems, and roots were considerably increased. The use of an excess of CaCO/sub 3/ which increased pH did not influence the trace metal concentrations of plants any more than did Ca/sup + +/. In a factorial experiment with bush beans (Phaseolus vulgaris L. C.V. Improved Tendergreen) with Camore » (10/sup -4/, 10/sup -2/, 10/sup -2/N) and Ni (0, 2 x 10/sup -6/ M, 2 x 10/sup -5/ M), Ni phytotoxicity and Ni uptake were decreased somewhat at the highest Ca level. High Ni tended to decrease the Ca concentration in leaves. High Ca and Ni both tended to decrease Fe, Cu, Zn, and Mn concentrations in leaves. The Ni had some interactions on the P concentrations of shoots.« less

Normocalcemia without hyperparathyroidism in vitamin D-deficient rats.

PubMed

Kollenkirchen, U; Fox, J; Walters, M R

1991-03-01

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D3, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 +/- 0.8 and 7.2 +/- 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 +/- 3 versus 20 +/- 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 +/- 7 and 48 +/- 10 pg/ml, respectively). Plasma 25-OHD3 and 1,25-(OH)2D3 levels were reduced to less than 120 and less than 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei

PubMed Central

Zheng, Nan; Raman, Indira M.

2009-01-01

In neurons of the cerebellar nuclei, long-term potentiation of EPSCs is induced by high-frequency synaptic excitation by mossy fibers followed by synaptic inhibition by Purkinje cells. Induction requires activation of synaptic receptors as well as voltage-gated Ca channels. To examine how Purkinje-mediated inhibition of nuclear neurons affects Ca levels during plasticity-inducing stimuli, we have combined electrophysiology, Ca imaging, and pharmacology of cerebellar nuclear neurons in mouse cerebellar slices. We find that spontaneous firing generates tonic Ca signals in both somata and dendrites, which drop during 500-ms, 100-Hz trains of Purkinje IPSPs or hyperpolarizing steps. Although the presence of low-voltage-activated (T-type) Ca channels in nuclear neurons has fostered the inference that disinhibition activates these channels, synaptic inhibition with a physiological ECl (−75 mV) fails to hyperpolarize neurons sufficiently for T-type channels to recover substantially. Consequently, after IPSPs, Ca signals return to baseline, although firing is accelerated by ∼20 Hz for ∼300 ms. Only after hyperpolarizations beyond ECl does Ca rise gradually beyond baseline, as firing further exceeds spontaneous rates. Cd2+ (100 μM), which nearly eliminates L-type, N-type, P/Q-type, and R-type Ca currents while sparing about half the T-type current, prevents Ca changes during and after hyperpolarizations to ECl. Thus, high-frequency IPSPs in cerebellar nuclear neurons evoke little post-inhibitory current through T-type channels. Instead, inhibition regulates Ca levels simply by preventing action potentials, which usually permit Ca influx through high-voltage-activated channels. The decreases and restoration of Ca levels associated with Purkinje-mediated inhibition are likely to contribute to synaptic plasticity. PMID:19657035

Distribution of magnesium in central nervous system tissue, trabecular and cortical bone in rats fed with unbalanced diets of minerals.

PubMed

Yasui, M; Yano, I; Yase, Y; Ota, K

1990-11-01

Recent epidemiological changes in patterns of foci of amyotrophic lateral sclerosis (ALS) in the Western Pacific suggest that environmental factors play a contributory role in the pathogenic process of this disorder. In this experimental study on rats, a similar situation of dietary mineral imbalance was created as is found in the soil and drinking water of these ALS foci with a low content of calcium (Ca) and magnesium (Mg) and a high content of aluminum (Al). In groups of rats fed a low Ca diet, low Ca-Mg diet, and low Ca-Mg plus high Al diet, serum Ca levels were found to be lower than those in a group fed a standard diet. Also, serum Mg levels were lower in the groups fed a low Ca-Mg diet and a low Ca-Mg plus high Al diet than in the groups fed a standard diet and only a low Ca diet. There was no significant difference in Mg content of central nervous system (CNS) tissues of groups fed unbalanced and standard diets, except for a significant decrease in Mg content of the spinal cord of rats fed a low Ca-Mg plus high Al diet. Mg content of the lumbar spine and cortical bone decreased in the unbalanced diet groups compared with that of a group fed a standard diet. These findings suggest that under the disturbed bone mineralization induced by unbalanced mineral diets, Mg may be mobilized from bone to maintain the level necessary for vital activity in soft tissues including CNS tissue.

Self-Esteem Trajectories and Their Social Determinants in Adolescents With Different Levels of Cognitive Ability.

PubMed

Morin, Alexandre J S; Arens, A Katrin; Tracey, Danielle; Parker, Philip D; Ciarrochi, Joseph; Craven, Rhonda G; Maïano, Christophe

2017-11-01

This study examines the development of self-esteem in a sample of 138 Australian adolescents (90 males; 48 females) with cognitive abilities in the lowest 15% (L-CA) and a matched sample of 556 Australian adolescents (312 males; 244 females) with average to high levels of cognitive abilities (A/H-CA). These participants were measured annually (Grade 7 to 12). The findings showed that adolescents with L-CA and A/H-CA experience similar high and stable self-esteem trajectories that present similar relations with key predictors (sex, school usefulness and dislike, parenting, and peer integration). Both groups revealed substantial gender differences showing higher levels of self-esteem for adolescent males remaining relatively stable over time, compared to lower levels among adolescent females which decreased until midadolescence before increasing back.

The last interglacial period on the Pacific Coast of North America: Timing and paleoclimate

USGS Publications Warehouse

Muhs, D.R.; Simmons, K.R.; Kennedy, G.L.; Rockwell, T.K.

2002-01-01

New, high-precision U-series ages of solitary corals (Balanophyllia elegans) coupled with molluscan faunal data from marine terraces on the Pacific Coast of North America yield information about the timing and warmth of the last interglacial sea-level highstand. Balanophyllia elegans takes up U in isotopic equilibrium with seawater during growth and shortly after death. Corals from the second terrace on San Clemente Island (offshore southern California), the third terrace on Punta Banda (on the Pacific Coast of northern Baja California), and the Discovery Point Formation on Isla de Guadalupe (in the Pacific Ocean offshore Baja California) date to the peak of the last interglacial period and have U-series ages ranging from ca. 123 to 114 ka. The first terrace on Punta Banda has corals with ages ranging from ca. 83 to 80 ka, which corresponds to a sea-level highstand formed in the late last interglacial period. U-series analyses of corals from the Cayucos terrace (central California) and the Nestor terrace at Point Loma (southern California) show that these fossils have evidence of open-system history, similar to what has been reported by other workers for the same localities. Nevertheless, a model of continuous, secondary U and Th uptake shows that two ages of corals are likely present at these localities, representing the ca. 105 and ca. 120 ka sea-level highstands reported elsewhere. U-series ages of last interglacial corals from the Pacific Coast overlap with, but are on average younger than the ages of corals from Barbados, the Bahamas, and Hawaii. This age difference is explained by the nature of the geomorphic response to sea-level change: fringing or barrier reefs on low-latitude coastlines have an accretionary growth style that keeps pace with rising sea level, whether on a tectonically rising or stable coastline. In contrast, midlatitude, high-energy coastlines are sites of platform cutting during the early part of a sea-level high stand and terrace scouring and concomitant sediment and fossil deposition as sea level starts to recede. The youngest ages of corals from the Pacific Coast suggest that sea level was still relatively high at ca. 116 ka, which is not in agreement with other estimates of relatively large global ice volume at that time. Reliably dated, ca. 120 ka marine-terrace deposits on the Pacific Coast have fossil mollusks that indicate water temperatures as warm or warmer than at present. In contrast, ca. 80 ka marine deposits reported here and elsewhere have fossil mollusks indicating cooler-than-modern water temperatures. The presence of both ca. 105 ka and ca. 120 ka corals on the Nestor and Cayucos terraces explains a previously enigmatic mixture of warm-water and cool-water mollusks. At ca. 105 ka, a relatively high sea level with cool waters may have "captured" the terrace formed during the 120 ka sea-level highstand, in areas of low uplift rate. The inference of cooler-than-modern waters off the Pacific Coast of North America at ca. 80 ka and ca. 105 ka, based on marine-terrace faunas, does not agree with estimates of sea-surface temperatures derived from alkenone studies in the Santa Barbara Basin. However, cooler water temperatures at these times are in agreement with paleo-temperature estimates from planktonic foraminiferal data for the Santa Barbara Basin. All records, from central California to Baja California, whether from marine terraces or offshore cores, indicate at least seasonably warmer-than-modern waters during the peak of the last interglacial period at ca. 120 ka.

Usefulness of CA125 and their kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer levels.

PubMed

Palomar Muñoz, Azahara; Cordero García, José Manuel; Talavera Rubio, Prado; García Vicente, Ana M; González García, Beatriz; Bellón Guardia, María Emiliana; Soriano Castrejón, Ángel; Aranda Aguilar, Enrique

2017-12-21

To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [ 18 F]FDG-PET/CT. A retrospective analysis was performed of 59 [ 18 F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). [ 18 F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Chronic toxicity of a mixture of chlorinated alkanes and alkenes in ICR mice.

PubMed

Wang, Fun-In; Kuo, Min-Liang; Shun, Chia-Tung; Ma, Yee-Chung; Wang, Jung-Der; Ueng, Tzuu-Huei

2002-02-01

The aim of this study was to determine the chronic toxicity of a mixture of chlorinated alkanes and alkenes (CA) consisting of chloroform, 1,1-dichloroethane, 1,1-dichloroethylene, 1,1,1-trichloroethane, trichloroethylene, and tetrachloroethylene. These chlorinated organic solvents were present in the underground water near an electronic appliances manufactory in Taoyuan, Taiwan. Male and female weanling ICR mice were treated with low-, medium-, and high-dose CA mixtures in drinking water for 16 and 18 mo, respectively. A significant number of male mice treated with the high-dose CA mixture developed tail alopecia and deformation, which was not prominent in CA-treated female mice. Medium- and high-dose CA mixtures induced marginal increases of liver and lung weights, blood urea nitrogen, and serum creatinine levels in male mice. In female mice, the high-dose CA mixture increased liver, kidney, and uterus and ovary total weights, without affecting serum biochemistry parameters. CA mixtures had no effects on the total glutathione content or the level of glutathione S-transferase activity in the livers and kid- neys of male and female mice. Treatments with CA mixtures produced a trend of increasing frequency of hepatocelluar neoplasms in male mice, compared to male and female controls and CA-treated female mice. The high-dose CA mixture induced a significantly higher incidence of mammary adenocarcinoma in female mice. The calculated odds ratios of mammary adenocarcinoma in female mice induced by low-, medium-, and high-dose CA mixtures were 1.14, 1.37, and 3.53 times that of the controls, respectively. The low-dose CA mixture induced a higher incidence of cysts and inflammation in and around the ovaries. This study has demonstrated that the CA mixture is a potential carcinogen to male and female mice. These animal toxicology data may be important in assessing the health effects of individuals exposed to the CA mixture.

Functional analysis of the omega-6 fatty acid desaturase (CaFAD2) gene family of the oil seed crop Crambe abyssinica

PubMed Central

2013-01-01

Background Crambe abyssinica produces high erucic acid (C22:1, 55-60%) in the seed oil, which can be further increased by reduction of polyunsaturated fatty acid (PUFA) levels. The omega-6 fatty acid desaturase enzyme (FAD2) is known to be involved in PUFA biosynthesis. In crambe, three CaFAD2 genes, CaFAD2-C1, CaFAD2-C2 and CaFAD2-C3 are expressed. Results The individual effect of each CaFAD2 gene on oil composition was investigated through studying transgenic lines (CaFAD2-RNAi) for differential expression levels in relation to the composition of seed-oil. Six first generation transgenic plants (T1) showed C18:1 increase (by 6% to 10.5%) and PUFA reduction (by 8.6% to 10.2%). The silencing effect in these T1-plants ranged from the moderate silencing (40% to 50% reduction) of all three CaFAD2 genes to strong silencing (95% reduction) of CaFAD2-C3 alone. The progeny of two T1-plants (WG4-4 and WG19-6) was further analysed. Four or five transgene insertions are characterized in the progeny (T2) of WG19-6 in contrast to a single insertion in the T2 progeny of WG4-4. For the individual T2-plants of both families (WG19-6 and WG4-4), seed-specific silencing of CaFAD2-C1 and CaFAD2-C2 was observed in several individual T2-plants but, on average in both families, the level of silencing of these genes was not significant. A significant reduction in expression level (P < 0.01) in both families was only observed for CaFAD2-C3 together with significantly different C18:1 and PUFA levels in oil. Conclusions CaFAD2-C3 expression is highly correlated to levels of C18:1 (r = -0.78) and PUFA (r = 0.75), which suggests that CaFAD2-C3 is the most important one for changing the oil composition of crambe. PMID:24083776

Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

PubMed

Blair, Hannah A; Dhillon, Sohita

2014-10-01

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Dietary maifanite supplementation did not affect the apparent total tract digestibility of calcium and phosphorus in growing pigs

PubMed Central

Bai, Li Li; Ming, Dong Xu; Dong, Shu Ren; Yang, Zhong Yue; Wang, Wen Hui; Zhang, Shuai; Piao, Xiang Shu

2018-01-01

Objective This study was conducted to determine the effects of dietary maifanite supplementation and fecal collection method on the apparent total tract digestibility (ATTD) of calcium (Ca) and phosphorus (P) and blood parameters in growing pigs. Methods Thirty-six growing barrows (Duroc×Landrace×Yorkshire; 27.0±2.6 kg) were allotted to six dietary treatments with 6 pigs per treatment according to body weight in a completely randomized design. The experimental treatments were: i) Low Ca+cornstarch (2.25%), ii) Low Ca+maifanite (2.25%), iii) Medium Ca+cornstarch (1.42%), iv) Medium Ca+maifanite (1.42%), v) High Ca+cornstarch (0.64%), and vi) High Ca+maifanite (0.64%). Feces were collected by the total collection (TC) and indicator method (IM). At the beginning and the end of the experiment, blood samples were collected from each pig. Results For the TC method, there were no difference in Ca intake, fecal Ca output, Ca retention and the ATTD of Ca between cornstarch and maifanite diets at the same dietary Ca level. However, urinary Ca excretion was lower (p = 0.01) in pigs fed low Ca diets without maifanite supplementation compared with other dietary treatments. Dietary maifanite supplementation had no effect on the P metabolism in growing pigs. For the IM method, there was no difference in Ca digestibility between cornstarch and maifanite diets at the same dietary Ca level. The ATTD of P was greater (p<0.01) in pigs fed the high Ca diet with maifanite supplementation compared with the high Ca diet with cornstarch treatment. Dietary inclusion of maifanite had no effect on blood parameters in growing pigs. Conclusion Dietary maifanite supplementation had no effect on the ATTD of Ca and P and serum parameters in growing pigs. The IM resulted in lower digestibility values than the TC method. PMID:28728391

Intestinal absorption of calcium from calcium ascorbate in rats.

PubMed

Tsugawa, N; Yamabe, T; Takeuchi, A; Kamao, M; Nakagawa, K; Nishijima, K; Okano, T

1999-01-01

The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

High cyclophilin D content of synaptic mitochondria results in increased vulnerability to permeability transition.

PubMed

Naga, Kranthi Kumari; Sullivan, Patrick G; Geddes, James W

2007-07-11

Mitochondria isolated from synaptosomes are more sensitive to Ca2+ overload and the resultant opening of the mitochondrial permeability transition pore (mPTP) than nonsynaptic mitochondria. To identify the mechanisms underlying these differences in Ca2+ dynamics, we examined relative levels of mPTP components in synaptic versus nonsynaptic mitochondria. Synaptic mitochondria had higher levels of cyclophilin D when compared with nonsynaptic mitochondria, whereas levels of the voltage-dependent anion channel and the adenine nucleotide translocase were similar in the two mitochondrial fractions. These differences in Ca2+ handling between synaptic and nonsynaptic mitochondria were greatly reduced in cyclophilin D null [Ppif-/- (peptidylprolyl isomerase F)] mice. Higher concentrations of cyclosporine A, which interacts with cyclophilin D to delay mPTP opening, were necessary to increase the Ca2+ uptake capacity of synaptic versus nonsynaptic mitochondria. To determine whether the differences in Ca2+ handling might reflect the relative abundance of neuronal and glial mitochondria in the two mitochondrial fractions, we compared cyclophilin D levels in primary cortical neurons and astrocytes. Primary rat cortical neurons possess higher cyclophilin D levels than do primary astrocytes. In the adult rat brain, cyclophilin D immunoreactivity was abundant in neurons but sparse in astrocytes. Together, these results demonstrate that the Ca2+ handling differences observed in synaptic versus nonsynaptic mitochondria are primarily the result of the high levels of cyclophilin D in synaptic mitochondria, reflecting the greater proportion of neuronal mitochondria in this fraction. The high levels of cyclophilin D in neuronal mitochondria result in their greater vulnerability to mPT and in higher levels of cyclosporine A being required to inhibit mPTP opening.

Effects of dietary aluminum, calcium, and phosphorus on egg and bone of European starlings

USGS Publications Warehouse

Miles, A.K.; Grue, C.E.; Pendleton, G.W.; Soares, J.H.

1993-01-01

Egg and bone of passerine birds nesting in acidified habitats may be affected by high levels of Al or P, or low levels of Ca. Nine treatments of three levels of dietary Al (target levels of 200, 1,000, and 5,000 ?g/g) and three levels of Ca:P (target levels of NN = 1.3% Ca: 0.9% P; LL = 0.19 Ca:0.45 P; LH = 0.19 Ca:1.65 P) were fed to 16-17 starling pairs during two breeding seasons. Eggs of starlings fed the LH diet were smaller and weighed less than eggs from the NN and LL treatments. Treatment effects on thickness, strength, and weight of eggshells were not consistent between seasons, probably because of differences in actual dietary levels of AI, Ca, and P or in incubation intervals. In one season, birds fed the highest Al diet had thicker eggshells than those from the other Al treatments (no effect from Ca:P); the following season, eggshells from the NN and LH treatments were thicker and stronger than those from the LL treatment. Eggshells from the NN treatment weighed more than those from the other Ca:P treatments. Starlings on the LH diet had the strongest femurs, but the effect was interactive with different levels of dietary AI. Effects of Ca:P on egg and bone were more evident than Al effects.

Drastic lake level changes of Lake Van (eastern Turkey) during the past ca. 600 ka: climatic, volcanic and tectonic control

NASA Astrophysics Data System (ADS)

Cukur, D.; Krastel, S.; Schmincke, H.; Sumita, M.; Tomonaga, Y.; Damci, E.

2013-12-01

Lake Van is the largest soda lake in the world with a present surface of 3,574 km2 and a maximum water depth of 450 m. Sedimentary deposits in the lake preserve one of the most complete record of continental climate in the Middle East since the Middle Pleistocene. We studied these deposits to characterize the evolution of the lake level and its possible relationships with changes in climate, volcanic, and regional tectonics since the formation of the lake ca. 600 ka ago. Changes in lake level were determined based on high-resolution seismic reflection profiles showing erosional surfaces, changes in stratal geometries such as downward shifts in coastal onlap, and recognition of distinctive stratigraphic features such as prograding delta clinoforms. Our results show that Lake Van has undergone drastic changes in surface elevation by as much as 600 meters over the past ca. 600 ka. Five major lowstands occurred at ca. ~600 ka, ca. 365-340 ka, ca 290-230 ka; ca. 150-130 ka; and ca. 30-14 ka. During a first period (A) (ca. 600-ca 230 ka) lake levels changed drastically by hundreds of m but at longer time intervals between low and high stands. Changes occurred more frequently but mostly by a few tens of m during the past ca. 230 ka years where we can distinguish a first period (B1) of stepwise transgressions between ca. 230 and 150 ka followed by a short regression between ca. 150 and 130 ka. Lake level rose stepwise again during period B2 lasting until ca 30 ka. During the past 30 ka a regression and a final transgression each lasted ca. 15 ka years. The major lowstand periods in Lake Van occurred during glacial periods, arguing for a climatic control of these lake-level fluctuations (i.e., significantly reduced precipitation leading to lake level low stands). Although climate forcing may have been the dominant cause for the drastic lake level changes of Lake Van, volcanic and tectonic forcing factors are also invoked. For example, the number of distinct tephra layers, some several meters thick, has drastically increased in the upper ca 100 m (the past ca. 230 ka). The highest density of excellent reflectors occurs in this interval. Tectonic activity evidenced by extensional and/or compressional faults across the basin margins may have also affected the lake level fluctuations in Lake Van. This series of reconstructions using seismic stratigraphy from this study enlighten the understanding of tectonically-active lacustrine basins and provide a model for similar basins elsewhere.

Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

PubMed Central

Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

2012-01-01

Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

PubMed

Antwi, Samuel O; Steck, Susan E; Zhang, Hongmei; Stumm, Lareissa; Zhang, Jiajia; Hurley, Thomas G; Hebert, James R

2015-10-01

Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence. Copyright © 2015. Published by Elsevier Ltd.

Neurite-specific Ca2+ dynamics underlying sound processing in an auditory interneurone.

PubMed

Baden, T; Hedwig, B

2007-01-01

Concepts on neuronal signal processing and integration at a cellular and subcellular level are driven by recording techniques and model systems available. The cricket CNS with the omega-1-neurone (ON1) provides a model system for auditory pattern recognition and directional processing. Exploiting ON1's planar structure we simultaneously imaged free intracellular Ca(2+) at both input and output neurites and recorded the membrane potential in vivo during acoustic stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed the onset spike rate of ON1, while the final Ca(2+) level depended on the mean spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations and only gradually in the axon and the cell body. Ca(2+) levels were particularly high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive K(+) current this may exhibit a specific control over the cell's electrical response properties. In all cellular compartments presentation of species-specific calling song caused distinct oscillations of the Ca(2+) level in the chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated hyperpolarization of ON1 suppressed background spike activity between chirps, acting as a noise filter. During directional auditory processing, the functional interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition was demonstrated. Upon stimulation with different sound frequencies, the dendrites, but not the axonal arborizations, demonstrated a tonotopic response profile. This mirrored the dominance of the species-specific carrier frequency and resulted in spatial filtering of high frequency auditory inputs. (c) 2006 Wiley Periodicals, Inc.

Peak bone strength is influenced by calcium intake in growing rats.

PubMed

Viguet-Carrin, S; Hoppler, M; Membrez Scalfo, F; Vuichoud, J; Vigo, M; Offord, E A; Ammann, P

2014-11-01

In this study we investigated the effect of supplementing the diet of the growing male rat with different levels of calcium (from low to higher than recommended intakes at constant Ca/P ratio), on multiple factors (bone mass, strength, size, geometry, material properties, turnover) influencing bone strength during the bone accrual period. Rats, age 28days were supplemented for 4weeks with high Ca (1.2%), adequate Ca (0.5%) or low Ca level (0.2%). Bone metabolism and structural parameters were measured. No changes in body weight or food intake were observed among the groups. As anticipated, compared to the adequate Ca intake, low-Ca intake had a detrimental impact on bone growth (33.63 vs. 33.68mm), bone strength (-19.7% for failure load), bone architecture (-58% for BV/TV) and peak bone mass accrual (-29% for BMD) due to the hormonal disruption implied in Ca metabolism. In contrast, novel, surprising results were observed in that higher than adequate Ca intake resulted in improved peak bone strength (106 vs. 184N/mm for the stiffness and 61 vs. 89N for the failure load) and bone material properties (467 vs. 514mPa for tissue hardness) but these effects were not accompanied by changes in bone mass, size, microarchitecture or bone turnover. Hormonal factors, IGF-I and bone modeling were also evaluated. Compared to the adequate level of Ca, IGF-I level was significantly lower in the low-Ca intake group and significantly higher in the high-Ca intake group. No detrimental effects of high Ca were observed on bone modeling (assessed by histomorphometry and bone markers), at least in this short-term intervention. In conclusion, the decrease in failure load in the low calcium group can be explained by the change in bone geometry and bone mass parameters. Thus, improvements in mechanical properties can be explained by the improved quality of intrinsic bone tissue as shown by nanoindentation. These results suggest that supplemental Ca may be beneficial for the attainment of peak bone strength and that multiple factors linked to bone mass and strength should be taken into account when setting dietary levels of adequate mineral intake to support optimal peak bone mass acquisition. Copyright © 2014 Elsevier Inc. All rights reserved.

High-Grade Serous Ovarian Cancer: Use of Machine Learning to Predict Abdominopelvic Recurrence on CT on the Basis of Serial Cancer Antigen 125 Levels.

PubMed

Shinagare, Atul B; Balthazar, Patricia; Ip, Ivan K; Lacson, Ronilda; Liu, Joyce; Ramaiya, Nikhil; Khorasani, Ramin

2018-05-19

The aim of this study was to use machine learning to predict abdominal recurrence on CT on the basis of serial cancer antigen 125 (CA125) levels in patients with advanced high-grade serous ovarian cancer on surveillance. This institutional review board-approved, HIPAA-compliant, retrospective, hypothesis-generating study included all 57 patients (mean age, 61 ± 11.2 years) with advanced high-grade serous ovarian cancer who underwent cytoreductive surgery from January to December 2012, followed by surveillance abdominopelvic CT and corresponding CA125 levels. A blinded radiologist reviewed abdominopelvic CT studies until recurrence was noted. Four measures of CA125 were assessed: actual CA125 levels at the time of CT, absolute change since prior CT, relative change since prior CT, and rate of change since prior CT. Using machine learning, support vector machine models were optimized and evaluated using 10-fold cross-validation to determine the CA125 measure most predictive of abdominal recurrence. The association of the most accurate CA125 measure was further analyzed using Cox proportional-hazards model along with age, tumor size, stage, and degree of cytoreduction. Rate of change in CA125 was most predictive of abdominal recurrence in a linear kernel support vector machine model and was significantly higher preceding CT studies showing abdominal recurrence (median 13.2 versus 0.6 units/month; P = .007). On multivariate analysis, a higher rate of CA125 increase was significantly associated with recurrence (hazard ratio, 1.02 per 10 units change; 95% confidence interval, 1.0006-1.04; P = .04). A higher rate of CA125 increase is associated with abdominal recurrence. The rate of increase of CA125 may help in the selection of patients who are most likely to benefit from abdominopelvic CT in surveillance of ovarian cancer. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

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

Bao, Quanwei; Chen, Sixu; Qin, Hao

Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice.more » Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone strength and bone qulity. • CA-β-catenin kept osteoblasts in high proliferative state. • Osteoblastic CA-β-catenin impaired the terminal osteoblast differentiation.« less

Reassigning the CaH+ 11Σ → 21Σ vibronic transition with CaD+

NASA Astrophysics Data System (ADS)

Condoluci, J.; Janardan, S.; Calvin, A. T.; Rugango, R.; Shu, G.; Sherrill, C. D.; Brown, K. R.

2017-12-01

We observe vibronic transitions in CaD+ between the 11Σ and 21Σ electronic states by resonance enhanced multiphoton photodissociation spectroscopy in a Coulomb crystal. The vibronic transitions are compared with previous measurements on CaH+. The result is a revised assignment of the CaH+ vibronic levels and a disagreement with multi-state-complete-active-space second-order perturbation theory theoretical calculations by approximately 700 cm-1. Updated high-level coupled-cluster calculations that include core-valence correlations reduce the disagreement between theory and experiment to 300 cm-1.

Free and membrane-bound calcium in microgravity and microgravity effects at the membrane level

NASA Astrophysics Data System (ADS)

Belyavskaya, N. A.

The changes of [Ca^2+]_i controlled is known to play a key regulatory role in numerous cellular processes especially associated with membranes. Previous studies from our laboratory have demonstrated an increase in calcium level in root cells of pea seedlings grown aboard orbital station ``Salyut 6'' /1/. These results: 1) indicate that observed Ca^2+-binding sites of membranes also consist in proteins and phospholipids; 2) suggest that such effects of space flight in membrane Ca-binding might be due to the enhancement of Ca^2+ influx through membranes. In model presented, I propose that Ca^2+-activated channels in plasma membrane in response to microgravity allow the movement of Ca^2+ into the root cells, causing a rise in cytoplasmic free Ca^2+ levels. The latter, in its turn, may induce the inhibition of a Ca^2+ efflux by Ca^2+-activated ATPases and through a Ca^2+/H^+ antiport. It is possible that increased cytosolic levels of Ca^2+ ions have stimulated hydrolysis and turnover of phosphatidylinositols, with a consequent elevation of cytosolic [Ca^2+]_i. Plant cell can response to such a Ca^2+ rise by an enhancement of membranous Ca^2+-binding activities to rescue thus a cell from an abundance of a cytotoxin. A Ca^2+-induced phase separation of membranous lipids assists to appear the structure nonstable zones with high energy level at the boundary of microdomains which are rich by some phospholipid components; there is mixing of molecules of the membranes contacted in these zones, the first stage of membranous fusion, which was found in plants exposed to microgravity. These results support the hypothesis that a target for microgravity effect is the flux mechanism of Ca^2+ to plant cell.

The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes.

PubMed

Bovo, Elisa; Huke, Sabine; Blatter, Lothar A; Zima, Aleksey V

2017-03-01

Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial. In this study, we characterized a functional link between PKA-mediated RyR2 phosphorylation level and sarcoplasmic reticulum (SR) Ca 2+ release and leak in permeabilized rabbit ventricular myocytes. Changes in cytosolic [Ca 2+ ] and intra-SR [Ca 2+ ] SR were measured with Fluo-4 and Fluo-5N, respectively. Changes in RyR2 phosphorylation at two PKA sites, serine-2031 and -2809, were measured with phospho-specific antibodies. cAMP (10μM) increased Ca 2+ spark frequency approximately two-fold. This effect was associated with an increase in SR Ca 2+ load from 0.84 to 1.24mM. PKA inhibitory peptide (PKI; 10μM) abolished the cAMP-dependent increase of SR Ca 2+ load and spark frequency. When SERCA was completely blocked by thapsigargin, cAMP did not affect RyR2-mediated Ca 2+ leak. The lack of a cAMP effect on RyR2 function can be explained by almost maximal phosphorylation of RyR2 at serine-2809 after sarcolemma permeabilization. This high RyR2 phosphorylation level is likely the consequence of a balance shift between protein kinase and phosphatase activity after permeabilization. When RyR2 phosphorylation at serine-2809 was reduced to its "basal" level (i.e. RyR2 phosphorylation level in intact myocytes) using kinase inhibitor staurosporine, SR Ca 2+ leak was significantly reduced. Surprisingly, further dephosphorylation of RyR2 with protein phosphatase 1 (PP1) markedly increased SR Ca 2+ leak. At the same time, phosphorylation of RyR2 at serine 2031 did not significantly change under identical experimental conditions. These results suggest that RyR2 phosphorylation by PKA has a complex effect on SR Ca 2+ leak in ventricular myocytes. At an intermediate level of RyR2 phosphorylation SR Ca 2+ leak is minimal. However, complete dephosphorylation and maximal phosphorylation of RyR2 increases SR Ca 2+ leak. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selenium Speciation in the Fountain Creek Watershed (Colorado, USA) Correlates with Water Hardness, Ca and Mg Levels.

PubMed

Carsella, James S; Sánchez-Lombardo, Irma; Bonetti, Sandra J; Crans, Debbie C

2017-04-30

The environmental levels of selenium (Se) are regulated and strictly enforced by the Environmental Protection Agency (EPA) because of the toxicity that Se can exert at high levels. However, speciation plays an important role in the overall toxicity of Se, and only when speciation analysis has been conducted will a detailed understanding of the system be possible. In the following, we carried out the speciation analysis of the creek waters in three of the main tributaries-Upper Fountain Creek, Monument Creek and Lower Fountain Creek-located in the Fountain Creek Watershed (Colorado, USA). There are statistically significant differences between the Se, Ca and Mg, levels in each of the tributaries and seasonal swings in Se, Ca and Mg levels have been observed. There are also statistically significant differences between the Se levels when grouped by Pierre Shale type. These factors are considered when determining the forms of Se present and analyzing their chemistry using the reported thermodynamic relationships considering Ca 2+ , Mg 2+ , SeO₄ 2- , SeO₃ 2- and carbonates. This analysis demonstrated that the correlation between Se and water hardness can be explained in terms of formation of soluble CaSeO₄. The speciation analysis demonstrated that for the Fountain Creek waters, the Ca 2+ ion may be mainly responsible for the observed correlation with the Se level. Considering that the Mg 2+ level is also correlating linearly with the Se levels it is important to recognize that without Mg 2+ the Ca 2+ would be significantly reduced. The major role of Mg 2+ is thus to raise the Ca 2+ levels despite the equilibria with carbonate and other anions that would otherwise decrease Ca 2+ levels.

Effect of dietary calcium level and source on mineral utilisation by piglets fed diets containing exogenous phytase.

PubMed

Schlegel, P; Gutzwiller, A

2017-10-01

Calcium and phosphorus are essential minerals, closely linked in digestive processes and metabolism. With widespread use of low P diets containing exogenous phytase, the optimal dietary Ca level was verified. The 40-day study evaluated the effects of Ca level (4, 7 and 10 g/kg diet) and Ca source (Ca from CaCO 3 and from Lithothamnium calcareum) on mineral utilisation in 72 piglets (7.9 ± 1.0 kg BW) fed an exogenous phytase containing diet with 2.9 g digestible P/kg. Measured parameters were growth performance, stomach mineral solubility, bone breaking strength and urinary, serum and bone mineral concentration. The apparent total tract digestibility of minerals was also assessed in the two diets with 7 g Ca/kg, using 12 additional pigs. Regardless of Ca source, increasing dietary Ca impaired feed conversion ratio, increased urinary pH, increased serum and urinary Ca, decreased serum and urinary P, decreased serum Mg and increased urinary Mg, increased serum AP activity, decreased bone Mg increased bone Zn. Bone breaking strength was improved with 7 compared to 4 g Ca/kg. Compared to CaCO 3 , Ca from Lithothamnium calcareum increased serum Mg and with, 10 g Ca/kg, it limited body weight gain. The dose response of Ca in a diet with 2.9 g digestible P/kg and including exogenous phytase indicated that: (i) a low dietary Ca was beneficial for piglet growth, but was limiting the metabolic use of P; (ii) a high dietary Ca level impaired P utilisation; (iii) the optimal P utilisation and bone breaking strength was obtained with a dietary Ca-to-digestible P ratio of 2.1 to 2.4:1; (iv). Increasing dietary Ca reduced Mg utilisation, but not Zn status, when fed at adequate level. Finally, Ca from Lithothamnium calcareum had similar effects on Ca and P metabolism as CaCO 3 , but impaired growth when fed at the highest inclusion level. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Calcium availability but not its content modulates metal toxicity in Scenedesmus quadricauda.

PubMed

Kováčik, Jozef; Dresler, Sławomir

2018-01-01

Impact of calcium nutrition (pre-culture on solid medium with standard or elevated Ca dose, i. e. 0.17 and 4.40mM marked as low and high Ca) on acute metal toxicity (Cd, Mn and Pb, 24h of exposure to 10µM) in freshwater green alga Scenedesmus quadricauda was studied. Surprisingly, Ca content differed only slightly between low and high Ca samples and applied metals rather suppressed its amount. Na content was higher in metal-exposed high Ca samples, indicating that Ca/Na ratio may affect accumulation of metals. Content of heavy metals increased in order Cd < Mn < Pb and high Ca samples contained less metal than low Ca samples at least in absorbed fraction. Accumulation of ascorbic acid and thiols (GSH - glutathione and PC2 - phytochelatin 2) was affected mainly by Cd, GSH also by Mn and PC2 by Pb with often significant differences between low Ca and high Ca samples. Calcium nutrition also affected responses of algae to metals at the level of antioxidative enzyme activities (SOD, APX, and CAT) and elevated values were typically found in high Ca samples while ROS (hydrogen peroxide and superoxide radical) were mainly depleted in Mn treatment. These data confirm that Ca nutrition affects accumulation of metals in algae and metabolic parameters as observed in vascular plants but, unlike them, rather Ca/Na ratio than absolute Ca content seems to regulate the uptake of metals. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor (CaSR)

PubMed Central

Vizard, Thomas N.; O'Keeffe, Gerard W.; Gutierrez, Humberto; Kos, Claudine H.; Riccardi, Daniela; Davies, Alun M.

2009-01-01

The extracellular calcium-sensing receptor (CaSR) monitors the systemic extracellular free ionized calcium level ([Ca2+]o) in organs involved in systemic [Ca2+]o homeostasis. However, the CaSR is also expressed in the nervous system where its role is unknown. Here we find high levels of the CaSR in perinatal mouse sympathetic neurons when their axons are innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca2+]o, using CaSR agonists and antagonists or expressing a dominant-negative CaSR markedly affects neurite growth in vitro Sympathetic neurons lacking the CaSR have smaller neurite arbors in vitro, and sympathetic innervation density is reduced in CaSR-deficient mice in vivo. Hippocampal pyramidal neurons, which also express the CaSR, have smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for the CaSR in regulating the growth of neural processes in the peripheral and central nervous systems. PMID:18223649

Additive effect of calcium depletion and low resource quality on Gammarus fossarum (Crustacea, Amphipoda) life history traits.

PubMed

Rollin, Marc; Coulaud, Romain; Danger, Michael; Sohm, Bénédicte; Flayac, Justine; Bec, Alexandre; Chaumot, Arnaud; Geffard, Olivier; Felten, Vincent

2018-04-01

Gammarus fossarum is an often-abundant crustacean detritivore that contributes importantly to leaf litter breakdown in oligotrophic, mainly heterotrophic, headwater streams. This species requires large amounts of Ca to moult, thus allowing growth and reproduction. Because resource quality is tightly coupled to the organism's growth and physiological status, we hypothesised that low Ca concentration [Ca] and low food resource quality (low phosphorus [P] and/or reduced highly unsaturated fatty acid [HUFA] contents) would interactively impair molecular responses (gene expression) and reproduction of G. fossarum. To investigate the effects of food resources quality, we experimentally manipulated the P content of sycamore leaves and also used diatoms because they contain high amounts of HUFAs. Three resource quality treatments were tested: low quality (LQ, unmanipulated leaves: low P content), high quality 1 (HQ1; P-manipulated leaves: high P content), and high quality 2 (unmanipulated leaves supplemented with a pellet containing diatoms: high P and HUFA content). Naturally, demineralised stream water was supplemented with CaSO 4 to obtain three Ca concentrations (2, 3.5, and 10.5 mg Ca L -1 ). For 21 days, pairs of G. fossarum were individually exposed to one of the nine treatments (3 [Ca] × 3 resource qualities). At the individual level, strong and significant delays in moult stage were observed in gammarids exposed to lower [Ca] and to lower resource quality, with additive effects lengthening the duration of the reproductive cycle. Effects at the molecular level were investigated by measuring expression of 12 genes involved in energy production, translation, or Ca or P homeostasis. Expression of ATP synthase beta (higher in HQ2), calcified cuticle protein (higher in HQ1 and HQ2), and tropomyosin (higher in HQ2 compared to HQ1) was significantly affected by resource quality, and significant additive effects on Ca transporting ATPase expression were induced by [Ca] and resource quality (higher for low [Ca] and higher resource quality). These results highlight the potential drastic deleterious effects of water [Ca] depletion on G. fossarum physiology, populations, and ecosystem functioning, especially in oligotrophic environments.

Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on Cheddar cheese quality: proteolysis during ripening.

PubMed

Upreti, P; Metzger, L E; Hayes, K D

2006-02-01

Proteolysis in cheese is influenced by the state of proteins (protein-calcium-phosphate interactions), level of indigenous milk enzymes (plasmin), externally added milk-clotting enzymes (chymosin), and endogenous and exogenous enzymes from starter and non-starter lactic acid bacteria (NSLAB). The objective of this study was to determine how different levels of calcium (Ca) and phosphorus (P), residual lactose, and salt-to-moisture ratio (S/M) in cheese influence proteolysis during ripening. Eight cheeses with 2 levels of Ca and P (0.67 and 0.47% vs. 0.53 and 0.39%, respectively), 2 levels of lactose at pressing (2.4 vs. 0.78%), and 2 levels of S/M (6.4 vs. 4.8%) were manufactured. The cheeses were analyzed for changes in pH 4.6-soluble N, and starter and NSLAB counts during 48 wk of ripening. Cheeses at d 1 were also analyzed for residual chymosin, plasmin, and plasminogen activity. A significant increase in soluble N was observed during ripening for all the treatments. Cheeses with low Ca and P, low lactose, and low S/M treatments exhibited higher levels of proteolysis as compared to their corresponding high treatments. Differences in the rate of proteolysis for cheeses with different levels of Ca and P might be due to changes in protein conformation and differences in residual chymosin in the cheeses. Cheeses with low Ca and P were manufactured by lowering the pH at set and drain, which led to higher chymosin retention in cheeses with low Ca and P compared with high Ca and P. Differences in proteolysis between treatments with different levels of lactose were also partly attributed to residual chymosin activity. In all treatments, a major fraction of plasmin existed as plasminogen, indicating minimal contribution of plasmin to proteolysis in Cheddar cheeses. The number of starter bacteria, in all treatments, decreased significantly during ripening. However, the decrease was larger in the case of high S/M treatments compared with low S/M treatments. In contrast, the number of NSLAB increased during ripening, and low S/M cheeses had higher counts compared with high S/M cheeses. The differences in proteolysis due to S/M were partially attributed to changes in protein conformation or bacterial proteolytic activity.

Contractile reserve and intracellular calcium regulation in mouse myocytes from normal and hypertrophied failing hearts

NASA Technical Reports Server (NTRS)

Ito, K.; Yan, X.; Tajima, M.; Su, Z.; Barry, W. H.; Lorell, B. H.; Schneider, M. (Principal Investigator)

2000-01-01

Mouse myocyte contractility and the changes induced by pressure overload are not fully understood. We studied contractile reserve in isolated left ventricular myocytes from mice with ascending aortic stenosis (AS) during compensatory hypertrophy (4-week AS) and the later stage of early failure (7-week AS) and from control mice. Myocyte contraction and [Ca(2+)](i) transients with fluo-3 were measured simultaneously. At baseline (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C), the amplitude of myocyte shortening and peak-systolic [Ca(2+)](i) in 7-week AS were not different from those of controls, whereas contraction, relaxation, and the decline of [Ca(2+)](i) transients were slower. In response to the challenge of high [Ca(2+)](o), fractional cell shortening was severely depressed with reduced peak-systolic [Ca(2+)](i) in 7-week AS compared with controls. In response to rapid pacing stimulation, cell shortening and peak-systolic [Ca(2+)](i) increased in controls, but this response was depressed in 7-week AS. In contrast, the responses to both challenge with high [Ca(2+)](o) and rapid pacing in 4-week AS were similar to those of controls. Although protein levels of Na(+)-Ca(2+) exchanger were increased in both 4-week and 7-week AS, the ratio of SR Ca(2+)-ATPase to phospholamban protein levels was depressed in 7-week AS compared with controls but not in 4-week AS. This was associated with an impaired capacity to increase sarcoplasmic reticulum Ca(2+) load during high work states in 7-week AS myocytes. In hypertrophied failing mouse myocytes, depressed contractile reserve is related to an impaired augmentation of systolic [Ca(2+)](i) and SR Ca(2+) load and simulates findings in human failing myocytes.

Serum Concentrations of Selenium and Copper in Patients Diagnosed with Pancreatic Cancer.

PubMed

Lener, Marcin R; Scott, Rodney J; Wiechowska-Kozłowska, Anna; Serrano-Fernández, Pablo; Baszuk, Piotr; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Marciniak, Wojciech; Muszyńska, Magdalena; Kładny, Józef; Gromowski, Tomasz; Kaczmarek, Katarzyna; Jakubowska, Anna; Lubiński, Jan

2016-07-01

Understanding of the etiology and pathogenesis of pancreatic cancer (PaCa) is still insufficient. This study evaluated the associations between concentrations of selenium (Se) and copper (Cu) in the serum of PaCa patients. The study included 100 PaCa patients and 100 control subjects from the same geographical region in Poland. To determine the average concentration of Se, Cu, and ratio Cu:Se in the Polish population, assay for Se and Cu was performed in 480 healthy individuals. Serum levels of Se and Cu were measured using inductively coupled plasma mass spectrometry. In the control group, the average Se level was 76 µg/L and Cu 1,098 µg/L. The average Se level among PaCa patients was 60 µg/L and the mean Cu level was 1,432 µg/L. The threshold point at which any decrease in Se concentration was associated with PaCa was 67.45 µg/L. The threshold point of Cu level above which there was an increase in the prevalence of PaCa was 1,214.58 µg/L. In addition, a positive relationship was observed between increasing survival time and Se plasma level. This retrospective study suggests that low levels of Se and high levels of Cu might influence development of PaCa and that higher levels of Se are associated with longer survival in patients with PaCa. The results suggest that determining the level of Se and Cu could be incorporated into a risk stratification scheme for the selection and surveillance control examination to complement existing screening and diagnostic procedures.

[Establishment of oxygen and glucose deprive model of in vitro cultured hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model neurons].

PubMed

Wan, Hai-tong; Wang, Yu; Yang, Jie-hong

2007-03-01

To establish the oxygen and glucose deprive (OGD) model in cultured hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+ level in the model neurons. The OGD model was established in cultured hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser scanning confocal microscope (LSCM). The OGD model was successfully established in cultured hippocampal neurons; the intracellular Ca2+ level in the OGD model group was significantly higher than that in the blank control group (P < 0.05), and that in the nemodipine and high and medium dosage of ligustrazine treated groups was lower than that in the OGD model group (P < 0.05). Intracellular Ca2+ overload occurs in OGD model neuron, which could be antagonized by ligustrazine, indicating that ligustrazine has a protective effect on hippocampal neuron from hypoxic-ischemic injury.

Alteration layer formation of Ca- and Zn-oxide bearing alkali borosilicate glasses for immobilisation of UK high level waste: A vapour hydration study

NASA Astrophysics Data System (ADS)

Cassingham, N. J.; Corkhill, C. L.; Stennett, M. C.; Hand, R. J.; Hyatt, N. C.

2016-10-01

The UK high level nuclear waste glass modified with CaO/ZnO was investigated using the vapour phase hydration test, performed at 200 °C, with the aim of understanding the impact of the modification on the chemical composition and microstructure of the alteration layer. Experiments were undertaken on non-modified and CaO/ZnO-modified base glass, with or without 25 wt% of simulant Magnox waste calcine. The modification resulted in a dramatic reduction in gel layer thickness and also a reduction in the reaction rate, from 3.4 ± 0.3 g m-2 d-1 without CaO/ZnO modification to 0.9 ± 0.1 g m-2 d-1 with CaO/ZnO. The precipitated phase assemblage for the CaO/ZnO-modified compositions was identified as hydrated Ca- and Zn-bearing silicate phases, which were absent from the non-modified counterpart. These results are in agreement with other recent studies showing the beneficial effects of ZnO additions on glass durability.

Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures.

PubMed

Connor, J A; Tseng, H Y; Hockberger, P E

1987-05-01

Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture.

A limited role for carbonic anhydrase in C 4 photosynthesis as revealed by a ca1ca2 double mutant in maize.

DOE PAGES

Studer, Anthony J.; Gandin, Anthony; Kolbe, Allison R.; ...

2014-04-04

Carbonic anhydrase (CA) catalyzes the first biochemical step of the carbon concentrating mechanism of C 4 plants, and in C 4 monocots, it has been suggested that CA activity is near limiting for photosynthesis. Here, we test this hypothesis through the characterization of transposon induced mutant alleles of Ca1 and Ca2 in Zea mays. In addition, these two isoforms account for more than 85% of the CA transcript pool. A significant change in isotopic discrimination is observed in mutant plants, which have as little as 3% of wild-type CA activity, but surprisingly, photosynthesis is not reduced under current or elevatedmore » pCO 2. However, growth and rates of photosynthesis under sub-ambient pCO 2 are significantly impaired in the mutants. These findings suggest, that while CA is not limiting for C 4 photosynthesis in Z. mays at current pCO 2, it likely maintains high rates of photosynthesis when CO 2 availability is reduced. Current atmospheric CO 2 levels now exceed 400 ppm (~40.53 Pa) and contrast the low CO 2 partial pressure (pCO 2) conditions under which C 4 plants expanded their range ~10 million years ago when the global atmospheric CO 2 was below 300 ppm (~30.40 Pa). Thus, as CO 2 levels continue to rise, selective pressures for high levels of CA may be limited to arid climates where stomatal closure reduces CO 2 availability to the leaf.« less

CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons

PubMed Central

Bok, Jinwoong; Wang, Qiong; Huang, Jie; Green, Steven H.

2007-01-01

By fusing the CaMKII inhibitory peptide AIP to GFP, we constructed a specific and effective CaMKII inhibitor, GFP-AIP. Expression of GFP-AIP and/or dominant-inhibitory CaMKIV in cultured neonatal rat spiral ganglion neurons (SGNs) shows that CaMKII and CaMKIV act additively and in parallel, to mediate the prosurvival effect of depolarization. Depolarization or expression of constitutively-active CaMKII functionally inactivates Bad, indicating that this is one means by which CaMKII promotes neuronal survival. CaMKIV, but not CaMKII, requires CREB to promote SGN survival, consistent with the exclusively nuclear localization of CaMKIV and indicating that the principal prosurvival function of CaMKIV is activation of CREB. Consistent with this, a constitutively-active CREB construct that provides a high level of CREB activity promotes SGN survival, although low levels of CREB activity did not do so. Also, in apoptotic SGNs, activation of CREB by depolarization is disabled, presumably as part of a cellular commitment to apoptosis. PMID:17651987

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.

Increasing the calcium content of mealworms (Tenebrio molitor) to improve their nutritional value for bone mineralization of growing chicks.

PubMed

Klasing, K C; Thacker, P; Lopez, M A; Calvert, C C

2000-12-01

The purpose of these studies was to determine the husbandry variables that optimize the Ca content of mealworms (Tenebrio molitor) and to determine the bioavailability of this Ca for bone mineralization in chicks that consume the mealworms. To determine the optimal level of Ca in the substrates used in short-term (< 14 days) holding of mealworms and to determine the length of time that mealworms should be exposed to high-Ca substrates, mealworms were placed in either a wheat bran or a chicken starter substrate supplemented with 0, 4, 8, or 12% Ca from CaCO3. The mealworms were harvested after 0.5, 1, 2, 3, 4, 7, or 14 days. The Ca content of the mealworms was greatest with the use of chicken starter and increased linearly with the Ca content of the substrate. In general, the Ca content of the mealworms increased during the first 24 hr and decreased after > or = 1 wk, especially at the higher levels of Ca supplementation. The chicken starter also resulted in higher levels of vitamin D in mealworms. Mealworms held in wheat bran with 8% Ca were fed to growing chicks. Ca bioavailability was calculated from the chicks' bone ash. The Ca in these mealworms was 76% as bioavailable as the Ca in oyster shell.

Calgranulin C Has Filariacidal and Filariastatic Activity

PubMed Central

Gottsch, John D.; Eisinger, Steven W.; Liu, Sammy H.; Scott, Alan L.

1999-01-01

The calgranulins are a family of calcium- and zinc-binding proteins produced by neutrophils, monocytes, and other cells. Calgranulins are released during inflammatory responses and have antimicrobial activity. Recently, one of the calgranulins, human calgranulin C (CaGC), has been implicated as an important component of the host responses that limit the parasite burden during filarial nematode infections. The goal of this work was to test the hypothesis that human CaGC has biologic activity against filarial parasites. Brugia malayi microfilariae and adults were exposed in vitro to 0.75 to 100 nM recombinant human CaGC. Recombinant CaGC affected adult and larval parasites in a dose-dependent fashion. Microfilariae were more sensitive to the action of CaGC than were adult parasites. At high levels, CaGC was both macrofilariacidal and microfilariacidal. At lower levels, the percentage of parasites killed was dependent on the level of CaGC in the culture system. The larvae not killed had limited motility. The filariastatic effect of low-level CaGC was reversed when the CaGC was removed from the culture system. Immunohistochemical analysis demonstrated that human CaGC accumulated in the cells of the hypodermis-lateral chord of adult and larval parasites. The antifilarial activity of CaGC was not due to the sequestration of zinc. Thus, the cellular and molecular mechanisms that result in the production and release of CaGC in humans may play a key role in the regulation of filarial parasite numbers. PMID:10569784

Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on Cheddar cheese quality: manufacture and composition.

PubMed

Upreti, P; Metzger, L E

2006-02-01

Eight Cheddar cheeses with 2 levels of calcium (Ca) and phosphorus (P), residual lactose, and salt-to-moisture ratio (S/M) were manufactured. All cheeses were made using a stirred-curd procedure and were replicated 3 times. Treatments with a high level of Ca and P were produced by setting the milk and drawing the whey at a higher pH (6.6 and 6.3, respectively) compared with the treatments with a low level of Ca and P (pH of 6.2 and 5.7, respectively). The lactose content in the cheeses was varied by adding lactose (2.5% by weight of milk) to the milk for high lactose cheeses, and washing the curd for low lactose cheeses. The difference in S/M was obtained by dividing the curds into halves, weighing each half, and salting at 3.5 and 2.25% of the weight of the curd for high and low S/M, respectively. All cheeses were salted at a pH of 5.4. Modifications in cheese-making protocols produced cheeses with desired differences in Ca and P, residual lactose, and S/M. Average Ca and P in the high Ca and P cheeses was 0.68 and 0.48%, respectively, vs. 0.53 and 0.41% for the low Ca and P cheeses. Average lactose content of the high lactose treatments at d 1 was 1.48% compared with 0.30% for the low lactose treatments. The S/M for the high and low S/M cheeses was 6.68 and 4.77%, respectively. Mean moisture, fat, and protein content of the cheeses ranged from 32.07 to 37.57%, 33.32 to 35.93%, and 24.46 to 26.40%, respectively. The moisture content differed among the treatments, whereas fat and protein content on dry basis was similar.

Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature-high humidity challenge in a positive feedback loop with CaWRKY40.

PubMed

Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

2016-04-01

CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature-high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63(pCabZIP63) and CaWRKY40(pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper's response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper's response to RSI and HTHH. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The Pepper WPP Domain Protein, CaWDP1, Acts as a Novel Negative Regulator of Drought Stress via ABA Signaling.

PubMed

Park, Chanmi; Lim, Chae Woo; Baek, Woonhee; Kim, Jung-Hyun; Lim, Sohee; Kim, Sang Hyon; Kim, Kyung-Nam; Lee, Sung Chul

2017-04-01

Plants are constantly challenged by various environmental stresses, including high salinity and drought, and they have evolved defense mechanisms to counteract the deleterious effects of these stresses. The plant hormone ABA regulates plant growth and developmental processes and mediates abiotic stress responses. Here, we report the identification and characterization of a novel CaWDP1 (Capsicum annuum) protein. The expression of CaWDP1 in pepper leaves was induced by ABA, drought and NaCl treatments, suggesting its role in the abiotic stress response. CaWDP1 proteins show conserved sequence homology with other known WDP1 proteins, and they are localized in the nucleus and cytoplasm. We generated CaWDP1-silenced peppers via virus-induced gene silencing (VIGS). We evaluated the responses of these CaWDP1-silenced pepper plants and CaWDP1-overexpressing (OX) transgenic Arabidopsis plants to ABA and drought. CaWDP1-silenced pepper plants displayed enhanced tolerance to drought stress, and this was characterized by low levels of leaf water loss in the drought-treated leaves. In contrast to CaWDP1-silenced plants, CaWDP1-OX plants exhibited an ABA-hyposensitive and drought-susceptible phenotype, which was accompanied by high levels of leaf water loss, low leaf temperatures, increased stomatal pore size and low expression levels of stress-responsive genes. Our results indicate that CaWDP1, a novel pepper negative regulator of ABA, regulates the ABA-mediated defense response to drought stress. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

PubMed

Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

2014-09-01

Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

First characterization of three cyclophilin family proteins in the oyster, Crassostrea ariakensis Gould.

PubMed

Xu, Ting; Xie, Jiasong; Yang, Shoubao; Ye, Shigen; Luo, Ming; Wu, Xinzhong

2016-08-01

Cyclophilins (CyPs) are a family of proteins that bind the immunosuppressive agent cyclosporin A (CsA) with high-affinity and belong to one of the three superfamilies of peptidyl-prolyl cis-trans isomerases (PPIase). In this report, three cyclophilin genes (Ca-CyPs), including Ca-CyPA, Ca-CyPB and Ca-PPIL3, were identified from oyster, Crassostrea ariakensis Gould in which Ca-CyPA encodes a protein with 165 amino acid sequences, Ca-CyPB encodes a protein with 217 amino acid sequences and Ca-PPIL3 encodes a protein with 162 amino acid sequences. All of the three Ca-CyPs genes contain a typical CyP-PPIase domain with its signature sequences and Ca-CyPB contains an N-signal peptide sequences. Tissue distribution study revealed that Ca-CyPs were ubiquitously expressed in all examined tissues and the highest levels were observed in hemocytes. RLO incubation upregulated the mRNA expression levels of Ca-CyPs, indicating that three Ca-CyPs might be involved in oyster immune response against RLO infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sedimentary constraints on late Quaternary lake-level fluctuations at Bear Lake, Utah and Idaho

USGS Publications Warehouse

Smoot, J.P.; Rosenbaum, J.G.

2009-01-01

A variety of sedimentological evidence was used to construct the lake-level history for Bear Lake, Utah and Idaho, for the past ???25,000 years. Shorelines provide evidence of precise lake levels, but they are infrequently preserved and are poorly dated. For cored sediment similar to that in the modern lake, grain-size distributions provide estimates of past lake depths. Sedimentary textures provide a highly sensitive, continuous record of lake-level changes, but the modern distribution of fabrics is poorly constrained, and many ancient features have no modern analog. Combining the three types of data yields a more robust lake-level history than can be obtained from any one type alone. When smooth age-depth models are used, lake-level curves from multiple cores contain inconsistent intervals (i.e., one record indicates a rising lake level while another record indicates a falling lake level). These discrepancies were removed and the multiple records were combined into a single lake-level curve by developing age-depth relations that contain changes in deposition rate (i.e., gaps) where indicated by sedimentological evidence. The resultant curve shows that, prior to 18 ka, lake level was stable near the modern level, probably because the lake was overflowing. Between ca. 17.5 and 15.5 ka, lake level was ???40 m below the modern level, then fluctuated rapidly throughout the post-glacial interval. Following a brief rise centered ca. 15 ka ( = Raspberry Square phase), lake level lowered again to 15-20 m below modern from ca. 14.8-11.8 ka. This regression culminated in a lowstand to 40 m below modern ca. 12.5 ka, before a rapid rise to levels above modern ca. 11.5 ka. Lake level was typically lower than present throughout the Holocene, with pronounced lowstands 15-20 m below the modern level ca. 10-9, 7.0, 6.5-4.5, 3.5, 3.0-2.5, 2.0, and 1.5 ka. High lake levels near or above the modern lake occurred ca. 8.5-8.0, 7.0-6.5, 4.5-3.5, 2.5, and 0.7 ka. This lake-level history is more similar to records from Pyramid Lake, Nevada, and Owens Lake, California, than to those from Lake Bonneville, Utah. Copyright ?? 2009 The Geological Society of America.

Incorporation of Mg, Sr, Ba, U, and B in High-Mg Calcite Benthic Foraminifers Cultured Under Controlled pCO2

NASA Astrophysics Data System (ADS)

Not, C.; Thibodeau, B.; Yokoyama, Y.

2018-01-01

Measurement of elemental ratios (E/Ca) has been performed in two symbiont-bearing species of high-Mg calcite benthic foraminifers (hyaline, Baculogypsina sphaerulata and porcelaneous, Amphisorus hemprichii), cultured under five pCO2 levels, representing preindustrial, modern, and three predicted future values. E/Ca ratios were analyzed by Laser Ablation coupled with Inductively Coupled Plasma Mass Spectrometer (LA-ICP-MS). We measured several E/Ca, such as Mg/Ca, Sr/Ca, Ba/Ca, U/Ca, and B/Ca simultaneously. We observed that high-Mg calcite benthic foraminifers possess higher E/Ca than low-Mg calcite foraminifers, irrespective of their calcification mode (hyaline or porcelaneous). In both modes of calcification, Mg, Sr, Ba, U, and B incorporation could be controlled by Rayleigh fractionation. However, more data are needed to validate and quantify the relative importance of this process and closely investigate the presence/absence of other mechanism. Therefore, it highlights the need for a multielemental approach when looking at trace element incorporation. Finally, no significant relationship was observed between the different ratios and the pCO2 of the water, suggesting that none of the Mg/Ca, Sr/Ca, Ba/Ca, U/Ca, and B/Ca is sensitive to bottom water pCO2 or pH for these species.

Self-propagating high-temperature synthesis of Ce-bearing zirconolite-rich minerals using Ca(NO3)2 as the oxidant

NASA Astrophysics Data System (ADS)

Zhang, Kuibao; Wen, Guanjun; Yin, Dan; Zhang, Haibin

2015-12-01

Synroc is recognized as the second generation waste form for the immobilization of high-level radioactive waste (HLW). Zirconolite-rich (CaZrTi2O7) Synroc minerals were attempted by self-propagating high-temperature synthesis (SHS) using Fe2O3, CrO3, Ca(NO3)2 as the oxidants and Ti as the reductant. All designed reactions were ignited and sustained using Ca(NO3)2 as the oxidant, and zirconolite-rich ceramic matrices were successfully prepared with pyrochlore (Ca2Ti2O6), perovskite (CaTiO3) and rutile (TiO2) as the minor phases. The sample CN-4, which was designed using Ca(NO3)2 as the oxidant with TiO2/Ti ratio of 7:9, was readily solidified with density of 4.62 g/cm3 and Vickers hardness of 1052 HV. CeO2 was successfully stabilized by the CN-4 sample with resultant phase constituent of 2M-CaZrTi2O7 and CaTiO3.

β-Adrenergic stimulation increases the intra-sarcoplasmic reticulum Ca2+ threshold for Ca2+ wave generation

PubMed Central

Domeier, Timothy L; Maxwell, Joshua T; Blatter, Lothar A

2012-01-01

β-Adrenergic signalling induces positive inotropic effects on the heart that associate with pro-arrhythmic spontaneous Ca2+ waves. A threshold level of sarcoplasmic reticulum (SR) Ca2+ ([Ca2+]SR) is necessary to trigger Ca2+ waves, and whether the increased incidence of Ca2+ waves during β-adrenergic stimulation is due to an alteration in this threshold remains controversial. Using the low-affinity Ca2+ indicator fluo-5N entrapped within the SR of rabbit ventricular myocytes, we addressed this controversy by directly monitoring [Ca2+]SR and Ca2+ waves during β-adrenergic stimulation. Electrical pacing in elevated extracellular Ca2+ ([Ca2+]o= 7 mm) was used to increase [Ca2+]SR to the threshold where Ca2+ waves were consistently observed. The β-adrenergic agonist isoproterenol (ISO; 1 μm) increased [Ca2+]SR well above the control threshold and consistently triggered Ca2+ waves. However, when [Ca2+]SR was subsequently lowered in the presence of ISO (by lowering [Ca2+]o to 1 mm and partially inhibiting sarcoplasmic/endoplasmic reticulum calcium ATPase with cyclopiazonic acid or thapsigargin), Ca2+ waves ceased to occur at a [Ca2+]SR that was higher than the control threshold. Furthermore, for a set [Ca2+]SR level the refractoriness of wave occurrence (Ca2+ wave latency) was prolonged during β-adrenergic stimulation, and was highly dependent on the extent that [Ca]SR exceeded the wave threshold. These data show that acute β-adrenergic stimulation increases the [Ca2+]SR threshold for Ca2+ waves, and therefore the primary cause of Ca2+ waves is the robust increase in [Ca2+]SR above this higher threshold level. Elevation of the [Ca2+]SR wave threshold and prolongation of wave latency represent potentially protective mechanisms against pro-arrhythmogenic Ca2+ release during β-adrenergic stimulation. PMID:22988136

Relationships between coronary heart disease risk factors and serum ionized calcium in Kennedy Space Center Cohort

NASA Technical Reports Server (NTRS)

Goodwin, Lisa Ann; Frey, Mary Anne Bassett; Merz, Marion P.; Alford, William R.

1987-01-01

Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population.

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy.

PubMed

Fujimoto, Yukie; Higuchi, Tomoko; Nishimukai, Arisa; Miyagawa, Yoshimasa; Kira, Ayako; Ozawa, Hiromi; Bun, Ayako; Imamura, Michiko; Miyoshi, Yasuo

2018-06-24

To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both pre- and post-NAC. A total of 185 breast cancer patients treated with NAC were recruited. Serum CEA and CA15-3 were measured at baseline and at completion of NAC. Among the non-pCR cancers (n = 142), disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = 0.0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.28-10.23; P = 0.0122) and residual invasive size (HR: 4.47, 1.26-28.39; P = 0.0171) were significant independent factors for DFS. The combination of these factors proved to be accurate predictor for DFS regardless of breast cancer subtypes. The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments. © 2018 Wiley Periodicals, Inc.

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer.

PubMed

Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei

2017-01-01

The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Measuring spatial and temporal Ca2+ signals in Arabidopsis plants.

PubMed

Zhu, Xiaohong; Taylor, Aaron; Zhang, Shenyu; Zhang, Dayong; Feng, Ying; Liang, Gaimei; Zhu, Jian-Kang

2014-09-02

Developmental and environmental cues induce Ca(2+) fluctuations in plant cells. Stimulus-specific spatial-temporal Ca(2+) patterns are sensed by cellular Ca(2+) binding proteins that initiate Ca(2+) signaling cascades. However, we still know little about how stimulus specific Ca(2+) signals are generated. The specificity of a Ca(2+) signal may be attributed to the sophisticated regulation of the activities of Ca(2+) channels and/or transporters in response to a given stimulus. To identify these cellular components and understand their functions, it is crucial to use systems that allow a sensitive and robust recording of Ca(2+) signals at both the tissue and cellular levels. Genetically encoded Ca(2+) indicators that are targeted to different cellular compartments have provided a platform for live cell confocal imaging of cellular Ca(2+) signals. Here we describe instructions for the use of two Ca(2+) detection systems: aequorin based FAS (film adhesive seedlings) luminescence Ca(2+) imaging and case12 based live cell confocal fluorescence Ca(2+) imaging. Luminescence imaging using the FAS system provides a simple, robust and sensitive detection of spatial and temporal Ca(2+) signals at the tissue level, while live cell confocal imaging using Case12 provides simultaneous detection of cytosolic and nuclear Ca(2+) signals at a high resolution.

Synergistic role of ADP and Ca2+ in diastolic myocardial stiffness

PubMed Central

Sequeira, Vasco; Najafi, Aref; McConnell, Mark; Fowler, Ewan D; Bollen, Ilse A E; Wüst, Rob C I; dos Remedios, Cris; Helmes, Michiel; White, Ed; Stienen, Ger J M; Tardiff, Jil; Kuster, Diederik W D; van der Velden, Jolanda

2015-01-01

Abstract Heart failure (HF) with diastolic dysfunction has been attributed to increased myocardial stiffness that limits proper filling of the ventricle. Altered cross-bridge interaction may significantly contribute to high diastolic stiffness, but this has not been shown thus far. Cross-bridge interactions are dependent on cytosolic [Ca2+] and the regeneration of ATP from ADP. Depletion of myocardial energy reserve is a hallmark of HF leading to ADP accumulation and disturbed Ca2+ handling. Here, we investigated if ADP elevation in concert with increased diastolic [Ca2+] promotes diastolic cross-bridge formation and force generation and thereby increases diastolic stiffness. ADP dose-dependently increased force production in the absence of Ca2+ in membrane-permeabilized cardiomyocytes from human hearts. Moreover, physiological levels of ADP increased actomyosin force generation in the presence of Ca2+ both in human and rat membrane-permeabilized cardiomyocytes. Diastolic stress measured at physiological lattice spacing and 37°C in the presence of pathological levels of ADP and diastolic [Ca2+] revealed a 76 ± 1% contribution of cross-bridge interaction to total diastolic stress in rat membrane-permeabilized cardiomyocytes. Inhibition of creatine kinase (CK), which increases cytosolic ADP, in enzyme-isolated intact rat cardiomyocytes impaired diastolic re-lengthening associated with diastolic Ca2+ overload. In isolated Langendorff-perfused rat hearts, CK inhibition increased ventricular stiffness only in the presence of diastolic [Ca2+]. We propose that elevations of intracellular ADP in specific types of cardiac disease, including those where myocardial energy reserve is limited, contribute to diastolic dysfunction by recruiting cross-bridges, even at low Ca2+, and thereby increase myocardial stiffness. Key points Diastolic dysfunction in heart failure patients is evident from stiffening of the passive properties of the ventricular wall. Increased actomyosin interactions may significantly limit diastolic capacity, however, direct evidence is absent. From experiments at the cellular and whole organ level, in humans and rats, we show that actomyosin-related force development contributes significantly to high diastolic stiffness in environments where high ADP and increased diastolic [Ca2+] are present, such as the failing myocardium. Our basal study provides a mechanical mechanism which may partly underlie diastolic dysfunction. PMID:26096258

Adaptive response of broilers to dietary phosphorus and calcium restrictions.

PubMed

Rousseau, Xavière; Valable, Anne-Sophie; Létourneau-Montminy, Marie-Pierre; Même, Nathalie; Godet, Estelle; Magnin, Michel; Nys, Yves; Duclos, Michel J; Narcy, Agnès

2016-12-01

The aim of this study was to evaluate the capacity of chickens to adapt to and compensate for early dietary restriction of non-phytate P ( NPP: ) and/or Ca (10 to 21 d) in a later phase (22 to 35 d), and to determine whether compensatory processes depend on the P and Ca concentrations in the finisher diet. Four diets were formulated and fed to broilers from 10 to 21 d in order to generate birds with different mineral status: L 1 (0.6% Ca, 0.30% NPP), L 2 (0.6% Ca, 0.45% NPP), H 1 (1.0% Ca, 0.30% NPP), and H 2 (1.0% Ca, 0.45% NPP). On d 22, each group was divided into three groups which received a low (L, 0.48% Ca, 0.24% NPP), moderate (M, 0.70% Ca, 0.35% NPP), or high (H, 0.90% Ca, 0.35% NPP) finisher diet until 35 d, resulting in a total of 12 treatments. Lowering the Ca level enhanced apparent ileal digestibility of P (P AID) at 21 d especially with the high NPP level (Ca × NPP, P < 0.01). The lower bone mineralization observed at 21 d in broilers fed the L 1 diet compared to those fed the H 2 diet had disappeared by 35 d with long-term stimulation of the P AID with the low NPP level (P < 0.001). Although P AID and growth performance were improved in birds fed the L 1 L compared to the L 1 H and H 2 H treatments, tibia characteristics tended to be lower in birds fed the L 1 L compared to those fed the L 1 H treatment. Birds fed the H 1 M treatment had higher P AID, growth performance and tibia ash content than those fed the H 1 H treatment. A significant increase in the mRNA levels of several genes encoding Ca and P transporters was observed at 35 d in birds fed the L 1 followed by the L diet compared to birds fed the L 1 followed by the M diet. In conclusion, chickens are able to adapt to early dietary changes in P and Ca through improvement of digestive efficiency in a later phase, and the extent of the compensation in terms of growth performance and bone mineralization depends on the P and Ca levels in the subsequent diet. © 2016 Poultry Science Association Inc.

High Ca2+ load promotes hydrogen peroxide generation via activation of α-glycerophosphate dehydrogenase in brain mitochondria.

PubMed

Tretter, Laszlo; Adam-Vizi, Vera

2012-12-01

H(2)O(2) generation associated with α-glycerophosphate (α-GP) oxidation was addressed in guinea pig brain mitochondria challenged with high Ca(2+) load (10 μM). Exposure to 10 μM Ca(2+) induced an abrupt 2.5-fold increase in H(2)O(2) release compared to that measured in the presence of a physiological cytosolic Ca(2+) concentration (100 nM) from mitochondria respiring on 5 mM α-GP in the presence of ADP (2 mM). The Ca(2+)-induced stimulation of H(2)O(2) generation was reversible and unaltered by the uniporter blocker Ru 360, indicating that it did not require Ca(2+) uptake into mitochondria. Enhanced H(2)O(2) generation by Ca(2+) was also observed in the absence of ADP when mitochondria exhibited permeability transition pore opening with a decrease in the NAD(P)H level, dissipation of membrane potential, and mitochondrial swelling. Furthermore, mitochondria treated with the pore-forming peptide alamethicin also responded with an elevated H(2)O(2) generation to a challenge with 10 μM Ca(2+). Ca(2+)-induced promotion of H(2)O(2) formation was further enhanced by the complex III inhibitor myxothiazol. With 20 mM α-GP concentration, stimulation of H(2)O(2) formation by Ca(2+) was detected only in the presence, not in the absence, of ADP. It is concluded that α-glycerophosphate dehydrogenase, which is accessible to and could be activated by a rise in the level of cytosolic Ca(2+), makes a major contribution to Ca(2+)-stimulated H(2)O(2) generation. This work highlights a unique high-Ca(2+)-stimulated reactive oxygen species-forming mechanism in association with oxidation of α-GP, which is largely independent of the bioenergetic state and can proceed even in damaged, functionally incompetent mitochondria. Copyright © 2012 Elsevier Inc. All rights reserved.

Atomic Processes for XUV Lasers: Alkali Atoms and Ions

NASA Astrophysics Data System (ADS)

Dimiduk, David Paul

The development of extreme ultraviolet (XUV) lasers is dependent upon knowledge of processes in highly excited atoms. Described here are spectroscopy experiments which have identified and characterized certain autoionizing energy levels in core-excited alkali atoms and ions. Such levels, termed quasi-metastable, have desirable characteristics as upper levels for efficient, powerful XUV lasers. Quasi -metastable levels are among the most intense emission lines in the XUV spectra of core-excited alkalis. Laser experiments utilizing these levels have proved to be useful in characterizing other core-excited levels. Three experiments to study quasi-metastable levels are reported. The first experiment is vacuum ultraviolet (VUV) absorption spectroscopy on the Cs 109 nm transitions using high-resolution laser techniques. This experiment confirms the identification of transitions to a quasi-metastable level, estimates transition oscillator strengths, and estimates the hyperfine splitting of the quasi-metastable level. The second experiment, XUV emission spectroscopy of Ca II and Sr II in a microwave-heated plasma, identifies transitions from quasi-metastable levels in these ions, and provides confirming evidence of their radiative, rather than autoionizing, character. In the third experiment, core-excited Ca II ions are produced by inner-shell photoionization of Ca with soft x-rays from a laser-produced plasma. This preliminary experiment demonstrated a method of creating large numbers of these highly-excited ions for future spectroscopic experiments. Experimental and theoretical evidence suggests the CA II 3{ rm p}^5 3d4s ^4 {rm F}^circ_{3/2 } quasi-metastable level may be directly pumped via a dipole ionization process from the Ca I ground state. The direct process is permitted by J conservation, and occurs due to configuration mixing in the final state and possibly the initial state as well. The experiments identifying and characterizing quasi-metastable levels are compared to calculations using the Hartree-Fock code RCN/RCG. Calculated parameters include energy levels, wavefunctions, and transition rates. Based on an extension of this code, earlier unexplained experiments showing strong two-electron radiative transitions from quasi-metastable levels are now understood.

Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

PubMed

Kim, Min Seong; Jeon, Tae Joo; Park, Ji Young; Choi, Jeongmin; Shin, Won Chang; Park, Seong Eun; Seo, Ji Young; Kim, Young Moon

2017-08-25

Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.

Ca 3d unoccupied states in Bi2Sr2CaCu2O8 investigated by Ca L2,3 x-ray-absorption near-edge structure

NASA Astrophysics Data System (ADS)

Borg, A.; King, P. L.; Pianetta, P.; Lindau, I.; Mitzi, D. B.; Kapitulnik, A.; Soldatov, A. V.; della Longa, S.; Bianconi, A.

1992-10-01

The high-resolution Ca L2,3 x-ray-absorption near-edge-structure (XANES) spectrum of a Bi2Sr2CaCu2O8 single crystal has been measured by use of a magnetic-projection x-ray microscope probing a surface area of 200×200 μm2. The Ca L2,3 XANES spectrum is analyzed by performing a multiple-scattering XANES calculation in real space and comparing the results with the spectrum of CaF2. Good agreement between the calculated and experimental crystal-field splitting Δf of the Ca 3d final states is found and the splitting is shown to be smaller by 0.5 eV than in the initial state. The Ca 3d partial density of states is found to be close to the Fermi level in the initial state. The Ca-O(in plane) distance is shown to be a critical parameter associated with the shift of the Ca 3d states relative to the Fermi level; in particular, we have studied the effect of the out-of-plane dimpling mode of the in-plane oxygen atoms O(in plane) that will move the Ca 3d states on or off the Fermi level. This mode can therefore play a role in modulating the charge transfer between the two CuO2 planes separated by the Ca ions.

Response of broiler chickens to different levels of calcium, non-phytate phosphorus and phytase.

PubMed

Akter, M; Graham, H; Iji, P A

2016-12-01

1. Five hundred and seventy six-d old Ross 308 broiler chicks (6 cages per diet, 8 birds per cage in 3 × 2 × 2 factorial arrangement) were fed on maize-soybean meal-based diets containing three concentrations of Ca (6, 8 or 10 g/kg), two concentrations of non-phytate phosphorus (NPP) (3 or 4 g/kg) and two levels of exogenous microbial phytase (0 or 500 FTU/kg) from d 0 to 35. 2. Body weight (BW), feed intake (FI) and mortality records were collected. Two birds per replicate were killed at 24 d of age to obtain tibia samples. 3. Increasing Ca level significantly reduced the FI and body weight gain (BWG) between hatch and 10 and 24 d, especially with the phytase-supplemented diets. However, phytase supplementation of the diet containing 4 g NPP/kg improved the FI and BWG at d 10 and 24. At d 24, phytase supplementation improved feed conversion ratio (FCR) of birds that consumed diets containing high NPP. The overall FCR was better in birds offered the phytase-supplemented, medium-Ca diet. 4. There was a significant reduction in length, width and breaking strength of the tibia bone in birds fed on a diet with high Ca and low NPP. Phytase supplementation improved the tibia ash content and bone breaking strength of chicks fed on the diet containing 8 and 4 g/kg Ca and NPP, respectively. The Ca content of the tibia bone was low in birds fed on diets with 6 and 4 g/kg Ca and NPP, respectively, but this was counteracted by phytase supplementation. 5. Birds fed on diets with 4 g/kg NPP had the best carcass percentage and parts yield. Phytase supplementation to high-Ca diets significantly reduced the carcass yield of birds. 6. These results confirmed the detrimental effect of high dietary Ca on phytase activity and subsequent growth and bone development of birds, especially when NPP is in short supply.

Carotenoid Intake and Adipose Tissue Carotenoid Levels in Relation to Prostate Cancer Aggressiveness among African-American and European-American Men in the North Carolina-Louisiana Prostate Cancer Project (PCaP)

PubMed Central

Antwi, Samuel O.; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Craft, Neal E.; Fontham, Elizabeth T. H.; Smith, Gary J.; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

2016-01-01

Background Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may be due to combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. Methods Data on African-American (AA, n=1,023) and European-American (EA, n=1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed food frequency questionnaire, and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analysis to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. Results Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β–cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR=0.55, 95%CI: 0.34–0.89, Ptrend=0.02), while an inverse association was observed between dietary β–cryptoxanthin intake and high aggressive CaP among AAs (OR=0.56, 95%CI: 0.36–0.87, Ptrend=0.01). Adipose tissue α–carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α–carotene (Ptrend=0.07) and lycopene (Ptrend=0.11), and CaP aggressiveness among EAs only. Conclusions These results suggest that diets high in lycopene and β–cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the racial differences in associations. PMID:27271547

Myogenic tone is impaired at low arterial pressure in mice deficient in the low-voltage-activated CaV 3.1 T-type Ca(2+) channel.

PubMed

Björling, K; Morita, H; Olsen, M F; Prodan, A; Hansen, P B; Lory, P; Holstein-Rathlou, N-H; Jensen, L J

2013-04-01

Using mice deficient in the CaV 3.1 T-type Ca(2+) channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. We used immunofluorescence microscopy to localize CaV 3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca(2+) currents, pressure myography and Ca(2+) imaging to test diameter and Ca(2+) responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca(2+) handling proteins in wild-type and CaV 3.1(-/-) mice. Our data indicated that CaV 3.1 channels are important for the maintenance of myogenic tone at low pressures (40-80 mm Hg), whereas they are not involved in high-voltage-activated Ca(2+) currents, Ca(2+) entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55-0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca(2+) currents in mouse mesenteric vascular smooth muscle cell. Our data using mice deficient in the CaV 3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV 3.1 channels are not involved in Ca(2+) entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55-0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca(2+) channels. Acta Physiologica © 2013 Scandinavian Physiological Society.

Fiber-specific regulation of Ca(2+)-ATPase isoform expression by thyroid hormone in rat skeletal muscle.

PubMed

van der Linden, C G; Simonides, W S; Muller, A; van der Laarse, W J; Vermeulen, J L; Zuidwijk, M J; Moorman, A F; van Hardeveld, C

1996-12-01

We studied the effect of thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) on the expression of sarcoplasmic reticulum (SR) fast- and slow-type Ca(2+)-ATPase isoforms, SERCA1 and SERCA2a, respectively, and total SR Ca(2+)-ATPase activity in rat skeletal muscle. Cross sections and homogenates of soleus and extensor digitorum longus muscles from hypo-, eu-, and hyperthyroid rats were examined, and expression of Ca(2+)-ATPase isoforms in individual fibers was compared with expression of fast (MHC II) and slow (MHC I) myosin heavy chain isoforms. In both muscles, T3 induced a coordinated and full conversion to a fast-twitch phenotype in one-half of the fibers that were slow twitch in the absence of T3. The conversion was partial in the other one-half of the fibers, giving rise to a mixed phenotype. The stimulation by T3 of total SERCA expression in all fibers was reflected by increased SR Ca(2+)-ATPase activity. The time course of the T3-induced changes of SERCA isoform expression was examined 1-14 days after the start of daily T3 treatment of euthyroid rats. SERCA1 expression was stimulated by T3 at a pretranslational level in all fibers. SERCA2a mRNA expression was transiently stimulated and disappeared in a subset of fibers. In these fibers SR Ca(2+)-ATPase activity was high because of high SERCA1 protein levels. These data suggest that the ultimate downregulation of SERCA2a expression, which is always associated with high SR Ca(2+)-ATPase activities, occurs at a pretranslational level.

Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats.

PubMed

Paßlack, Nadine; Schmiedchen, Bettina; Raila, Jens; Schweigert, Florian J; Stumpff, Friederike; Kohn, Barbara; Neumann, Konrad; Zentek, Jürgen

2016-01-01

Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P.

Relationship Between Gender, Age, and Weight and the Serum Ionized Calcium Variations in Dog Periodontal Disease Evolution.

PubMed

Carreira, L Miguel; Dias, Daniela; Azevedo, Pedro

2015-06-01

To analyze the relationships between gender, age, weight, and variations in the levels of serum ionized calcium ([iCa(2+)]) during periodontal disease (PD) evolution. In this study, dogs (n = 50) were divided into 5 groups according to the stage of PD: G0 (no PD), G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). Statistically significant correlations were observed between age, [iCa(2+)] levels, and PD stage. Older dogs had lower [iCa(2+)] levels and more advanced PD stages (high positive correlation), and their body weight decreased as PD developed (negative correlation). Lower [iCa(2+)] values were associated with more severe PD. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification and suppression of the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase in Zea mays L.

PubMed Central

Marita, Jane M; Hatfield, Ronald D; Rancour, David M; Frost, Kenneth E

2014-01-01

Grasses, such as Zea mays L. (maize), contain relatively high levels of p-coumarates (pCA) within their cell walls. Incorporation of pCA into cell walls is believed to be due to a hydroxycinnamyl transferase that couples pCA to monolignols. To understand the role of pCA in maize development, the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase (pCAT) was isolated and purified from maize stems. Purified pCAT was subjected to partial trypsin digestion, and peptides were sequenced by tandem mass spectrometry. TBLASTN analysis of the acquired peptide sequences identified a single full-length maize cDNA clone encoding all the peptide sequences obtained from the purified enzyme. The cDNA clone was obtained and used to generate an RNAi construct for suppressing pCAT expression in maize. Here we describe the effects of suppression of pCAT in maize. Primary screening of transgenic maize seedling leaves using a new rapid analytical platform was used to identify plants with decreased amounts of pCA. Using this screening method, mature leaves from fully developed plants were analyzed, confirming reduced pCA levels throughout plant development. Complete analysis of isolated cell walls from mature transgenic stems and leaves revealed that lignin levels did not change, but pCA levels decreased and the lignin composition was altered. Transgenic plants with the lowest levels of pCA had decreased levels of syringyl units in the lignin. Thus, altering the levels of pCAT expression in maize leads to altered lignin composition, but does not appear to alter the total amount of lignin present in the cell walls. PMID:24654730

Identification and suppression of the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase in Zea mays L.

PubMed

Marita, Jane M; Hatfield, Ronald D; Rancour, David M; Frost, Kenneth E

2014-06-01

Grasses, such as Zea mays L. (maize), contain relatively high levels of p-coumarates (pCA) within their cell walls. Incorporation of pCA into cell walls is believed to be due to a hydroxycinnamyl transferase that couples pCA to monolignols. To understand the role of pCA in maize development, the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase (pCAT) was isolated and purified from maize stems. Purified pCAT was subjected to partial trypsin digestion, and peptides were sequenced by tandem mass spectrometry. TBLASTN analysis of the acquired peptide sequences identified a single full-length maize cDNA clone encoding all the peptide sequences obtained from the purified enzyme. The cDNA clone was obtained and used to generate an RNAi construct for suppressing pCAT expression in maize. Here we describe the effects of suppression of pCAT in maize. Primary screening of transgenic maize seedling leaves using a new rapid analytical platform was used to identify plants with decreased amounts of pCA. Using this screening method, mature leaves from fully developed plants were analyzed, confirming reduced pCA levels throughout plant development. Complete analysis of isolated cell walls from mature transgenic stems and leaves revealed that lignin levels did not change, but pCA levels decreased and the lignin composition was altered. Transgenic plants with the lowest levels of pCA had decreased levels of syringyl units in the lignin. Thus, altering the levels of pCAT expression in maize leads to altered lignin composition, but does not appear to alter the total amount of lignin present in the cell walls. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Hemothorax with a high carbohydrate antigen 19-9 level caused by a bronchogenic cyst.

PubMed

Tsuzuku, Akifumi; Asano, Fumihiro; Murakami, Anri; Masuda, Atsunori; Sobajima, Takuya; Matsuno, Yoshihiko; Matsumoto, Shinsuke; Mori, Yoshio; Takiya, Hiroshi; Iwata, Hitoshi

2014-01-01

A 58-year-old man presented with right-sided chest pain. Radiography and computed tomography showed a pleural effusion in the right chest and a mass in the right hilum. Thoracentesis showed a hemothorax. The carbohydrate antigen (CA) 19-9 level in the pleural effusion was very high, requiring differentiation from malignancy. Positron emission tomography showed no significant fluorodeoxy glucose (FDG) accumulation. Magnetic resonance imaging revealed a cystic lesion. The tumor was resected for both a diagnosis and treatment. A pathological examination demonstrated a bronchogenic cyst. An immunohistochemical study suggested that the cyst was the source of the hemothorax and the high CA19-9 level.

Production of volatiles in fresh-cut apple: effect of applying alginate coatings containing linoleic acid or isoleucine.

PubMed

Maya-Meraz, Irma O; Espino-Díaz, Miguel; Molina-Corral, Francisco J; González-Aguilar, Gustavo A; Jacobo-Cuellar, Juan L; Sepulveda, David R; Olivas, Guadalupe I

2014-11-01

One of the main quality parameters in apples is aroma, its main precursors are fatty acids (FA) and amino acids (AA). In this study, alginate edible coatings were used as carriers of linoleic acid or isoleucine to serve as precursors for the production of aroma in cut apples. Apple wedges were immersed in a CaCl2 solution and coated with one of the following formulations: alginate solution (Alg-Ca), Alg-Ca-low-level linoleic acid (0.61 g/Lt), (LFA), Alg-Ca-high-level linoleic acid (2.44 g/L; HFA), Alg-Ca-low-level isoleucine (0.61 g/L; LAA), and Alg-Ca-high-level isoleucine (2.44 g/L; HAA). Apple wedges were stored at 3 °C and 85% relative humidity for 21 d and key volatiles were studied during storage. Addition of precursors, mainly isoleucine, showed to increase the production of some key volatiles on coated fresh-cut apples during storage. The concentration of 2-methyl-1-butanol was 4 times higher from day 12 to day 21 in HAA, while 2-methyl butyl acetate increased from day 12 to day 21 in HAA. After 21 d, HAA-apples presented a 40-fold value of 2-methyl-butyl acetate, compared to Alg-Ca cut apples. Values of hexanal increased during cut apple storage when the coating carried linoleic acid, mainly on HFA, from 3 to 12 d. The ability of apples to metabolize AA and FA depends on the concentration of precursors, but also depends on key enzymes, previous apple storage, among others. Further studies should be done to better clarify the behavior of fresh-cut apples as living tissue to metabolize precursors contained in edible coatings for the production of volatiles. © 2014 Institute of Food Technologists®

ENHANCED RETENTION AND SENSITIVITY IN THE ANALYSIS OF CYANURIC ACID IN WATER USING POROUS GRAPHITIC CARBON AND UV DETECTION IN HIGH PRESSURE LIQUID CHROMATOGRAPHY

EPA Science Inventory

Cyanuric acid (CA) has found application as a chlorine stabilizer in pool waters. The National Swimming Pool Foundation recommends CA levels between 30-50 ppm and a chlorine residual of 1.0-3.0 ppm. These chlorine levels are needed to destroy harmful pathogenic organisms. Develo...

Self-Esteem Trajectories and Their Social Determinants in Adolescents with Different Levels of Cognitive Ability

ERIC Educational Resources Information Center

Morin, Alexandre J. S.; Arens, A. Katrin; Tracey, Danielle; Parker, Philip D.; Ciarrochi, Joseph; Craven, Rhonda G.; Maïano, Christophe

2017-01-01

This study examines the development of self-esteem in a sample of 138 Australian adolescents (90 males; 48 females) with cognitive abilities in the lowest 15% (L-CA) and a matched sample of 556 Australian adolescents (312 males; 244 females) with average to high levels of cognitive abilities (A/H-CA). These participants were measured annually…

High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis.

PubMed

Relling, David P; Esberg, Lucy B; Fang, Cindy X; Johnson, W Thomas; Murphy, Eric J; Carlson, Edward C; Saari, Jack T; Ren, Jun

2006-03-01

Obesity is associated with dyslipidemia, which leads to elevated triglyceride and ceramide levels, apoptosis and compromised cardiac function. To determine the role of high-fat diet-induced obesity on cardiomyocyte function, weanling male Sprague-Dawley rats were fed diets incorporating 10% of kcal or 45% of kcal from fat. Mechanical function of ventricular myocytes was evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening and relengthening (+/- dl/dt). Intracellular Ca properties were assessed using fluorescent microscopy. High-fat diet induced hyperinsulinemic insulin-resistant obesity with depressed PS, +/- dl/dt, prolonged TPS/TR90 reduced intracellular Ca release and Ca clearing rate in the absence of hypertension, diabetes, lipotoxicity and apoptosis. Myocyte responsiveness to increased stimulus frequency and extracellular Ca was compromised. SERCA2a and phospholamban levels were increased, whereas phosphorylated phospholamban and potassium channel (Kv1,2) were reduced in high-fat diet group. High-fat diet upregulated the forkhead transcription factor Foxo3a, and suppressed mitochondrial aconitase activity without affecting expression of the caloric sensitive gene silent information regulator 2 (Sir2), protein nitrotyrosine formation, lipid peroxidation and apoptosis. Levels of endothelial nitric oxide synthase (NOS), inducible NOS, triglycerides and ceramide were similar between the two groups. Collectively, our data show that high-fat diet-induced obesity resulted in impaired cardiomyocyte function, upregulated Foxo3a transcription factor and mitochondrial damage without overt lipotoxicity or apoptosis.

Assessment of repeatability of composition of perfumed waters by high-performance liquid chromatography combined with numerical data analysis based on cluster analysis (HPLC UV/VIS - CA).

PubMed

Ruzik, L; Obarski, N; Papierz, A; Mojski, M

2015-06-01

High-performance liquid chromatography (HPLC) with UV/VIS spectrophotometric detection combined with the chemometric method of cluster analysis (CA) was used for the assessment of repeatability of composition of nine types of perfumed waters. In addition, the chromatographic method of separating components of the perfume waters under analysis was subjected to an optimization procedure. The chromatograms thus obtained were used as sources of data for the chemometric method of cluster analysis (CA). The result was a classification of a set comprising 39 perfumed water samples with a similar composition at a specified level of probability (level of agglomeration). A comparison of the classification with the manufacturer's declarations reveals a good degree of consistency and demonstrates similarity between samples in different classes. A combination of the chromatographic method with cluster analysis (HPLC UV/VIS - CA) makes it possible to quickly assess the repeatability of composition of perfumed waters at selected levels of probability. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Dandelion Root Extract Induces Intracellular Ca2+ Increases in HEK293 Cells.

PubMed

Gerbino, Andrea; Russo, Daniela; Colella, Matilde; Procino, Giuseppe; Svelto, Maria; Milella, Luigi; Carmosino, Monica

2018-04-07

Dandelion (Taraxacum officinale Weber ex F.H.Wigg.) has been used for centuries as an ethnomedical remedy. Nonetheless, the extensive use of different kinds of dandelion extracts and preparations is based on empirical findings. Some of the tissue-specific effects reported for diverse dandelion extracts may result from their action on intracellular signaling cascades. Therefore, the aim of this study was to evaluate the effects of an ethanolic dandelion root extract (DRE) on Ca 2+ signaling in human embryonic kidney (HEK) 293 cells. The cytotoxicity of increasing doses of crude DRE was determined by the Calcein viability assay. Fura-2 and the fluorescence resonance energy transfer (FRET)-based probe ERD1 were used to measure cytoplasmic and intraluminal endoplasmic reticulum (ER) Ca 2+ levels, respectively. Furthermore, a green fluorescent protein (GFP)-based probe was used to monitor phospholipase C (PLC) activation (pleckstrin homology [PH]-PLCδ-GFP). DRE (10-400 µg/mL) exposure, in the presence of external Ca 2+ , dose-dependently increased intracellular Ca 2+ levels. The DRE-induced Ca 2+ increase was significantly reduced in the absence of extracellular Ca 2+ . In addition, DRE caused a significant Ca 2+ release from the ER of intact cells and a concomitant translocation of PH-PLCδ-GFP. In conclusion, DRE directly activates both the release of Ca 2+ from internal stores and a significant Ca 2+ influx at the plasma membrane. The resulting high Ca 2+ levels within the cell seem to directly stimulate PLC activity.

Dandelion Root Extract Induces Intracellular Ca2+ Increases in HEK293 Cells

PubMed Central

Russo, Daniela; Svelto, Maria; Carmosino, Monica

2018-01-01

Dandelion (Taraxacum officinale Weber ex F.H.Wigg.) has been used for centuries as an ethnomedical remedy. Nonetheless, the extensive use of different kinds of dandelion extracts and preparations is based on empirical findings. Some of the tissue-specific effects reported for diverse dandelion extracts may result from their action on intracellular signaling cascades. Therefore, the aim of this study was to evaluate the effects of an ethanolic dandelion root extract (DRE) on Ca2+ signaling in human embryonic kidney (HEK) 293 cells. The cytotoxicity of increasing doses of crude DRE was determined by the Calcein viability assay. Fura-2 and the fluorescence resonance energy transfer (FRET)-based probe ERD1 were used to measure cytoplasmic and intraluminal endoplasmic reticulum (ER) Ca2+ levels, respectively. Furthermore, a green fluorescent protein (GFP)-based probe was used to monitor phospholipase C (PLC) activation (pleckstrin homology [PH]–PLCδ–GFP). DRE (10–400 µg/mL) exposure, in the presence of external Ca2+, dose-dependently increased intracellular Ca2+ levels. The DRE-induced Ca2+ increase was significantly reduced in the absence of extracellular Ca2+. In addition, DRE caused a significant Ca2+ release from the ER of intact cells and a concomitant translocation of PH–PLCδ–GFP. In conclusion, DRE directly activates both the release of Ca2+ from internal stores and a significant Ca2+ influx at the plasma membrane. The resulting high Ca2+ levels within the cell seem to directly stimulate PLC activity. PMID:29642457

Calcium mobilization elicited by two types of nicotinic acetylcholine receptors in mouse substantia nigra pars compacta.

PubMed

Tsuneki, H; Klink, R; Léna, C; Korn, H; Changeux, J P

2000-07-01

Nicotinic acetylcholine receptors (nAChRs) are expressed in the midbrain ascending dopaminergic system, a target of many addictive drugs. Here we assessed the intracellular Ca2+ level by imaging fura-2-loaded cells in substantia nigra pars compacta in mouse brain slices, and we examined the influence on this level of prolonged exposures to nicotine using mice lacking the nAChR beta2-subunit. In control cells, superfusion with nicotine (10-100 microM) caused a long-lasting rise of intracellular Ca2+ level which depended on extracellular Ca2+. This nicotinic response was almost completely absent in beta2-/- mutant mice, leaving a small residual response to a high concentration (100 microM) of nicotine which was inhibited by the alpha7-subunit-selective antagonist, methyllycaconitine. Conversely, the alpha7-subunit-selective agonist choline (10 mM) caused a methyllycaconitine-sensitive increase in intracellular Ca2+ level both in wild-type and beta2-/- mutant mice. Nicotine-elicited Ca2+ mobilization was reduced by the Na+ channel blocker tetrodotoxin (TTX) and by T-type Ca2+ channel blocking agents, whereas the choline-elicited Ca2+ increase was insensitive to TTX. Neither nicotine nor choline produced Ca2+ increase following inhibition of the release of Ca2+ from intracellular stores by dantrolene. These results demonstrate that in nigral dopaminergic neurons, nicotine can elicit Ca2+ mobilization via activation of two distinct nAChR subtypes: that of beta2-subunit-containing nAChR followed by activation of Na+ channel and T-type Ca2+ channels, and/or activation of alpha7-subunit-containing nAChR. The Ca2+ influx due to nAChR activation is subsequently amplified by the recruitment of intracellular Ca2+ stores. This Ca2+ mobilization may possibly contribute to the long-term effects of nicotine on the dopaminergic system.

Elevated Vitamin D Receptor Levels in Genetic Hypercalciuric Stone-Forming Rats Are Associated With Downregulation of Snail

PubMed Central

Bai, Shaochun; Wang, Hongwei; Shen, Jikun; Zhou, Randal; Bushinsky, David A; Favus, Murray J

2010-01-01

Patients with idiopathic hypercalciuria (IH) and genetic hypercalciuric stone-forming (GHS) rats, an animal model of IH, are both characterized by normal serum Ca, hypercalciuria, Ca nephrolithiasis, reduced renal Ca reabsorption, and increased bone resorption. Serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are elevated or normal in IH and are normal in GHS rats. In GHS rats, vitamin D receptor (VDR) protein levels are elevated in intestinal, kidney, and bone cells, and in IH, peripheral blood monocyte VDR levels are high. The high VDR is thought to amplify the target-tissue actions of normal circulating 1,25(OH)2D levels to increase Ca transport. The aim of this study was to elucidate the molecular mechanisms whereby Snail may contribute to the high VDR levels in GHS rats. In the study, Snail gene expression and protein levels were lower in GHS rat tissues and inversely correlated with VDR gene expression and protein levels in intestine and kidney cells. In human kidney and colon cell lines, ChIP assays revealed endogenous Snail binding close to specific E-box sequences within the human VDR promoter region, whereas only one E-box specifically bound Snail in the rat promoter. Snail binding to rat VDR promoter E-box regions was reduced in GHS compared with normal control intestine and was accompanied by hyperacetylation of histone H3. These results provide evidence that elevated VDR in GHS rats likely occurs because of derepression resulting from reduced Snail binding to the VDR promoter and hyperacetylation of histone H3. © 2010 American Society for Bone and Mineral Research. PMID:19929616

A study on the influence of different promoter and 5'UTR (URM) cassettes from Arabidopsis thaliana on the expression level of the reporter gene β glucuronidase in tobacco and cotton.

PubMed

Agarwal, Parul; Garg, Varsha; Gautam, Taru; Pillai, Beena; Kanoria, Shaveta; Burma, Pradeep Kumar

2014-04-01

Several reports of promoters from plants, viral and artificial origin that confer high constitutive expression are known. Among these the CaMV 35S promoter is used extensively for transgene expression in plants. We identified candidate promoters from Arabidopsis based on their transcript levels (meta-analysis of available microarray control datasets) to test their activity in comparison to the CaMV 35S promoter. A set of 11 candidate genes were identified which showed high transcript levels in the aerial tissue (i.e. leaf, shoot, flower and stem). In the initial part of the study binary vectors were developed wherein the promoter and 5'UTR region of these candidate genes (Upstream Regulatory Module, URM) were cloned upstream to the reporter gene β glucuronidase (gus). The promoter strengths were tested in transformed callus of Nicotiana tabacum and Gossypium hirsutum. On the basis of the results obtained from the callus, the influence of the URM cassettes on transgene expression was tested in transgenic tobacco. The URM regions of the genes encoding a subunit of photosystem I (PHOTO) and geranyl geranyl reductase (GGR) in A. thaliana genome showed significantly high levels of GUS activity in comparison to the CaMV 35S promoter. Further, when the 5'UTRs of both the genes were placed downstream to the CaMV 35S promoter it led to a substantial increase in GUS activity in transgenic tobacco lines and cotton callus. The enhancement observed was even higher to that observed with the viral leader sequences like Ω and AMV, known translational enhancers. Our results indicate that the two URM cassettes or the 5'UTR regions of PHOTO and GGR when placed downstream to the CaMV 35S promoter can be used to drive high levels of transgene expression in dicotyledons.

Authigenic apatite and octacalcium phosphate formation due to adsorption-precipitation switching across estuarine salinity gradients

NASA Astrophysics Data System (ADS)

Oxmann, J. F.; Schwendenmann, L.

2015-02-01

Mechanisms governing phosphorus (P) speciation in coastal sediments remain largely unknown due to the diversity of coastal environments and poor analytical specificity for P phases. We investigated P speciation across salinity gradients comprising diverse ecosystems in a P-enriched estuary. To determine P load effects on P speciation we compared the high P site with a low P site. Octacalcium phosphate (OCP), authigenic apatite (carbonate fluorapatite, CFAP) and detrital apatite (fluorapatite) were quantitated in addition to Al/Fe-bound P (Al/Fe-P) and Ca-bound P (Ca-P). Gradients in sediment pH strongly affected P fractions across ecosystems and independent of the site-specific total P status. We found a pronounced switch from adsorbed Al/Fe-P to mineral Ca-P with decreasing acidity from land to sea. This switch occurred at near-neutral sediment pH and has possibly been enhanced by redox-driven phosphate desorption from iron oxyhydroxides. The seaward decline in Al/Fe-P was counterbalanced by the precipitation of Ca-P. Correspondingly, two location-dependent accumulation mechanisms occurred at the high P site due to the switch, leading to elevated Al/Fe-P at pH < 6.6 (landward; adsorption) and elevated Ca-P at pH > 6.6 (seaward; precipitation). Enhanced Ca-P precipitation by increased P loads was also evident from disproportional accumulation of metastable Ca-P (Ca-Pmeta) at the high P site. Here, sediments contained on average 6-fold higher Ca-Pmeta levels compared with the low P site, although these sediments contained only 2-fold more total Ca-P than the low P sediments. Phosphorus species distributions indicated that these elevated Ca-Pmeta levels resulted from transformation of fertilizer-derived Al/Fe-P to OCP and CFAP in nearshore areas. Formation of CFAP as well as its precursor, OCP, results in P retention in coastal zones and can thus lead to substantial inorganic P accumulation in response to anthropogenic P input.

Conditions of Mytilus edulis extracellular body fluids and shell composition in a pH-treatment experiment: Acid-base status, trace elements and δ11B

NASA Astrophysics Data System (ADS)

Heinemann, Agnes; Fietzke, Jan; Melzner, Frank; BöHm, Florian; Thomsen, JöRn; Garbe-SchöNberg, Dieter; Eisenhauer, Anton

2012-01-01

Mytilus edulis were cultured for 3 months under six different seawater pCO2 levels ranging from 380 to 4000 μatm. Specimen were taken from Kiel Fjord (Western Baltic Sea, Germany) which is a habitat with high and variable seawater pCO2 and related shifts in carbonate system speciation (e.g., low pH and low CaCO3 saturation state). Hemolymph (HL) and extrapallial fluid (EPF) samples were analyzed for pH and total dissolved inorganic carbon (CT) to calculate pCO2 and [HCO3-]. A second experiment was conducted for 2 months with three different pCO2 levels (380, 1400 and 4000 μatm). Boron isotopes (δ11B) were investigated by LA-MC-ICP-MS (Laser Ablation-Multicollector-Inductively Coupled Plasma-Mass Spectrometry) in shell portions precipitated during experimental treatment time. Additionally, elemental ratios (B/Ca, Mg/Ca and Sr/Ca) in the EPF of specimen from the second experiment were measured via ICP-OES (Inductively Coupled Plasma-Optical Emission Spectrometry). Extracellular pH was not significantly different in HL and EPF but systematically lower than ambient water pH. This is due to high extracellular pCO2 values, a prerequisite for metabolic CO2 excretion. No accumulation of extracellular [HCO3-] was measured. Elemental ratios (B/Ca, Mg/Ca and Sr/Ca) in the EPF increased slightly with pH which is in accordance with increasing growth and calcification rates at higher seawater pH values. Boron isotope ratios were highly variable between different individuals but also within single shells. This corresponds to a high individual variability in fluid B/Ca ratios and may be due to high boron concentrations in the organic parts of the shell. The mean δ11B value shows no trend with pH but appears to represent internal pH (EPF) rather than ambient water pH.

High Ca2+ Influx During Traumatic Brain Injury Leads to Caspase-1-Dependent Neuroinflammation and Cell Death.

PubMed

Abdul-Muneer, P M; Long, Mathew; Conte, Adriano Andrea; Santhakumar, Vijayalakshmi; Pfister, Bryan J

2017-08-01

We investigated the hypothesis that high Ca 2+ influx during traumatic brain injury induces the activation of the caspase-1 enzyme, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury and an in vivo model of fluid percussion injury (FPI). We first established that stretch injury causes a rapid increase in the intracellular Ca 2+ level, which activates interleukin-converting enzyme caspase-1. The increase in the intracellular Ca 2+ level and subsequent caspase-1 activation culminates into neuroinflammation via the maturation of IL-1β. Further, we analyzed caspase-1-mediated apoptosis by TUNEL staining and PARP western blotting. The voltage-gated sodium channel blocker, tetrodotoxin, mitigated the stretch injury-induced neuroinflammation and subsequent apoptosis by blocking Ca 2+ influx during the injury. The effect of tetrodotoxin was similar to the caspase-1 inhibitor, zYVAD-fmk, in neuronal culture. To validate the in vitro results, we demonstrated an increase in caspase-1 activity, neuroinflammation and neurodegeneration in fluid percussion-injured animals. Our data suggest that neuronal injury/traumatic brain injury (TBI) can induce a high influx of Ca 2+ to the cells that cause neuroinflammation and cell death by activating caspase-1, IL-1β, and intrinsic apoptotic pathways. We conclude that excess IL-1β production and cell death may contribute to neuronal dysfunction and cognitive impairment associated with TBI.

Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

PubMed

Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

2014-11-20

The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

[Changes in Ca(2+)concentration and caspase-3 expression and their relationship in Raji cells exposed to electromagnetic radiation].

PubMed

Wang, Wei; Liu, Huan-xin; Wang, De-wen; Zuo, Hong-yan; Peng, Rui-yun

2013-02-01

To study the effects of electromagnetic pulse (EMP), S-band high power microwave (S-HPM), and X-band high power microwave (X-HPM) on the Ca(2+) concentration and caspase-3 expression in Raji cells and the relationship between Ca(2+) concentration and caspase-3 expression, and to investigate the regulatory mechanism of electromagnetic radiation damage. Raji cells were cultured conventionally. Some cells were irradiated by EMP, S-HPM, and X-HPM in the logarithmic growth phase for 6 hours and then collected; others received sham irradiation as a control. The Ca(2+) concentration in the cells was measured by laser scanning confocal microscope; the caspase-3 expression in the cells was evaluated by Western blot. Compared with the control group (Ca(2+) fluorescence intensity = 43.08 ± 2.08; caspase-3 expression level = 0.444 ± 0.13), the EMP,S-HPM, and X-HPM groups had significantly increased Ca(2+) concentrations, with Ca(2+) fluorescence intensities of 69.56 ± 1.71, 50.06 ± 1.89, and 70.68 ± 1.59, respectively (P < 0.01), and had upregulated caspase-3 expression, with expression levels of 0.964 ± 0.12, 0.586 ± 0.16, and 0.970 ± 0.07, respectively (P < 0.01). Each of the EMP and X-HPM groups had significantly higher Ca(2+) fluorescence intensity and caspase-3 expression level than the S-HPM group (P < 0.01), but there were no significant differences between the EMP and X-HPM groups. The linear regression analysis showed that the caspase-3 expression was upregulated as the Ca(2+) concentration increased, with a positive correlation between them (P < 0.01). EMP, S-HPM, and X-HPM cause damage probably by increasing the Ca(2+) concentration in cells and in turn inducing caspase-3 overexpression.

Weekday/weekend differences in ambient aerosol level and chemical characteristics of water-soluble components in the city centre

NASA Astrophysics Data System (ADS)

Khoder, M. I.; Hassan, S. K.

Weekday and weekend ambient aerosol samples were collected from the city centre of Cairo, namely "Ramsis" during the summer season of the year 2006, and have been analyzed for water-soluble ionic species. The average concentrations of the total suspended particulate matter (TSP) and their water-soluble components were higher during weekdays than on weekends, indicating that the decreased traffic density on weekends leads to a decrease in the levels of the TSP and their water-soluble ionic species. The average concentrations of the TSP were 454 μg m -3 on weekdays and 298 μg m -3 on weekends. The weekday/weekend concentration ratios were 1.52 for TSP, 1.27 for SO 42-, 1.64 for Cl -, 1.54 for NO 3-, 1.17 for NH 4+, 1.67 for Ca 2+, 1.83 for Na +, 1.75 for K + and 1.73 for Mg 2+. City centre of Cairo has high levels of the TSP and their water-soluble ionic species compared with many polluted cities in the world. Among all of the measured water-soluble components, SO 42- was the most abundant species followed by Ca 2+ on weekdays and weekends. The average mass ratios of NO 3-/SO 42- in the TSP were 0.41 on weekdays and 0.34 on weekends, suggesting that the stationary source emissions were more predominant. The NH 4+/SO 42- molar ratios and its relation with the concentrations of TSP and Ca 2+ during the weekdays and weekends indicate that the chemical form of sulfate and ammonium in aerosol particles varies with TSP and Ca 2+ levels. At high TSP and Ca 2+ levels, and NH 4+/SO 42- molar ratios less than one, SO 42- in aerosol particles may be present as CaSO 4 and (NH 4) 2SO 4·CaSO 4·2H 2O, whereas it is expected to be present as (NH 4) 2SO 4, (NH 4) 2SO 4·CaSO 4·2H 2O and CaSO 4 at low levels of TSP and Ca 2+, and NH 4+/SO 42- molar ratios between 1 and 2. The mean pH values of the TSP were 7.65 on weekdays and 6.97 on weekends, indicating that aerosol particles brought a large amount of crustal species, and might alleviate the tendency of acidification. The relationships between the concentrations of acidic components (NO 3- and SO 42-) and basic components (NH 4+, Ca 2+ and Mg 2+) on weekdays and weekends indicate that the acidity of aerosol particles is neutralized. Ca 2+ and NH 4+ are the most dominant neutralization substances in Cairo atmosphere.

Phosphate removal in agro-industry: pilot- and full-scale operational considerations of struvite crystallization.

PubMed

Moerman, Wim; Carballa, Marta; Vandekerckhove, Andy; Derycke, Dirk; Verstraete, Willy

2009-04-01

Pilot-scale struvite crystallization tests using anaerobic effluent from potato processing industries were performed at three different plants. Two plants (P1 & P2) showed high phosphate removal efficiencies, 89+/-3% and 75+/-8%, resulting in final effluent levels of 12+/-3 mg PO(4)(3-)-PL(-1) and 11+/-3mg PO(4)(3-)-PL(-1), respectively. In contrast, poor phosphate removal (19+/-8%) was obtained at the third location (P3). Further investigations at P3 showed the negative effect of high Ca(2+)/PO(4)(3-)-P molar ratio (ca. 1.25+/-0.11) on struvite formation. A full-scale struvite plant treating anaerobic effluent from a dairy industry showed the same Ca(2+) interference. A shift in the influent Ca(2+)/PO(4)(3-)-P molar ratio from 2.69 to 1.36 resulted in average total phosphorus removal of 78+/-7%, corresponding with effluent levels of 14+/-4 mg P(total)L(-1) (9+/-3 mg PO(4)(3-)-PL(-1)). Under these conditions high quality spherical struvite crystals of 2-6mm were produced.

High-energy physics software parallelization using database techniques

NASA Astrophysics Data System (ADS)

Argante, E.; van der Stok, P. D. V.; Willers, I.

1997-02-01

A programming model for software parallelization, called CoCa, is introduced that copes with problems caused by typical features of high-energy physics software. By basing CoCa on the database transaction paradimg, the complexity induced by the parallelization is for a large part transparent to the programmer, resulting in a higher level of abstraction than the native message passing software. CoCa is implemented on a Meiko CS-2 and on a SUN SPARCcenter 2000 parallel computer. On the CS-2, the performance is comparable with the performance of native PVM and MPI.

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+)].

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

1995-01-01

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Predictors of Calcium Retention in Adolescent Boys

PubMed Central

Hill, Kathleen M.; Braun, Michelle; Kern, Mark; Martin, Berdine R.; Navalta, James W.; Sedlock, Darlene A.; McCabe, Linda; McCabe, George P.; Peacock, Munro; Weaver, Connie M.

2008-01-01

Context: The relationship between calcium (Ca) intake and Ca retention in adolescent boys was recently reported. Objective: This study evaluated the influence of Ca intake, serum hormone levels, biomarkers of bone metabolism, habitual physical activity, habitual Ca intake, and physical fitness on Ca retention in the same sample. Design: This study was a randomized, cross-over design that consisted of two 3-wk metabolic balance periods. Setting: The study took place on a university campus as a summer camp. Patients or Other Participants: A total of 31 American white boys (13–15 yr) participated in the study. Interventions: Each subject consumed a controlled diet with one of five high-low Ca intake pairs that ranged from 670-2003 mg/d, which was manipulated utilizing a fortified beverage. Main Outcome Measures: Ca retention was determined by Ca intake minus urinary and fecal Ca excretion during each balance period. Results: Ca intake explained 21.7% of the variability in Ca retention, and serum IGF-I concentration explained an additional 11.5%. Other serum hormone levels did not significantly add to the model. Biomarkers of bone metabolism, habitual physical activity, habitual Ca intake, and physical fitness were not significant predictors of Ca retention in adolescent boys. Conclusions: IGF-I, a regulator of growth during puberty, is an important predictor of Ca retention in adolescent boys. However, dietary Ca intake is an even greater predictor of Ca retention during this period of growth. PMID:18840643

Molecular characterisation of a calmodulin gene, VcCaM1, that is differentially expressed under aluminium stress in highbush blueberry.

PubMed

Inostroza-Blancheteau, C; Aquea, F; Loyola, R; Slovin, J; Josway, S; Rengel, Z; Reyes-Díaz, M; Alberdi, M; Arce-Johnson, P

2013-11-01

Calmodulin (CaM), a small acidic protein, is one of the best characterised Ca(2+) sensors in eukaryotes. This Ca(2+) -regulated protein plays a critical role in decoding and transducing environmental stress signals by activating specific targets. Many environmental stresses elicit changes in intracellular Ca(2+) activity that could initiate adaptive responses under adverse conditions. We report the first molecular cloning and characterisation of a calmodulin gene, VcCaM1 (Vaccinium corymbosum Calmodulin 1), in the woody shrub, highbush blueberry. VcCaM1 was first identified as VCAL19, a gene induced by aluminium stress in V. corymbosum L. A full-length cDNA of VcCaM1 containing a 766-bp open reading frame (ORF) encoding 149 amino acids was cloned from root RNA. The sequence encodes four Ca(2+) -binding motifs (EF-hands) and shows high similarity (99%) with the isoform CaM 201 of Daucus carota. Expression analyses showed that following Al treatment, VcCaM1 message level decreased in roots of Brigitta, an Al-resistant cultivar, and after 48 h, was lower than in Bluegold, an Al-sensitive cultivar. VcCAM1 message also decreased in leaves of both cultivars within 2 h of treatment. Message levels in leaves then increased by 24 h to control levels in Brigitta, but not in Bluegold, but then decreased again by 48 h. In conclusion, VcCaM1 does not appear to be directly involved in Al resistance, but may be involved in improved plant performance under Al toxicity conditions through regulation of Ca(2+) homeostasis and antioxidant systems in leaves. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Effects of acidic deposition and soil acidification on sugar maple trees in the Adirondack Mountains, New York.

PubMed

Sullivan, T J; Lawrence, G B; Bailey, S W; McDonnell, T C; Beier, C M; Weathers, K C; McPherson, G T; Bishop, D A

2013-11-19

We documented the effects of acidic atmospheric deposition and soil acidification on the canopy health, basal area increment, and regeneration of sugar maple (SM) trees across the Adirondack region of New York State, in the northeastern United States, where SM are plentiful but not well studied and where widespread depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant canopy species in the Adirondack Mountain ecoregion, and it has a high demand for Ca. Trees in this region growing on soils with poor acid-base chemistry (low exchangeable Ca and % base saturation [BS]) that receive relatively high levels of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM seedling regeneration and lower crown vigor compared with study plots with relatively high exchangeable Ca and BS and lower levels of acidic deposition. Basal area increment averaged over the 20th century was correlated (p < 0.1) with acid-base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack SM regeneration, reduced canopy condition, and possibly decreased basal area growth over recent decades are associated with low concentrations of nutrient base cations in this region that has undergone soil Ca depletion from acidic deposition.

Effects of acidic deposition and soil acidification on sugar maple trees in the Adirondack Mountains, New York

USGS Publications Warehouse

Sullivan, Timothy J.; Lawrence, Gregory B.; Bailey, Scott W.; McDonnell, Todd C.; Beier, Colin M.; Weathers, K.C.; McPherson, G.T.; Bishop, Daniel A.

2013-01-01

We documented the effects of acidic atmospheric deposition and soil acidification on the canopy health, basal area increment, and regeneration of sugar maple (SM) trees across the Adirondack region of New York State, in the northeastern United States, where SM are plentiful but not well studied and where widespread depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant canopy species in the Adirondack Mountain ecoregion, and it has a high demand for Ca. Trees in this region growing on soils with poor acid–base chemistry (low exchangeable Ca and % base saturation [BS]) that receive relatively high levels of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM seedling regeneration and lower crown vigor compared with study plots with relatively high exchangeable Ca and BS and lower levels of acidic deposition. Basal area increment averaged over the 20th century was correlated (p < 0.1) with acid–base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack SM regeneration, reduced canopy condition, and possibly decreased basal area growth over recent decades are associated with low concentrations of nutrient base cations in this region that has undergone soil Ca depletion from acidic deposition.

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

PubMed

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP).

PubMed

Antwi, Samuel O; Steck, Susan E; Su, L Joseph; Hebert, James R; Zhang, Hongmei; Craft, Neal E; Fontham, Elizabeth T H; Smith, Gary J; Bensen, Jeannette T; Mohler, James L; Arab, Lenore

2016-09-01

Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend  = 0.02), while an inverse association was observed between dietary β-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend  = 0.01). Adipose tissue α-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α-carotene (Ptrend  = 0.07) and lycopene (Ptrend  = 0.11), and CaP aggressiveness among EAs only. These results suggest that diets high in lycopene and β-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate 76:1053-1066, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Determination of element/Ca ratios in foraminifera and corals using cold- and hot-plasma techniques in inductively coupled plasma sector field mass spectrometry

NASA Astrophysics Data System (ADS)

Lo, Li; Shen, Chuan-Chou; Lu, Chia-Jung; Chen, Yi-Chi; Chang, Ching-Chih; Wei, Kuo-Yen; Qu, Dingchuang; Gagan, Michael K.

2014-02-01

We have developed a rapid and precise procedure for measuring multiple elements in foraminifera and corals by inductively coupled plasma sector field mass spectrometry (ICP-SF-MS) with both cold- [800 W radio frequency (RF) power] and hot- (1200 W RF power) plasma techniques. Our quality control program includes careful subsampling protocols, contamination-free workbench spaces, and refined plastic-ware cleaning process. Element/Ca ratios are calculated directly from ion beam intensities of 24Mg, 27Al, 43Ca, 55Mn, 57Fe, 86Sr, and 138Ba, using a standard bracketing method. A routine measurement time is 3-5 min per dissolved sample. The matrix effects of nitric acid, and Ca and Sr levels, are carefully quantified and overcome. There is no significant difference between data determined by cold- and hot-plasma methods, but the techniques have different advantages. The cold-plasma technique offers a more stable plasma condition and better reproducibility for ppm-level elements. Long-term 2-sigma relative standard deviations (2-RSD) for repeat measurements of an in-house coral standard are 0.32% for Mg/Ca and 0.43% for Sr/Ca by cold-plasma ICP-SF-MS, and 0.69% for Mg/Ca and 0.51% for Sr/Ca by hot-plasma ICP-SF-MS. The higher sensitivity and enhanced measurement precision of the hot-plasma procedure yields 2-RSD precision for μmol/mol trace elements of 0.60% (Mg/Ca), 9.9% (Al/Ca), 0.68% (Mn/Ca), 2.7% (Fe/Ca), 0.50% (Sr/Ca), and 0.84% (Ba/Ca) for an in-house foraminiferal standard. Our refined ICP-SF-MS technique, which has the advantages of small sample size (2-4 μg carbonate consumed) and fast sample throughput (5-8 samples/hour), should open the way to the production of high precision and high resolution geochemical records for natural carbonate materials.

The roles of serum and urinary carbohydrate antigen 19-9 in the management of patients with antenatal hydronephrosis.

PubMed

Atar, Arda; Oktar, Tayfun; Kucukgergin, Canan; Kalelioglu, Ibrahim; Seckin, Sule; Ander, Haluk; Ziylan, Orhan; Kadioglu, Teoman Cem

2015-06-01

Serum carbohydrate antigen (CA) 19-9 has been clinically applied as a valuable tumor marker for pancreatic and gastrointestinal carcinoma. CA 19-9 is expressed in normal excretory epithelium tissues. Increased CA 19-9 has also been observed in uroepithelial tumors as well as in nonmalignant conditions including hydronephrosis secondary to ureteral stones. The purpose of this article is to evaluate the role of urinary CA 19-9 as a non-invasive biomarker in the postnatal differentiation of obstructive and non-obstructive hydronephrosis in patients with unilateral antenatal hydronephrosis. Infants with isolated renal pelvic dilatation, defined as the presence of anteroposterior pelvic diameter (APPD) equal to or greater than 7 mm based on antenatal ultrasound after 28 weeks' gestation, underwent systematic investigation for uropathies and were prospectively followed up. The pyeloplasty group consisted of 17 patients with ureteropelvic junction (UPJ) obstruction who had undergone pyeloplasty. The non-obstructive dilatation (NOD) group consisted of 17 patients with non-obstructive hydronephrosis, and the control group consisted of 21 healthy children. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure the urinary and serum CA 19-9 levels. In both hydronephrosis groups (pyeloplasty and non-obstructive dilatation), the correlations between urinary and serum CA 19-9 levels with the anteroposterior pelvic diameter measured at the third trimester and the postnatal initial evaluation and differential renal function were investigated. The initial median urinary CA 19-9 levels were significantly greater in children who underwent pyeloplasty than in both the non-obstructive hydronephrosis (143 ± 38 vs. 68 ± 23, respectively; p = 0.007) and the healthy control groups (143 ± 38 vs. 13 ± 3, respectively; p = 0.001) (Figure). Three months after surgery, the urinary CA 19-9 levels had decreased significantly according to the preoperative levels in the pyeloplasty group (143 ± 38 vs. 55 ± 16, p = 0.039). In both the pyeloplasty and NOD groups, there was a correlation of urinary CA 19-9 levels with differential renal function and a correlation of serum CA 19-9 levels with the initial anteroposterior pelvic diameter. Receiver operator characteristic (ROC) analysis revealed a better diagnostic profile for the urinary CA 19-9 level than for the serum CA 19-9 level in terms of identifying obstruction in the hydronephrosis groups (areas under the curve = 0.8 and 0.7, respectively). The best cut-off value of for urinary CA 19-9 was 85.5 U/mL with 76% sensitivity, 85% specificity. The negative predictive value was 80%. The results suggest that voided urine CA 19-9 levels seems to be a more useful marker than serum CA 19-9 in obstructive dilatation. An appropriate decrease in urinary CA 19-9 levels after pyeloplasty may be used as a predictor of surgical outcome. In addition, the results have a number of important diagnostic implications that should be further validated in a larger study population. Based on these results, we suggest that a high urinary CA 19-9 level is a non-invasive clinically applicable marker for differentiating between obstruction and non-obstructive dilatation. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The role of hydrothermal processes in the granite-hosted Zr, Y, REE deposit at Strange Lake, Quebec/Labrador: Evidence from fluid inclusions

NASA Astrophysics Data System (ADS)

Salvi, Stefano; Williams-Jones, Anthony E.

1990-09-01

The Strange Lake Zr, Y, REE, Nb, and Be deposit is hosted by a small, high-level, Late-Proterozoic peralkaline granite stock that intruded into high-grade metamorphic gneisses on the Quebec-Labrador border. The stock is extensively altered. Early alteration is manifested by the replacement of arfvedsonite with aegirine. Later alteration involved Ca-Na exchange. Zr, Ti, Y, REEs, Nb, and Be are concentrated in Ca-bearing minerals that, together with quartz, commonly pseudomorph Na-bearing minerals. Fluid inclusions in pseudomorphs comprise several distinct types: high-salinity (13 to 24 wt% NaCl eq.), Ca-rich aqueous inclusions that homogenize to liquid between 135 and 195°C; mixed aqueousmethane inclusions; methane inclusions; and solid-bearing inclusions. Aqueous-methane inclusions represent heterogeneous entrapment of immiscible high-salinity aqueous liquid and methane. Bastnäsite (tentatively identified by SEM analysis) occurs as a daughter mineral. Other daughter or trapped minerals include a Y, HREE-bearing mineral, possibly gagarinite, and hematite, galena, sphalerite, fluorite, pyrochlore, kutnahorite (?), and griceite (?). The first three inclusion types also occur in quartz in pegmatites and veins together with lower-temperature, lower-salinity, Na-dominated aqueous inclusions. The entrapment temperature inferred for the aqueous inclusions from microthermometry and the Na-K-Ca geothermometer range from 155 to 195°C for the higher-salinity inclusions and 100 to 165°C for the low-salinity inclusions. A model is proposed in which the intrusion of a peralkaline granite to high crustal levels initiated a ground/formational water-dominated hydrothermal system in adjacent gabbroic, calc-silicate, and graphitic gneisses. Reaction of the high-salinity, Ca-rich liquid with the graphitic gneisses led to the production of an immiscible methane gas. Subsequent interaction of this liquid with the granite led to extensive replacement of sodic minerals by calcium analogues at temperatures of less than 200°C. Some time after the onset of Ca metasomatism the high-salinity liquid mixed with a Ca-poor, low-salinity, low-temperature liquid that had leached F and rare metals from the granite. Yttrium and REE mineral deposition occurred as a result of the decreased ligand concentration that accompanied fluorite deposition during mixing of the Ca-rich and Ca-poor aqueous liquids.

Efficient 41Ca measurements for biomedical applications

NASA Astrophysics Data System (ADS)

Vockenhuber, C.; Schulze-König, T.; Synal, H.-A.; Aeberli, I.; Zimmermann, M. B.

2015-10-01

We present the performance of 41Ca measurements using low-energy Accelerator Mass Spectrometry (AMS) at the 500 kV facility TANDY at ETH Zurich. We optimized the measurement procedure for biomedical applications where reliability and high sample throughput is required. The main challenge for AMS measurements of 41Ca is the interfering stable isobar 41K. We use a simplified sample preparation procedure to produce calcium fluoride (CaF2) and extract calcium tri-fluoride ions (CaF3-) ions to suppress the stable isobar 41K. Although 41K is not completely suppressed we reach 41Ca/40Ca background level in the 10-12 range which is adequate for biomedical studies. With helium as a stripper gas we can use charge state 2+ at high transmission (∼50%). The new measurement procedure with the approximately 10 × improved efficiency and the higher accuracy due to 41K correction allowed us to measure more than 600 samples for a large biomedical study within only a few weeks of measurement time.

Role of calcium in phosphatidylserine externalisation in red blood cells from sickle cell patients.

PubMed

Weiss, Erwin; Rees, David Charles; Gibson, John Stanley

2011-01-01

Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca(2+) entry, providing an obvious link with phosphatidylserine exposure. The role of Ca(2+) was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca(2+)] was increased. This effect was inhibited by dipyridamole, intracellular Ca(2+) chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K(+) saline. Ca(2+) levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca(2+) entry through the deoxygenation-induced pathway (P(sickle)), activating the Gardos channel. [Ca(2+)] required for phosphatidylserine scrambling are in the range achievable in vivo.

MIPS: a calmodulin-binding protein of Gracilaria lemaneiformis under heat shock.

PubMed

Zhang, Xuan; Zhou, Huiyue; Zang, Xiaonan; Gong, Le; Sun, Hengyi; Zhang, Xuecheng

2014-08-01

To study the Ca(2+)/Calmodulin (CaM) signal transduction pathway of Gracilaria lemaneiformis under heat stress, myo-inositol-1-phosphate synthase (MIPS), a calmodulin-binding protein, was isolated using the yeast two-hybrid system. cDNA and DNA sequences of mips were cloned from G. lemaneiformis by using 5'RACE and genome walking procedures. The MIPS DNA sequence was 2,067 nucleotides long, containing an open reading frame (ORF) of 1,623 nucleotides with no intron. The mips ORF was predicted to encode 540 amino acids, which included the conserved MIPS domain and was 61-67 % similar to that of other species. After analyzing the amino acid sequence of MIPS, the CaM-Binding Domain (CaMBD) was inferred to be at a site spanning from amino acid 212 to amino acid 236. The yeast two-hybrid results proved that MIPS can interact with CaM and that MIPS is a type of calmodulin-binding protein. Next, the expression of CaM and MIPS in wild-type G. lemaneiformis and a heat-tolerant G. lemaneiformis cultivar, "981," were analyzed using real-time PCR under a heat shock of 32 °C. The expression level displayed a cyclical upward trend. Compared with wild type, the CaM expression levels of cultivar 981 were higher, which might directly relate to its resistance to high temperatures. This paper indicates that MIPS and CaM may play important roles in the high-temperature resistance of G. lemaneiformis.

Rechargeable calcium phosphate orthodontic cement with sustained ion release and re-release

NASA Astrophysics Data System (ADS)

Zhang, Ling; Weir, Michael D.; Chow, Laurence C.; Reynolds, Mark A.; Xu, Hockin H. K.

2016-11-01

White spot lesions (WSL) due to enamel demineralization are major complications for orthodontic treatments. Calcium phosphate (CaP) dental resins with Ca and P ion releases are promising for remineralization. However, previous Ca and P releases lasted for only weeks. Experimental orthodontic cements were developed using pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at mass ratio of 1:1 (PE); and PE plus 10% of 2-hydroxyethyl methacrylate (HEMA) and 5% of bisphenol A glycidyl dimethacrylate (BisGMA) (PEHB). Particles of amorphous calcium phosphate (ACP) were incorporated into PE and PEHB at 40% filler level. Specimens were tested for bracket-enamel shear bond strength, water sorption, CaP release, and ion recharge and re-release. PEHB+40ACP had higher bracket-enamel bond strength and ion release and rechargeability than PE+40ACP. ACP incorporation into the novel orthodontic cement did not adversely affect the bracket-enamel bond strength. Ion release and re-release from the novel ACP orthodontic cement indicated favorable release and re-release patterns. The recharged orthodontic cement could release CaP ions continuously for four weeks without further recharge. Novel rechargeable orthodontic cement containing ACP was developed with a high bracket-enamel bond strength and the ability to be repeatedly recharged to maintain long-term high levels of CaP ion releases.

TMBIM-mediated Ca 2+ homeostasis and cell death

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

Liu, Qun

Ca 2+ is a ubiquitous intracellular messenger that regulates numerous physiological activities in humans, animals, plants, and bacteria. Cytosolic Ca 2+ is kept at a low level, but subcellular organelles such as the endoplasmic reticulum (ER) and Golgi Apparatus maintain high-concentration Ca 2+ stores. Under resting conditions, store Ca 2+ homeostasis is dynamically regulated to equilibrate between active Ca 2+ uptake and passive Ca 2+ leak processes. The evolutionarily conserved Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) proteins mediate Ca 2+ homeostasis and cell death. This review focuses on recent advances in functional and structural analysis of TMBIM proteins in regulation ofmore » the two related functions. The roles of TMBIM proteins in pathogen infection and cancer are also discussed with prospects for treatment.« less

TMBIM-mediated Ca 2+ homeostasis and cell death

DOE PAGES

Liu, Qun

2017-01-05

Ca 2+ is a ubiquitous intracellular messenger that regulates numerous physiological activities in humans, animals, plants, and bacteria. Cytosolic Ca 2+ is kept at a low level, but subcellular organelles such as the endoplasmic reticulum (ER) and Golgi Apparatus maintain high-concentration Ca 2+ stores. Under resting conditions, store Ca 2+ homeostasis is dynamically regulated to equilibrate between active Ca 2+ uptake and passive Ca 2+ leak processes. The evolutionarily conserved Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) proteins mediate Ca 2+ homeostasis and cell death. This review focuses on recent advances in functional and structural analysis of TMBIM proteins in regulation ofmore » the two related functions. The roles of TMBIM proteins in pathogen infection and cancer are also discussed with prospects for treatment.« less

Increase in Ca2+ current by sustained cAMP levels enhances proliferation rate in GH3 cells.

PubMed

Rodrigues, Andréia Laura; Brescia, Marcella; Koschinski, Andreas; Moreira, Thaís Helena; Cameron, Ryan T; Baillie, George; Beirão, Paulo S L; Zaccolo, Manuela; Cruz, Jader S

2018-01-01

Ca 2+ and cAMP are important intracellular modulators. In order to generate intracellular signals with various amplitudes, as well as different temporal and spatial properties, a tightly and precise control of these modulators in intracellular compartments is necessary. The aim of this study was to evaluate the effects of elevated and sustained cAMP levels on voltage-dependent Ca 2+ currents and proliferation in pituitary tumor GH3 cells. Effect of long-term exposure to forskolin and dibutyryl-cyclic AMP (dbcAMP) on Ca 2+ current density and cell proliferation rate were determined by using the whole-cell patch-clamp technique and real time cell monitoring system. The cAMP levels were assayed, after exposing transfected GH3 cells with the EPAC-1 cAMP sensor to forskolin and dbcAMP, by FRET analysis. Sustained forskolin treatment (24 and 48h) induced a significant increase in total Ca 2+ current density in GH3 cells. Accordingly, dibutyryl-cAMP incubation (dbcAMP) also elicited increase in Ca 2+ current density. However, the maximum effect of dbcAMP occurred only after 72h incubation, whereas forskolin showed maximal effect at 48h. FRET-experiments confirmed that the time-course to elevate intracellular cAMP was distinct between forskolin and dbcAMP. Mibefradil inhibited the fast inactivating current component selectively, indicating the recruitment of T-type Ca 2+ channels. A significant increase on cell proliferation rate, which could be related to the elevated and sustained intracellular levels of cAMP was observed. We conclude that maintaining high levels of intracellular cAMP will cause an increase in Ca 2+ current density and this phenomenon impacts proliferation rate in GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

PubMed Central

Baltruškevičienė, Edita; Mickys, Ugnius; Žvirblis, Tadas; Stulpinas, Rokas; Pipirienė Želvienė, Teresė; Aleknavičius, Eduardas

2016-01-01

Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19–9 level and KRAS mutation was detected (mean CA 19–9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19–9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information. PMID:28356789

Zinc and calcium alter the relationship between mitochondrial respiration, ROS and membrane potential in rainbow trout (Oncorhynchus mykiss) liver mitochondria.

PubMed

Sharaf, Mahmoud S; Stevens, Don; Kamunde, Collins

2017-08-01

At excess levels, zinc (Zn) disrupts mitochondrial functional integrity and induces oxidative stress in aquatic organisms. Although much is known about the modulation of Zn toxicity by calcium (Ca) in fish, their interactions at the mitochondrial level have scarcely been investigated. Here we assessed the individual and combined effects of Zn and Ca on the relationship between mitochondrial respiration, ROS and membrane potential (ΔΨ mt ) in rainbow trout liver mitochondria. We tested if cation uptake through the mitochondrial calcium uniporter (MCU) is a prerequisite for Zn- and/or Ca-induced alteration of mitochondrial function. Furthermore, using our recently developed real-time multi-parametric method, we investigated the changes in respiration, ΔΨ mt , and reactive oxygen species (ROS, as hydrogen peroxide (H 2 O 2 )) release associated with Ca-induced mitochondrial depolarization imposed by transient and permanent openings of the mitochondrial permeability transition pore (mPTP). We found that independent of the MCU, Zn precipitated an immediate depolarization of the ΔΨ mt that was associated with relatively slow enhancement of H 2 O 2 release, inhibition of respiration and reversal of the positive correlation between ROS and ΔΨ mt . In contrast, an equitoxic dose of Ca caused transient depolarization, and stimulation of both respiration and H 2 O 2 release, effects that were completely abolished when the MCU was blocked. Contrary to our expectation that mitochondrial transition ROS Spike (mTRS) would be sensitive to both Zn and Ca, only Ca suppressed it. Moreover, Zn and Ca in combination immediately depolarized the ΔΨ mt , and caused transient and sustained stimulation of respiration and H 2 O 2 release, respectively. Lastly, we uncovered and characterized an mPTP-independent Ca-induced depolarization spike that was associated with exposure to moderately elevated levels of Ca. Importantly, we showed the stimulation of ROS release associated with highly elevated but not unrealistic Ca loads was not the cause but a result of mPTP opening in the high conductance mode. Copyright © 2017 Elsevier B.V. All rights reserved.

Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat-diet-induced obesity and metabolic syndrome in mice.

PubMed

Zhao, Yantao; Sedighi, Rashin; Wang, Pei; Chen, Huadong; Zhu, Yingdong; Sang, Shengmin

2015-05-20

In this study, we investigated the preventive effects of carnosic acid (CA) as a major bioactive component in rosemary extract (RE) on high-fat-diet-induced obesity and metabolic syndrome in mice. The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks. There was the same CA content in the RE#1H and RE#2 diets and half of this amount in the RE#1L diet. The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride, and free fatty acid levels in comparison with the mice fed with a HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs), and the liver expression of receptor for AGE (RAGE) in comparison with those for mice of the HF group. Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE in comparison with that of HF-diet-fed mice. Meanwhile, RE administration enhanced fecal lipid excretion to inhibit lipid absorption and increased the liver GSH/GSSG ratio to perform antioxidant activity compared with HF group. Our results demonstrate that rosemary is a promising dietary agent to reduce the risk of obesity and metabolic syndrome.

Association of neighborhood-level factors with hospitalization for community-associated methicillin-resistant Staphylococcus aureus, New York City, 2006: a multilevel observational study.

PubMed

Farr, Amanda M; Marx, Melissa A; Weiss, Don; Nash, Denis

2013-02-13

Hospitalizations with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection have increased in New York City, with substantial geographic variation across neighborhoods. While individual-level risk factors, such as age, sex, HIV infection, and diabetes have been described, the role of neighborhood-level factors (e.g., neighborhood HIV prevalence or income) has not been examined. To explore plausible neighborhood-level factors associated with CA-MRSA-related hospitalizations, a retrospective analysis was conducted using New York City hospital discharges from 2006 and New York City-specific survey and health department surveillance data. CA-MRSA-related hospitalizations were identified using diagnosis codes and admission information. Associations were determined by using sex-specific multilevel logistic regression. The CA-MRSA hospitalization rate varied by more than six-fold across New York City neighborhoods. Females hospitalized with CA-MRSA had more than twice the odds of residing in neighborhoods in the highest quintile of HIV prevalence (adjusted odds ratio [AOR](Q5 vs. Q1) 2.3, 95% CI: 1.2, 2.7). Both males and females hospitalized with CA-MRSA had nearly twice the odds of residing in neighborhoods with moderately high proportion of men who have sex with men (MSM) residing in the neighborhood (males: AOR(Q4 vs. Q1) 1.7, 95% CI: 1.1, 2.7; females: AOR(Q4 vs. Q1) 2.0, 95% CI: 1.1, 3.6); but this association did not hold for neighborhoods in the highest quintile (males: AOR(Q5 vs. Q1) 1.2, 95% CI: 0.76, 1.8; females: AOR(Q5 vs. Q1) 1.5, 95% CI: 0.82, 2.7). Neighborhood-level characteristics were associated with CA-MRSA hospitalization odds, independent of individual-level risk factors, and may contribute to the population-level burden of CA-MRSA infection.

In vitro and in vivo evaluation of zinc-modified ca-si-based ceramic coating for bone implants.

PubMed

Yu, Jiangming; Li, Kai; Zheng, Xuebin; He, Dannong; Ye, Xiaojian; Wang, Meiyan

2013-01-01

The host response to calcium silicate ceramic coatings is not always favorable because of their high dissolution rates, leading to high pH within the surrounding physiological environment. Recently, a zinc-incorporated calcium silicate-based ceramic Ca2ZnSi2O7 coating, developed on a Ti-6Al-4V substrate using plasma-spray technology, was found to exhibit improved chemical stability and biocompatibility. This study aimed to investigate and compare the in vitro response of osteoblastic MC3T3-E1 cells cultured on Ca2ZnSi2O7 coating, CaSiO3 coating, and uncoated Ti-6Al-4V titanium control at cellular and molecular level. Our results showed Ca2ZnSi2O7 coating enhanced MC3T3-E1 cell attachment, proliferation, and differentiation compared to CaSiO3 coating and control. In addition, Ca2ZnSi2O7 coating increased mRNA levels of osteoblast-related genes (alkaline phosphatase, procollagen α1(I), osteocalcin), insulin-like growth factor-I (IGF-I), and transforming growth factor-β1 (TGF-β1). The in vivo osteoconductive properties of Ca2ZnSi2O7 coating, compared to CaSiO3 coating and control, was investigated using a rabbit femur defect model. Histological and histomorphometrical analysis demonstrated new bone formation in direct contact with the Ca2ZnSi2O7 coating surface in absence of fibrous tissue and higher bone-implant contact rate (BIC) in the Ca2ZnSi2O7 coating group, indicating better biocompatibility and faster osseointegration than CaSiO3 coated and control implants. These results indicate Ca2ZnSi2O7 coated implants have applications in bone tissue regeneration, since they are biocompatible and able to osseointegrate with host bone.

[The immune-enzyme technique of detection of Ca2+ ATPase of sarcoplasmic reticulum--a new biologic marker of acute cardiac infarction].

PubMed

Tchobanu, L M; Syrbu, S I; Popovitch, I M; Ivanova, V M; Gudumak, V S; Popovitch, M I

2013-05-01

The immune-enzyme system of testing was developed to detect the level of Ca2+ ATPase of sarcoplasmic reticulum using monoclonal IgM and IgG antibodies to Ca2+ ATPase. The clinical approbation of the technique was carried out using the sample of 19 patients with acute cardiac infarction Q validated by the increase of content of such common markers of myocardium necrosis as troponin T and creatine phosphokinase MB. The increase of the level of Ca2+ ATPase of sarcoplasmic reticulum was detected in all patients. This occurrence is detected approximately in 4-6 hours after debut and it disappears in 144 hours (6 days). At the same time, Ca2+ ATPase was not detected in 10 Patients with acute traumatic damages of skeleton musculature, in 10 patients with chronic renal failure under hemodialysis and in 20 patients with acute coronary syndrome without rise of ST-segment of cardiogram. These facts testify rather high specificity and sensitivity of the developed technique of detection of the level of Ca2+ ATPase of sarcoplasmic reticulum in blood as biological marker of myocardium necrosis.

Functional Cooperation between the IP3 Receptor and Phospholipase C Secures the High Sensitivity to Light of Drosophila Photoreceptors In Vivo

PubMed Central

Kohn, Elkana; Katz, Ben; Yasin, Bushra; Peters, Maximilian; Rhodes, Elisheva; Zaguri, Rachel; Weiss, Shirley

2015-01-01

Drosophila phototransduction is a model system for the ubiquitous phosphoinositide signaling. In complete darkness, spontaneous unitary current events (dark bumps) are produced by spontaneous single Gqα activation, while single-photon responses (quantum bumps) arise from synchronous activation of several Gqα molecules. We have recently shown that most of the spontaneous single Gqα activations do not produce dark bumps, because of a critical phospholipase Cβ (PLCβ) activity level required for bump generation. Surpassing the threshold of channel activation depends on both PLCβ activity and cellular [Ca2+], which participates in light excitation via a still unclear mechanism. We show here that in IP3 receptor (IP3R)-deficient photoreceptors, both light-activated Ca2+ release from internal stores and light sensitivity were strongly attenuated. This was further verified by Ca2+ store depletion, linking Ca2+ release to light excitation. In IP3R-deficient photoreceptors, dark bumps were virtually absent and the quantum-bump rate was reduced, indicating that Ca2+ release from internal stores is necessary to reach the critical level of PLCβ catalytic activity and the cellular [Ca2+] required for excitation. Combination of IP3R knockdown with reduced PLCβ catalytic activity resulted in highly suppressed light responses that were partially rescued by cellular Ca2+ elevation, showing a functional cooperation between IP3R and PLCβ via released Ca2+. These findings suggest that in contrast to the current dogma that Ca2+ release via IP3R does not participate in light excitation, we show that released Ca2+ plays a critical role in light excitation. The positive feedback between PLCβ and IP3R found here may represent a common feature of the inositol-lipid signaling. PMID:25673847

Interactions of dietary calcium with toxic levels of lead and zinc in pigs

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

Hsu, F.A.; Krook, L.; Pond, W.G.

1975-01-01

Twenty-four weanling Yorkshire pigs were used in a 2 x 2 x 2 factorial arrangement of treatments to determine their response to high levels of dietary lead (Pb) (1000 ppm) and zinc (Zn) (4000 ppm) (as lead acetate and zinc oxide), to investigate the influence of high dietary calcium (Ca) (1.1%) on the biochemical and morphological manifestations of Pb and Zn toxicity, and to determine the effect of excess Zn on Pb toxicity. Clinical signs of Pb toxicity included behavioral changes, lameness, and anorexia. Pb content of blood, soft tissues, and bone was increased markedly by 1000 ppm Pb inmore » the diet during the 13-week experiment. Zn and Pb fed together, as compared with Pb alone, tended to increase Pb levels in blood, soft tissues, and bone and to enhance the toxic effects of Pb as shown by reduced weight gains, severe clinical signs, and pathological changes. High Ca reduced blood and bone Zn and Pb concentrations. The results indicate that high dietary Ca has a protective effect against the adverse effects of diet Pb and Zn, and that Zn aggravates Pb toxicity in growing pigs.« less

Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes.

PubMed

Raos, B J; Graham, E S; Unsworth, C P

2017-06-01

Astrocytes respond to various stimuli resulting in intracellular Ca 2+ signals that can propagate through organized functional networks. Recent literature calls for the development of techniques that can stimulate astrocytes in a fast and highly localized manner to emulate more closely the characteristics of astrocytic Ca 2+ signals in vivo. In this article we demonstrate, for the first time, how nanosecond UV lasers are capable of reproducibly stimulating Ca 2+ transients in human hNT astrocytes. We report that laser pulses with a beam energy of 4-29 µJ generate transient increases in cytosolic Ca 2+ . These Ca 2+ transients then propagate to adjacent astrocytes as intercellular Ca 2+ waves. We propose that nanosecond laser stimulation provides a valuable tool for enabling the study of Ca 2+ dynamics in human astrocytes at both a single cell and network level. Compared to previously developed techniques nanosecond laser stimulation has the advantage of not requiring loading of photo-caged or -sensitising agents, is non-contact, enables stimulation with a high spatiotemporal resolution and is comparatively cost effective.

High-dose chlorogenic acid induces inflammation reactions and oxidative stress injury in rats without implication of mast cell degranulation.

PubMed

Du, Wen-Yuan; Chang, Cheng; Zhang, Yu; Liu, Yu-Ying; Sun, Kai; Wang, Chuan-She; Wang, Ming-Xia; Liu, Yuan; Wang, Fu; Fan, Jing-Yu; Li, Peng-Tao; Han, Jing-Yan

2013-05-02

Chlorogenic acid (CA) exits widely in those Chinese herbal injections that have antibacterial and antiphlogistic effects and belongs to the ethnopharmacological family of medicines. Chinese herbal injections containing high levels of CA have been reported to increase the adverse drug reactions, but the mechanism for which is still unclear. In this study, we investigated the mechanism of the CA derived adverse drug reactions. The present study was to explore the potential role of CA in initiating inflammatory reaction and the underlying mechanism. Male Wistar rats were treated with different dosages of CA for different time period. The variables examined included microcirculation by intravital microscopy, histology of ileum tissue, expression of adhesion molecules CD11b and CD18 on leukocytes by flow cytometry, myeloperoxidase activity and maleic dialdehyde content in ileum tissue by spectrophotometry, activity of superoxide dismutase and catalase in serum by ELISA, and expression of NADPH oxidase subunits by PCR and Western blot. High-dose CA increased the number of adherent leukocytes, generation of peroxides in the venular walls and induced albumin leakage from mesentery venules. High-dose CA induced changes also included an increase in maleic dialdehyde, myeloperoxidase, inflammatory cytokines and NADPH oxidase activities, and a decline in activity of superoxide dismutase and catalase. High-dose, but not Low-dose CA induced inflammation reaction, and in this process an imbalance between oxidant and antioxidant mechanism may be involved, providing more information for better understanding the rationale behind the adverse effects of CA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

CA State Profile. California: California High School Exit Examination (CAHSEE)

ERIC Educational Resources Information Center

Center on Education Policy, 2010

2010-01-01

This paper provides information about California High School Exit Examination, a comprehensive standards-based exam. The purpose of the exam is to: (1) Determine prospective high school graduates' knowledge and skill levels relative to those needed for entry-level employment; (2) Determine prospective high school graduates' mastery of the state…

Role of calreticulin in the sensitivity of myocardiac H9c2 cells to oxidative stress caused by hydrogen peroxide.

PubMed

Ihara, Yoshito; Urata, Yoshishige; Goto, Shinji; Kondo, Takahito

2006-01-01

Calreticulin (CRT), a Ca2+-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac apoptosis in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In the present study, the effect of overexpression of CRT on susceptibility to apoptosis under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. Under oxidative stress due to H2O2, the CRT-overexpressing cells were highly susceptible to apoptosis compared with controls. In the overexpressing cells, the levels of cytoplasmic free Ca2+ ([Ca2+]i) were significantly increased by H2O2, whereas in controls, only a slight increase was observed. The H2O2-induced apoptosis was enhanced by the increase in [Ca2+]i caused by thapsigargin in control cells but was suppressed by BAPTA-AM, a cell-permeable Ca2+ chelator in the CRT-overexpressing cells, indicating the importance of the level of [Ca2+]i in the sensitivity to H2O2-induced apoptosis. Suppression of CRT by the introduction of the antisense cDNA of CRT enhanced cytoprotection against oxidative stress compared with controls. Furthermore, we found that the levels of activity of calpain and caspase-12 were elevated through the regulation of [Ca2+]i in the CRT-overexpressing cells treated with H2O2 compared with controls. Thus we conclude that the level of CRT regulates the sensitivity to apoptosis under oxidative stress due to H2O2 through a change in Ca2+ homeostasis and the regulation of the Ca2+-calpain-caspase-12 pathway in myocardiac cells.

A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide

PubMed Central

Klaiber, Michael; Dankworth, Beatrice; Kruse, Martin; Hartmann, Michael; Nikolaev, Viacheslav O.; Yang, Ruey-Bing; Völker, Katharina; Gaßner, Birgit; Oberwinkler, Heike; Feil, Robert; Freichel, Marc; Groschner, Klaus; Skryabin, Boris V.; Frantz, Stefan; Birnbaumer, Lutz; Pongs, Olaf; Kuhn, Michaela

2011-01-01

Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca2+]i increases in myocytes. In chronic cardiac hypertrophy, however, ANP levels are markedly increased and GC-A/cGMP responses to ANP are blunted due to receptor desensitization. Here we show that, in this situation, ANP binding to GC-A stimulates a unique cGMP-independent signaling pathway in cardiac myocytes, resulting in pathologically elevated intracellular Ca2+ levels. This pathway involves the activation of Ca2+‐permeable transient receptor potential canonical 3/6 (TRPC3/C6) cation channels by GC-A, which forms a stable complex with TRPC3/C6 channels. Our results indicate that the resulting cation influx activates voltage-dependent L-type Ca2+ channels and ultimately increases myocyte Ca2+i levels. These observations reveal a dual role of the ANP/GC-A–signaling pathway in the regulation of cardiac myocyte Ca2+i homeostasis. Under physiological conditions, activation of a cGMP-dependent pathway moderates the Ca2+i-enhancing action of hypertrophic factors such as angiotensin II. By contrast, a cGMP-independent pathway predominates under pathophysiological conditions when GC-A is desensitized by high ANP levels. The concomitant rise in [Ca2+]i might increase the propensity to cardiac hypertrophy and arrhythmias. PMID:22027011

A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

PubMed

Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

2009-10-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

Crop area estimation using high and medium resolution satellite imagery in areas with complex topography

USGS Publications Warehouse

Husak, G.J.; Marshall, M. T.; Michaelsen, J.; Pedreros, Diego; Funk, Christopher C.; Galu, G.

2008-01-01

Reliable estimates of cropped area (CA) in developing countries with chronic food shortages are essential for emergency relief and the design of appropriate market-based food security programs. Satellite interpretation of CA is an effective alternative to extensive and costly field surveys, which fail to represent the spatial heterogeneity at the country-level. Bias-corrected, texture based classifications show little deviation from actual crop inventories, when estimates derived from aerial photographs or field measurements are used to remove systematic errors in medium resolution estimates. In this paper, we demonstrate a hybrid high-medium resolution technique for Central Ethiopia that combines spatially limited unbiased estimates from IKONOS images, with spatially extensive Landsat ETM+ interpretations, land-cover, and SRTM-based topography. Logistic regression is used to derive the probability of a location being crop. These individual points are then aggregated to produce regional estimates of CA. District-level analysis of Landsat based estimates showed CA totals which supported the estimates of the Bureau of Agriculture and Rural Development. Continued work will evaluate the technique in other parts of Africa, while segmentation algorithms will be evaluated, in order to automate classification of medium resolution imagery for routine CA estimation in the future.

Crop area estimation using high and medium resolution satellite imagery in areas with complex topography

NASA Astrophysics Data System (ADS)

Husak, G. J.; Marshall, M. T.; Michaelsen, J.; Pedreros, D.; Funk, C.; Galu, G.

2008-07-01

Reliable estimates of cropped area (CA) in developing countries with chronic food shortages are essential for emergency relief and the design of appropriate market-based food security programs. Satellite interpretation of CA is an effective alternative to extensive and costly field surveys, which fail to represent the spatial heterogeneity at the country-level. Bias-corrected, texture based classifications show little deviation from actual crop inventories, when estimates derived from aerial photographs or field measurements are used to remove systematic errors in medium resolution estimates. In this paper, we demonstrate a hybrid high-medium resolution technique for Central Ethiopia that combines spatially limited unbiased estimates from IKONOS images, with spatially extensive Landsat ETM+ interpretations, land-cover, and SRTM-based topography. Logistic regression is used to derive the probability of a location being crop. These individual points are then aggregated to produce regional estimates of CA. District-level analysis of Landsat based estimates showed CA totals which supported the estimates of the Bureau of Agriculture and Rural Development. Continued work will evaluate the technique in other parts of Africa, while segmentation algorithms will be evaluated, in order to automate classification of medium resolution imagery for routine CA estimation in the future.

Coral Skeletons Provide Historical Evidence of Phosphorus Runoff on the Great Barrier Reef

PubMed Central

Mallela, Jennie; Lewis, Stephen E.; Croke, Barry

2013-01-01

Recently, the inshore reefs of the Great Barrier Reef have declined rapidly because of deteriorating water quality. Increased catchment runoff is one potential culprit. The impacts of land-use on coral growth and reef health however are largely circumstantial due to limited long-term data on water quality and reef health. Here we use a 60 year coral core record to show that phosphorus contained in the skeletons (P/Ca) of long-lived, near-shore Porites corals on the Great Barrier Reef correlates with annual records of fertiliser application and particulate phosphorus loads in the adjacent catchment. Skeletal P/Ca also correlates with Ba/Ca, a proxy for fluvial sediment loading, again linking near-shore phosphorus records with river runoff. Coral core records suggest that phosphorus levels increased 8 fold between 1949 and 2008 with the greatest levels coinciding with periods of high fertiliser-phosphorus use. Periods of high P/Ca correspond with intense agricultural activity and increased fertiliser application in the river catchment following agricultural expansion and replanting after cyclone damage. Our results demonstrate how coral P/Ca records can be used to assess terrestrial nutrient loading of vulnerable near-shore reefs. PMID:24086606

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

PubMed

Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Thematic Accuracy Assessment of the 2011 National Land ...

EPA Pesticide Factsheets

Accuracy assessment is a standard protocol of National Land Cover Database (NLCD) mapping. Here we report agreement statistics between map and reference labels for NLCD 2011, which includes land cover for ca. 2001, ca. 2006, and ca. 2011. The two main objectives were assessment of agreement between map and reference labels for the three, single-date NLCD land cover products at Level II and Level I of the classification hierarchy, and agreement for 17 land cover change reporting themes based on Level I classes (e.g., forest loss; forest gain; forest, no change) for three change periods (2001–2006, 2006–2011, and 2001–2011). The single-date overall accuracies were 82%, 83%, and 83% at Level II and 88%, 89%, and 89% at Level I for 2011, 2006, and 2001, respectively. Many class-specific user's accuracies met or exceeded a previously established nominal accuracy benchmark of 85%. Overall accuracies for 2006 and 2001 land cover components of NLCD 2011 were approximately 4% higher (at Level II and Level I) than the overall accuracies for the same components of NLCD 2006. The high Level I overall, user's, and producer's accuracies for the single-date eras in NLCD 2011 did not translate into high class-specific user's and producer's accuracies for many of the 17 change reporting themes. User's accuracies were high for the no change reporting themes, commonly exceeding 85%, but were typically much lower for the reporting themes that represented change. Only forest l

M-CSF in a new biomarker panel with HE4 and CA 125 in the diagnostics of epithelial ovarian cancer patients.

PubMed

Będkowska, Grażyna Ewa; Ławicki, Sławomir; Gacuta, Ewa; Pawłowski, Przemysław; Szmitkowski, Maciej

2015-05-03

We investigated plasma levels of M-CSF and conventional tumor markers (HE4 and CA 125) in epithelial ovarian cancer patients as compared to control groups: benign ovarian tumor patients (cysts) and healthy subjects. M-CSF levels were determined by ELISA, HE4 and CA 125 levels - by CMIA method. Our results have demonstrated significant differences in the concentration levels of M-CSF, CA 125 and HE4 between the groups of ovarian cancer patients, cysts patients and the healthy controls. In the groups tested M-CSF demonstrated equal to or higher values than both CA 125 and HE4 in diagnostic sensitivity (SE), positive and negative predictive values (PPV, NPV), and in the area under the ROC curve (AUC), particularly in the group with the serous epithelial sub-type of OC. Moreover, CA 125 showed better results of the aforementioned diagnostic criteria than HE4. The combined use of the parameters studied resulted in a further, significant increase in the value of the diagnostic indicators and in the value of the diagnostic power (AUC), especially in the early stages of ovarian cancer. These findings suggest a high usefulness of M-CSF in diagnosing the serous sub-type of epithelial ovarian cancer and in discriminating between cancer and non-carcinoma lesions, particularly in new diagnostic panels in combination with CA 125 and HE4 for the detection of EOC in the early stages.

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.

CO2 sensing properties of electro-spun Ca-doped ZnO fibres.

PubMed

Pantò, Fabiola; Leonardi, Salvatore Gianluca; Fazio, Enza; Frontera, Patrizia; Bonavita, Anna; Neri, Giovanni; Antonucci, Pierluigi; Neri, Fortunato; Santangelo, Saveria

2018-07-27

The availability of low-cost, high-performing sensors for carbon dioxide detection in the environment may play a crucial role for reducing CO 2 emissions and limiting global warming. In this study, calcium-doped zinc oxide nanofibres with different Ca to Zn loading ratios (1:40 or 1:20) are synthesised via electro-spinning, thoroughly characterised and, for the first time, tested as an active material for the detection of carbon dioxide. The results of their characterisation show that the highly porous fibres consist of interconnected grains of oxide with the hexagonal wurtzite structure of zincite. Depending on the Ca:Zn loading ratio, calcium fully or partly segregates to form calcite on the fibre surface. The high response of the sensor based on the fibres with the highest Ca-doping level can be attributed to the synergy between the fibre morphology and the basicity of Ca-ion sites, which favour the diffusion of the gas molecules within the sensing layer and the CO 2 adsorption, respectively.

The initial 41Ca/40Ca ratios in two type A Ca-Al-rich inclusions: Implications for the origin of short-lived 41Ca

NASA Astrophysics Data System (ADS)

Liu, Ming-Chang

2017-03-01

This paper reports new 41Ca-41K isotopic data for two Type A CAIs, NWA 3118 #1Nb (Compact Type A) and Vigarano 3138 F8 (Fluffy Type A), from reduced CV3 chondrites. The NWA CAI is found to have carried live 41Ca at the level of (4.6 ± 1.9) ×10-9 , consistent with the proposed Solar System initial 41Ca /40Ca = 4.2 ×10-9 by Liu et al. (2012a). On the other hand, the Vigarano CAI does not have resolvable radiogenic 41K excesses that can be attributed to the decay of 41Ca. Combined with the 26Al data that have been reported for these two CAIs, we infer that the 41Ca distribution was not homogeneous when 26Al was widespread at the canonical level of 26Al /27Al = 5.2 ×10-5 . Such a 41Ca heterogeneity can be understood under two astrophysical contexts: in situ charged particle irradiation by the protoSun in the solar nebula that had inherited some baseline 10Be abundance from the molecular cloud, and Solar System formation in a molecular cloud enriched in 26Al and 41Ca contaminated by massive star winds. That said, more high quality 41Ca data are still needed to better understand the origin of this radionuclide.

New calcium-selective smart contrast agents for magnetic resonance imaging.

PubMed

Verma, Kirti Dhingra; Forgács, Attila; Uh, Hyounsoo; Beyerlein, Michael; Maier, Martin E; Petoud, Stéphane; Botta, Mauro; Logothetis, Nikos K

2013-12-23

Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca(2+) in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca(2+) present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls in the range required to sense and report changes in extracellular Ca(2+) levels followed by an increase in neural activity. In buffer, with the addition of Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca(2+) addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Vitro and In Vivo Evaluation of Zinc-Modified Ca–Si-Based Ceramic Coating for Bone Implants

PubMed Central

Zheng, Xuebin; He, Dannong; Ye, Xiaojian; Wang, Meiyan

2013-01-01

The host response to calcium silicate ceramic coatings is not always favorable because of their high dissolution rates, leading to high pH within the surrounding physiological environment. Recently, a zinc-incorporated calcium silicate-based ceramic Ca2ZnSi2O7 coating, developed on a Ti-6Al-4V substrate using plasma-spray technology, was found to exhibit improved chemical stability and biocompatibility. This study aimed to investigate and compare the in vitro response of osteoblastic MC3T3-E1 cells cultured on Ca2ZnSi2O7 coating, CaSiO3 coating, and uncoated Ti-6Al-4V titanium control at cellular and molecular level. Our results showed Ca2ZnSi2O7 coating enhanced MC3T3-E1 cell attachment, proliferation, and differentiation compared to CaSiO3 coating and control. In addition, Ca2ZnSi2O7 coating increased mRNA levels of osteoblast-related genes (alkaline phosphatase, procollagen α1(I), osteocalcin), insulin-like growth factor-I (IGF-I), and transforming growth factor-β1 (TGF-β1). The in vivo osteoconductive properties of Ca2ZnSi2O7 coating, compared to CaSiO3 coating and control, was investigated using a rabbit femur defect model. Histological and histomorphometrical analysis demonstrated new bone formation in direct contact with the Ca2ZnSi2O7 coating surface in absence of fibrous tissue and higher bone-implant contact rate (BIC) in the Ca2ZnSi2O7 coating group, indicating better biocompatibility and faster osseointegration than CaSiO3 coated and control implants. These results indicate Ca2ZnSi2O7 coated implants have applications in bone tissue regeneration, since they are biocompatible and able to osseointegrate with host bone. PMID:23483914

cis-Cinnamic Acid Is a Novel, Natural Auxin Efflux Inhibitor That Promotes Lateral Root Formation1[OPEN

PubMed Central

Steenackers, Ward; Corneillie, Sander; Araújo, Pedro; Viaene, Tom; Nowack, Moritz K.; Blakeslee, Joshua J.; Novák, Ondřej; Zažímalová, Eva

2017-01-01

Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis. PMID:27837086

The leading role of mitochondrial depolarization in the mechanism of glutamate-induced disruptions in Ca2+ homeostasis.

PubMed

Khodorov, B I; Storozhevykh, T P; Surin, A M; Yuryavichyus, A I; Sorokina, E G; Borodin, A V; Vinskaya, N P; Khaspekov, L G; Pinelis, V G

2002-01-01

Data obtained in studies of the nature of the correlation which we have previously observed [10,17] between mitochondrial depolarization and the level of disruption of Ca2+ homeostasis in cultivated brain neuronsare summarized. Experiments were performed on cultured cerebellar granule cells loaded with Fura-2-AM or rhodamine 123 to measure changes in cytoplasmic Ca2+ and mitochondrial potential during pathogenic treatments of the cells. Prolonged exposure to 100 microM glutamate induced a reversible increase in [Ca2+]i, which was accompanied by only a small degree of mitochondrial depolarization. A sharp increase in this mitochondrial depolarization, induced by addition of 3 mM NaCN or 300 microM dinitrophenol (DNP) to the glutamate-containing solution, resulted in further increase in [Ca2+]i, due to blockade of electrophoretic mitochondrial Ca2+ uptake. Prolonged exposure to CN- or DNP in the post-glutamate period maintained [Ca2+]i at a high level until the metabolic inhibitors were removed. In most cells, this plateau was characterized by low sensitivity to removal of external Ca2+, demonstrating that the mechanisms of Ca2+ release from neurons were disrupted. Addition of oligomycin, a blocker of mitochondrial ATP synthase/ATPase, to the solution containing glutamate and CN- or DNP eliminated the post-glutamate plateau. Parallel experiments with direct measurements of intracellular ATP levels ([ATP]) showed that profound mitochondrial depolarization induced by CN- or DNP sharply enhanced the drop in ATP due to glutamate, while oligomycin significantly weakened this effect of the metabolic inhibitors. Analysis of these data led to the conclusion that blockade of mitochondrial Ca2+ uptake and inhibition of ATP synthesis resulted from mitochondrial depolarization and plays a key role in the mechanism disrupting [Ca2+]i homeostasis after toxic exposure to glutamate.

The calcium sensor GhCaM7 promotes cotton fiber elongation by modulating reactive oxygen species (ROS) production.

PubMed

Tang, Wenxin; Tu, Lili; Yang, Xiyan; Tan, Jiafu; Deng, Fenglin; Hao, Juan; Guo, Kai; Lindsey, Keith; Zhang, Xianlong

2014-04-01

Fiber elongation is the key determinant of fiber quality and output in cotton (Gossypium hirsutum). Although expression profiling and functional genomics provide some data, the mechanism of fiber development is still not well understood. Here, a gene encoding a calcium sensor, GhCaM7, was isolated based on its high expression level relative to other GhCaMs in fiber cells at the fast elongation stage. The level of expression of GhCaM7 in the wild-type and the fuzzless/lintless mutant correspond to the presence and absence, respectively, of fiber initials. Overexpressing GhCaM7 promotes early fiber elongation, whereas GhCaM7 suppression by RNAi delays fiber initiation and inhibits fiber elongation. Reactive oxygen species (ROS) play important roles in early fiber development. ROS induced by exogenous hydrogen peroxide (H2 O2 ) and Ca(2+) starvation promotes early fiber elongation. GhCaM7 overexpression fiber cells show increased ROS concentrations compared with the wild-type, while GhCaM7 RNAi fiber cells have reduced concentrations. Furthermore, we show that H2 O2 enhances Ca(2+) influx into the fiber and feedback-regulates the expression of GhCaM7. We conclude that GhCaM7, Ca(2+) and ROS are three important regulators involved in early fiber elongation. GhCaM7 might modulate ROS production and act as a molecular link between Ca(2+) and ROS signal pathways in early fiber development. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

PubMed Central

Oleaga, Carlota; Ciudad, Carlos J.; Noé, Véronique; Izquierdo-Pulido, Maria

2012-01-01

Background. Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown. Objective. To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC) or caffeic acid (CA) using whole-genome microarrays. Results. ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells. Conclusions. Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2. PMID:22919439

A national patient dose survey and setting of reference levels for interventional radiology in Bulgaria.

PubMed

Zotova, R; Vassileva, J; Hristova, J; Pirinen, M; Järvinen, H

2012-06-01

A national study on patient dose values in interventional radiology and cardiology was performed in order to assess current practice in Bulgaria, to estimate the typical patient doses and to propose reference levels for the most common procedures. Fifteen units and more than 1,000 cases were included. Average values of the measured parameters for three procedures-coronary angiography (CA), combined procedure (CA + PCI) and lower limb arteriography (LLA)--were compared with data published in the literature. Substantial variations were observed in equipment and procedure protocols used. This resulted in variations in patient dose: air-kerma area product ranges were 4-339, 6-1,003 and 0.2-288 Gy cm(2) for CA, CA + PCI and LLA respectively. Reference levels for air kerma-area product were proposed: 40 Gy cm(2) for CA, 140 Gy cm(2) for CA + PCI and 45 Gy cm(2) for LLA. Auxiliary reference intervals were proposed for other dose-related parameters: fluoroscopy time, number of images and entrance surface air kerma rate in fluoroscopy and cine mode. There is an apparent necessity for improvement in the classification of peripheral procedures and for standardisation of the protocols applied. It is important that patient doses are routinely recorded and compared with reference levels. • Patient doses in interventional radiology are high and vary greatly • Better standardisation of procedures and techniques is needed to improve practice • Dose reference levels for most common procedures are proposed.

Calcium contributes to photoprotection and repair of photosystem II in peanut leaves during heat and high irradiance.

PubMed

Yang, Sha; Wang, Fang; Guo, Feng; Meng, Jing-Jing; Li, Xin-Guo; Wan, Shu-Bo

2015-05-01

In this study, we investigated the effects of exogenous calcium nitrate on photoinhibition and thylakoid protein level in peanut plants under heat (40°C) and high irradiance (HI) (1,200 µmol/m(2) per s) stress. Compared with control seedlings (cultivated in 0 mmol/L Ca(NO3 )2 medium), the maximal photochemical efficiency of photosystem II (PSII) in Ca(2+) -treated plants showed a slight decrease after 5 h stress, accompanied by lower degree of PSII closure (1-qP), higher non-photochemical quenching, and lower level of membrane damage. Ca(2+) inhibitors were used to analyze the varieties of antioxidant enzymes activity and PSII proteins. These results indicated that Ca(2+) could protect the subunits of PSII reaction centers from photoinhibition by reducing the generation of reactive oxygen species. In the presence of both ethyleneglycol-bis(2-aminoethylether)-tetraacetic acid and ascorbic acid (AsA), the net degradation of the damaged D1 protein was faster than that only treated with AsA. Our previous study showed that either the transcriptional or the translational level of calmodulin was obviously higher in Ca(2+) -treated plants. These results suggested that, under heat and HI stress, the Ca(2+) signal transduction pathway can alleviate the photoinhibition through regulating the protein repair process besides an enhanced capacity for scavenging reactive oxygen species. © 2014 The Authors. Journal of Integrative Plant Biology published by Wiley Publishing Asia Pty Ltd on behalf of Institute of Botany, The Chinese Academy of Sciences.

Quality changes of highbush blueberries fruit stored in CA with different CO levels.

PubMed

Duarte, Carolina; Guerra, María; Daniel, Peter; Camelo, Andrés López; Yommi, Alejandra

2009-01-01

Quality changes of blueberries (Vacccinium corymbosum L. cv Brigitta) were evaluated during CA storage (0 degrees C) with different concentrations of CO(2) (5%, 10%, and 15%) combined with 5% O(2), respectively. Atmospheric air (20.9% O(2)+ 0.03% CO(2)) was used as control. From samples taken at 0, 24, and 48 d of storage, unmarketable fruits and weight loss were recorded as well as color (h), firmness (g), soluble solid content (%), titratable acidity (% citric acid), ratio, and the monomeric anthocyanin content (ppm). At each sampling time, additional units were kept for 3 d at 10 degrees C to simulate retail holding conditions. Irrespective of gas concentration, 0.9% of the initial fresh weight was lost after 48 d at 0 degrees C. CA fruit had better quality than control at the 24 d sampling but due to the high number of unmarketable fruits, this advantage was not observed at 48 d at 0 degrees C. After 24 d of storage, fruits for CA treatments were more firm and had better color, with higher anthocyanin and acidity levels. Soluble solid content showed no significant differences throughout the cold storage period. Residual effect of CA storage was observed at the retail holding condition yielding better firmness, acidity, and ratio. However, the CO(2) level tested increased the number of unmarketable fruit in long-term storage (48 d). Response of "Brigitta" blueberries to the different CO(2) levels studied was moderate and could be related to the high storage potential of this cultivar.

Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis.

PubMed

Schlievert, Patrick M; Strandberg, Kristi L; Lin, Ying-Chi; Peterson, Marnie L; Leung, Donald Y M

2010-01-01

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have emerged as serious health threats in the last 15 years. They are associated with large numbers of atopic dermatitis skin and soft tissue infections, but when they originate from skin and mucous membranes, have the capacity to produce sepsis and highly fatal pulmonary infections characterized as necrotizing pneumonia, purpura fulminans, and postviral toxic shock syndrome. This review is a discussion of the emergence of 3 major CA-MRSA organisms, designated CA-MRSA USA400, followed by USA300, and most recently USA200. CA-MRSA USA300 and USA400 isolates and their methicillin-sensitive counterparts (community-associated methicillin-sensitive S aureus) typically produce highly inflammatory cytolysins alpha-toxin, gamma-toxin, delta-toxin (as representative of the phenol soluble modulin family of cytolysins), and Panton Valentine leukocidin. USA300 isolates produce the superantigens enterotoxin-like Q and a highly pyrogenic deletion variant of toxic shock syndrome toxin 1 (TSST-1), whereas USA400 isolates produce the superantigens staphylococcal enterotoxin B or staphylococcal enterotoxin C. USA200 CA-MRSA isolates produce small amounts of cytolysins but produce high levels of TSST-1. In contrast, their methicillin-sensitive S aureus counterparts produce various cytolysins, apparently in part dependent on the niche occupied in the host and levels of TSST-1 expressed. Significant differences seen in production of secreted virulence factors by CA-MRSA versus hospital-associated methicillin-resistant S aureus and community-associated methicillin-sensitive S aureus strains appear to be a result of the need to specialize as the result of energy drains from both virulence factor production and methicillin resistance. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

1.5 My benthic foraminiferal B/Ca record of carbonate chemistry in the deep Atlantic: Implications for ocean alkalinity and atmospheric CO2

NASA Astrophysics Data System (ADS)

Rosenthal, Y.; Sosdian, S. M.; Toggweiler, J. R.

2017-12-01

Most hypotheses to explain glacial-interglacial changes in atmospheric CO2 invoke shifts in ocean alkalinity explain roughly half the reduction in glacial CO2 via CaCO3 compensatory mechanism. It follows that changes in CaCO3 burial occur in response to an increase in deep ocean respired carbon content. To date our understanding of this process comes from benthic carbon isotope and %CaCO3 records. However, to understand the nature of the ocean's buffering capacity and its role in modulating pCO2, orbitally resolved reconstructions of the deep ocean carbonate system parameters are necessary. Here we present a 1.5 Myr orbitally resolved deep ocean calcite saturation record (ΔCO32-) derived from benthic foraminiferal B/Ca ratios in the North Atlantic. Glacial B/Ca values decline across the mid-Pleistocene transition (MPT) suggesting increased sequestration of carbon in the deep Atlantic. The magnitude, timing, and structure of deep Atlantic Ocean ΔCO32- and %CaCO3 cycles contrast with the small amplitude, anti-phased swings in IndoPacific ΔCO32- and %CaCO3 during the mid-to-late Pleistocene. Increasing corrosivity of the deep Atlantic causes the locus of CaCO3 burial to shift into the equatorial Pacific where the flux of CaCO3 to the seafloor is high enough to establish and maintain a new "hot spot". We propose that the CO32- in the deep IndoPacific rises in response to the same mechanism that keeps the CO32- in the deep Atlantic low and the atmospheric CO2 low. The increase in interglacial atmospheric pCO2 levels following the Mid-Brunhes event ( 400ka) are associated with increased G/IG ΔCO3 amplitude, expressed by a decrease in the glacial ΔCO32- values. We propose the low persistent ΔCO32- levels at Marine Isotope Stage (MIS) 12 set the stage for the high pCO2 levels at MIS 11 via an increase in whole ocean alkalinity followed by enhanced CaCO3 preservation. Based on this, we suggest that the development of classic (`anticorrelated') CaCO3 patterns was driven by increased stratification and worsening ventilation in the deep Atlantic across the MPT.

Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

NASA Technical Reports Server (NTRS)

Ito, Kenta; Nakayama, Masaharu; Hasan, Faisal; Yan, Xinhua; Schneider, Michael D.; Lorell, Beverly H.

2003-01-01

BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.

The influence of calcium and pH on growth in primary roots of Zea mays

NASA Technical Reports Server (NTRS)

Hasenstein, K. H.; Evans, M. L.

1988-01-01

We investigated the interaction of Ca2+ and pH on root elongation in Zea mays L. cv. B73 x Missouri 17 and cv. Merit. Seedlings were raised to contain high levels of Ca2+ (HC, imbibed and raised in 10 mM CaCl2) or low levels of Ca2+ (LC, imbibed and raised in distilled water). In HC roots, lowering the pH (5 mM MES/Tris) from 6.5 to 4.5 resulted in strong, long-lasting growth promotion. Surprisingly, increasing the pH from 6.5 to 8.5 also resulted in strong growth promotion. In LC roots acidification of the medium (pH 6.5 to 4.5) resulted in transient growth stimulation followed by a gradual decline in the growth rate toward zero. Exposure of LC roots to high pH (pH shift from 6.5 to 8.5) also promoted growth. Addition of EGTA resulted in strong growth promotion in both LC and HC roots. The ability of EGTA to stimulate growth appeared not to be related to H+ release from EGTA upon Ca2+ chelation since, 1) LC roots showed a strong and prolonged response to EGTA, but only a transient response to acid pH, and 2) promotion of growth by EGTA was observed in strongly buffered solutions. We also examined the pH dependence of the release of 45Ca2+ from roots of 3-day-old seedlings grown from grains imbibed in 45Ca2+. Release of 45Ca2+ from the root into agar blocks placed on the root surface was greater the more acidic the pH of the blocks. The results indicate that Ca2+ may be necessary for the acid growth response in roots.

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

PubMed

Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

2017-01-25

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group ( P >0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type ( P <0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC ( P =0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

High Expression of P38α and Preoperative Carbohydrate Antigen 19-9 Indicate Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

PubMed

Chen, Jionghuang; Zhao, Ting; Jia, Shengnan; Zhou, Senhao; Zhou, Liangjing; Wang, Shaowen; Ding, Guoping; Jiang, Guixing; Cao, Liping

2018-01-01

Background: P38α is a ubiquitous protein kinase, which plays diverse roles in cancers. Surprisingly, P38α functions vary markedly in different cancers (e.g., cancer suppressor vs cancer promoter). However, there is no report on the expression of P38α, the family's most important member, in pancreatic ductal adenocarcinoma (PDAC) and its association with clinicoathological parameters and patients' prognosis. Materials and methods: We retrospectively analyzed 152 patients who underwent surgery and were pathologically diagnosed with PDAC from September 2013 to September 2015. We used immunohistochemistry to detect P38α expression in tumor and adjacent normal tissues. The significance of the association between P38α and clinicopathological parameters was evaluated using the χ² test and t tests. The Kaplan-Meier method was used to assess the association between P38α expression and preoperative carbohydrate antigen 19-9 (CA19-9) levels and patients' overall survival. The Cox regression model was used to analyze the association between clinicopathological parameters, P38α and preoperative CA19-9 levels, and prognosis. Statistical significance was defined as P < 0.05. Results: P38α was expressed in 63.16% tumor tissues of PDAC, which was significantly higher compared with the adjacent normal tissues (26.32%, P < 0.001). High expression of P38α was associated with patients' histological grade ( P = 0.013), lymphatic metastasis ( P = 0.025) and TNM stage ( P = 0.048). The median survival time of the P38α-high group was 9.2 months, which was shorter compared with that of the P38α-low group (17.3 months, P = 0.011). The median survival time of the CA19-9 > 43.63 group was 11.1 months shorter than that of the CA19-9 < 43.63 group (24.8 months, P < 0.001). The Cox regression model revealed that age ( P = 0.003), lymphatic invasion ( P = 0.015), TNM stage ( P = 0.003), histological grade ( P < 0.001), preoperative CA19-9 ( P = 0.049), and P38α expression ( P = 0.008) were statistically significant independent risk factors affecting prognosis. Specifically, overall survival was 28.4 months in the P38α-low and CA19-9 < 43.63 groups, 16.3 months in the P38α-high or CA19-9 > 43.63 groups, and 9.7 months in the P38α-high and CA19-9 > 43.63 groups ( P < 0.001). Conclusions: High expression of P38α was significantly associated with histological grade, lymphatic metastasis, TNM stage and prognosis in patients with PDAC. P38α and preoperative CA19-9 levels were independent risk factors affecting the prognosis of PDAC patients. High expression of p38α and preoperative carbohydrate antigen 19-9 indicate poor prognosis in patients with PDAC.

Functional analysis of the pepper protein phosphatase, CaAIPP1, and its interacting partner CaAIRF1: Modulation of ABA signalling and the drought stress response.

PubMed

Baek, Woonhee; Lim, Chae Woo; Lee, Sung Chul

2017-10-01

Plant adaptive responses to abiotic stress are coordinated by restriction of plant growth and development. The plant hormone abscisic acid (ABA) is the key regulator of the response to abiotic stress, and its sensitivity determines abiotic stress tolerance levels. We previously showed that the E3 ubiquitin ligase CaAIRF1 functions as a positive regulator of ABA and drought stress via modulation of transcription and stability of the type 2C protein phosphatase CaADIP1. Here, we report the identification and functional analysis of a novel-type 2C phosphatase, CaAIPP1 (Capsicum annuum CaAIRF1 Interacting Protein Phosphatase 1). CaAIPP1 interacted with and was ubiquitinated by CaAIRF1. CaAIPP1 gene expression in pepper leaves was induced by ABA and drought. CaAIPP1 degradation was faster in crude protein extracts from ABA-treated pepper plants than in those from control plants. CaAIPP1-overexpressing plants displayed an ABA-hyposensitive phenotype during seed germination and seedling growth. Moreover, these plants exhibited a drought-sensitive phenotype characterized by high levels of transpirational water loss via decreased stomatal closure and reduced leaf temperatures. Our data indicate that CaAIPP1 is a negative regulator of the drought stress response via ABA-mediated signalling. Our findings provide a valuable insight into the plant defence mechanism that operates during drought stress. © 2017 John Wiley & Sons Ltd.

Hepatoprotective effect of Cirsium arisanense Kitamura in tacrine-treated hepatoma Hep 3B cells and C57BL mice.

PubMed

Ku, Kuo-Lung; Tsai, Chu-Tsai; Chang, Wei-Min; Shen, Mei-Lin; Wu, Chia-Tien; Liao, Hui-Fen

2008-01-01

Cirsium arisanense Kitamura (Compositae) has been used for hundreds of years in Taiwan as a folk medicine for hepatoprotection. However, no scientific research has demonstrated this effect. In the present study, we extracted the phenol-containing aqueous components of C. arisanense roots (CaR) and leaves/stem (CaL), and then assessed their hepatoprotective activities in both human hepatocellular carcinoma Hep 3B cells and C57BL/6 mice strain. High performance liquid chromatography (HPLC) analysis revealed that the components of CaR and CaL differed from those of the positive control silymarin. CaR exhibited a higher phenolic content and antioxidant capacity than CaL. Hep 3B cells treated with silymarin (0-200 microg/ml) demonstrated a concentration-dependent decrease in viability; however, both CaR and CaL did not exhibit any apparent cytotoxicity. Silymarin at 100 microg/ml, as well as CaR and CaL, not only protect Hep 3B cells from tacrine-induced hepatotoxicity but also decrease the expression of hepatitis B surface antigen (HBsAg). Moreover, an animal experiment demonstrated that CaR, CaL, and silymarin have hepatoprotective effects in C57BL/6 mice injected with tacrine, and they significantly decrease the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These effects of CaR and silymarin, but not of CaL, may occur via an increase in the hepatic glutathione level and the elimination of the nitric oxide production. In conclusion, the phenol-containing aqueous components from C. arisanense have potential in hepatoprotection.

Serum levels of endothelial and neural cell adhesion molecules in prostate cancer.

PubMed

Lynch, D F; Hassen, W; Clements, M A; Schellhammer, P F; Wright, G L

1997-08-01

Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell lung carcinoma (SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease. Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring CaP patients following definitive radiotherapy, radical prostatectomy, or hormonal therapy. The results of this study indicate that serum ICAM-1, VCAM-1, NCAM, and E-selectin are not clinically useful biomarkers for differentiating CaP from BPH, for predicting progression, for identifying metastatic potential, or for monitoring treatment.

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.

Rechargeable calcium phosphate orthodontic cement with sustained ion release and re-release

PubMed Central

Zhang, Ling; Weir, Michael D.; Chow, Laurence C.; Reynolds, Mark A.; Xu, Hockin H. K.

2016-01-01

White spot lesions (WSL) due to enamel demineralization are major complications for orthodontic treatments. Calcium phosphate (CaP) dental resins with Ca and P ion releases are promising for remineralization. However, previous Ca and P releases lasted for only weeks. Experimental orthodontic cements were developed using pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at mass ratio of 1:1 (PE); and PE plus 10% of 2-hydroxyethyl methacrylate (HEMA) and 5% of bisphenol A glycidyl dimethacrylate (BisGMA) (PEHB). Particles of amorphous calcium phosphate (ACP) were incorporated into PE and PEHB at 40% filler level. Specimens were tested for bracket-enamel shear bond strength, water sorption, CaP release, and ion recharge and re-release. PEHB+40ACP had higher bracket-enamel bond strength and ion release and rechargeability than PE+40ACP. ACP incorporation into the novel orthodontic cement did not adversely affect the bracket-enamel bond strength. Ion release and re-release from the novel ACP orthodontic cement indicated favorable release and re-release patterns. The recharged orthodontic cement could release CaP ions continuously for four weeks without further recharge. Novel rechargeable orthodontic cement containing ACP was developed with a high bracket-enamel bond strength and the ability to be repeatedly recharged to maintain long-term high levels of CaP ion releases. PMID:27808251

Experimental study on the relationship between the mineral production capability and the physiochemical properties in the coproduction of Q phase-3CaO·3Al2O3·CaSO4 cement clinker.

PubMed

He, Chao; Tian, Chaochao; Li, Gang; Mei, Yahe; Zhang, Quanguo; Jiao, Youzhou

2018-01-01

A coproduction tests of quaternary (Q) phase(6CaO·4Al2O3·MgO·SiO2) -3CaO·3Al2O3·CaSO4 cement clinker and an experimental study on the relationship between the mineral production capability and the physiochemical properties are conducted in a two-stage multiphase reaction test bed with Changguang coal. X-ray diffractometer (XRD) analyses are performed on the coproduction clinker samples. The results demonstrate that, with the reduction in particle sizes of the coal powder and the additives and expanded screening level differences between them, both the proportion of Q phase and the mass of 3CaO·3Al2O3·CaSO4 in the clinker increase accordingly. When mixed coal powder particles are prepared through reducing particle sizes and expanding screening level differences between coal powder and additives, the additives CaO and MgO are more likely to be enclosed by coal powder to form globular polymerized particles. In addition, this preparation aids in polymerization and promotes even distribution of CaO, MgO and coal minerals, thus facilitating clinker mineral formation reactions of inorganic substances in the mixed coal powder. Target minerals, such as 2CaO·SiO2 and Q phase, are found in both industrial high-calcium limestone and low-calcium limestone coproduction clinker samples. A diffraction peak of free CaO is also evident in both samples. Compared with a coproduction clinker sample of high-calcium limestone, that of low-calcium limestone exhibits higher diffraction peaks for 2CaO·SiO2 and Q phase. With the current state of the art, it is not yet the optimum choice to substitute CaCO3 for CaO in Q-phase cement clinker coproduction. Before the technology matures and gains practical application, further study on the form and the mixing process of calcium-based additives for cement clinker coproduction will be required.

Experimental study on the relationship between the mineral production capability and the physiochemical properties in the coproduction of Q phase-3CaO·3Al2O3·CaSO4 cement clinker

PubMed Central

Tian, Chaochao; Li, Gang; Mei, Yahe; Zhang, Quanguo; Jiao, Youzhou

2018-01-01

A coproduction tests of quaternary (Q) phase(6CaO·4Al2O3·MgO·SiO2) -3CaO·3Al2O3·CaSO4 cement clinker and an experimental study on the relationship between the mineral production capability and the physiochemical properties are conducted in a two-stage multiphase reaction test bed with Changguang coal. X-ray diffractometer (XRD) analyses are performed on the coproduction clinker samples. The results demonstrate that, with the reduction in particle sizes of the coal powder and the additives and expanded screening level differences between them, both the proportion of Q phase and the mass of 3CaO·3Al2O3·CaSO4 in the clinker increase accordingly. When mixed coal powder particles are prepared through reducing particle sizes and expanding screening level differences between coal powder and additives, the additives CaO and MgO are more likely to be enclosed by coal powder to form globular polymerized particles. In addition, this preparation aids in polymerization and promotes even distribution of CaO, MgO and coal minerals, thus facilitating clinker mineral formation reactions of inorganic substances in the mixed coal powder. Target minerals, such as 2CaO·SiO2 and Q phase, are found in both industrial high-calcium limestone and low-calcium limestone coproduction clinker samples. A diffraction peak of free CaO is also evident in both samples. Compared with a coproduction clinker sample of high-calcium limestone, that of low-calcium limestone exhibits higher diffraction peaks for 2CaO·SiO2 and Q phase. With the current state of the art, it is not yet the optimum choice to substitute CaCO3 for CaO in Q-phase cement clinker coproduction. Before the technology matures and gains practical application, further study on the form and the mixing process of calcium-based additives for cement clinker coproduction will be required. PMID:29634732

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C.

PubMed

Tang, Y; Li, G D

2004-12-01

Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. NO production and intracellular Ca(2+) levels ([Ca(2+)](i)) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca(2+) ionophore) in a time- and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca(2+)](i) under these conditions, since a close correlation between [Ca(2+)](i) increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca(2+) mobilisation and extracellular Ca(2+) entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P(3), a phospholipase C product leading to increases in [Ca(2+)](i), was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca(2+)](i), and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D: -alpha-tocopherol (antioxidant). Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca(2+) signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium-dependent relaxation and thus to the development of cardiovascular diseases in diabetes.

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

Dietary, Supplement, and Adipose Tissue Tocopherols Levels in Relation to Prostate Cancer Aggressiveness Among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP)

PubMed Central

Antwi, Samuel; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Fontham, Elizabeth T. H.; Smith, Gary; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

2016-01-01

Background Controversies remain over the safety and efficacy of vitamin E (i.e., α–tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. Methods This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n=1,023) and European-American (EA, n=1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated from logistic regression comparing high aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Results Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95% CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95% CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95% CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)]. Conclusions The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. PMID:26053590

Phosphorus utilization in finishing broiler chickens: effects of dietary calcium and microbial phytase.

PubMed

Rousseau, X; Létourneau-Montminy, M P; Même, N; Magnin, M; Nys, Y; Narcy, A

2012-11-01

A decrease in dietary P, especially in finishing broilers (21 to 38 d old), is a crucial issue in poultry production from an environmental and economic point of view. Nevertheless, P must be considered together with other dietary components such as Ca and microbial phytase. Different corn and soybean meal-based diets varying in Ca [low (LCa) 0.37, medium (MCa) 0.57, and high (HCa) 0.77%], and nonphytate P [nPP; low (LnPP) 0.18 and high (HnPP) 0.32%] content were tested with and without microbial phytase [0 or 500 phytase units (FTU)/kg]. Feed intake, BW gain, bone mineralization, and mineral retention were examined in 144 Ross PM3 broilers (22 to 38 d old) reared in individual cages. Growth performance was not significantly affected by the treatments. Nevertheless, a numerical decrease of ADG and ADFI was observed in HCa-LnPP and LCa-HnPP associated with an increase of feed conversion ratio. Decreased dietary Ca reduced tibia ash content (Ca, linear: P < 0.001; quadratic: P = 0.034) and tibia ash weight for the highest level of nPP (Ca × nPP; P = 0.035). In parallel, increasing dietary Ca reduced the flow of retained P (P = 0.022) but also tibia ash weight in LnPP diets (Ca × nPP; P = 0.035). The responses of the animals in terms of tibia ash content and P retention were improved by the addition of microbial phytase especially for the lowest P diets (nPP × phytase, P = 0.021 and P = 0.009; respectively). Phytase increased dry tibia weight, bone breaking strength, and tibia diameter in broilers fed the highest Ca diets (Ca × phytase; P < 0.05). We conclude that is possible to decrease P levels in finishing broilers, if the Ca content is appropriate. Nevertheless, decreasing the dietary P and Ca cannot allow a maximization of bone mineralization, but the optimal threshold remains to be determined.

Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+ exchanger-mediated mitochondrial calcium overload.

PubMed

Hong, Quan; Qi, Ka; Feng, Zhe; Huang, Zhiyong; Cui, Shaoyuan; Wang, Liyuan; Fu, Bo; Ding, Rui; Yang, Jurong; Chen, Xiangmei; Wu, Di

2012-05-01

Uric acid (UA) has proven to be a causal agent in endothelial dysfunction in which ROS production plays an important role. Calcium overload in mitochondria can promote the mitochondrial production of ROS. We hypothesize that calcium transduction in mitochondria contributes to UA-induced endothelial dysfunction. We first demonstrated that high concentrations of UA cause endothelial dysfunction, marked by a reduction in eNOS protein expression and NO release in vitro. We further found that a high concentration of UA increased levels of [Ca2+]mito, total intracellular ROS, H2O2, and mitochondrial O2·-, and Δψmito but not the [Ca2+]cyt level. When the mitochondrial calcium channels NCXmito and MCU were blocked by CGP-37157 and Ru360, respectively, the UA-induced increases in the levels of [Ca2+]mito and total intracellular ROS were significantly reduced. Mitochondrial levels of O2·- and Δψmito were reduced by inhibition of NCXmito but not of MCU. Moreover, inhibition of NCXmito, but not of MCU, blocked the UA-induced reductions in eNOS protein expression and NO release. The increased generation of mitochondrial O2·- induced by a high concentration of UA is triggered by mitochondrial calcium overload and ultimately leads to endothelial dysfunction. In this process, the activation of NCXmito is the major cause of the influx of calcium into mitochondria. Our results provide a new pathophysiological mechanism for UA-induced endothelial dysfunction and may offer a new therapeutic target for clinicians. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Analysis of the intensity of professional collaboration among nurses in a critical care area].

PubMed

Bengoechea Calpe, L; Marín Fernández, B; Regaira Martínez, E

2016-01-01

To analyse the intensity of professional collaboration (IPC) between the nurses in a multidisciplinary critical area (CA) and the relationship with the workplace "intensive care unit (ICU) and special hospitalisation area (SHA)", educational level, age, and years of professional activity in CA. A cross-sectional descriptive study was conducted with 57 nurses from CA, recording socio-demographic data: age, educational level, speciality titles, years of professional activity and workday type, years of professional activity in the CA, and involvement in scientific works. Tool: Intensity of Inter-professional Collaboration Questionnaire. SPSS 20.0. The study included a total of 47 nurses (ICU/SHA), with a mean age of 35.91 (9.59) years. Almost three-quarters (74.46%) were nursing graduates with a posgraduate in ICU. Median and interquartile range of professional experience was 14 and 14.50 years, respectively, and years working in CA was 8.50 and 16 years, respectively. Just over half of them (51.10%) worked part-time, and 61.70% participated in scientific works. The mean IPC score was 61.68 (6.84), with 57.40% providing values of high IPC. The relationship between the workplace (ICU/SHA) and educational level with IPC was not statistically significant (p>.05). There are statistical significant differences between IPC with age and years of professional activity in CA (p<.05). The present study demonstrates the existence of good IPC in the CA. Younger nurses obtain a better IPC score, as well as nurses who have been working for less time in CA. Nurses with a Degree or Masters have a higher level of IPC than the rest, as well as nurses who perform professional activity combining ICU and SHA. Copyright © 2015 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

PubMed

Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

2014-05-21

Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

PubMed Central

Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

2009-01-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

Density of high-spin states in38Ar and42Ca

NASA Astrophysics Data System (ADS)

Kern, Th.; Betz, P.; Bitterwolf, E.; Glatz, F.; Röpke, H.

1980-03-01

The γ-decay modes of38Ar levels with E x ≦11,630keV and of42Ca levels with E x ≦10,036keV have been studied using the35Cl( α, pγ) reaction at 16MeV and the39K( α, pγ) reaction at 15.14 MeV, respectively. In both nuclei the number of states with J≧6 exceeds fifty. Weak coupling calculations of the Bansal and French type reproduce the density of high-spin states. The success of the model implies that the excitations of up to four particles from the d 3/2 into the f 7/2 shell play a role in both nuclei. The structure of deformed states was found to be predominantly 4 p/s 6 h in38Ar and 4 p/s 2 h in42Ca, respectively.

Porcine calbindin-D9k gene: expression in endometrium, myometrium, and placenta in the absence of a functional estrogen response element in intron A.

PubMed

Krisinger, J; Jeung, E B; Simmen, R C; Leung, P C

1995-01-01

The expression of Calbindin-D9k (CaBP-9k) in the pig uterus and placenta was measured by Northern blot analysis and reverse transcription polymerase chain reaction (PCR), respectively. Progesterone (P4) administration to ovariectomized pigs decreased CaBP-9k mRNA levels. Expression of endometrial CaBP-9k mRNA was high on pregnancy Days 10-12 and below the detection limit on Days 15 and 18. On Day 60, expression could be detected at low levels. In myometrium and placenta, CaBP-9k mRNA expression was not detectable by Northern analysis using total RNA. Reverse-transcribed RNA from both tissues demonstrated the presence of CaBP-9k transcripts by means of PCR. The partial CaBP-9k gene was amplified by PCR and cloned to determine the sequence of intron A. In contrast to the rat CaBP-9k gene, the pig gene does not contain a functional estrogen response element (ERE) within this region. A similar ERE-like sequence located at the identical location was examined by gel retardation analysis and failed to bind the estradiol receptor. A similar disruption of this ERE-like sequence has been described in the human CaBP-9k gene, which is not expressed at any level in placenta, myometrium, or endometrium. It is concluded that the pig CaBP-9k gene is regulated in these reproductive tissues in a manner distinct from that in rat and human tissues. The regulation is probably due to a regulatory region outside of intron A, which in the rat gene contains the key cis element for uterine expression of the CaBP-9k gene.

Adult dogs are capable of regulating calcium balance, with no adverse effects on health, when fed a high-calcium diet.

PubMed

Stockman, Jonathan; Watson, Phillip; Gilham, Matthew; Allaway, David; Atwal, Jujhar; Haydock, Richard; Colyer, Alison; Renfrew, Helen; Morris, Penelope J

2017-05-01

Although the implications of long-term high Ca intakes have been well documented in growing dogs, the health consequences of Ca excess in adult dogs remain to be established. To evaluate the impact of feeding a diet containing 7·1 g/4184 kJ (1000 kcal) Ca for 40 weeks on Ca balance and health parameters in adult dogs, eighteen neutered adult Labrador Retrievers, (nine males and nine females) aged 2·5-7·4 years were randomised to one of two customised diets for 40 weeks. The diets were manufactured according to similar nutritional specifications, with the exception of Ca and P levels. The diets provided 1·7 and 7·1 g/4184 kJ (1000 kcal) (200(SD26) and 881(SD145) mg/kg body weight0·75 per d, respectively) Ca, respectively, with a Ca:P ratio of 1·6. Clinical examinations, ultrasound scans, radiographs, health parameters, metabolic effects and mineral balance were recorded at baseline and at 8-week intervals throughout the study. Dogs in both groups were healthy throughout the trial without evidence of urinary, renal or orthopaedic disease. In addition, there were no clinically relevant changes in any of the measures made in either group (all P>0·05). The high-Ca diet resulted in a 3·3-fold increase in faecal Ca excretion (P0·05). Ca intakes of up to 7·1 g/4184 kJ (1000 kcal) are well tolerated over a period of 40 weeks, with no adverse effects that could be attributed to the diet or to a high mineral intake.

The Ca2+/Calcineurin-Regulated cup Gene Family in Dictyostelium discoideum and Its Possible Involvement in Development

PubMed Central

Coukell, Barrie; Li, Yi; Moniakis, John; Cameron, Anne

2004-01-01

Changes in free intracellular Ca2+ are thought to regulate several major processes during Dictyostelium development, including cell aggregation and cell type-specific gene expression, but the mechanisms involved are unclear. To learn more about Ca2+ signaling and Ca2+ homeostasis in this organism, we used suppression subtractive hybridization to identify genes up-regulated by high extracellular Ca2+. Unexpectedly, many of the genes identified belong to a novel gene family (termed cup) with seven members. In vegetative cells, the cup genes were up-regulated by high Ca2+ but not by other ions or by heat, oxidative, or osmotic stress. cup induction by Ca2+ was blocked completely by inhibitors of calcineurin and protein synthesis. In developing cells, cup expression was high during aggregation and late development but low during the slug stage. This pattern correlates closely with reported levels of free intracellular Ca2+ during development. The cup gene products are highly homologous, acidic proteins possessing putative ricin domains. BLAST searches failed to reveal homologs in other organisms, but Western analyses suggested that Cup-like proteins might exist in certain other cellular slime mold species. Localization experiments indicated that Cup proteins are primarily cytoplasmic but become cell membrane-associated during Ca2+ stress and cell aggregation. When cup expression was down-regulated by antisense RNA, the cells failed to aggregate. However, this developmental block was overcome by partially up-regulating cup expression. Together, these results suggest that the Cup proteins in Dictyostelium might play an important role in stabilizing and/or regulating the cell membrane during Ca2+ stress and/or certain stages of development. PMID:14871937

Printability of calcium phosphate: calcium sulfate powders for the application of tissue engineered bone scaffolds using the 3D printing technique.

PubMed

Zhou, Zuoxin; Buchanan, Fraser; Mitchell, Christina; Dunne, Nicholas

2014-05-01

In this study, calcium phosphate (CaP) powders were blended with a three-dimensional printing (3DP) calcium sulfate (CaSO4)-based powder and the resulting composite powders were printed with a water-based binder using the 3DP technology. Application of a water-based binder ensured the manufacture of CaP:CaSO4 constructs on a reliable and repeatable basis, without long term damage of the printhead. Printability of CaP:CaSO4 powders was quantitatively assessed by investigating the key 3DP process parameters, i.e. in-process powder bed packing, drop penetration behavior and the quality of printed solid constructs. Effects of particle size, CaP:CaSO4 ratio and CaP powder type on the 3DP process were considered. The drop penetration technique was used to reliably identify powder formulations that could be potentially used for the application of tissue engineered bone scaffolds using the 3DP technique. Significant improvements (p<0.05) in the 3DP process parameters were found for CaP (30-110 μm):CaSO4 powders compared to CaP (<20 μm):CaSO4 powders. Higher compressive strength was obtained for the powders with the higher CaP:CaSO4 ratio. Hydroxyapatite (HA):CaSO4 powders showed better results than beta-tricalcium phosphate (β-TCP):CaSO4 powders. Solid and porous constructs were manufactured using the 3DP technique from the optimized CaP:CaSO4 powder formulations. High-quality printed constructs were manufactured, which exhibited appropriate green compressive strength and a high level of printing accuracy. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibitory ryanodine prevents ryanodine receptor-mediated Ca²⁺ release without affecting endoplasmic reticulum Ca²⁺ content in primary hippocampal neurons.

PubMed

Adasme, Tatiana; Paula-Lima, Andrea; Hidalgo, Cecilia

2015-02-27

Ryanodine is a cell permeant plant alkaloid that binds selectively and with high affinity to ryanodine receptor (RyR) Ca(2+) release channels. Sub-micromolar ryanodine concentrations activate RyR channels while micromolar concentrations are inhibitory. Several reports indicate that neuronal synaptic plasticity, learning and memory require RyR-mediated Ca(2+)-release, which is essential for muscle contraction. The use of micromolar (inhibitory) ryanodine represents a common strategy to suppress RyR activity in neuronal cells: however, micromolar ryanodine promotes RyR-mediated Ca(2+) release and endoplasmic reticulum Ca(2+) depletion in muscle cells. Information is lacking in this regard in neuronal cells; hence, we examined here if addition of inhibitory ryanodine elicited Ca(2+) release in primary hippocampal neurons, and if prolonged incubation of primary hippocampal cultures with inhibitory ryanodine affected neuronal ER calcium content. Our results indicate that inhibitory ryanodine does not cause Ca(2+) release from the ER in primary hippocampal neurons, even though ryanodine diffusion should produce initially low intracellular concentrations, within the RyR activation range. Moreover, neurons treated for 1 h with inhibitory ryanodine had comparable Ca(2+) levels as control neurons. These combined findings imply that prolonged incubation with inhibitory ryanodine, which effectively abolishes RyR-mediated Ca(2+) release, preserves ER Ca(2+) levels and thus constitutes a sound strategy to suppress neuronal RyR function. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

PubMed

Heidari, Mohammad Hassan; Porghasem, Mohsen; Mirzaei, Nazanin; Mohseni, Jafar Hesam; Heidari, Matine; Azargashb, Eznollah; Movafagh, Abolfazl; Heidari, Reihane; Molouki, Aidin; Larijani, Leila

2014-02-01

Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coping with Stresses: Roles of Calcium- and Calcium/Calmodulin-Regulated Gene Expression[W][OA

PubMed Central

Reddy, Anireddy S.N.; Ali, Gul S.; Celesnik, Helena; Day, Irene S.

2011-01-01

Abiotic and biotic stresses are major limiting factors of crop yields and cause billions of dollars of losses annually around the world. It is hoped that understanding at the molecular level how plants respond to adverse conditions and adapt to a changing environment will help in developing plants that can better cope with stresses. Acquisition of stress tolerance requires orchestration of a multitude of biochemical and physiological changes, and most of these depend on changes in gene expression. Research during the last two decades has established that different stresses cause signal-specific changes in cellular Ca2+ level, which functions as a messenger in modulating diverse physiological processes that are important for stress adaptation. In recent years, many Ca2+ and Ca2+/calmodulin (CaM) binding transcription factors (TFs) have been identified in plants. Functional analyses of some of these TFs indicate that they play key roles in stress signaling pathways. Here, we review recent progress in this area with emphasis on the roles of Ca2+- and Ca2+/CaM-regulated transcription in stress responses. We will discuss emerging paradigms in the field, highlight the areas that need further investigation, and present some promising novel high-throughput tools to address Ca2+-regulated transcriptional networks. PMID:21642548

Comparison of mRNA, Protein, and Urinary Nucleic Acid Levels of S100A8 and S100A9 between Prostate Cancer and BPH.

PubMed

Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Lee, Ok-Jun; Kim, Won Tae; Moon, Sung-Kwon; Kim, Isaac Yi; Choi, Yung-Hyun; Kim, Wun-Jae

2015-07-01

Infections and inflammation in the prostate play a critical role in carcinogenesis, and S100A8 and S100A9 are key mediators in acute and chronic inflammation. Therefore, we investigated the differences of S100A8/A9 expression between prostate cancer (CaP) and benign prostatic hyperplasia (BPH) tissues, and we evaluated the possibilities of urinary nucleic acids of S100A8/A9 as diagnostic and prognostic markers. Tissues from 132 CaP patients who underwent prostatectomy or transurethral resection and 90 BPH patients who underwent transurethral prostatectomy were assessed.sd In addition, S100A8 and S100A9 nucleic acid levels were measured in the urine of 283 CaP patients and 363 BPH controls. S100A8 and S100A9 mRNA levels were lower in CaP than BPH tissues (P < 0.001). S100A8 and S100A9 expression was increased in cancer tissues with poorer prognosis. In 69 specimens from prostatectomy patients, S100A8/A9 were the independent predictor of biochemical recurrence (hazard ratio 5.22, 95 % confidence interval 1.800-15.155, P = 0.002). Immunohistochemical staining revealed that BPH tissues stained more strongly for both S100A8 and S100A9 than CaP tissues (P < 0.001). S100A8 and S100A9 urinary nucleic acid levels were lower in CaP than in BPH (P = 0.001 and <0.001, respectively). S100A8/A9 levels are lower in CaP than in BPH. Both were more highly expressed in patients with aggressive disease and shorter biochemical recurrence-free time. S100A8/A9 urinary cell-free nucleic acid levels correlated positively with expression levels obtained from tissue staining. Therefore, S100A8/A9 measurement in tissues and urine may have diagnostic and prognostic value in CaP.

Characterization of carbonic anhydrase XIII in the erythrocytes of the Burmese python, Python molurus bivittatus.

PubMed

Esbaugh, A J; Secor, S M; Grosell, M

2015-09-01

Carbonic anhydrase (CA) is one of the most abundant proteins found in vertebrate erythrocytes with the majority of species expressing a low activity CA I and high activity CA II. However, several phylogenetic gaps remain in our understanding of the expansion of cytoplasmic CA in vertebrate erythrocytes. In particular, very little is known about isoforms from reptiles. The current study sought to characterize the erythrocyte isoforms from two squamate species, Python molurus and Nerodia rhombifer, which was combined with information from recent genome projects to address this important phylogenetic gap. Obtained sequences grouped closely with CA XIII in phylogenetic analyses. CA II mRNA transcripts were also found in erythrocytes, but found at less than half the levels of CA XIII. Structural analysis suggested similar biochemical activity as the respective mammalian isoforms, with CA XIII being a low activity isoform. Biochemical characterization verified that the majority of CA activity in the erythrocytes was due to a high activity CA II-like isoform; however, titration with copper supported the presence of two CA pools. The CA II-like pool accounted for 90 % of the total activity. To assess potential disparate roles of these isoforms a feeding stress was used to up-regulate CO2 excretion pathways. Significant up-regulation of CA II and the anion exchanger was observed; CA XIII was strongly down-regulated. While these results do not provide insight into the role of CA XIII in the erythrocytes, they do suggest that the presence of two isoforms is not simply a case of physiological redundancy. Copyright © 2015. Published by Elsevier Inc.

Northwest corner, showing arcade at ground level, and triple leaded ...

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

Northwest corner, showing arcade at ground level, and triple leaded glass windows of bender room high on north elevation. - Stanford University Library, Stanford University, Palo Alto, Santa Clara County, CA

Function of Protein Phosphatase 2A in Control of Proliferation: Isolation and Analysis of Dominant-Defective Mutants

DTIC Science & Technology

1998-06-01

the Ca gene. In the case of pWZLneo, translation of Ca and the neomycin phosphotransferase (Neo) protein are coupled by an IRES site. In the case of...expression of both the hygromycin resistance (Hyg) and PP2A-C cassettes. In the colony formation assay, cells infected with the retroviral construct are...than hygromycin in selecting for cells expressing high levels of drug resistance (Hanson and Sedivy, 1995). Cells expressing a relatively low level of

A dynamic leaf gas-exchange strategy is conserved in woody plants under changing ambient CO2 : evidence from carbon isotope discrimination in paleo and CO2 enrichment studies.

PubMed

Voelker, Steven L; Brooks, J Renée; Meinzer, Frederick C; Anderson, Rebecca; Bader, Martin K-F; Battipaglia, Giovanna; Becklin, Katie M; Beerling, David; Bert, Didier; Betancourt, Julio L; Dawson, Todd E; Domec, Jean-Christophe; Guyette, Richard P; Körner, Christian; Leavitt, Steven W; Linder, Sune; Marshall, John D; Mildner, Manuel; Ogée, Jérôme; Panyushkina, Irina; Plumpton, Heather J; Pregitzer, Kurt S; Saurer, Matthias; Smith, Andrew R; Siegwolf, Rolf T W; Stambaugh, Michael C; Talhelm, Alan F; Tardif, Jacques C; Van de Water, Peter K; Ward, Joy K; Wingate, Lisa

2016-02-01

Rising atmospheric [CO2 ], ca , is expected to affect stomatal regulation of leaf gas-exchange of woody plants, thus influencing energy fluxes as well as carbon (C), water, and nutrient cycling of forests. Researchers have proposed various strategies for stomatal regulation of leaf gas-exchange that include maintaining a constant leaf internal [CO2 ], ci , a constant drawdown in CO2 (ca  - ci ), and a constant ci /ca . These strategies can result in drastically different consequences for leaf gas-exchange. The accuracy of Earth systems models depends in part on assumptions about generalizable patterns in leaf gas-exchange responses to varying ca . The concept of optimal stomatal behavior, exemplified by woody plants shifting along a continuum of these strategies, provides a unifying framework for understanding leaf gas-exchange responses to ca . To assess leaf gas-exchange regulation strategies, we analyzed patterns in ci inferred from studies reporting C stable isotope ratios (δ(13) C) or photosynthetic discrimination (∆) in woody angiosperms and gymnosperms that grew across a range of ca spanning at least 100 ppm. Our results suggest that much of the ca -induced changes in ci /ca occurred across ca spanning 200 to 400 ppm. These patterns imply that ca  - ci will eventually approach a constant level at high ca because assimilation rates will reach a maximum and stomatal conductance of each species should be constrained to some minimum level. These analyses are not consistent with canalization toward any single strategy, particularly maintaining a constant ci . Rather, the results are consistent with the existence of a broadly conserved pattern of stomatal optimization in woody angiosperms and gymnosperms. This results in trees being profligate water users at low ca , when additional water loss is small for each unit of C gain, and increasingly water-conservative at high ca , when photosystems are saturated and water loss is large for each unit C gain. © 2015 John Wiley & Sons Ltd.

A dynamic leaf gas-exchange strategy is conserved in woody plants under changing ambient CO2: evidence from carbon isotope discrimination in paleo and CO2 enrichment studies

USGS Publications Warehouse

Voelker, Steven L.; Brooks, J. Renée; Meinzer, Frederick C.; Anderson, Rebecca D.; Bader, Martin K.-F.; Battipaglia, Giovanna; Becklin, Katie M.; Beerling, David; Bert, Didier; Betancourt, Julio L.; Dawson, Todd E.; Domec, Jean-Christophe; Guyette, Richard P.; Körner, Christian; Leavitt, Steven W.; Linder, Sune; Marshall, John D.; Mildner, Manuel; Ogée, Jérôme; Panyushkina, Irina P.; Plumpton, Heather J.; Pregitzer, Kurt S.; Saurer, Matthias; Smith, Andrew R.; Siegwolf, Rolf T.W.; Stambaugh, Michael C.; Talhelm, Alan F.; Tardif, Jacques C.; Van De Water, Peter K.; Ward, Joy K.; Wingate, Lisa

2016-01-01

Rising atmospheric [CO2], ca, is expected to affect stomatal regulation of leaf gas-exchange of woody plants, thus influencing energy fluxes as well as carbon (C), water, and nutrient cycling of forests. Researchers have proposed various strategies for stomatal regulation of leaf gas-exchange that include maintaining a constant leaf internal [CO2], ci, a constant drawdown in CO2(ca − ci), and a constant ci/ca. These strategies can result in drastically different consequences for leaf gas-exchange. The accuracy of Earth systems models depends in part on assumptions about generalizable patterns in leaf gas-exchange responses to varying ca. The concept of optimal stomatal behavior, exemplified by woody plants shifting along a continuum of these strategies, provides a unifying framework for understanding leaf gas-exchange responses to ca. To assess leaf gas-exchange regulation strategies, we analyzed patterns in ci inferred from studies reporting C stable isotope ratios (δ13C) or photosynthetic discrimination (∆) in woody angiosperms and gymnosperms that grew across a range of ca spanning at least 100 ppm. Our results suggest that much of the ca-induced changes in ci/ca occurred across ca spanning 200 to 400 ppm. These patterns imply that ca − ci will eventually approach a constant level at high ca because assimilation rates will reach a maximum and stomatal conductance of each species should be constrained to some minimum level. These analyses are not consistent with canalization toward any single strategy, particularly maintaining a constant ci. Rather, the results are consistent with the existence of a broadly conserved pattern of stomatal optimization in woody angiosperms and gymnosperms. This results in trees being profligate water users at low ca, when additional water loss is small for each unit of C gain, and increasingly water-conservative at high ca, when photosystems are saturated and water loss is large for each unit C gain.

High pH-Sensitive TRPA1 Activation in Odontoblasts Regulates Mineralization.

PubMed

Kimura, M; Sase, T; Higashikawa, A; Sato, M; Sato, T; Tazaki, M; Shibukawa, Y

2016-08-01

Calcium hydroxide and mineral trioxide aggregate are widely used for indirect and direct pulp capping and root canal filling. Their dissociation into Ca(2+) and OH(-) in dental pulp creates an alkaline environment, which activates reparative/reactionary dentinogenesis. However, the mechanisms by which odontoblasts detect the pH of the extracellular environment remain unclear. We examined the alkali-sensitive intracellular Ca(2+) signaling pathway in rat odontoblasts. In the presence or absence of extracellular Ca(2+), application of alkaline solution increased intracellular Ca(2+) concentration, or [Ca(2+)]i Alkaline solution-induced [Ca(2+)]i increases depended on extracellular pH (8.5 to 10.5) in both the absence and the presence of extracellular Ca(2+) The amplitude was smaller in the absence than in the presence of extracellular Ca(2+) Each increase in [Ca(2+)]i, activated by pH 7.5, 8.5, or 9.5, depended on extracellular Ca(2+) concentration; the equilibrium binding constant for extracellular Ca(2+) concentration decreased as extracellular pH increased (1.04 mM at pH 7.5 to 0.11 mM at pH 9.5). Repeated applications of alkaline solution did not have a desensitizing effect on alkali-induced [Ca(2+)]i increases and inward currents. In the presence of extracellular Ca(2+), alkaline solution-induced [Ca(2+)]i increases were suppressed by application of an antagonist of transient receptor potential ankyrin subfamily member 1 (TRPA1) channels. Ca(2+) exclusion efficiency during alkaline solution-induced [Ca(2+)]i increases was reduced by a Na(+)-Ca(2+) exchanger antagonist. Alizarin red and von Kossa staining revealed increased mineralization levels under repeated high pH stimulation, whereas the TRPA1 antagonist strongly reduced this effect. These findings indicate that alkaline stimuli-such as the alkaline environment inside dental pulp treated with calcium hydroxide or mineral trioxide aggregate-activate Ca(2+) mobilization via Ca(2+) influx mediated by TRPA1 channels and intracellular Ca(2+) release in odontoblasts. High pH-sensing mechanisms in odontoblasts are important for activating dentinogenesis induced by an alkaline environment. © International & American Associations for Dental Research 2016.

The importance of serum serotonin levels in the measurement of radiation-induced bystander cell death in HaCaT cells.

PubMed

Lyng, Fiona M; Desplanques, Maxime; Jella, Kishore Kumar; Garcia, Amaya; McClean, Brendan

2012-10-01

The aim of this study was to investigate the importance of serum serotonin levels in the measurement of bystander cell death. The study was undertaken as part of an intercomparison exercise involving seven European laboratories funded under the European Union Sixth Framework Programme (FP6) Non-Targeted Effects (NOTE) integrated project. Three batches of foetal bovine serum were tested; serum with high and low serotonin content from the intercomparison exercise as well as serum from the home laboratory. Three sets of human keratinocytes (HaCaT cell line) were cultured in DMEM:F12 medium supplemented with serum with high or low serotonin content or serum from the home laboratory and both donor and recipient HaCaT cells were plated. The donor HaCaT cells were irradiated (0.5 Gy) using a cobalt 60 teletherapy unit, the medium was harvested 1 hour post irradiation and transferred to the recipient HaCaT cells. Bystander induced cell death was measured by the clonogenic survival assay and the Alamar blue viability assay. A significant reduction in cell survival, as measured by the clonogenic assay, and in cell viability, as measured by the Alamar blue assay, was observed in the recipient HaCaT cells treated with medium from irradiated cells compared to the cells treated with medium from unirradiated cells. No significant difference was found between the three batches of serum. The data suggest that in our cell system and with our endpoints (clonogenic assay and Alamar blue assay), serum serotonin levels do not play a role in bystander-induced cell death.

Effect of chronic ethanol consumption on the response of parathyroid hormone to hypocalcemia in the pregnant rat.

PubMed

Duggal, Shalu; Simpson, Mary Elizabeth; Keiver, Kathy

2007-01-01

Chronic alcohol (ethanol) consumption during pregnancy results in maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level, and PTH does not increase in response to ethanol-induced hypocalcemia. However, it is not known whether ethanol actually prevents PTH from responding, or whether the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca maintained. The objective of this study was to determine whether chronic ethanol consumption impairs the ability of the pregnant female to increase PTH in response to acute hypocalcemia. Rats were fed isocaloric diets with ethanol (36% ethanol-derived calories, E group) or without ethanol [pair-fed (PF) and control (C) groups], before and throughout 21 days of gestation. On day 21 gestation, rats received an intraperitoneal injection of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (300 or 500 mumol/kg body weight) or saline (saline group), or no injection (baseline group). Blood was collected from the baseline group, and at 30 or 60 minutes postinjection (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH. Consistent with previous studies, ethanol consumption decreased blood iCa levels at baseline, but PTH levels did not differ among groups. Administration of EGTA significantly decreased blood iCa levels by 30 minutes, but ethanol did not prevent PTH from increasing in response to the hypocalcemia. In all diet groups, PTH levels were significantly increased by 30 minutes. Ethanol did, however, appear to decrease the maximum PTH level achievable in blood. These data suggest that chronic ethanol consumption does not impair the ability of the pregnant rat to raise serum PTH levels in response to acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair the ability of the pregnant female to sustain high PTH levels in response to chronic hypocalcemia.

Calreticulin expression in relation to exchangeable Ca(2+) level that changes dynamically during anthesis, progamic phase, and double fertilization in Petunia.

PubMed

Lenartowski, Robert; Suwińska, Anna; Lenartowska, Marta

2015-01-01

Calcium (Ca(2+)) plays essential roles in plant sexual reproduction, but the sites and the mechanism of Ca(2+) mobile storage during pollen-pistil interactions have not been fully defined. Because the Ca(2+)-buffering protein calreticulin (CRT) is able to bind and sequester Ca(2+), it can serve as a mobile intracellular store of easily releasable Ca(2+) and control its local concentration within the cytoplasm. Our previous studies showed an enhanced expression of Petunia hybrida CRT gene (PhCRT) during pistil transmitting tract maturation, pollen germination and tube outgrowth on the stigma, gamete fusion, and early embryogenesis. Here, we demonstrate that elevated expression of CRT results in the accumulation of this protein in response to anthesis, pollination, sperm cells deposition within the receptive synergid and fertilization, when the level of exchangeable Ca(2+) changes dynamically. CRT localizes mainly to the endoplasmic reticulum and Golgi compartments in the pistil transmitting tract cells, germinated pollen/tubes, and sporophytic/gametophytic cells of the ovule and corresponds with loosely bound Ca(2+). Additionally, the immunogold research shows, for the first time, highly selective CRT distribution in specific nuclear sub-domains. On the basis of our results, we discuss the possible functions of CRT with respect to the critical role of Ca(2+) homeostasis during key events of the multi-step process of generative reproduction in angiosperms.

Brain-state dependent astrocytic Ca2+ signals are coupled to both positive and negative BOLD-fMRI signals.

PubMed

Wang, Maosen; He, Yi; Sejnowski, Terrence J; Yu, Xin

2018-02-13

Astrocytic Ca 2+ -mediated gliovascular interactions regulate the neurovascular network in situ and in vivo. However, it is difficult to measure directly both the astrocytic activity and fMRI to relate the various forms of blood-oxygen-level-dependent (BOLD) signaling to brain states under normal and pathological conditions. In this study, fMRI and GCaMP-mediated Ca 2+ optical fiber recordings revealed distinct evoked astrocytic Ca 2+ signals that were coupled with positive BOLD signals and intrinsic astrocytic Ca 2+ signals that were coupled with negative BOLD signals. Both evoked and intrinsic astrocytic calcium signal could occur concurrently or respectively during stimulation. The intrinsic astrocytic calcium signal can be detected globally in multiple cortical sites in contrast to the evoked astrocytic calcium signal only detected at the activated cortical region. Unlike propagating Ca 2+ waves in spreading depolarization/depression, the intrinsic Ca 2+ spikes occurred simultaneously in both hemispheres and were initiated upon the activation of the central thalamus and midbrain reticular formation. The occurrence of the intrinsic astrocytic calcium signal is strongly coincident with an increased EEG power level of the brain resting-state fluctuation. These results demonstrate highly correlated astrocytic Ca 2+ spikes with bidirectional fMRI signals based on the thalamic regulation of cortical states, depicting a brain-state dependency of both astrocytic Ca 2+ and BOLD fMRI signals.

Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle

PubMed Central

Ørtenblad, Niels; Nielsen, Joachim; Saltin, Bengt; Holmberg, Hans-Christer

2011-01-01

Little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. The aim of the present study was to examine the effect of glycogen on sarcoplasmic reticulum (SR) function in the arm and leg muscles of elite cross-country skiers (n= 10, 72 ± 2 ml kg−1 min−1) before, immediately after, and 4 h and 22 h after a fatiguing 1 h ski race. During the first 4 h recovery, skiers received either water or carbohydrate (CHO) and thereafter all received CHO-enriched food. Immediately after the race, arm glycogen was reduced to 31 ± 4% and SR Ca2+ release rate decreased to 85 ± 2% of initial levels. Glycogen noticeably recovered after 4 h recovery with CHO (59 ± 5% initial) and the SR Ca2+ release rate returned to pre-exercise levels. However, in the absence of CHO during the first 4 h recovery, glycogen and the SR Ca2+ release rate remained unchanged (29 ± 2% and 77 ± 8%, respectively), with both parameters becoming normal after the remaining 18 h recovery with CHO. Leg muscle glycogen decreased to a lesser extent (71 ± 10% initial), with no effects on the SR Ca2+ release rate. Interestingly, transmission electron microscopy (TEM) analysis revealed that the specific pool of intramyofibrillar glycogen, representing 10–15% of total glycogen, was highly significantly correlated with the SR Ca2+ release rate. These observations strongly indicate that low glycogen and especially intramyofibrillar glycogen, as suggested by TEM, modulate the SR Ca2+ release rate in highly trained subjects. Thus, low glycogen during exercise may contribute to fatigue by causing a decreased SR Ca2+ release rate. PMID:21135051

Regulating Intracellular Calcium in Plants: From Molecular Genetics to Physiology

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

Heven Sze

To grow, develop, adapt, and reproduce, plants have evolved mechanisms to regulate the uptake, translocation and sorting of calcium ions into different cells and subcellular compartments. Yet how plants accomplish this remarkable feat is still poorly understood. The spatial and temporal changes in intracellular [Ca2+] during growth and during responses to hormonal and environmental stimuli indicate that Ca2+ influx and efflux transporters are diverse and tightly regulated in plants. The specific goals were to determine the biological roles of multiple Ca pumps (ECAs) in the model plant Arabidopsis thaliana. We had pioneered the use of K616 yeast strain to functionallymore » express plant Ca pumps, and demonstrated two distinct types of Ca pumps in plants (Sze et al., 2000. Annu Rev Plant Biol. 51,433). ACA2 represented one type that was auto-inhibited by the N-terminal region and stimulated by calmodulin. ECA1 represented another type that was not sensitive to calmodulin and phylogenetically distinct from ACAs. The goal to determine the biological roles of multiple ECA-type Ca pumps in Arabidopsis has been accomplished. Although we demonstrated ECA1 was a Ca pump by functional expression in yeast, the in vivo roles of ECAs was unclear. A few highlights are described. ECA1 and/or ECA4 are Ca/Mn pumps localized to the ER and are highly expressed in all cell types. Using homozygous T-DNA insertional mutants of eca1, we demonstrated that the ER-bound ECA1 supports growth and confers tolerance of plants growing on medium low in Ca or containing toxic levels of Mn. This is the first genetic study to determine the in vivo function of a Ca pump in plants. A phylogenetically distinct ECA3 is also a Ca/Mn pump that is localized to endosome, such as post-Golgi compartments. Although it is expressed at lower levels than ECA1, eca3 mutants are impaired in Ca-dependent root growth and in pollen tube elongation. Increased secretion of wall proteins in mutants suggests that Ca and Mn homeostasis in post-Golgi compartments are critical for secretory activities. Moreover, perturbation of the secretory machinery limits growth possibly by upsetting the synthesis, processing and assembly of cell wall components. Analyses of whole genome transcriptome of pollen shows that a subset of Ca pump genes are developmentally regulated. Each ECA Ca pump is localized to distinct endomembrane compartments and regulate Ca and Mn homeostasis required for optimal growth and for tolerance to high Mn stress. Ca and Mn levels within endomembrane lumen appear to be critical for activities of the secretory machinery including post-Golgi compartments that coordinate membrane traffic and sorting of materials to the vacuole and the cell wall. Significance: Thus sorting of Ca/Mn by ECA pumps in endomembranes is critical for membrane trafficking pattern which serves as a central coordinator of plant growth, development and adaptation to abiotic and biotic stress.« less

A Pseudomonas aeruginosa EF-Hand Protein, EfhP (PA4107), Modulates Stress Responses and Virulence at High Calcium Concentration

PubMed Central

Sarkisova, Svetlana A.; Lotlikar, Shalaka R.; Guragain, Manita; Kubat, Ryan; Cloud, John

2014-01-01

Pseudomonas aeruginosa is a facultative human pathogen, and a major cause of nosocomial infections and severe chronic infections in endocarditis and in cystic fibrosis (CF) patients. Calcium (Ca2+) accumulates in pulmonary fluids of CF patients, and plays a role in the hyperinflamatory response to bacterial infection. Earlier we showed that P. aeruginosa responds to increased Ca2+ levels, primarily through the increased production of secreted virulence factors. Here we describe the role of putative Ca2+-binding protein, with an EF-hand domain, PA4107 (EfhP), in this response. Deletion mutations of efhP were generated in P. aeruginosa strain PAO1 and CF pulmonary isolate, strain FRD1. The lack of EfhP abolished the ability of P. aeruginosa PAO1 to maintain intracellular Ca2+ homeostasis. Quantitative high-resolution 2D-PAGE showed that the efhP deletion also affected the proteomes of both strains during growth with added Ca2+. The greatest proteome effects occurred when the pulmonary isolate was cultured in biofilms. Among the proteins that were significantly less abundant or absent in the mutant strains were proteins involved in iron acquisition, biosynthesis of pyocyanin, proteases, and stress response proteins. In support, the phenotypic responses of FRD1 ΔefhP showed that the mutant strain lost its ability to produce pyocyanin, developed less biofilm, and had decreased resistance to oxidative stress (H2O2) when cultured at high [Ca2+]. Furthermore, the mutant strain was unable to produce alginate when grown at high [Ca2+] and no iron. The effect of the ΔefhP mutations on virulence was determined in a lettuce model of infection. Growth of wild-type P. aeruginosa strains at high [Ca2+] causes an increased area of disease. In contrast, the lack of efhP prevented this Ca2+-induced increase in the diseased zone. The results indicate that EfhP is important for Ca2+ homeostasis and virulence of P. aeruginosa when it encounters host environments with high [Ca2+]. PMID:24918783

Elastic and inelastic light scattering from single bacterial spores in an optical trap allows the monitoring of spore germination dynamics

PubMed Central

Peng, Lixin; Chen, De; Setlow, Peter; Li, Yong-qing

2009-01-01

Raman scattering spectroscopy and elastic light scattering intensity (ESLI) were used to simultaneously measure levels of Ca-dipicolinic acid (CaDPA) and changes in spore morphology and refractive index during germination of individual B. subtilis spores with and without the two redundant enzymes (CLEs), CwlJ and SleB, that degrade spores’ peptidoglycan cortex. Conclusions from these measurements include: 1) CaDPA release from individual wild-type germinating spores was biphasic; in a first heterogeneous slow phase, Tlag, CaDPA levels decreased ∼15% and in the second phase ending at Trelease, remaining CaDPA was released rapidly; 2) in L-alanine germination of wild-type spores and spores lacking SleB: a) the ESLI rose ∼2-fold shortly before Tlag at T1; b) following Tlag, the ESLI again rose ∼2-fold at T2 when CaDPA levels had decreased ∼50%; and c) the ESLI reached its maximum value at ∼Trelease and then decreased; 3) in CaDPA germination of wild-type spores: a) Tlag increased and the first increase in ESLI occurred well before Tlag, consistent with different pathways for CaDPA and L-alanine germination; b) at Trelease the ESLI again reached its maximum value; 4) in L-alanine germination of spores lacking both CLEs and unable to degrade their cortex, the time ΔTrelease (Trelease–Tlag) for excretion of ≥75% of CaDPA was ∼15-fold higher than that for wild-type or sleB spores; and 5) spores lacking only CwlJ exhibited a similar, but not identical ESLI pattern during L-alanine germination to that seen with cwlJ sleB spores, and the high value for ΔTrelease. PMID:19374431

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

PubMed Central

Schultz, Nicolai A.; Christensen, Ib J.; Werner, Jens; Giese, Nathalia; Jensen, Benny V.; Larsen, Ole; Bjerregaard, Jon K.; Pfeiffer, Per; Calatayud, Dan; Nielsen, Svend E.; Yilmaz, Mette K.; Holländer, Niels H.; Wøjdemann, Morten; Bojesen, Stig E.; Nielsen, Kaspar R.; Johansen, Julia S.

2013-01-01

Purpose We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival. Patients and Methods In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay. Results Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months). Conclusions Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis. PMID:23840582

Long-term effects of low calcium dialysates on the serum calcium levels during maintenance hemodialysis treatments: A systematic review and meta-analysis.

PubMed

Yoshikawa, Masahiro; Takase, Osamu; Tsujimura, Taro; Sano, Etsuko; Hayashi, Matsuhiko; Takato, Tsuyoshi; Hishikawa, Keiichi

2018-03-28

Hypercalcemia and hyperparathyroidism in patients receiving maintenance hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal concentration remains controversial. Here, we conducted a systematic review and a meta-analysis of seven randomized controlled trials examining a total of 622 patients to investigate the optimal concentration for MHD for 6 months or longer. The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52 mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38), respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three studies showed that a low concentration was preferred for lowering arterial calcifications or atherosclerosis in different arteries, but one study showed that coronary arterial calcifications increased with a low concentration. Two studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed that a dialysate with a low Ca concentration lowered the serum Ca levels in patients receiving long-term MHD, but further studies are needed to determine the optimal Ca concentration in terms of CVD and MBD.

Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

PubMed

Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

1996-05-01

Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII

PubMed Central

Fischer, Thomas H.; Herting, Jonas; Mason, Fleur E.; Hartmann, Nico; Watanabe, Saera; Nikolaev, Viacheslav O.; Sprenger, Julia U.; Fan, Peidong; Yao, Lina; Popov, Aron-Frederik; Danner, Bernhard C.; Schöndube, Friedrich; Belardinelli, Luiz; Hasenfuss, Gerd; Maier, Lars S.; Sossalla, Samuel

2015-01-01

Aims Enhanced cardiac late Na current (late INa) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late INa and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late INa enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late INa (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIδc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late INa-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late INa did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late INa activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late INa, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late INa exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late INa represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late INa inhibition. PMID:25990311

Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting

PubMed Central

Fraize, Nicolas; Hamieh, Al Mahdy; Joseph, Mickaël Antoine; Touret, Monique; Parmentier, Régis; Salin, Paul Antoine; Malleret, Gaël

2017-01-01

Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference. To determine the role of CaMKII and GluA1 in adaptive forgetting, we adopted a comparative approach to assess the relative quantity and phosphorylation state of these proteins in the brain of rats trained in one of three radial maze paradigms: a RM task, a WM task involving a high level of adaptive forgetting, or a WM involving a low level of adaptive forgetting. Surprisingly, Western blot analyses revealed that training in a WM task involving a high level of adaptive forgetting specifically increased the expression of AMPA receptor GluA1 subunit and the activity of CaMKII in the dentate gyrus. These results highlight that WM with proactive interference involves mechanisms of synaptic plasticity selectively in the dentate gyrus. PMID:28096498

Differential changes in hippocampal CaMKII and GluA1 activity after memory training involving different levels of adaptive forgetting.

PubMed

Fraize, Nicolas; Hamieh, Al Mahdy; Joseph, Mickaël Antoine; Touret, Monique; Parmentier, Régis; Salin, Paul Antoine; Malleret, Gaël

2017-02-01

Phosphorylation of CaMKII and AMPA receptor GluA1 subunit has been shown to play a major role in hippocampal-dependent long-term/reference memory (RM) and in the expression of long-term synaptic potentiation (LTP). In contrast, it has been proposed that dephosphorylation of these proteins could be involved in the opposite phenomenon of hippocampal long-term synaptic depression (LTD) and in adaptive forgetting. Adaptive forgetting allows interfering old memories to be forgotten to give new ones the opportunity to be stored in memory, and in particular in short-term/working memory (WM) that was shown to be very sensitive to proactive interference. To determine the role of CaMKII and GluA1 in adaptive forgetting, we adopted a comparative approach to assess the relative quantity and phosphorylation state of these proteins in the brain of rats trained in one of three radial maze paradigms: a RM task, a WM task involving a high level of adaptive forgetting, or a WM involving a low level of adaptive forgetting. Surprisingly, Western blot analyses revealed that training in a WM task involving a high level of adaptive forgetting specifically increased the expression of AMPA receptor GluA1 subunit and the activity of CaMKII in the dentate gyrus. These results highlight that WM with proactive interference involves mechanisms of synaptic plasticity selectively in the dentate gyrus. © 2017 Fraize et al.; Published by Cold Spring Harbor Laboratory Press.

Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated HaCaT cells via a p38MAPK-independent mechanism

PubMed Central

Guo, Yan; Sun, Juan; Ye, Juan; Ma, Wenyu; Yan, Hualing; Wang, Gang

2016-01-01

Objective To investigate whether Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones exert apoptosis-inhibiting effects in ultraviolet B (UVB)-irradiated HaCaT cells. Methods We divided HaCaT cells into low radiation UVB and high radiation UVB groups. Low radiation UVB and high radiation UVB groups were further divided into a control group, UVB radiation group (UVB group), S. tridactyla Sch. Bip.-derived polysaccharides and flavones low-dose group, and S. tridactyla Sch. Bip.-derived polysaccharides and flavones high-dose group. Cell viability and morphology were assayed by MTT and trypan blue staining. Superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity test kits were used to detect superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity, respectively. Cell apoptosis, intracellular Ca2+ levels, and mitochondrial membrane potential (Δψ) were detected by flow cytometry. Protein levels were analyzed by Western blotting and immunofluorescence. Results S. tridactyla Sch. Bip.-derived polysaccharides and flavones were found to increase the absorbance of MTT, decrease cell death, alleviate the degree of cell edema, restore the cell morphology, reduce cell death fragments and chip phenomenon, increase superoxide dismutase activity, glutathione content, and catalase activity while decreasing the content of malondialdehyde, lowering the population of apoptotic cells, reducing the intracellular Ca2+ fluorescence, increasing the mitochondrial membrane potential (Δψ), increasing the expressions of p-38, p-53, Bcl-2, and decreasing the expressions of Bax and active-caspase-3. Conclusion S. tridactyla Sch. Bip.-derived polysaccharides and flavones can reduce cell apoptosis to protect HaCaT cells from oxidative damage after UVB irradiation; however, this effect does not occur via the p38MAPK pathway. PMID:26855564

MT6415CA: a 640×512-15µm CTIA ROIC for SWIR InGaAs detector arrays

NASA Astrophysics Data System (ADS)

Eminoglu, Selim; Isikhan, Murat; Bayhan, Nusret; Gulden, M. Ali; Incedere, O. Samet; Soyer, S. Tuncer; Kocak, Serhat; Yilmaz, Gokhan S.; Akin, Tayfun

2013-06-01

This paper reports the development of a new low-noise CTIA ROIC (MT6415CA) suitable for SWIR InGaAs detector arrays for low-light imaging applications. MT6415CA is the second product in the MT6400 series ROICs from Mikro-Tasarim Ltd., which is a fabless IC design house specialized in the development of monolithic imaging sensors and ROICs for hybrid imaging sensors. MT6415CA is a low-noise snapshot CTIA ROIC, has a format of 640 × 512 and pixel pitch of 15 µm, and has been developed with the system-on-chip architecture in mind, where all the timing and biasing for this ROIC are generated on-chip without requiring any external inputs. MT6415CA is a highly configurable ROIC, where many of its features can be programmed through a 3-wire serial interface allowing on-the-fly configuration of many ROIC features. It performs snapshot operation both using Integrate-Then-Read (ITR) and Integrate-While-Read (IWR) modes. The CTIA type pixel input circuitry has three gain modes with programmable full-well-capacity (FWC) values of 10.000 e-, 20.000 e-, and 350.000 e- in the very high gain (VHG), high-gain (HG), and low-gain (LG) modes, respectively. MT6415CA has an input referred noise level of less than 5 e- in the very high gain (VHG) mode, suitable for very low-noise SWIR imaging applications. MT6415CA has 8 analog video outputs that can be programmed in 8, 4, or 2-output modes with a selectable analog reference for pseudo-differential operation. The ROIC runs at 10 MHz and supports frame rate values up to 200 fps in the 8-output mode. The integration time can be programmed up to 1s in steps of 0.1 µs. The ROIC uses 3.3 V and 1.8V supply voltages and dissipates less than 150 mW in the 4-output mode. MT6415CA is fabricated using a modern mixed-signal CMOS process on 200 mm CMOS wafers, and tested parts are available at wafer or die levels with test reports and wafer maps. A compact USB 3.0 camera and imaging software have been developed to demonstrate the imaging performance of SWIR sensors built with MT6415CA ROIC

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-05-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions.

Role of calbindin-D9k in buffering cytosolic free Ca2+ ions in pig duodenal enterocytes.

PubMed Central

Schröder, B; Schlumbohm, C; Kaune, R; Breves, G

1996-01-01

1. The aim of the present study was to test whether the vitamin D-dependent Ca(2+)-binding protein calbindin-D9k could function as an important cytosolic Ca2+ buffer in duodenal enterocytes while facilitating transepithelial active transport of Ca2+ ions. For the investigations we used dual-wavelength, fluorescence ratio imaging, with fura-2 as the Ca(2+)-sensitive dye, to measure changes in cytosolic concentrations of free Ca2+ ions ([Ca2+]i) in isolated pig duodenal enterocytes affected by different cytosolic calbindin-D9k concentrations. 2. Epithelial cells were obtained from weaned piglets with normal calbindin-D9k concentrations (con-piglets), from piglets with low calbindin-D9k levels due to inherited calcitriol deficiency caused by defective renal 25-hydroxycholecalciferol D3-1 alpha-hydroxylase activity (def-piglets), and from piglets with reconstituted calbindin-D9k concentrations, i.e. def-animals treated with high doses of vitamin D3 which elevated plasma calcitriol levels by extrarenal production (def-D3-piglets). Basal levels of [Ca2+]i ranged between 170 and 205 nM and did not differ significantly between the groups. 3. After addition of 5 mM theophylline, the [Ca2+]i in enterocytes from con-piglets doubled during the 10 min incubation. This effect, however, was three times higher in enterocytes from def-piglets compared with those from con-piglets. Similar results were obtained after 4 min incubation of enterocytes from con- and def-piglets in the presence of 1 microM ionomycin. In preparations from def-D3-piglets, ionomycin-induced increases in [Ca2+]i were significantly lower compared with enterocytes from def-piglets and were not different from the control values. 4. From the results, substantial support is given for the hypothesis that one of the major functions of mucosal calbindin-D9k is the effective buffering of Ca2+ ions. PMID:8734984

Influence of calcium and phosphorus feeding on markers of bone metabolism in transition cows.

PubMed

Moreira, V R; Zeringue, L K; Williams, C C; Leonardi, C; McCormick, M E

2009-10-01

A study was carried out to verify the effect of Ca and P levels on production, digestibility, and serum bone metabolism biomarkers in dairy cows. Fifty-two nonlactating multiparous cows (>or=3 lactations) were confined in a free-stall barn approximately 20 d before calving. A standard close-up diet was fed to cows once daily until d 2 postpartum. Cows were randomly assigned to 1 of 4 dietary treatments arranged in a 2 x 2 factorial approach averaging 0.64% Ca for high Ca (HCa), 0.46% Ca for low Ca (LCa), 0.47% P for high P (HP), and 0.38% P for low P (LP) on a dry matter basis. Experimental diets were fed twice daily from 3 d in milk (DIM) until 31 DIM. Intake and milk yield were recorded daily. Milk samples were collected on d 28, 29, and 30 postpartum for components analyses. Blood samples were drawn 10 d before expected calving, at calving, and at 15 and 30 DIM for serum analyses of osteocalcin, a biomarker of bone accretion, and pyridinoline, a biomarker of bone resorption. Total fecal collection was conducted when cows in a block averaged 20 DIM. Intake and production traits were not significantly affected by any of the dietary treatments. Cows averaged nearly 21 kg/d dry matter intake and 44 kg/d milk yield from 6 to 31 DIM. There were no significant differences across treatments in body weight or body condition score loss. Phosphorus intake, P fecal output, P digestibility, and P apparent absorption were affected by dietary P content. Calcium intake was higher with HCa, but Ca fecal output, digestibility, and apparent absorption showed an interaction between dietary Ca and dietary P. Calcium fecal output was 100.6 g/d for cows fed HCaHP, intermediate for cows on the HCaLP diet (89 g/d), and similar among cows fed the 2 LCa diets (70 g/d with LCaHP and 75 with LCaLP). There was no significant effect of Ca or P on osteocalcin measurements. Pyridinoline concentrations were affected by dietary Ca levels and tended to have a significant dietary Ca x dietary P interaction. Phosphorus apparent digestibility occurred independently of dietary Ca levels. Results of this study suggest that more bone was mobilized in cows fed LCa diets, but excess dietary P caused greater and prolonged bone mobilization regardless of dietary Ca content.

Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness

PubMed Central

Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R.

2015-01-01

In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states. PMID:26056284

A ryanodine receptor-dependent Ca(i)(2+) asymmetry at Hensen's node mediates avian lateral identity.

PubMed

Garic-Stankovic, Ana; Hernandez, Marcos; Flentke, George R; Zile, Maija H; Smith, Susan M

2008-10-01

In mouse, the establishment of left-right (LR) asymmetry requires intracellular calcium (Ca(i)(2+)) enrichment on the left of the node. The use of Ca(i)(2+) asymmetry by other vertebrates, and its origins and relationship to other laterality effectors are largely unknown. Additionally, the architecture of Hensen's node raises doubts as to whether Ca(i)(2+) asymmetry is a broadly conserved mechanism to achieve laterality. We report here that the avian embryo uses a left-side enriched Ca(i)(2+) asymmetry across Hensen's node to govern its lateral identity. Elevated Ca(i)(2+) was first detected along the anterior node at early HH4, and its emergence and left-side enrichment by HH5 required both ryanodine receptor (RyR) activity and extracellular calcium, implicating calcium-induced calcium release (CICR) as the novel source of the Ca(i)(2+). Targeted manipulation of node Ca(i)(2+) randomized heart laterality and affected nodal expression. Bifurcation of the Ca(i)(2+) field by the emerging prechordal plate may permit the independent regulation of LR Ca(i)(2+) levels. To the left of the node, RyR/CICR and H(+)V-ATPase activity sustained elevated Ca(i)(2+). On the right, Ca(i)(2+) levels were actively repressed through the activities of H(+)K(+) ATPase and serotonin-dependent signaling, thus identifying a novel mechanism for the known effects of serotonin on laterality. Vitamin A-deficient quail have a high incidence of situs inversus hearts and had a reversed calcium asymmetry. Thus, Ca(i)(2+) asymmetry across the node represents a more broadly conserved mechanism for laterality among amniotes than had been previously believed.

Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness.

PubMed

Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R

2015-06-23

In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca(2+) channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.

High-resolution simultaneous voltage and Ca2+ imaging

PubMed Central

Vogt, Kaspar E; Gerharz, Stephan; Graham, Jeremy; Canepari, Marco

2011-01-01

Combining voltage and Ca2+ imaging allows the correlation of electrical and chemical activity at sub-cellular level. Here we describe a novel apparatus designed to obtain simultaneous voltage and Ca2+ measurements with single-trial resolution from sites as small as a few microns. These measurements can be obtained with negligible optical cross-talk between the two signals and negligible photo-damage of the preparation. The capability of the technique was assessed recording either from individual neurons in brain slices or from networks of cultured neurons. The present achievements open the gate to many novel physiological investigations requiring simultaneous measurement of voltage and Ca2+ signals. PMID:21115640

Purification of chicken carbonic anhydrase isozyme-III (CA-III) and its measurement in White Leghorn chickens.

PubMed

Nishita, Toshiho; Tomita, Yuichiro; Yorifuji, Daisuke; Orito, Kensuke; Ochiai, Hideharu; Arishima, Kazuyosi

2011-11-26

The developmental profile of chicken carbonic anhydrase-III (CA-III) blood levels has not been previously determined or reported. We isolated CA-III from chicken muscle and investigated age-related changes in the levels of CA-III in blood. CA-III was purified from chicken muscle. The levels of CA-III in plasma and erythrocytes from 278 female chickens (aged 1-93 weeks) and 68 male chickens (aged 3-59 weeks) were determined by ELISA. The mean level of CA-III in female chicken erythrocytes (1 week old) was 4.6 μg/g of Hb, and the CA-III level did not change until 16 weeks of age. The level then increased until 63 weeks of age (11.8 μg/g of Hb), decreased to 4.7 μg/g of Hb at 73 weeks of age, and increased again until 93 weeks of age (8.6 μg/g of Hb). The mean level of CA-III in erythrocytes from male chickens (3 weeks old) was 2.4 μg/g of Hb, and this level remained steady until 59 weeks of age. The mean plasma level of CA-III in 1-week-old female chickens was 60 ng/mL, and this level was increased at 3 weeks of age (141 ng/mL) and then remained steady until 80 weeks of age (122 ng/mL). The mean plasma level of CA-III in 3-week-old male chickens was 58 ng/mL, and this level remained steady until 59 weeks of age. We observed both developmental changes and sex differences in CA-III concentrations in White Leghorn (WL) chicken erythrocytes and plasma. Simple linear regression analysis showed a significant association between the erythrocyte CA-III level and egg-laying rate in WL-chickens 16-63 weeks of age (p < 0.01).

Overexpression of hexokinase 2 reduces mitochondrial calcium overload in coronary endothelial cells of type 2 diabetic mice.

PubMed

Pan, Minglin; Han, Ying; Basu, Aninda; Dai, Anzhi; Si, Rui; Willson, Conor; Balistrieri, Angela; Scott, Brian T; Makino, Ayako

2018-03-07

Coronary microvascular rarefaction due to endothelial cell (EC) dysfunction is one of the causes of increased morbidity and mortality in diabetes. Coronary ECs in diabetes are more apoptotic due partly to mitochondrial calcium overload. This study was designed to investigate the role of hexokinase 2 (HK2, an endogenous inhibitor of voltage-dependent anion channel) in coronary endothelial dysfunction in type 2 diabetes. We used mouse coronary ECs (MCECs) isolated from type 2 diabetic mice and human coronary ECs (HCECs) from type 2 diabetic patients to examine protein levels and mitochondrial functions. ECs were more apoptotic and capillary density was lower in the left ventricle of diabetic mice than the control. MCECs from diabetic mice exhibited significant increase in mitochondrial Ca 2+ concentration ([Ca 2+ ] mito ) compared to the control. Among several regulatory proteins for [Ca 2+ ] mito , HK1 and HK2 were significantly lower in MCECs from diabetic mice than control MCECs. We also found that the level of HK2 ubiquitination was higher in MCECs from diabetic mice than in control MCECs. In line with the data from MCECs, HCECs from diabetic patients showed lower HK2 protein levels than HCECs from non-diabetic patients. High-glucose treatment, but not high-fat treatment, significantly decreased HK2 protein levels in the MCEC. HK2 overexpression in MCECs of diabetic mice not only lowered the level of [Ca 2+ ] mito , but also reduced mitochondrial ROS production toward the level seen in control MCECs. These data suggest that HK2 is a potential therapeutic target for coronary microvascular disease in diabetes by restoring mitochondrial function in coronary ECs.

Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice.

PubMed

Nakamura, Tomoe Y; Nakao, Shu; Nakajo, Yukako; Takahashi, Jun C; Wakabayashi, Shigeo; Yanamoto, Hiroji

2017-01-01

Intracellular Ca2+ signaling regulates diverse functions of the nervous system. Many of these neuronal functions, including learning and memory, are regulated by neuronal calcium sensor-1 (NCS-1). However, the pathways by which NCS-1 regulates these functions remain poorly understood. Consistent with the findings of previous reports, we revealed that NCS-1 deficient (Ncs1-/-) mice exhibit impaired spatial learning and memory function in the Morris water maze test, although there was little change in their exercise activity, as determined via treadmill-analysis. Expression of brain-derived neurotrophic factor (BDNF; a key regulator of memory function) and dopamine was significantly reduced in the Ncs1-/- mouse brain, without changes in the levels of glial cell-line derived neurotrophic factor or nerve growth factor. Although there were no gross structural abnormalities in the hippocampi of Ncs1-/- mice, electron microscopy analysis revealed that the density of large dense core vesicles in CA1 presynaptic neurons, which release BDNF and dopamine, was decreased. Phosphorylation of Ca2+/calmodulin-dependent protein kinase II-α (CaMKII-α, which is known to trigger long-term potentiation and increase BDNF levels, was significantly reduced in the Ncs1-/- mouse brain. Furthermore, high voltage electric potential stimulation, which increases the levels of BDNF and promotes spatial learning, significantly increased the levels of NCS-1 concomitant with phosphorylated CaMKII-α in the hippocampus; suggesting a close relationship between NCS-1 and CaMKII-α. Our findings indicate that NCS-1 may regulate spatial learning and memory function at least in part through activation of CaMKII-α signaling, which may directly or indirectly increase BDNF production.

Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

PubMed

Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

2008-10-01

L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (p<0.001). Logistic regression and ROC analysis have demonstrated that the DDC expression has significant discriminatory value between CaP and BPH (p<0.001). DDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

Late Pleistocene to Holocene lake levels of Lake Warner, Oregon (USA) and their effect on archaeological site distribution patterns

NASA Astrophysics Data System (ADS)

Wriston, T.; Smith, G. M.

2017-12-01

Few chronological controls are available for the rise and fall of small pluvial lake systems in the Northwestern Great Basin. Within Warner Basin this control was necessary for interpretation of known archaeological sites and for predicting where evidence of its earliest inhabitants might be expected. We trenched along relic beach ridges of Lake Warner, surveyed a stratified sample of the area for archaeological sites, and excavated some sites and a nearby rockshelter. These efforts produced new ages that we used to construct a lake level curve for Lake Warner. We found that the lake filled the valley floor between ca. 30,000 cal yr BP and ca. 10,300 cal yr BP. In nearby basins, several oscillations are evident before ca. 21,100 cal yr BP, but a steep rise to the LGM maximum occurred between 21,000 and 20,000 cal yr BP. Lake Warner likely mirrored these changes, dropped to the valley floor ca. 18,340 cal yr BP, and then rose to its maximum highstand when its waters briefly reached 1454 m asl. After this highstand the lake receded to moderately high levels. Following ca. 14,385 cal yr BP, the lake oscillated between moderate to moderately-high levels through the Bolling-Allerod interstadials and into the Younger Dryas stadial. The basin's first occupants arrived along its shore around this time, while the lake still filled the valley floor. These earliest people carried either Western Stemmed or Clovis projectile points, both of which are found along the lake margin. The lake receded into the valley floor ca. 10,300 cal yr BP and dune development began, ringing wetlands and small lakes that persisted in the footprint of the once large lake. By the time Mazama tephra fell 7,600 cal yr BP it blanketed pre-existing dunes and marsh peats. Our Lake Warner lake level curve facilitates interdisciplinary testing and refinement of it and similar curves throughout the region while helping us understand the history of lake and the people who lived along its shores.

[Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients].

PubMed

Grotowski, M; Maruszyński, M; Piechota, W

2001-12-01

Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known tumor markers expressed by colorectal cancer (CRC), particularly in advanced cases. In this study serological expression of CEA and CA19-9 concerning different clinicopathological factors and sensitivity of diagnosis of CRC by combination of both markers were evaluated. Eighty one patients with diagnosed CRC were in this study included. According to Dukes' classification there were 11 in stage A, 34 in stage B, 17 in stage C and 19 in stage D. Blood samples were collected before operation. CEA and CA19-9 were determined by MEIA (normal range 0-3 ng/ml for CEA and 0-37 U/ml for CA19-9). The statistical analysis revealed that the CEA well correlated with histological type, liver metastasis and term of symptoms. The CA19-9 well correlated with liver metastasis, peritoneal dissemination, nodal involvement and cancer localization. The levels of CEA and CA19-9 increased with stage of the tumor, but only in stage D the difference was statistically significant (for CEA p = 0.005, for CA19-9 p = 0.039). At time of diagnosis 50.6% of the patients had elevated serum levels of CEA and 29.6% of CA19-9. In combination of both antigens this elevation was in 54.3% of CRC patients. The common use of CEA and CA19-9 was more efficacious in identification of patients at high risk. The combination assay of CEA and CA19-9 did not cause a significant increase of sensitivity in diagnosis CRC.

Disrupting mitochondrial Ca2+ homeostasis causes tumor-selective TRAIL sensitization through mitochondrial network abnormalities.

PubMed

Ohshima, Yohei; Takata, Natsuhiko; Suzuki-Karasaki, Miki; Yoshida, Yukihiro; Tokuhashi, Yasuaki; Suzuki-Karasaki, Yoshihiro

2017-10-01

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent with high tumor-selective cytotoxicity. The congenital and acquired resistance of some cancer types including malignant melanoma and osteosarcoma impede the current TRAIL therapy of these cancers. Since fine tuning of the intracellular Ca2+ level is essential for cell function and survival, Ca2+ dynamics could be a promising target for cancer treatment. Recently, we demonstrated that mitochondrial Ca2+ removal increased TRAIL efficacy toward malignant melanoma and osteosarcoma cells. Here we report that mitochondrial Ca2+ overload leads to tumor-selective sensitization to TRAIL cytotoxicity. Treatment with the mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157 and oxidative phosphorylation inhibitor antimycin A and FCCP resulted in a rapid and persistent mitochondrial Ca2+ rise. These agents also increased TRAIL sensitivity in a tumor-selective manner with a switching from apoptosis to a nonapoptotic cell death. Moreover, we found that mitochondrial Ca2+ overload led to increased mitochondrial fragmentation, while mitochondrial Ca2+ removal resulted in mitochondrial hyperfusion. Regardless of their reciprocal actions on the mitochondrial dynamics, both interventions commonly exacerbated TRAIL-induced mitochondrial network abnormalities. These results expand our previous study and suggest that an appropriate level of mitochondrial Ca2+ is essential for maintaining the mitochondrial dynamics and the survival of these cells. Thus, disturbing mitochondrial Ca2+ homeostasis may serve as a promising approach to overcome the TRAIL resistance of these cancers with minimally compromising the tumor-selectivity.

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes.

PubMed

Nishita, Toshiho; Tomita, Yuichiro; Imanari, Takao; Ichihara, Nobutsune; Orito, Kensuke; Arishima, Kazuyoshi

2011-03-07

Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes. Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens. The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p<0.01). Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p<0.01). © 2011 Nishita et al; licensee BioMed Central Ltd.

Influence of dietary calcium level, calcium source, and phytase on bird performance and mineral digestibility during a natural necrotic enteritis episode.

PubMed

Paiva, D M; Walk, C L; McElroy, A P

2013-12-01

The objective of this study was to determine the influence of Ca source [highly soluble calcified seaweed (HSC) or limestone], phytase supplementation, and dietary levels of Ca on bird performance and mineral digestibility (Ca and P) during a necrotic enteritis (NE) episode. Cobb 500 male broilers were weighed and randomized into 8 treatment groups (9 pens/treatment; 30 birds/pen) at day of hatch. The 21-d trial was designed as a 2 × 2 × 2 factorial, which included 2 dietary levels of Ca (0.6 and 0.9%), 2 Ca sources (limestone or HSC), and 2 levels of an Escherichia coli phytase (0 or 1,000 FTU/kg). One unit of phytase (FTU) is defined as the quantity of enzyme that releases 1 μmol of inorganic phosphorus/min from 0.00015 mol/L of sodium phytate at pH 5.5 at 37° C. Birds were placed on used litter from a previous flock that exhibited clinical signs of NE. Birds and feed were weighed on d 7, 14, and 21, and BW gain, feed intake, and feed conversion were calculated for each of these periods and cumulatively. Mortality was recorded daily and pH of the gizzard and duodenum were measured on d 7, 14, and 21. Ileal digesta (8 birds/pen) was collected on d 7, 14, and 21. Significance is reported at P < 0.05. Birds began exhibiting clinical signs of NE on d 9, and elevated NE-associated mortality persisted until the end of the trial. Significantly higher mortality was observed when broilers were fed diets with 0.9% Ca from HSC compared with birds fed diets with 0.6% Ca, regardless of Ca source. Broilers fed 0.6% Ca diets supplemented with phytase were heavier than the other treatments regardless of Ca source. Broilers fed diets formulated with HSC had significantly higher feed conversion then broilers fed diets formulated with limestone. The gizzard of broilers fed 0.9% Ca in the diet was significantly less acidic than the gizzard of broilers fed 0.6% Ca in the diet. Broilers fed 0.6% Ca in diets supplemented with phytase showed significant improvements in P and Ca digestibility. In conclusion, higher dietary Ca (0.9% vs. 0.6%) had a negative effect on mortality associated with NE and on bird performance.

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 site of net absorption of Ca from the intestinal tract of growing pigs and effect of phytic acid, Ca level and Ca source on Ca digestibility.

PubMed

González-Vega, J Caroline; Walk, Carrie L; Liu, Yanhong; Stein, Hans H

2014-01-01

An experiment was conducted to test the hypothesis that the standardised digestibility of Ca in calcium carbonate and Lithothamnium calcareum Ca is not different regardless of the level of dietary Ca, and that phytic acid affects the digestibility of Ca in these two ingredients to the same degree. The objectives were to determine where in the intestinal tract Ca absorption takes place and if there are measurable quantities of basal endogenous Ca fluxes in the stomach, small intestine or large intestine. Diets contained calcium carbonate or L. calcareum Ca as the sole source of Ca, 0% or 1% phytic acid and 0.4% or 0.8% Ca. A Ca-free diet was also formulated and used to measure endogenous fluxes and losses of Ca. Nine growing pigs (initial body weight 23.8 ± 1.3 kg) were cannulated in the duodenum and in the distal ileum, and faecal, ileal and duodenal samples were collected. Duodenal endogenous fluxes of Ca were greater (p < 0.05) than ileal endogenous fluxes and total tract endogenous losses of Ca, but ileal endogenous fluxes were less (p < 0.05) than total tract endogenous losses. Standardised digestibility of Ca was not affected by the level of phytic acid, but decreased (p < 0.05) as Ca level increased in L. calcareum Ca diets, but that was not the case if calcium carbonate was the source of Ca (interaction, p < 0.05). The standardised duodenal digestibility (SDD), standardised ileal digestibility (SID) and standardised total tract digestibility (STTD) of Ca were not different if calcium carbonate was the source of dietary Ca. However, the STTD of Ca in L. calcareum Ca was greater (p < 0.05) than the SID and SDD of Ca. The SDD, SID and STTD of Ca in calcium carbonate were greater (p < 0.05) than those of L. calcareum Ca. In conclusion, under the conditions of this experiment, standardised digestibility of Ca is not affected by the level of phytic acid, but may be affected by dietary Ca level depending on the Ca source. Calcium from calcium carbonate is mostly absorbed before the duodenum, but Ca from L. calcareum Ca is mostly absorbed in the jejunum and ileum.

Reactive oxygen species triggering systemic programmed cell death process via elevation of nuclear calcium ion level in tomatoes resisting tobacco mosaic virus.

PubMed

Li, Yang; Li, Qi; Hong, Qiang; Lin, Yichun; Mao, Wang; Zhou, Shumin

2018-05-01

Programmed cell death (PCD) plays a positive role in the systemic response of plants to pathogen resistance. It has been confirmed that local tobacco mosaic virus (TMV) infecting tomato leaves can induce systemic PCD process in root-tip tissues. But up to now the underlying physiological mechanisms are poorly understood. This study focused on the detailed investigation of the physiological responses of root-tip cells during the initiation of systemic PCD. Physiological, biochemical examination and cytological observation showed that 1 day post-inoculation (dpi) of TMV inoculation there was an increase in calcium fluorescence intensity in root tip tissue cells. Then at 2 dpi, 4 dpi, 8 dpi and 15 dpi, the fluorescence intensity of calcium ion continued to increase. However, at 5 dpi, the reactive oxygen species (ROS) began to accumulate in the root-tip cells. And finally at 20 dpi, the obvious PCD reaction was detected. In addition, the experimental results also showed that the above process involved the elevation of two types of intracellular Ca 2+ , including cytoplasmic calcium ([Ca 2+ ] cyt ) and nuclear calcium ([Ca 2+ ] nuc ). The [Ca 2+ ] cyt , as a pilot signal could lead to the subsequent elevation of intracellular ROS concentration. Then, the high levels of ROS stimulated an increase of [Ca 2+ ] nuc and eventually caused PCD reactions in the root-tip tissues. In particular, the high level of nuclear calcium is an essential mediator in systemic PCD of plants. Copyright © 2018 Elsevier B.V. All rights reserved.

In Silico Analysis of Expression Data for Identification of Genes Involved in Spatial Accumulation of Calcium in Developing Seeds of Rice

PubMed Central

Goel, Anshita; Gaur, Vikram S.; Arora, Sandeep; Gupta, Sanjay

2012-01-01

Abstract The calcium (Ca2+) transporters, like Ca2+ channels, Ca2+ ATPases, and Ca2+ exchangers, are instrumental for signaling and transport. However, the mechanism by which they orchestrate the accumulation of Ca2+ in grain filling has not yet been investigated. Hence the present study was designed to identify the potential calcium transporter genes that may be responsible for the spatial accumulation of calcium during grain filling. In silico expression analyses were performed to identify Ca2+ transporters that predominantly express during the different developmental stages of Oryza sativa. A total of 13 unique calcium transporters (7 from massively parallel signature sequencing [MPSS] data analysis, and 9 from microarray analysis) were identified. Analysis of variance (ANOVA) revealed differential expression of the transporters across tissues, and principal component analysis (PCA) exhibited their seed-specific distinctive expression profile. Interestingly, Ca2+ exchanger genes are highly expressed in the initial stages, whereas some Ca2+ ATPase genes are highly expressed throughout seed development. Furthermore, analysis of the cis-elements located in the promoter region of the subset of 13 genes suggested that Dof proteins play essential roles in regulating the expression of Ca2+ transporter genes during rice seed development. Based on these results, we developed a hypothetical model explaining the transport and tissue specific distribution of calcium in developing cereal seeds. The model may be extrapolated to understand the mechanism behind the exceptionally high level of calcium accumulation seen in grains like finger millet. PMID:22734689

High-fat diet-induced obesity leads to resistance to leptin-induced cardiomyocyte contractile response.

PubMed

Ren, Jun; Zhu, Bang-Hao; Relling, David P; Esberg, Lucy B; Ceylan-Isik, Asli F

2008-11-01

Levels of the obese gene product leptin are often elevated in obesity and may contribute to obesity-induced cardiovascular complications. However, the role of leptin in obesity-associated cardiac abnormalities has not been clearly defined. This study was designed to determine the influence of high-fat diet-induced obesity on cardiac contractile response of leptin. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix system in cardiomyocytes from adult rats fed low- and high-fat diets for 12 weeks. Cardiomyocyte contractile and intracellular Ca(2+) properties were examined including peak shortening, duration and maximal velocity of shortening/relengthening (TPS/TR(90), +/-dl/dt), Fura-2-fluorescence intensity change (DeltaFFI), and intracellular Ca(2+) decay rate (tau). Expression of the leptin receptor (Ob-R) was evaluated by western blot analysis. High-fat diet increased systolic blood pressure and plasma leptin levels. PS and +/-dl/dt were depressed whereas TPS and TR(90) were prolonged after high-fat diet feeding. Leptin elicited a concentration-dependent (0-1,000 nmol/l) inhibition of PS, +/-dl/dt, and DeltaFFI in low-fat but not high-fat diet-fed rat cardiomyocytes without affecting TPS and TR(90). The Janus kinase 2 (JAK2) inhibitor AG490, the mitogen-activated protein kinase (MAPK) inhibitor SB203580, and the nitric oxide synthase (NOS) inhibitor L-NAME abrogated leptin-induced cardiomyocyte contractile response in low-fat diet group without affecting the high-fat diet group. High-fat diet significantly downregulated cardiac expression of Ob-R. Elevation of extracellular Ca(2+) concentration nullified obesity-induced cardiomyocyte mechanical dysfunction and leptin-induced depression in PS. These data indicate presence of cardiac leptin resistance in diet-induced obesity possibly associated with impaired leptin receptor signaling.

Age and height distribution of holocene transgressive deposits in eastern North Island, New Zealand

USGS Publications Warehouse

Ota, Y.; Berryman, K.R.; Hull, A.G.; Miyauchi, T.; Iso, N.

1988-01-01

Holocene transgressive deposits are frequently exposed near the present-day coastline of the study area along eastern North Island, New Zealand. They occur in sites of former estuaries that were filled during the postglacial rise in sea level. We present one hundred radiocarbon dates of Holocene transgressive deposits from the study area, ranging in age from ca. 10,000 to 5500 yr B.P. Relative sea level curves up to ca. 6000 yr B.P. were reconstructed for six locations. The curves have similar slopes prior to about 7000 yr B.P., indicating that sea level rise was much more rapid than any tectonic uplift at that time. The postglacial rise in sea level in New Zealand is considered, in general, to have culminated at about 6500 yr B.P. but the upper limit ages of transgressive deposits in our study area vary from ca. 5500 to 7000 yr B.P. At sites where the uplift rate is high the postglacial transgression culminated rather earlier than ca. 6500 yr B.P., and at sites where there is subsidence or there is very low uplift the culmination is later than ca. 6500 yr B.P. Nine of fourteen dates from fossil trees in growth position, that grew in and were buried by estuarine silt, cluster in the age range ca. 8000-8400 yr B.P. These data support the view that there was a minor regression or stillstand in the eustatic sea level rise at that time. Eleven tectonic subregions are recognized in the study area on the basis of average uplift rate. Most of these subregions coincide with those established from the number and ages of younger Holocene marine terraces of probable coseismic origin. ?? 1988.

Trees grow on money: Urban tree canopy cover and environmental justice

Treesearch

Kirsten Schwarz; Michail Fragkias; Christopher G. Boone; Weiqi Zhou; Melissa McHale; J. Morgan Grove; Jarlath O' Neil-Dunne; Joseph P. McFadden; Geoffrey L. Buckley; Dan Childers; Laura Ogden; Stephanie Pincetl; Diane Pataki; Ali Whitmer; Mary L. Cadenasso; Steven Arthur Loiselle

2015-01-01

This study examines the distributional equity of urban tree canopy (UTC) cover for Baltimore, MD, Los Angeles, CA, New York, NY, Philadelphia, PA, Raleigh, NC, Sacramento, CA, and Washington, D.C. using high spatial resolution land cover data and census data. Data are analyzed at the Census Block Group levels using Spearman’s correlation, ordinary least squares...

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

PubMed

Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

2018-06-01

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Ionotropic NMDA receptor signaling is required for the induction of long-term depression in the mouse hippocampal CA1 region.

PubMed

Babiec, Walter E; Guglietta, Ryan; Jami, Shekib A; Morishita, Wade; Malenka, Robert C; O'Dell, Thomas J

2014-04-09

Previous studies have provided strong support for the notion that NMDAR-mediated increases in postsynaptic Ca(2+) have a crucial role in the induction of long-term depression (LTD). This view has recently been challenged, however, by findings suggesting that LTD induction is instead attributable to an ion channel-independent, metabotropic form of NMDAR signaling. Thus, to explore the role of ionotropic versus metabotropic NMDAR signaling in LTD, we examined the effects of varying extracellular Ca(2+) levels or blocking NMDAR channel ion fluxes with MK-801 on LTD and NMDAR signaling in the mouse hippocampal CA1 region. We find that the induction of LTD in the adult hippocampus is highly sensitive to extracellular Ca(2+) levels and that MK-801 blocks NMDAR-dependent LTD in the hippocampus of both adult and immature mice. Moreover, MK-801 inhibits NMDAR-mediated activation of p38-MAPK and dephosphorylation of AMPAR GluA1 subunits at sites implicated in LTD. Thus, our results indicate that the induction of LTD in the hippocampal CA1 region is dependent on ionotropic, rather than metabotropic, NMDAR signaling.

Comparing corn types for differences in cell wall characteristics and p-coumaroylation of lignin.

PubMed

Hatfield, Ronald D; Chaptman, Ann K

2009-05-27

This study was undertaken to compare cell wall characteristics including levels of p-coumarate (pCA) and lignin in corn (Zea mays L.) types. Five different types of corn, four commercial and Teosinte, were grown in the greenhouse in individual pots. For each corn type replicate stems were harvested at tassel emergence. Tissues for cell wall analysis were harvested from stems (separated into rind and pith tissues) and roots. Stem cell wall characteristics across the different corn types were similar for total neutral sugars, total uronosyls, lignin, and phenolic acids. However, the neutral sugar composition of root cell walls was markedly different, with high levels of galactose and arabinose. Levels of pCA in the different tissues ranged from 13.8 to 33.1 mg g(-1) of CW depending upon the type of tissue. There was no evidence that pCA was incorporated into cell walls attached to arabinoxylans. Lignin levels were similar within a given tissue, with pith ranging from 86.1 to 132.0 mg g(-1) of CW, rind from 178.4 to 236.6 mg g(-1) of CW, and roots from 216.5 to 242.6 mg g(-1) of CW. The higher values for lignins in root tissue may be due to suberin remaining in the acid-insoluble residue, forming Klason lignins. With the exception of root tissues, higher pCA levels accompanied higher lignin levels. This may indicate a potential role of pCA aiding lignin formation in corn cell walls during the lignification process.

Somatostatin promotes glucose generation of Ca2+oscillations in pancreatic islets both in the absence and presence of tolbutamide.

PubMed

Hellman, Bo; Dansk, Heléne; Grapengiesser, Eva

2018-06-01

Many cellular processes, including pulsatile release of insulin, are triggered by increase of cytoplasmic Ca 2+ . This study examines how somatostatin affects glucose generation of cytoplasmic Ca 2+ oscillations in mouse islets in absence and presence of tolbutamide blockade of the K ATP channels. Ca 2+ was measured with dual wavelength microflurometry in isolated islets loaded with the indicator Fura-2. Rise of glucose from 3 to 20 mM evoked introductory lowering of Ca 2+ prolonged by activation of somatostatin receptors. During continued superfusion exposure to somatostatin triggered oscillations mediated by periodic increase from the basal level (absence of tolbutamide) or by periodic interruption of an elevated level (presence of tolbutamide). In the latter situation the oscillations were transformed into sustained elevation by activation of muscarinic receptors (acetylcholine) or increase of cyclic AMP (IBMX, 8-bromo-cyclic AMP, forskolin). The observed effect of cyclic AMP raises the question whether high proportions of the glucagon-producing α-cells promote steady-state elevation of Ca 2+ . In support for this idea somatostatin was found to trigger glucose-induced Ca 2+ oscillations essentially in small islets that contain very few α-cells. The results indicate that somatostatin promotes glucose generation of Ca 2+ oscillations with similar characteristics both in the absence and presence of functional K ATP channels. Copyright © 2018. Published by Elsevier Ltd.

Mechanical properties, biocompatibility, and biodegradation of cross-linked cellulose acetate-reinforced polyester composites.

PubMed

Wu, Chin-San

2014-05-25

Composites of treated (cross-linked) cellulose acetate (t-CA) and acrylic acid-grafted poly(hydroxyalkanoate) (PHA-g-AA/t-CA) exhibited noticeably superior mechanical properties compared with PHA/CA composites due to greater compatibility between the two components. The dispersion covering of t-CA in the PHA-g-AA matrix was highly homogeneous as a result of condensation reactions. Human lung fibroblasts (FBs) were seeded on these two series of composites to characterize the biocompatibility properties. In a time-dependent course, the FB proliferation results demonstrated higher performance from the PHA/CA series of composites than from the PHA-g-AA/t-CA composites. The water resistance of PHA-g-AA/t-CA was higher than that of PHA/CA, although the weight loss of both composites buried in Acetobacter pasteurianus (A. pasteurianus) indicated that they were both biodegradable, especially at higher levels of cellulose acetate substitution. The PHA/CA and PHA-g-AA/t-CA composites were more biodegradable than pure PHA, implying a strong connection between cellulose acetate content and biodegradability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Melatonin inhibits voltage-sensitive Ca(2+) channel-mediated neurotransmitter release.

PubMed

Choi, Tae-Yong; Kwon, Ji Eun; Durrance, Eunice Sung; Jo, Su-Hyun; Choi, Se-Young; Kim, Kyong-Tai

2014-04-04

Melatonin is involved in various neuronal functions such as circadian rhythmicity and thermoregulation. Melatonin has a wide range of pharmacologically effective concentration levels from the nanomolar to millimolar levels. Recently, the antiepileptic effect of high dose melatonin has been the focus of clinical studies; however, its detailed mechanism especially in relation to neurotransmitter release and synaptic transmission remains unclear. We studied the effect of melatonin at high concentrations on the neurotransmitter release by monitoring norepinephrine release in PC12 cells, and excitatory postsynaptic potential in rat hippocampal slices. Melatonin inhibits the 70mM K(+)-induced Ca(2+) increase at millimolar levels without effect on bradykinin-triggered Ca(2+) increase in PC12 cells. Melatonin (1mM) did not affect A2A adenosine receptor-evoked cAMP production, and classical melatonin receptor antagonists did not reverse the melatonin-induced inhibitory effect, suggesting G-protein coupled receptor independency. Melatonin inhibits the 70mM K(+)-induced norepinephrine release at a similar effective concentration range in PC12 cells. We confirmed that melatonin (100µM) inhibits excitatory synaptic transmission of the hippocampal Schaffer collateral pathway with the decrease in basal synaptic transmission and the increase in paired pulse ratio. These results show that melatonin inhibits neurotransmitter release through the blocking of voltage-sensitive Ca(2+) channels and suggest a possible mechanism for the antiepileptic effect of melatonin. Copyright © 2014 Elsevier B.V. All rights reserved.

Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs

PubMed Central

Yu, Byung-Sik; Na, Duck-Mi; Kang, Mi-Young

2009-01-01

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 µg/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 µM) and McN-A-343 (100 µM). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 µg/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 µM), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 µM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 µg/ml) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 µg/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase. PMID:20054501

All‐optical functional synaptic connectivity mapping in acute brain slices using the calcium integrator CaMPARI

PubMed Central

Sha, Fern; Johenning, Friedrich W.; Schreiter, Eric R.; Looger, Loren L.; Larkum, Matthew E.

2016-01-01

Key points The genetically encoded fluorescent calcium integrator calcium‐modulated photoactivatable ratiobetric integrator (CaMPARI) reports calcium influx induced by synaptic and neural activity. Its fluorescence is converted from green to red in the presence of violet light and calcium.The rate of conversion – the sensitivity to activity – is tunable and depends on the intensity of violet light.Synaptic activity and action potentials can independently initiate significant CaMPARI conversion.The level of conversion by subthreshold synaptic inputs is correlated to the strength of input, enabling optical readout of relative synaptic strength.When combined with optogenetic activation of defined presynaptic neurons, CaMPARI provides an all‐optical method to map synaptic connectivity. Abstract The calcium‐modulated photoactivatable ratiometric integrator (CaMPARI) is a genetically encoded calcium integrator that facilitates the study of neural circuits by permanently marking cells active during user‐specified temporal windows. Permanent marking enables measurement of signals from large swathes of tissue and easy correlation of activity with other structural or functional labels. One potential application of CaMPARI is labelling neurons postsynaptic to specific populations targeted for optogenetic stimulation, giving rise to all‐optical functional connectivity mapping. Here, we characterized the response of CaMPARI to several common types of neuronal calcium signals in mouse acute cortical brain slices. Our experiments show that CaMPARI is effectively converted by both action potentials and subthreshold synaptic inputs, and that conversion level is correlated to synaptic strength. Importantly, we found that conversion rate can be tuned: it is linearly related to light intensity. At low photoconversion light levels CaMPARI offers a wide dynamic range due to slower conversion rate; at high light levels conversion is more rapid and more sensitive to activity. Finally, we employed CaMPARI and optogenetics for functional circuit mapping in ex vivo acute brain slices, which preserve in vivo‐like connectivity of axon terminals. With a single light source, we stimulated channelrhodopsin‐2‐expressing long‐range posteromedial (POm) thalamic axon terminals in cortex and induced CaMPARI conversion in recipient cortical neurons. We found that POm stimulation triggers robust photoconversion of layer 5 cortical neurons and weaker conversion of layer 2/3 neurons. Thus, CaMPARI enables network‐wide, tunable, all‐optical functional circuit mapping that captures supra‐ and subthreshold depolarization. PMID:27861906

Silencing of the CaCP Gene Delays Salt- and Osmotic-Induced Leaf Senescence in Capsicum annuum L.

PubMed Central

Xiao, Huai-Juan; Yin, Yan-Xu; Chai, Wei-Guo; Gong, Zhen-Hui

2014-01-01

Cysteine proteinases have been known to participate in developmental processes and in response to stress in plants. Our present research reported that a novel CP gene, CaCP, was involved in leaf senescence in pepper (Capsicum annuum L.). The full-length CaCP cDNA is comprised of 1316 bp, contains 1044 nucleotides in open reading frame (ORF), and encodes a 347 amino acid protein. The deduced protein belongs to the papain-like cysteine proteases (CPs) superfamily, containing a highly conserved ERFNIN motif, a GCNGG motif and a conserved catalytic triad. This protein localized to the vacuole of plant cells. Real-time quantitative PCR analysis revealed that the expression level of CaCP gene was dramatically higher in leaves and flowers than that in roots, stems and fruits. Moreover, CaCP transcripts were induced upon during leaf senescence. CaCP expression was upregulated by plant hormones, especially salicylic acid. CaCP was also significantly induced by abiotic and biotic stress treatments, including high salinity, mannitol and Phytophthora capsici. Loss of function of CaCP using the virus-induced gene-silencing technique in pepper plants led to enhanced tolerance to salt- and osmotic-induced stress. Taken together, these results suggest that CaCP is a senescence-associated gene, which is involved in developmental senescence and regulates salt- and osmotic-induced leaf senescence in pepper. PMID:24823878

Calcium in Gravitropism of the Moss Pohlia nutans (Hedw.) Lindb. protonemata

NASA Astrophysics Data System (ADS)

Khorkavtsiv, O. Ya; Demkiv, O. T.; Khorkavtsiv, Ya. D.

Protonemata of mosses of Pohlia nutans grow both by extension and division of single apical cells which are negatively gravitropic in darkness. The fluorescence of Ca2+ increased in the tip of apical cells from the first hours of gravitropism stimulation. Cytochemical investigations confirmed the existence of a well pronounced tip-to-base Ca2+-gradient, its formation being favoured by localization of calcium influx in the tip of the apical cell. Measurement of the cytochemical reaction intensity showed that the level of Ca2+-ATFase activity is low in apex and increases towards the base of the apical cell. The gravitropic protonemata and filaments which grew on the clinostat showed similar distributions of the Ca2+ and Ca2+-ATFase activity along the apical cell axis. Thus, these data demonstrate that growing apical cells of gravitropic protonemata have a high tip-to-base Ca2+ gradient, the Ca2+ transport being afforded by Ca2+-ATFase.

CA19-9 serum levels predict micrometastases in patients with gastric cancer

PubMed Central

Potrc, Stojan; Mis, Katarina; Plankl, Mojca; Mars, Tomaz

2016-01-01

Abstract Background We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases. PMID:27247553

Combined Raman and SEM study on CaF2 formed on/in enamel by APF treatments.

PubMed

Tsuda, H; Jongebloed, W L; Stokroos, I; Arends, J

1993-01-01

Raman spectra containing the distinct band at 322 cm-1 due to CaF2 or CaF2-like material formed in/on fluoridated bovine enamel were recorded using a micro-Raman spectrograph. Due to increasing levels of background fluorescence with increasing thickness of enamel, the Raman measurements were carried out on thin regions of wedged enamel sections. The distribution of the CaF2 or CaF2-like material was estimated using a simple model. The results indicate that 1/3 of the total CaF2 was concentrated within the narrow depth < 2 microns with high CaF2 concentrations (> 10 wt%), and that the majority of the CaF2 was distributed over the depths up to 26 microns (1 wt% CaF2). SEM observations on fractured fluoridated enamel confirmed that morphological changes were present in the depth range comparable to that of the high CaF2 concentration region expected from the Raman analysis. In deeper regions where lower concentration (< 10%) but a large amount of CaF2 was still expected, the SEM images failed to distinguish between the normal and fluoridated enamel. After KOH treatment, the Raman spectra did not show evidence of the CaF2 peak and the SEM micrographs also confirmed the removal of globules. The peak position of the Raman band of the CaF2 formed by the fluoridation was identical to that of pure CaF2. However, the linewidth was 23 cm-1 (FWHM) and a factor of 2 broader than that of pure CaF2 (12 cm-1). This implies that the lattice dynamics of the CaF2 formed by fluoridation is different from of pure CaF2, and that the material formed is 'CaF2-like' or 'disordered CaF2'.

A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

PubMed

Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

2014-01-01

The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover.

Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Antwi, Samuel O; Steck, Susan E; Su, L Joseph; Hébert, James R; Zhang, Hongmei; Fontham, Elizabeth T H; Smith, Gary J; Bensen, Jeannette T; Mohler, James L; Arab, Lenore

2015-09-01

Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend)  = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend)  = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend)  = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend)  = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)]. The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. © 2015 Wiley Periodicals, Inc.

Involvement of plasma membrane-located calmodulin in the response decay of cyclic nucleotide-gated cation channel of cultured carrot cells.

PubMed

Kurosaki, F; Kaburaki, H; Nishi, A

1994-03-07

Increase in cytoplasmic cyclic AMP concentration stimulates Ca2+ influx through the cyclic AMP-gated cation channel in the plasma membrane of cultured carrot cells. However, the Ca2+ current terminated after a few minutes even in the presence of high concentrations of cyclic AMP indicating that hydrolysis of the nucleotide is not responsible for stop of the Ca2+ influx. Cyclic AMP evoked discharge of Ca2+ from inside-out sealed vesicles of carrot plasma membrane, and it was strongly inhibited when the suspension of the vesicles was supplemented with 1 microM of free Ca2+, while Ca2+ lower than 0.1 microM did not affect the Ca(2+)-release. The Ca2+ flux across plasma membrane was restored from this Ca(2+)-induced inhibition by the addition of calmodulin inhibitors or anti-calmodulin. These results suggest that Ca2+ influx initiated by the increase in intracellular cAMP in cultured carrot cells is terminated when the cytosolic Ca2+ concentration reaches the excitatory level in the cells, and calmodulin located in the plasma membrane plays an important role in the response decay of the cyclic nucleotide-gated Ca2+ channel.

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

PubMed

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

2014-01-01

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

Functional reconstitution of an ATP-driven Ca sup 2+ -transport system from the plasma membrane of Commelina communis L

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

Graef, P.; Weiler, E.W.

1990-10-01

The protein(s) that constitute(s) the ATP-driven Ca{sup 2+}-translocator of plasma membrane enriched vesicles obtained by aqueous two-phase partitioning from leaves of Commelina communis L. has/have been solubilized and reincorporated into tightly sealed liposomes. The reconstituted Ca{sup 2+}-transport system was studied using ATP-driven {sup 45}Ca{sup 2+} import into the proteoliposomes as a measure of activity. The detergent, 3- ((3-cholamidopropyl) dimethylammonio) -1-propane-sulfonate proved to be the most suitable and was used at 10 millimolar concentration, i.e. just above its critical micellar concentration. The presence of additional phospholipid and ATP improved the solubilization and/or reconstitution. The characteristics of the reconstituted system were similarmore » to those of the plasma membrane-bound activity, including the apparent K{sub m} for Ca{sup 2+} inhibition by relatively high levels of vanadate and lacking response to added calmodulin. The reconstituted transport system was very strongly inhibited by erythrosine B and had a low apparent K{sub m} for ATP levels of the Ca{sup 2+}-ionophore A 23187 instantaneously discharged 90% of the Ca{sup 2+} associated with the vesicles, proving that it had been accumulated in the intravesicular volume in soluble, freely exchangeable form. Ca{sup 2+}-transport in the reconstituted system was thus primary active, through a Ca{sup 2+}-translocating ATPase.« less

Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways.

PubMed

Conigrave, Arthur D; Ward, Donald T

2013-06-01

In this article we consider the mechanisms by which the calcium-sensing receptor (CaSR) induces its cellular responses via the control (activation or inhibition) of signaling pathways. We consider key features of CaSR-mediated signaling including its control of the heterotrimeric G-proteins Gq/11, Gi/o and G12/13 and the downstream consequences recognizing that very few CaSR-mediated cell phenomena have been fully described. We also consider the manner in which the CaSR contributes to the formation of specific signaling scaffolds via peptide recognition sequences in its intracellular C-terminal along with the origins of its high level of cooperativity, particularly for Ca(2+)o, and its remarkable resistance to desensitization. We also consider the nature of the mechanisms by which the CaSR controls oscillatory and sustained Ca(2+)i mobilizing responses and inhibits or elevates cyclic adenosine monophosphate (cAMP) levels dependent on the cellular and signaling context. Finally, we consider the diversity of the receptor's ligands, ligand binding sites and broader compartment-dependent physiological roles leading to the identification of pronounced ligand-biased signaling for agonists including Sr(2+) and modulators including l-amino acids and the clinically effective calcimimetic cinacalcet. We note the implications of these findings for the development of new designer drugs that might target the CaSR in pathophysiological contexts beyond those established for the treatment of disorders of calcium metabolism. Copyright © 2013 Elsevier Ltd. All rights reserved.

Strong Nanocomposites with Ca, PO4, and F Release for Caries Inhibition

PubMed Central

Xu, H.H.K.; Weir, M.D.; Sun, L.; Moreau, J.L.; Takagi, S.; Chow, L.C.; Antonucci, J.M.

2010-01-01

This article reviews recent studies on: (1) the synthesis of novel calcium phosphate and calcium fluoride nanoparticles and their incorporation into dental resins to develop nanocomposites; (2) the effects of key microstructural parameters on Ca, PO4, and F ion release from nanocomposites, including the effects of nanofiller volume fraction, particle size, and silanization; and (3) mechanical properties of nanocomposites, including water-aging effects, flexural strength, fracture toughness, and three-body wear. This article demonstrates that a major advantage of using the new nanoparticles is that high levels of Ca, PO4, and F release can be achieved at low filler levels in the resin, because of the high surface areas of the nanoparticles. This leaves room in the resin for substantial reinforcement fillers. The combination of releasing nanofillers with stable and strong reinforcing fillers is promising to yield a nanocomposite with both stress-bearing and caries-inhibiting capabilities, a combination not yet available in current materials. PMID:19948941

Effect of poultry decontaminants concentration on growth kinetics for pathogenic and spoilage bacteria.

PubMed

del Río, Elena; González de Caso, Beatriz; Prieto, Miguel; Alonso-Calleja, Carlos; Capita, Rosa

2008-10-01

Various chemical compounds are currently under review for final approval as poultry decontaminants in the European Union (EU). Concentration is among the factors considered by the EU authorities in the evaluation of these treatments. The aim of this research was to compare the growth parameters for pathogenic and spoilage bacteria in presence of high and low concentrations of poultry decontaminants to assess whether such treatments could involve a potential sanitary risk for consumers. Growth curves for Salmonella enterica serotype Enteritidis, Listeria monocytogenes, Pseudomonas fluorescens and Brochothrix thermosphacta were obtained at different levels of trisodium phosphate (TSP; 1.74%; 0.58%), acidified sodium chlorite (ASC; 210 ppm; 70 ppm) and citric acid (CA; 0.27%; 0.09%). The modified Gompertz equation was used as primary model to fit observed data. ASC and TSP were the most effective compounds in increasing lag phase (L) and reducing maximum growth rate (mu) in Gram-negative bacteria. Gram-positive bacteria were more influenced by CA. At high TSP levels, mu for Salmonella decreased. Low TSP levels increased mu for Salmonella and Listeria relative to control samples. In presence of 0.27% CA, Brochothrix showed the highest L and the lowest mu among strains tested. These results suggest that low TSP and high CA concentrations could favour the outgrowth of pathogenic bacteria (e.g. Salmonella) relative to spoilage bacteria, rending these treatments potentially dangerous for consumers. The findings of this study may be useful to the EU authorities and meat processors in their efforts to select adequate treatments for control of bacteria on poultry.

Auto-luminescent genetically encoded ratiometric indicator for real-time Ca2+ imaging at the single cell level

NASA Astrophysics Data System (ADS)

Saito, Kenta; Kobayashi, Kentaro; Nagai, Takeharu

2011-12-01

Efficient bioluminescence resonance energy transfer (BRET) from a bioluminescent protein to a fluorescent protein with high fluorescent quantum yield has been utilized to enhance luminescence intensity, allowing single-cell imaging in near real time without external light illumination. We have applied this strategy to develop an autoluminescent Ca2+ indicator, BRAC, which is composed of Ca2+-binding protein, calmodulin, and its target peptide, M13, sandwiched between a yellow fluorescent protein variant, Venus, and an enhanced Renilla luciferase, RLuc8. With this BRAC, we succeeded visualization of Ca2+ dynamics at the single-cell level with temporal resolution at 1 Hz. Moreover, BRAC signals were acquired by ratiometric imaging capable of canceling out Ca2+-independent signal drifts due to change in cell shape, focus shift, etc. Taking advantage of the bioluminescence imaging property that does not require external excitation light, BRAC might become a powerful tool applicable in conjunction with so-called optogenetic technology by which we can control cellular and protein function by light illumination.

Optimization of Submerged Cultivation Conditions for Production of Big Cup Culinary-Medicinal Mushroom Clitocybe maxima (Agaricomycetes) Biomass with Significant Antioxidative and Antihyperlipidemic Activities.

PubMed

Hu, Shu-Hui; Chen, Ker-Shew; Liu, Ming-Yi; Cheung, Peter Chi Keung; Wang, Jinn-Chyi; Chang, Sue-Joan

2017-01-01

In this study, a large Clitocybe maxima mycelium biomass was obtained by submerged cultivation under optimal conditions. Three test samples from lyophilized mycelia, including hot water extract (CW) and elutes from solvents with different polarity (CA and CB), were combined and used to explore antioxidant and antihyper-lipidemic activities in vitro and in vivo. The CA group showed the highest DPPH free radical scavenging activity and iron-reducing capability at concentrations of 6.0% and 3.0% (w/v), respectively. Further, the CA group showed the highest glutathione peroxidase and superoxide dismutase activities at a dose of 0.25 mg/kg body weight (CA-0.25 group) in all hyperlipidemic hamsters tested. Serum lipid levels (apart from high-density lipoprotein cholesterol levels) of hamsters in the CA-0.25 group were lower than those of hamsters in the negative control group in antihy-perlipidemic tests. Therefore, we believe that extracts from C. maxima mycelia are rich reservoirs of antioxidant and antihyperlipidemic activities.

Mineral and sensory profile of seasoned cracked olives packed in diverse salt mixtures.

PubMed

Moreno-Baquero, J M; Bautista-Gallego, J; Garrido-Fernández, A; López-López, A

2013-05-01

This work studies the effect of packing cracked seasoned olives with NaCl, KCl, and CaCl(2) mixture brines on their mineral nutrients and sensory attributes, using RSM methodology. The Na, K, Ca, and residual natural Mn contents in flesh as well as saltiness, bitterness and fibrousness were significantly related to the initial concentrations of salts in the packing solution. This new process led to table olives with a significantly lower sodium content (about 31%) than the traditional product but fortified in K and Ca. High levels of Na and Ca in the flesh led to high scores of acidity and saltiness (the first descriptor) and bitterness (the second) while the K content was unrelated to any sensory descriptor. The new presentations using moderate proportions of alternative salts will therefore have improved nutritional value and healthier characteristics but only a slightly modified sensory profile. Copyright © 2012 Elsevier Ltd. All rights reserved.

High Resolution Glacial-interglacial Climatic Variations in the South China Sea during the Last 220,000 Years

NASA Astrophysics Data System (ADS)

Huang, K.; You, C.; Li, M.; Shieh, Y.

2002-12-01

The Asian monsoon plays an important role of both regional and global climatic variations. The South China Sea (SCS) located between Southeast Asia continent and Western Pacific Ocean is an ideal place for studying oceanographic responses and changes of monsoon system in the past. Planktonic foraminiferal shells separated from two deep sea cores, ODP Site 1144 and SCS 15B, located near the northeast continental slope and the central ocean basin respectively were used to reconstruct high-resolution climatic records during the last 220 kyrs. Average of 20 individual foraminiferal shells were hand picked and cleaned thoroughly for high precision trace element/calcium ratios (i.e., Mg/Ca, Sr/Ca, and Ba/Ca) determination using a Thermo-Fannigan Element II ICP-MS installed at NCKU. Isotopic compositions of oxygen, carbon, boron and strontium also were measured by stable isotope ratio or Triton TI thermal ionization mass spectrometer. Mg/Ca and Sr/Ca in foraminiferal shells are sensitive proxies for sea surface temperature, chemical weathering and hydrothermal activity on seafloor. The SCS foraminiferal shells Mg/Ca and Sr/Ca show negative correlation with interesting glacial-interglacial variations. The calculated Mg/Ca SSTs varied as large as 6-7 °C with the highest temperature occurred at oxygen stage 5. The Sr/Ca ratios change about 16 % (1.200-1.429 mmole/mole), possibly a result of periodic sea level changes which influencing terrigenous inputs or continental shelves weathering. On the other hand, the Ba/Ca display large variations (0.031-0.117 mmole/mole), possibly reflecting upwelling intensity or SCS bottom water chemistry. The boron isotopic compositions in planktonic foraminiferal shells are used to estimate pH in the surface ocean. Combining these proxies, high-resolution oceanic environmental records in the SCS were reconstructed for the last 220 kyrs. The results obtained from the SCS can be used to gain a better understanding of land-sea interaction in this region.

Utilization of fluidized bed material as a calcium and sulfur source for apples

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

Korcak, R.F.

1984-01-01

Fluidized bed material (FBM), a dry, high Ca, alkaline waste product which results from combining coal and limestone, was used as a Ca or S source or lime substitute in an established apple orchard (Malus domestica Borkh., cv. York Imperial) over a four year period. Treatment comparisons were made between FBM was applied at one or two times (1x or 2x) the soil lime requirement and CaCO/sub 3/ applied at the lime requirement (1x). Additionally, FBM 1x was compared to a combination treatment consisting of CaCO/sub 3/ plus gypsum to apply similar amounts of Ca and S. All treatments weremore » also compared to an untreated control. No significant treatment comparisons were noted on leaf Ca levels, however, leaf Mg significantly decreased when FBM applied at the 1x or 2x level compared to CaCO/sub 3/ 1x. When FBM was compared with CaCO/sub 3/ plus gypsum there was a significant decrease in leaf Ca with FBM but no difference in leaf Mg. These effects were probably due to either a solubility difference between nutrients or to actual amount of Mg applied by the different sources. Leaf S levels were unaffected by treatments. Yields, fresh fruit weight and the incidence of cork spot were little affected by treatments. Soil extractable Mg, 1N NH/sub 4/Ac, was not a good prediction of leaf Mg content or Mg added to the soil. Only soil Al was significantly reduced, compared to the control, by the treatments among the metals studied (Zn, Mn, Cu, Cd, Pb and Al). FBM applied at twice the lime requirement (wt. basis) resulted in similar soil pH to CaCO/sub 3/ applied at the lime requirement. 14 references, 6 figures, 1 table.« less

Regulation of Bicarbonate Secretion in Marine Fish Intestine by the Calcium-Sensing Receptor.

PubMed

Gregório, Sílvia F; Fuentes, Juan

2018-04-04

In marine fish, high epithelial intestinal HCO₃ − secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR) in the regulation of HCO₃ − secretion in the intestine of the sea bream ( Sparus aurata L.). Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine. CaSR expression reflected intestinal fluid calcium concentration. In addition, anterior intestine tissue was mounted in Ussing chambers to test the putative regulation of HCO₃ − secretion in vitro using the anterior intestine. HCO₃ − secretion was sensitive to varying calcium levels in luminal saline and to calcimimetic compounds known to activate/block the CaSR i.e., R 568 and NPS-2143. Subsequent experiments were performed in intestinal sacs to measure water absorption and the sensitivity of water absorption to varying luminal levels of calcium and calcimimetics were exposed as well. It appears, that CaSR mediates HCO₃ − secretion and water absorption in marine fish as shown by responsiveness to calcium levels and calcimimetic compounds.

Regulation of sugar transport and metabolism by the Candida albicans Rgt1 transcriptional repressor.

PubMed

Sexton, Jessica A; Brown, Victoria; Johnston, Mark

2007-10-01

The ability of the fungal pathogen Candida albicans to cause systemic infections depends in part on the function of Hgt4, a cell surface sugar sensor. The orthologues of Hgt4 in Saccharomyces cerevisiae, Snf3 and Rgt2, initiate a signalling cascade that inactivates Rgt1, a transcriptional repressor of genes encoding hexose transporters. To determine whether Hgt4 functions similarly through the C. albicans orthologue of Rgt1, we analysed Cargt1 deletion mutants. We found that Cargt1 mutants are sensitive to the glucose analogue 2-deoxyglucose, a phenotype probably due to uncontrolled expression of genes encoding glucose transporters. Indeed, transcriptional profiling revealed that expression of about two dozen genes, including multiple HGT genes encoding hexose transporters, is increased in the Cargt1 mutant in the absence of sugars, suggesting that CaRgt1 represses expression of several HGT genes under this condition. Some of the HGT genes (probably encoding high-affinity transporters) are also repressed by high levels of glucose, and we show that this repression is mediated by CaMig1, the orthologue of the major glucose-activated repressor in S. cerevisiae, but not by its paralogue CaMig2. Therefore, CaRgt1 and CaMig1 collaborate to control expression of C. albicans hexose transporters in response to different levels of sugars. We were surprised to find that CaRgt1 also regulates expression of GAL1, suggesting that regulation of galactose metabolism in C. albicans is unconventional. Finally, Cargt1 mutations cause cells to hyperfilament, and suppress the hypofilamented phenotype of an hgt4 mutant, indicating that the Hgt4 glucose sensor may affect filamentation by modulating sugar import and metabolism via CaRgt1. Copyright 2007 John Wiley & Sons, Ltd.

Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers.

PubMed

Roux, S; Baudoin, C; Boute, D; Brazier, M; De La Guéronniere, V; De Vernejoul, M C

2004-01-01

To compare the effects of 2 drinking waters containing similar calcium (Ca) concentration in order to analyze the role of ions other than Ca on bone metabolism. These mineral drinking-waters differed by their mineral composition primarily concerning the concentration of bicarbonate (HCO3-), high in the HB, and sulfate, high in HS water. Of 60 included women, 39 completed the study. Patients were randomly assigned to an intake of 1 liter per day of mineral water HB or HS for 28 d, followed by cross-over to the alternative drinking-water for a further 28 d. At baseline and after each period of one month, Ca metabolism parameters, acid-base status, and bone remodeling markers were measured. Changes in Ca metabolism were significant in the HB group where the ionized Ca increased and the PTH decreased. Serum pH showed a similar increase whatever the used drinking water compared to baseline. In the HB group, significant increase in urine pH, and significant decrease in AT-HCO3- and NH4+ were observed. Bone resorption markers, urinary CTx/Cr, Pyr/Cr, and D-Pyr/Cr, significantly decreased in the HB group compared to baseline, and were not significantly modified in the HS group. These results showed a beneficial effect of the bicarbonaterich HB water on bone metabolism. This may account for a better bioavailability of the Ca, a greater alkalinization, and a larger decrease in PTH level secondary to a higher ionized Ca level. The higher content of silica in HB water may have also participated to the positive action on bone balance that was observed. In this short term study, these data underlined the potential role of the mineral drinking water composition on bone metabolism.

Antioxidant response and carboxylate metabolism in Brassica rapa exposed to different external Zn, Ca, and Mg supply.

PubMed

Blasco, Begoña; Graham, Neil S; Broadley, Martin R

2015-03-15

Zinc (Zn), calcium (Ca), and magnesium (Mg) malnutrition are common deficiencies in many developed and developing countries, resulting in a widespread health problem. Biofortification of food crops is an agricultural strategy that can be used to increase the levels of these elements in the edible portions of crops. Deficiency or toxicity of these cations in soils reduces plant growth, crop yield, and the quality of plant foodstuff. The aim of this study was to investigate the effect of external Zn, Ca, and Mg supply on accumulation and distribution of this elements as well as antioxidant response and organic acid composition of Brassica rapa ssp. trilocularis line R-o-18. Plants were grown at low Zn (0.05 μM Zn) and high Zn (500 μM Zn), low Ca (0.4 mM) and high Ca (40 mM), and low Mg (0.2 mM), and high Mg (20 mM) to simulate deficiency and toxicity conditions. Larger shoot biomass reductions were observed under high Zn, Ca and Mg treatments, and superoxide dismutase (SOD), ascorbate peroxidase (APX), H2O2, malondialdehyde (MDA), and total ascorbate (AA) showed a marked increase in these treatments. Therefore, Brassica plants might be more sensitive to excess of these elements in the nutrient solution. The translocation factor (TF) and distribution coefficient (DC) values of Zn, Ca, and Mg indicated higher translocation and accumulation in deficient conditions. High biosynthesis and citrate content in Brassica plants may be associated mainly with a high-nutrient solution extraction ability of these plants. These results provide background data, which will be used to characterize TILLING mutants to study the effects of mutations in genes involved in regulating Zn, Ca, and Mg distribution and accumulation in plants. Copyright © 2014 Elsevier GmbH. All rights reserved.

Study of grain boundary transparency in (Y b1 -xC ax) B a2C u3O bicrystal thin films over a wide temperature, field, and field orientation range

NASA Astrophysics Data System (ADS)

Li, Pei; Abraimov, Dmytro; Polyanskii, Anatolii; Kametani, Fumitake; Larbalestier, David

2015-03-01

The residual low-angle grain boundary (GB) network is still the most important current-limiting mechanism operating in biaxially textured rare-earth barium-copper-oxide (REBCO) coated conductors. While Ca doping is well established to improve supercurrent flow across low-angle GBs in weak fields at high temperatures, Ca doping also depresses Tc, making it so far impractical for high-temperature applications of REBCO coated conductors. On the other hand, high-field-magnet applications of REBCO require low temperatures. Here we systematically evaluate the effectiveness of Ca doping in improving the GB transparency, rGB=JcGB/ Jcgrain , of low-angle Y b1 -xC axBaCuO [001] tilt bicrystal films down to 10 K and with magnetic fields perpendicular and parallel to the film surfaces, while varying the Ca and oxygen doping level. Using low-temperature scanning laser microscopy and magneto-optical imaging, we found rGB to strongly depend on the angle between magnetic field and the GB plane and clearly identified regimes in which JcGB can exceed Jcgrain(rGB>1 ) where the GB pinning is optimized by the field being parallel to the GB dislocations. However, even in this favorable situation, we found that rGB became much smaller at lower temperatures. Calculations of the GB Ca segregation profile predict that the high-Jc channels between the GB dislocation cores are almost Ca free. It may be therefore that the positive effects of Ca doping seen by many authors near Tc are partly a consequence of the higher Tc of these Ca-free channels.

Hydrophobic Peptides Affect Binding of Calmodulin and Ca2+ as Explored by H/D Amide Exchange and Mass Spectrometry

PubMed Central

Sperry, Justin B.; Huang, Richard Y-C.; Zhu, Mei M.; Rempel, Don L.; Gross, Michael L.

2010-01-01

Calmodulin (CaM), a ubiquitous intracellular sensor protein, binds Ca2+ and interacts with various targets as part of signal transduction. Using hydrogen/deuterium exchange (H/DX) and a high resolution PLIMSTEX (Protein-Ligand Interactions by Mass Spectrometry, Titration, and H/D Exchange) protocol, we examined five different states of calmodulin: calcium-free, calcium-loaded, and three states of calcium-loaded in the presence of either melittin, mastoparan, or skeletal myosin light-chain kinase (MLCK). When CaM binds Ca2+, the extent of HDX decreased, consistent with the protein becoming stabilized upon binding. Furthermore, Ca2+-saturated calmodulin exhibits increased protection when bound to the peptides, forming high affinity complexes. The protocol reveals significant changes in EF hands 1, 3, and 4 with saturating levels of Ca2+. Titration of the protein using PLIMSTEX provides the binding affinity of Ca2+ to calmodulin within previously reported values. The affinities of calmodulin to Ca2+ increase by factors of 300 and 1000 in the presence of melittin and mastoparan, respectively. A modified PLIMSTEX protocol whereby the protein is digested to component peptides gives a region-specific titration. The titration data taken in this way show a decrease in the root mean square fit of the residuals, indicating a better fit of the data. The global H/D exchange results and those obtained in a region-specific way provide new insight into the Ca2+-binding properties of this well-studied protein. PMID:21765646

Postglacial history of alpine vegetation, fire, and climate from Laguna de Río Seco, Sierra Nevada, southern Spain

NASA Astrophysics Data System (ADS)

Anderson, R. S.; Jiménez-Moreno, G.; Carrión, J. S.; Pérez-Martínez, C.

2011-06-01

The Sierra Nevada of southern Spain is a landscape with a rich biological and cultural heritage. The range was extensively glaciated during the late Pleistocene. However, the postglacial paleoecologic history of the highest range in southern Europe is nearly completely unknown. Here we use sediments from a small lake above present treeline - Laguna de Río Seco at 3020 m elevation - in a paleoecological study documenting over 11,500 calendar years of vegetation, fire and climate change, addressing ecological and paleoclimatic issues unique to this area through comparison with regional paleoecological sequences. The early record is dominated by Pinus pollen, with Betula, deciduous Quercus, and grasses, with an understory of shrubs. It is unlikely that pine trees grew around the lake, and fire was relatively unimportant at this site during this period. Aquatic microfossils indicate that the wettest conditions and highest lake levels at Laguna de Río Seco occurred before 7800 cal yr BP. This is in contrast to lower elevation sites, where wettest conditions occurred after ca 7800. Greater differences in early Holocene seasonal insolation may have translated to greater snowpack and subsequently higher lake levels at higher elevations, but not necessarily at lower elevations, where higher evaporation rates prevailed. With declining seasonality after ca 8000 cal yr BP, but continuing summer precipitation, lake levels at the highest elevation site remained high, but lake levels at lower elevation sites increased as evaporation rates declined. Drier conditions commenced regionally after ca 5700 cal yr BP, shown at Laguna de Río Seco by declines in wetland pollen, and increases in high elevation steppe shrubs common today ( Juniperus, Artemisia, and others). The disappearance or decline of mesophytes, such as Betula from ca 4000 cal yr BP is part of a regional depletion in Mediterranean Spain and elsewhere in Europe from the mid to late Holocene. On the other hand, Castanea sativa increased in Laguna de Río Seco record after ca 4000 cal yr BP, and especially in post-Roman times, probably due to arboriculture. Though not as important at high than at low elevations, fire occurrence was elevated, particularly after ca 3700 years ago, in response to regional human population expansion. The local and regional impact of humans increased substantially after ca 2700 years ago, with the loss of Pinus forest within the mountain range, increases in evidence of pasturing herbivores around the lake, and Olea cultivation at lower elevations. Though human impact was not as extensive at high elevation as at lower elevation sites in southern Iberia, this record confirms that even remote sites were not free of direct human influence during the Holocene.

Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group

PubMed Central

Palumbo, Antonio; Avet-Loiseau, Hervé; Oliva, Stefania; Lokhorst, Henk M.; Goldschmidt, Hartmut; Rosinol, Laura; Richardson, Paul; Caltagirone, Simona; Lahuerta, Juan José; Facon, Thierry; Bringhen, Sara; Gay, Francesca; Attal, Michel; Passera, Roberto; Spencer, Andrew; Offidani, Massimo; Kumar, Shaji; Musto, Pellegrino; Lonial, Sagar; Petrucci, Maria T.; Orlowski, Robert Z.; Zamagni, Elena; Morgan, Gareth; Dimopoulos, Meletios A.; Durie, Brian G.M.; Anderson, Kenneth C.; Sonneveld, Pieter; San Miguel, Jésus; Cavo, Michele; Rajkumar, S. Vincent; Moreau, Philippe

2015-01-01

Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival. PMID:26240224

Molecular aspects of calcium signalling at the crossroads of unikont and bikont eukaryote evolution--the ciliated protozoan Paramecium in focus.

PubMed

Plattner, Helmut

2015-03-01

The ciliated protozoan, Paramecium tetraurelia has a high basic Ca(2+) leakage rate which is counteracted mainly by export through a contractile vacuole complex, based on its V-type H(+)-ATPase activity. In addition Paramecium cells dispose of P-type Ca(2+)-ATPases, i.e. a plasmamembrane and a sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (PMCA, SERCA). Antiporter systems are to be expected, as inferred from indirect evidence. Among the best known cytosolic Ca(2+)-binding proteins, calmodulin activates Ca(2+) influx channels in the somatic cell membrane, but inactivates Ca(2+) influx channels in cilia, where it, thus, ends ciliary reversal induced by depolarization via channels in the somatic cell membrane. Centrin inactivates Ca(2+) signals after stimulation by its high capacity/low affinity binding sites, whereas its high affinity sites regulate some other functions. Cortical Ca(2+) stores (alveolar sacs) are activated during stimulated trichocyst exocytosis and thereby mediate store-operated Ca(2+) entry (SOCE). Ca(2+) release channels (CRCs) localised to alveoli and underlying SOCE are considered as Ryanodine receptor-like proteins (RyR-LPs) which are members of a CRC family with 6 subfamilies. These also encompass genuine inositol 1,4,5-trisphosphate receptors (IP3Rs) and intermediates between the two channel types. All IP3R/RyR-type CRCs possess six carboxyterminal transmembrane domains (TMD), with a pore domain between TMD 5 and 6, endowed with a characteristic selectivity filter. There are reasons to assume a common ancestor molecule for such channels and diversification further on in evolution. The distinct distribution of specific CRCs in the different vesicles undergoing intracellular trafficking suggests constitutive formation of very locally restricted Ca(2+) signals during vesicle-vesicle interaction. In summary, essential steps of Ca(2+) signalling already occur at this level of evolution, including an unexpected multitude of CRCs. For dis-/similarities with other bikonts see "Conclusions". Copyright © 2014 Elsevier Ltd. All rights reserved.

Supplementation with Ca salts of soybean oil interacts with concentrate level in grazing dairy cows: intake, ingestive behavior, and ruminal parameters.

PubMed

Macedo, Fernanda Lopes; Batistel, Fernanda; de Souza, Jonas; Chagas, Lucas Jado; Santos, Flávio Augusto Portela

2016-12-01

In this study, we investigated the associative effects of concentrate levels and Ca salts of soybean oil (CSSO) supplementation on performance and ruminal parameters of mid-lactation dairy cows grazing on tropical pasture. Twenty-four Jersey × Holstein cows were used in a randomized block design and assigned to four treatments arranged in a 2 × 2 factorial design. Factors evaluated were concentrate levels (low, 3 kg/day vs. high, 7 kg/day of concentrate) and CSSO supplementation (without CSSO vs. with 250 g CSSO cow/day). All cows grazed on elephant grass (Pennisetum purpureum cv. Cameroon) and received the supplemental treatments for a 90-day period. The high concentrate level decreased forage intake and grazing time. In addition, the high concentrate level increased rumen propionate concentration and microbial synthesis and tended to decrease ammonia-N compared with low concentrate level. The addition of CSSO tended to decrease valerate, isobutyrate, isovalerate, and microbial synthesis. In conclusion, feeding CSSO for mid lactating cows grazing on tropical pasture had negative effects on rumen function. In contrast, CSSO supplementation tended to interact with concentrate level and increased energy intake when fed at low concentrate level. Feeding the high level of concentrate was an effective strategy to increase energy intake and microbial synthesis and improve N utilization.

Neuroprotective effect of Aronia melanocarpa extract against glutamate-induced oxidative stress in HT22 cells.

PubMed

Lee, Hyeon Yong; Weon, Jin Bae; Ryu, Gahee; Yang, Woo Seung; Kim, Nam Young; Kim, Myong Ki; Ma, Choong Je

2017-04-11

Glutamate (an endogenous excitatory neurotransmitter) at high concentrations contributes to the development of neurodegenerative diseases. Aronia melanocarpa (A. melanocarpa) berries contain anthocyanins and have high antioxidant activities. In this study, we evaluated whether A. melanocarpa berries could protect neuronal cells against glutamate-induced oxidative stress. A. melanocarpa berries exerted a protective effect against cytotoxicity in HT22 mouse hippocampal cells by MTT assay. We evaluated oxidative stress parameters including ROS level, intracellular Ca 2+ level, glutathione level and antioxidant enzyme activity in HT22 cells to elucidate the mechanism of its neuroprotective effect. A. melanocarpa berries decreased glutamate-induced death of HT22 cells. In addition, A. melanocarpa berries reduced ROS and intracellular Ca 2+ levels. Glutathione level, antioxidant enzymes, glutathione reductase and glutathione peroxide activities and mitochondrial membrane potential were also increased in HT22 cells. These results suggested that A. melanocarpa berries protected HT22 cells by exerting an antioxidant effect.

Cloning and Stress-Induced Expression Analysis of Calmodulin in the Antarctic Alga Chlamydomonas sp. ICE-L.

PubMed

He, Ying-Ying; Wang, Yi-Bin; Zheng, Zhou; Liu, Fang-Ming; An, Mei-Ling; He, Xiao-Dong; Qu, Chang-Feng; Li, Lu-Lu; Miao, Jin-Lai

2017-08-01

Calmodulin (CaM) is a Ca 2+ -binding protein that plays a role in several Ca 2+ signaling pathways, which dynamically regulates the activities of hundreds of proteins. The ice alga Chlamydomonas sp. ICE-L, which has the ability to adapt to extreme polar conditions, is a crucial primary producer in Antarctic ecosystem. This study hypothesized that Cam helps the ICE-L to adapt to the fluctuating conditions in the polar environment. It first verified the overall length of Cam, through RT-PCR and RACE-PCR, based on partial Cam transcriptome library of ICE-L. Then, the nucleotide and predicted amino acid sequences were, respectively, analyzed by various bioinformatics approaches to gain more insights into the computed physicochemical properties of the CaM. Potential involvements of Cam in responding to certain stimuli (i.e., UVB radiation, high salinity, and temperature) were investigated by differential expression, measuring its transcription levels by means of quantitative RT-PCR. Results showed that CaM was indeed inducible and regulated by high UVB radiation, high salinity, and nonoptimal temperature conditions. Different conditions had different expression tendencies, which provided an important basis for investigating the adaptation mechanism of Cam in ICE-L.

Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans.

PubMed

Chao, Linda L; Kriger, Stephen; Buckley, Shannon; Ng, Peter; Mueller, Susanne G

2014-09-01

More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure relative to matched, unexposed GW veterans estimated from 1.5T magnetic resonance images (MRI). Here we investigate, in a different cohort of GW veterans, whether low-level GB/GF exposure is associated with structural alterations in specific hippocampal subfields, estimated from 4T MRI. The Automatic Segmentation of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2-weighted images acquired on a 4T MR scanner in 56 GW veterans with suspected GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49±7 years). GB/GF exposed veterans had smaller CA2 (p=0.003) and CA3/DG (p=0.01) subfield volumes compared to matched, unexposed GW veterans. There were no group difference in total hippocampal volume, quantified with FreeSurfer, and no dose-response relationship between estimated levels of GB/GF exposure and total hippocampal or subfield volume. These findings extend our previous report of structural alterations in the hippocampi of GW veterans with suspected GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in a different cohort of GW veterans with suspected GB/GF exposure. Published by Elsevier B.V.

Interactive effects of aluminum, phosphorus and mycorrhizae on growth and nutrient uptake of Panicum virgatum L. (Poaceae).

PubMed

Koslowsky, S D; Boener, R E

1989-01-01

The effects of Al on Panicum virgatum (switchgrass), a widespread perennial grass, were determined in relation to factors which might interact with Al in the soil. Plants were grown for 8 weeks in sand culture and were treated with 3 Al levels (0.5, 2.0, 5.0 mM), 2 P levels (0.065, 0.161 mM), 2 inoculum types (vesicular-arbuscular mycorrhizal (VAM) inoculum or VAM-free soil inoculum) and 2 inoculum sources (a high Al forest in NY or a low Al forest in Ohio) in a factorial design. Plant growth decreased with increasing Al and increased with increasing P, but the Al effect was less at high P than low P. VAM-inoculated plants outgrew non-VAM plants, especially at low and medium Al levels. Total P and Ca uptake decreased with increasing Al concentration, especially at low P levels. VAM inoculation did not result in increased P uptake at any Al level though VAM plants took up significantly more Ca than non-VAM plants at any Al level. VAM plants had lower tissue Al concentrations and took up less Al than non-VAM plants; Al uptake increased with increasing soil Al in non-VAM plants but not in VAM plants. Plants given inoculum from the high Al site had significantly lower tissue Al than plants given the low Al site inoculum, regardless of VAM status. We conclude that the presence of a VAM infection, moderate levels of soil P, and the source of the inoculum can reduce the effects of soluble Al. We discuss potential physiological and edaphic mechanisms by which Al may be immobilized and Ca availability increased in the presence of VAM fungi and other soil microflora.

Associations Between Hormonal Biomarkers and Cognitive, Motor, and Language Developmental Status in Very Low Birth Weight Infants.

PubMed

Cho, June; Holditch-Davis, Diane; Su, Xiaogang; Phillips, Vivien; Biasini, Fred; Carlo, Waldemar A

Male infants are more prone to health problems and developmental delays than female infants. On the basis of theories of gender differences in brain development and social relationships, we explored associations between testosterone and cortisol levels with infant cognitive, motor, and language development ("infant development") in very low birth weight (VLBW) infants, controlling for mother-infant interactions, characteristics of mothers and infants, and days of saliva collection after birth. A total of 62 mother-VLBW infant pairs were recruited from the newborn intensive care unit of a tertiary medical center in the Southeast United States. Data were collected through infant medical record review, biochemical measurement, observation of mother-infant interactions, and standard questionnaires. Infant development was assessed at 6 months corrected age (CA), and mother-infant interactions were observed at 3 and 6 months CA. General linear regression with separate analyses for each infant gender showed that high testosterone levels were positively associated with language development of male infants after controlling for mother-infant interactions and other covariates, whereas high cortisol levels were negatively associated with motor development of female infants after controlling for mother-infant interactions. Steroid hormonal levels may well be more fundamental factors for assessing infant development than infant gender or mother-infant interactions at 6 months CA.

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

PubMed Central

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Mechanisms of Intracellular Calcium Homeostasis in MC3T3-E1 Cells and Bone Tissues of Sprague-Dawley Rats Exposed to Fluoride.

PubMed

Duan, Xiao-qin; Li, Yan-hui; Zhang, Xiu-yun; Zhao, Zhi-tao; Wang, Ying; Wang, Huan; Li, Guang-sheng; Jing, Ling

2016-04-01

Calcium homeostasis of osteoblasts (OBs) has an important role in the physiology and pathology of bone tissue. In order to study the mechanisms of intracellular calcium homeostasis, MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, we examined intracellular-free calcium ion ([Ca(2+)]i) in MC3T3-E1 cells as well as mRNA and protein levels of Cav1.2, the main subunit of L-type voltage-dependent calcium channels (VDCCs), Na(+)/Ca(2+) exchange carriers (NCS), and plasma membrane Ca(2+)-ATPase (PMCA), inositol 1,4,5-trisphosphate receptor (IP3R) channels, sarco/endoplasmic reticulum calcium ATPase 2b (SERCA2b)/ATP2A2 in vitro, and rat bone tissues in vivo. Our results showed that [Ca(2+)]i of fluoride-treated OBs increased in a concentration-dependent manner with an increase in the concentration of fluoride. We also found that the low dose of fluoride led to high expression levels of Cav1.2, NCS-1, and PMCA and low expression levels of IP3R and SERCA2b/ATP2A2, while the high dose of fluoride induced an increase in SERCA2b/ATP2A2 levels and decrease in Cav1.2, PMCA, NCS-1, and IP3R levels. These results demonstrate that calcium channels and calcium pumps of plasma and endoplasmic reticulum (ER) membranes keep intracellular calcium homeostasis by regulating Cav1.2, NCS-1, PMCA, IP3R, and SERCA2b/ATP2A2 expression.

Step 1:Human System Integration (HSI) FY05 Pilot-Technology Interface Requirements for Collision Avoidance

NASA Technical Reports Server (NTRS)

2007-01-01

This document provides definition of technology human interface requirements for Collision Avoidance (CA). This was performed through a review of CA-related, HSI requirements documents, standards, and recommended practices. Technology concepts in use by the Access 5 CA work package were considered... Beginning with the HSI high-level functional requirement for CA, and CA technology elements, HSI requirements for the interface to the pilot were identified. Results of the analysis describe (1) the information required by the pilot to have knowledge CA system status, and (2) the control capability needed by the pilot to obtain CA information and affect an avoidance maneuver. Fundamentally, these requirements provide the candidate CA technology concepts with the necessary human-related elements to make them compatible with human capabilities and limitations. The results of the analysis describe how CA operations and functions should interface with the pilot to provide the necessary CA functionality to the UA-pilot system .Requirements and guidelines for CA are partitioned into four categories: (1) General, (2) Alerting, (3) Guidance, and (4) Cockpit Display of Traffic Information. Each requirement is stated and is supported with a rationale and associated reference(s).

Roles of Ca(v) channels and AHNAK1 in T cells: the beauty and the beast.

PubMed

Matza, Didi; Flavell, Richard A

2009-09-01

T lymphocytes require Ca2+ entry though the plasma membrane for their activation and function. Recently, several routes for Ca2+ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP3Rs). Herein we review the emergence of a fourth new route for Ca2+ entry, composed of Ca(v) channels (also known as L-type voltage-gated calcium channels) and the scaffold protein AHNAK1 (AHNAK/desmoyokin). Both helper (CD4+) and killer (CD8+) T cells express high levels of Ca(v)1 alpha1 subunits (alpha1S, alpha1C, alpha1D, and alpha1F) and AHNAK1 after their differentiation and require these molecules for Ca2+ entry during an immune response. In this article, we describe the observations and open questions that ultimately suggest the involvement of multiple consecutive routes for Ca2+ entry into lymphocytes, one of which may be mediated by Ca(v) channels and AHNAK1.

Correlation between ovarian chocolate cyst and serum carbohydrate antigen 125 level and the effect of ultrasound-guided interventional sclerotherapy on serum carbohydrate antigen 125 level.

PubMed

Wang, Si-Ming; Cai, Huai-Qiu; Dong, Xiao-Qiu; Fan, Qiu-Lan; Wang, Lu-Lu; Shao, Xiao-Hui; Zhang, Li-Wei

2015-01-01

This study was to investigate the correlation between ovarian chocolate cysts and serum carbohydrate antigen (CA)-125 levels and to demonstrate the effect of ultrasound-guided interventional sclerotherapy (UGIS) on serum CA-125 levels. Based on the serum CA-125 level, as determined by chemiluminescence detection prior to UGIS, 105 patients with ovarian chocolate cysts were divided into the normal group (CA-125 ≤ 35 U/mL, 45 patients) and the abnormal group (35 U/mL < CA-125 ≤ 200 U/mL, 60 patients). There were six clinical indicators including age, disease duration, dysmenorrhea history, child-bearing history, abortion history and surgical history. The ultrasonography characteristics were cyst diameter, cyst wall thickness and the side on which the cyst occurred. The correlations between serum CA-125 levels pretreatment and the clinical indicators and ultrasonography characteristics was analyzed. The serum CA-125 levels pretreatment, 3 months post-treatment and 6 months post-treatment were compared. The pretreatment serum CA-125 levels of the 105 patients positively correlated with disease duration (r = 0.3932, P = 0.0040), dysmenorrhea history (r = 0.2351, P = 0.0111), cyst diameter (r = 0.3415, P < 0.0001) and cyst wall thickness (r = 0.4263, P < 0.0001). Compared with the pretreatment level, the mean serum CA-125 level in the abnormal group at 3 months post-treatment was significantly lower (P < 0.01), and at 6 months post-treatment, the mean serum CA-125 level had decreased to a normal level (P < 0.01). UGIS significantly decreased abnormal serum CA-125 levels in patients with ovarian chocolate cysts. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

The Impact of Transforming Growth Factor-β1 Level on Outcome After Catheter Ablation in Patients With Atrial Fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2017-04-01

Transforming growth factor-β 1 (TGF-β 1 ) is an important factor that induces atrial fibrosis and atrial fibrillation (AF). The purpose of this study was to evaluate the association between TGF-β 1 level and clinical factors before catheter ablation (CA), and to investigate the impact of TGF-β 1 level on the outcome after CA for AF. This prospective study included 151 patients (persistent AF group: n = 59, paroxysmal AF [PAF] group: n = 54, and control group: n = 38). All patients who underwent CA for AF were followed up for 12 months. The PAF group had the highest TGF-β 1 levels in all patients. An early recurrence of AF (ERAF: defined as episodes of atrial tachyarrhythmia within a 3-month blanking period) was detected in 60 patients (53%). Recurrent AF after the blanking period was detected in 36 patients (32%). On multivariate analysis, low TGF-β 1 level was the only independent factor associated with recurrent AF. Moreover, the AF recurrence ratio was higher in the low TGF-β 1 group (< 12.56 ng/mL) than in the high TGF-β 1 group (16 of 29 patients, 55% vs. 20 of 84 patients, 24%, P = 0.002 by log-rank test). PAF was associated with a higher TGF-β 1 level. Moreover, lower TGF-β 1 level in AF patients could be a cause of recurrent AF after CA. © 2017 Wiley Periodicals, Inc.

Tension Recovery following Ramp-Shaped Release in High-Ca and Low-Ca Rigor Muscle Fibers: Evidence for the Dynamic State of AMADP Myosin Heads in the Absence of ATP

PubMed Central

Sugi, Haruo; Yamaguchi, Maki; Ohno, Tetsuo; Kobayashi, Takakazu; Chaen, Shigeru; Okuyama, Hiroshi

2016-01-01

During muscle contraction, myosin heads (M) bound to actin (A) perform power stroke associated with reaction, AMADPPi → AM + ADP + Pi. In this scheme, A • M is believed to be a high-affinity complex after removal of ATP. Biochemical studies on extracted protein samples show that, in the AM complex, actin-binding sites are located at both sides of junctional peptide between 50K and 20K segments of myosin heavy chain. Recently, we found that a monoclonal antibody (IgG) to the junctional peptide had no effect on both in vitro actin-myosin sliding and skinned muscle fiber contraction, though it covers the actin-binding sites on myosin. It follows from this that, during muscle contraction, myosin heads do not pass through the static rigor AM configuration, determined biochemically and electron microscopically using extracted protein samples. To study the nature of AM and AMADP myosin heads, actually existing in muscle, we examined mechanical responses to ramp-shaped releases (0.5% of Lo, complete in 5ms) in single skinned rabbit psoas muscle fibers in high-Ca (pCa, 4) and low-Ca (pCa, >9) rigor states. The fibers exhibited initial elastic tension drop and subsequent small but definite tension recovery to a steady level. The tension recovery was present over many minutes in high-Ca rigor fibers, while it tended to decrease quickly in low-Ca rigor fibers. EDTA (10mM, with MgCl2 removed) had no appreciable effect on the tension recovery in high-Ca rigor fibers, while it completely eliminated the tension recovery in low-Ca rigor fibers. These results suggest that the AMADP myosin heads in rigor muscle have long lifetimes and dynamic properties, which show up as the tension recovery following applied release. Possible AM linkage structure in muscle is discussed in connection with the X-ray diffraction pattern from contracting muscle, which is intermediate between resting and rigor muscles. PMID:27583360

Tension Recovery following Ramp-Shaped Release in High-Ca and Low-Ca Rigor Muscle Fibers: Evidence for the Dynamic State of AMADP Myosin Heads in the Absence of ATP.

PubMed

Sugi, Haruo; Yamaguchi, Maki; Ohno, Tetsuo; Kobayashi, Takakazu; Chaen, Shigeru; Okuyama, Hiroshi

2016-01-01

During muscle contraction, myosin heads (M) bound to actin (A) perform power stroke associated with reaction, AMADPPi → AM + ADP + Pi. In this scheme, A • M is believed to be a high-affinity complex after removal of ATP. Biochemical studies on extracted protein samples show that, in the AM complex, actin-binding sites are located at both sides of junctional peptide between 50K and 20K segments of myosin heavy chain. Recently, we found that a monoclonal antibody (IgG) to the junctional peptide had no effect on both in vitro actin-myosin sliding and skinned muscle fiber contraction, though it covers the actin-binding sites on myosin. It follows from this that, during muscle contraction, myosin heads do not pass through the static rigor AM configuration, determined biochemically and electron microscopically using extracted protein samples. To study the nature of AM and AMADP myosin heads, actually existing in muscle, we examined mechanical responses to ramp-shaped releases (0.5% of Lo, complete in 5ms) in single skinned rabbit psoas muscle fibers in high-Ca (pCa, 4) and low-Ca (pCa, >9) rigor states. The fibers exhibited initial elastic tension drop and subsequent small but definite tension recovery to a steady level. The tension recovery was present over many minutes in high-Ca rigor fibers, while it tended to decrease quickly in low-Ca rigor fibers. EDTA (10mM, with MgCl2 removed) had no appreciable effect on the tension recovery in high-Ca rigor fibers, while it completely eliminated the tension recovery in low-Ca rigor fibers. These results suggest that the AMADP myosin heads in rigor muscle have long lifetimes and dynamic properties, which show up as the tension recovery following applied release. Possible AM linkage structure in muscle is discussed in connection with the X-ray diffraction pattern from contracting muscle, which is intermediate between resting and rigor muscles.

Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

PubMed Central

Vinogradova, Tatiana M.; Lakatta, Edward G.

2009-01-01

Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

Silicate versus carbonate weathering in Iceland: New insights from Ca isotopes

NASA Astrophysics Data System (ADS)

Jacobson, Andrew D.; Grace Andrews, M.; Lehn, Gregory O.; Holmden, Chris

2015-04-01

Several studies have measured riverine fluxes of Ca and carbonate alkalinity in Iceland with the aim of quantifying the role of basalt weathering in the long-term carbon cycle. A major assumption is that all of the Ca and alkalinity originates from the dissolution of Ca-bearing silicate minerals, such as plagioclase and clinopyroxene. However, hydrothermal calcite occurs throughout Iceland, and even trace levels are expected to impact river geochemistry owing to the mineral's high solubility and fast dissolution rate. To test this hypothesis, we used a new, high-precision Ca isotope MC-TIMS method (δ44/40Ca; 2σSD = ± 0.04 ‰) to trace sources of Ca in Icelandic rivers. We report elemental and Ca isotope data for rivers, high- and low-temperature groundwater, basalt, hydrothermal calcite (including Iceland Spar), and stilbite and heulandite, which are two types of zeolites commonly formed during low-grade metamorphism of basalt. In agreement with previous research, we find that rivers have higher δ44/40Ca values than basalt, with a maximum difference of ∼0.40‰. This difference may reflect isotope fractionation in the weathering zone, i.e., preferential uptake of 40Ca during clay mineral formation, adsorption, and other geochemical processes that cycle Ca. However, calcite δ44/40Ca values are also up to ∼0.40‰ higher than bedrock values, and on a diagram of δ44/40Ca versus Sr/Ca, nearly all waters plot within a plausible mixing domain bounded by the measured compositions of basalt and calcite, with glacial rivers plotting closer to calcite than non-glacial rivers. Calcite and heulandite form during hydrothermal alteration of basalt in the deep lava pile and often occur together in metabasalts now exposed at the surface. Because heulandite δ44/40Ca values are ∼1-2‰ lower than basalt, we suggest that 40Ca uptake by heudlandite explains the relatively high δ44/40Ca values of calcite and that calcite weathering in turn elevates riverine δ44/40Ca values. High mechanical erosion rates are known to facilitate the exposure and weathering of calcite, which explains the isotopic contrast between glacial and non-glacial watersheds. Using a mixing model, we find that calcite weathering provides ∼0-65% of the Ca in non-glacial rivers and ∼25-90% of the Ca in glacial rivers, with silicate weathering providing the remainder. Icelandic hydrothermal calcite contains mantle carbon. Noting that zeolite facies metamorphism and hydrothermal fluid circulation are ubiquitous characteristics of basaltic eruptions and assuming that hydrothermal calcite in other basaltic settings also contains mantle carbon, we suggest that the contribution of basalt weathering to long-term CO2 drawdown and climate regulation may be less significant than previously realized.

Phase evolution and grain-boundary contributions in CaCu3-xZnxTi4O12

NASA Astrophysics Data System (ADS)

Kwon, Oh Hyeon; Kim, Byeong Kon; Jo, Yeon Hwa; Sankar, Paul Gouri; Jung, Yul Gyo; Jung, Tae Sung; Lee, Jung Won; Cho, Yong Soo

2011-12-01

Extensive substitutions of Zn in Ca(Cu1-xZnx)3Ti4O12 (x = 0, 0.1, 0.5, 1.0 and 2.0) dielectrics are investigated in terms of the phase evolution, dielectric properties and grain boundary resistivity. The composition of CaCu2.9Zn0.1Ti4O12 (x = 0.1) densified at a relatively low sintering temperature of 1000°C showed a k value of approximately 7,000 and a tanδ value of approximately 0.07 at 10 kHz, which is better than the values for pure CaCu3Ti4O12 (CCTO). The improved dielectric properties are also believed to be related to the lower grain boundary resistivity of ˜1676 kΩ.cm, as obtained from a Cole-Cole plot. Beyond this level of Zn, the degradation of the dielectric constant was associated with unexpected crystalline phases, in this case Ca2Zn4Ti16O38, CaTiO3, and Zn2TiO4, which were observed as the level of Zn increased. Although the degradation does not match that of pure CCTO, an addition of Zn up to x=1.0 can hold the dielectric constant at the level of a few thousands, which is still promising compared to other high-k dielectric materials that must be densified below -1000°C to meet the subsequent microcircuit requirements.

Late Quaternary Climate and Vegetation of the Sudanian Zone of Northeast Nigeria

NASA Astrophysics Data System (ADS)

Salzmann, Ulrich; Hoelzmann, Philipp; Morczinek, Irena

2002-07-01

The Lake Tilla crater lake in northeastern Nigeria (10°23'N, 12°08'E) provides a ca. 17,000 14C yr multiproxy record of the environmental history of a Sudanian savanna in West Africa. Evaluation of pollen, diatoms, and sedimentary geochemistry from cores suggests that dry climatic conditions prevailed throughout the late Pleistocene. Before the onset of the Holocene, the slow rise in lake levels was interrupted by a distinct dry event between ca. 10,900 and 10,500 14C yr B.P., which may coincide with the Younger Dryas episode. The onset of the Holocene is marked by an abrupt increase in lake levels and a subsequent spread of Guinean and Sudanian tree taxa into the open grass savanna that predominated throughout the Late Pleistocene. The dominance of the mountain olive Olea hochstetteri suggests cool climatic conditions prior to ca. 8600 14C yr B.P. The early to mid-Holocene humid period culminated between ca. 8500 and 7000 14C yr B.P. with the establishment of a dense Guinean savanna during high lake levels. Frequent fires were important in promoting the open character of the vegetation. The palynological and palaeolimnological data demonstrate that the humid period terminated after ca. 7000 14C yr B.P. in a gradual decline of the precipitation/evaporation ratio and was not interrupted by abrupt climatic events. The aridification trend intensified after ca. 3800 14C yr B.P. and continued until the present.

Hepatitis B virus modulates store-operated calcium entry to enhance viral replication in primary hepatocytes

PubMed Central

Casciano, Jessica C.; Duchemin, Nicholas J.; Lamontagne, R. Jason; Steel, Laura F.; Bouchard, Michael J.

2017-01-01

Many viruses modulate calcium (Ca2+) signaling to create a cellular environment that is more permissive to viral replication, but for most viruses that regulate Ca2+ signaling, the mechanism underlying this regulation is not well understood. The hepatitis B virus (HBV) HBx protein modulates cytosolic Ca2+ levels to stimulate HBV replication in some liver cell lines. A chronic HBV infection is associated with life-threatening liver diseases, including hepatocellular carcinoma (HCC), and HBx modulation of cytosolic Ca2+ levels could have an important role in HBV pathogenesis. Whether HBx affects cytosolic Ca2+ in a normal hepatocyte, the natural site of an HBV infection, has not been addressed. Here, we report that HBx alters cytosolic Ca2+ signaling in cultured primary hepatocytes. We used single cell Ca2+ imaging of cultured primary rat hepatocytes to demonstrate that HBx elevates the cytosolic Ca2+ level in hepatocytes following an IP3-linked Ca2+ response; HBx effects were similar when expressed alone or in the context of replicating HBV. HBx elevation of the cytosolic Ca2+ level required extracellular Ca2+ influx and store-operated Ca2+ (SOC) entry and stimulated HBV replication in hepatocytes. We used both targeted RT-qPCR and transcriptome-wide RNAseq analyses to compare levels of SOC channel components and other Ca2+ signaling regulators in HBV-expressing and control hepatocytes and show that the transcript levels of these various proteins are not affected by HBV. We also show that HBx regulation of SOC-regulated Ca2+ accumulation is likely the consequence of HBV modulation of a SOC channel regulatory mechanism. In support of this, we link HBx enhancement of SOC-regulated Ca2+ accumulation to Ca2+ uptake by mitochondria and demonstrate that HBx stimulates mitochondrial Ca2+ uptake in primary hepatocytes. The results of our study may provide insights into viral mechanisms that affect Ca2+ signaling to regulate viral replication and virus-associated diseases. PMID:28151934

Keratinocytes negatively regulate the N-cadherin levels of melanoma cells via contact-mediated calcium regulation.

PubMed

Chung, Heesung; Jung, Hyejung; Jho, Eek-Hoon; Multhaupt, Hinke A B; Couchman, John R; Oh, Eok-Soo

2018-06-14

In human skin, melanocytes and their neighboring keratinocytes have a close functional interrelationship. Keratinocytes, which represent the prevalent cell type of human skin, regulate melanocytes through various mechanisms. Here, we use a keratinocyte and melanoma co-culture system to show for the first time that keratinocytes regulate the cell surface expression of N-cadherin through cell-cell contact. Compared to mono-cultured human melanoma A375 cells, which expressed high levels of N-cadherin, those co-cultured with the HaCaT human keratinocyte cell line showed reduced levels of N-cadherin. This reduction was most evident in areas of A375 cells that underwent cell-cell contact with the HaCaT cells, whereas HaCaT cell-derived extracellular matrix and conditioned medium both failed to reduce N-cadherin levels. The intracellular level of calcium in co-cultured A375 cells was lower than that in mono-cultured A375 cells, and treatment with a cell-permeant calcium chelator (BAPTA) reduced the N-cadherin level of mono-cultured A375 cells. Furthermore, co-culture with HaCaT cells reduced the expression levels of transient receptor potential cation channel (TRPC) 1, -3 and -6 in A375 cells, and siRNA-mediated multi-depletion of TRPC1, -3 and -6 reduced the N-cadherin level in these cells. Taken together, these data suggest that keratinocytes negatively regulate the N-cadherin levels of melanoma cells via cell-to-cell contact-mediated calcium regulation. Copyright © 2018. Published by Elsevier Inc.

Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

PubMed

Forte, Giovanni; Bocca, Beatrice; Oggiano, Riccardo; Clemente, Simonetta; Asara, Yolande; Sotgiu, Maria Alessandra; Farace, Cristiano; Montella, Andrea; Fois, Alessandro Giuseppe; Malaguarnera, Michele; Pirina, Pietro; Madeddu, Roberto

2017-09-01

Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.

Extracellular calcium triggers unique transcriptional programs and modulates staurosporine-induced cell death in Neurospora crassa

PubMed Central

Gonçalves, A. P.; Monteiro, João; Lucchi, Chiara; Kowbel, David J.; Cordeiro, J. M.; Correia-de-Sá, Paulo; Rigden, Daniel J.; Glass, N. L.; Videira, Arnaldo

2014-01-01

Alterations in the intracellular levels of calcium are a common response to cell death stimuli in animals and fungi and, particularly, in the Neurospora crassa response to staurosporine. We highlight the importance of the extracellular availability of Ca2+ for this response. Limitation of the ion in the culture medium further sensitizes cells to the drug and results in increased accumulation of reactive oxygen species (ROS). Conversely, an approximately 30-fold excess of external Ca2+ leads to increased drug tolerance and lower ROS generation. In line with this, distinct staurosporine-induced cytosolic Ca2+ signaling profiles were observed in the absence or presence of excessive external Ca2+. High-throughput RNA sequencing revealed that different concentrations of extracellular Ca2+ define distinct transcriptional programs. Our transcriptional profiling also pointed to two putative novel Ca2+-binding proteins, encoded by the NCU08524 and NCU06607 genes, and provides a reference dataset for future investigations on the role of Ca2+ in fungal biology. PMID:28357255

Molecular and biochemical characterization of calmodulin from Echinococcus granulosus.

PubMed

Wang, Ning; Zhong, Xiuqin; Song, Xingju; Gu, Xiaobin; Lai, Weiming; Xie, Yue; Peng, Xuerong; Yang, Guangyou

2017-12-04

Echinococcus granulosus is a harmful cestode parasite that causes cystic echinococcosis in humans as well as various livestock species and wild animals. Calmodulin (CaM), a Ca 2+ sensor protein, is widely expressed in eukaryotes and mediates a variety of cellular signaling activities. In the present study, the cDNA encoding CaM in Echinococcus granulosus (rEgCaM) was successfully cloned and the molecular and biochemical characterizations carried out. The antigenicity and immunoreactivity of rEgCaM was detected and the preliminary enzyme-linked immunosorbent assay (ELISA)-based serodiagnostic potential of EgCaM was assessed. The locations of this protein in the adult worm and larval stage, and the mRNA expression in different states of E. granulosus protoscoleces (PSCs) were defined clearly. Moreover, the Ca 2+ -binding properties of EgCaM were measured. rEgCaM is a highly conserved calcium-binding protein, consisting of 149 amino acids. Immunoblotting analysis revealed that rEgCaM could be identified using E. granulosus infected sheep serum. The use of rEgCaM as an antigen was evaluated by indirect ELISA which exhibited a high sensitivity (90.3%), but low specificity (47.1%). rEgCaM was ubiquitously expressed in protoscoleces and adults of E. granulosus, as well as in the germinal layer of the cyst wall. The mRNA expression level of rEgCaM was increased from the start of H 2 O 2 exposure and then gradually decreased because of the increased apoptosis of PSCs. In electrophoretic mobility tests and 1-anilinonaphthalene-8-sulfonic acid assays, rEgCaM showed a typical characteristic of a calcium-binding protein. To our knowledge, this is the first report on CaM from E. granulosus and rEgCaM is likely to be involved in some important biological function of E. granulosus as a calcium-binding protein.

Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer

PubMed Central

Gillespie, Earl; Leeman, Susan E.; Watts, Luisa A.; Coukos, Jennifer A.; O'Brien, Michael J.; Cerda, Sandra R.; Farraye, Francis A.; Stucchi, Arthur F.; Becker, James M.

2011-01-01

Patients with chronic ulcerative colitis (UC) are at high risk for developing colorectal cancer. In this study, archival formalin-fixed paraffin-embedded colonic tissue from patients with UC who developed carcinoma (CA) or high-grade dysplasia (HGD) was examined for changes in expression of the proinflammatory and mitogenic neurokinin-1 receptor (NK-1R). Laser capture microscopy was used to microdissect epithelia from areas of colons that showed histologic evidence of CA, HGD, and epithelia that were not dysplastic or cancerous but did contain evidence of prior inflammation (quiescent colitis). mRNA was extracted from the dissected tissue, and PCR array analysis was performed on extracted mRNA. Two antibodies were necessary to separately estimate the protein levels of the truncated (tr-NK-1R) and full-length (fl-NK-1R) receptors by immunohistochemistry. mRNA expression of tr-NK-1R increased 14-fold (P = 0.02) when comparing the HGD and CA groups. In contrast, the fl-NK-1R transcript showed no significant differences among groups. The protein levels of the total NK-1R increased by 40% (P = 0.02) in HGD and 80% (P = 0.0007) in CA compared with quiescent colitis. There were no significant changes in protein levels of the fl-NK-1R. We conclude that the increase in total NK-1R protein in HGD and CA is attributable to an increase in tr-NK-1R, suggesting there may be a functional role for tr-NK-1R in malignant transformation in colitis-associated cancer. The tr-NK-1R could prove useful as a diagnostic marker to identify patients at risk for neoplasia and may serve as a useful therapeutic target in the treatment of colitis-associated cancer. PMID:21969570

Effect of exchangeable cation concentration on sorption and desorption of dissolved organic carbon in saline soils.

PubMed

Setia, Raj; Rengasamy, Pichu; Marschner, Petra

2013-11-01

Sorption is a very important factor in stabilization of dissolved organic carbon (DOC) in soils and thus C sequestration. Saline soils have significant potential for C sequestration but little is known about the effect of type and concentration of cations on sorption and release of DOC in salt-affected soils. To close this knowledge gap, three batch sorption and desorption experiments were conducted using soils treated with solutions either low or high in salinity. In Experiment 1, salinity was developed with either NaCl or CaCl2 to obtain an electrical conductivity (EC) in a 1:5 soil: water extract (EC1:5) of 2 and 4 dS m(-1). In Experiments 2 and 3, NaCl and CaCl2 were added in various proportions (between 25 and 100%) to obtain an EC1:5 of 0.5 and 4 dS m(-1), respectively. At EC1:5 of 4 dS m(-1), the sorption of DOC (derived from wheat straw) was high even at a low proportion of added Ca(2+) and did not change with proportion of Ca added, but at EC1:5 of 0.5 dS m(-1) increasing proportion of Ca(2+) added increased DOC sorption. This can be explained by the differences in exchangeable Ca(2+) at the two salinity levels. At EC1:5 of 4 dS m(-1), the exchangeable Ca(2+) concentration did not increase beyond a proportion of 25% Ca(2+), whereas it increased with increasing Ca(2+) proportion in the treatments at EC1:5 of 0.5 dS m(-1). The DOC sorption was lowest with a proportion of 100% as Na(+). When Ca(2+) was added, DOC sorption was highest, but least was desorbed (with deionised water), thus sorption and desorption of added DOC were inversely related. The results of this study suggest that DOC sorption in salt-affected soils is mainly controlled by the levels of exchangeable Ca(2+) irrespective of the Ca(2+) concentration in the soil solution which has implications on carbon stabilization in salt-affected soils. Copyright © 2013 Elsevier B.V. All rights reserved.

The growth and aggressive behavior of human osteosarcoma is regulated by a CaMKII-controlled autocrine VEGF signaling mechanism.

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Fabrication of Heterogeneous-Phase Solid-Solution Promoting Band Structure and Charge Separation for Enhancing Photocatalytic CO2 Reduction: A Case of ZnXCa1-XIn2S4.

PubMed

Zeng, Chao; Huang, Hongwei; Zhang, Tierui; Dong, Fan; Zhang, Yihe; Hu, Yingmo

2017-08-23

Photocatalytic CO 2 reduction into solar fuels illustrates huge charm for simultaneously settling energy and environmental issues. The photoreduction ability of a semiconductor is closely correlated to its conduction band (CB) position. A homogeneous-phase solid-solution with the same crystal system always has a monotonously changed CB position, and the high CB level has to be sacrificed to achieve a benign photoabsorption. Herein, we report the fabrication of heterogeneous-phase solid-solution Zn X Ca 1-X In 2 S 4 between trigonal ZnIn 2 S 4 and cubic CaIn 2 S 4 . The Zn X Ca 1-X In 2 S 4 solid solutions with orderly tuned photoresponsive range from 540 to 640 nm present a more negative CB level and highly enhanced charge-separation efficiency. Profiting from these merits, all of these Zn X Ca 1-X In 2 S 4 solid solutions exhibit remarkably strengthened photocatalytic CO 2 reduction performance under visible light (λ > 420 nm) irradiation. Zn 0.4 Ca 0.6 In 2 S 4 , bearing the most negative CB position and highest charge-separation efficiency, casts the optimal photocatalytic CH 4 and CO evolution rates, which reach 16.7 and 6.8 times higher than that of ZnIn 2 S 4 and 7.2 and 3.9 times higher than that of CaIn 2 S 4 , respectively. To verify the crucial role of the heterogeneous-phase solid solution in promoting the band structure and photocatalytic performance, another heterogeneous-phase solid-solution Zn X Cd 1-X In 2 S 4 has been synthesized. It also displays an upshifted CB level and promoted charge separation. This work may provide a new perspective into the development of an efficient visible-light driven photocatalyst for CO 2 reduction and other photoreduction reactions.

Involvement of specific calmodulin isoforms in salicylic acid-independent activation of plant disease resistance responses.

PubMed

Heo, W D; Lee, S H; Kim, M C; Kim, J C; Chung, W S; Chun, H J; Lee, K J; Park, C Y; Park, H C; Choi, J Y; Cho, M J

1999-01-19

The Ca2+ signal is essential for the activation of plant defense responses, but downstream components of the signaling pathway are still poorly defined. Here we demonstrate that specific calmodulin (CaM) isoforms are activated by infection or pathogen-derived elicitors and participate in Ca2+-mediated induction of plant disease resistance responses. Soybean CaM (SCaM)-4 and SCaM-5 genes, which encode for divergent CaM isoforms, were induced within 30 min by a fungal elicitor or pathogen, whereas other SCaM genes encoding highly conserved CaM isoforms did not show such response. This pathogen-triggered induction of these genes specifically depended on the increase of intracellular Ca2+ level. Constitutive expression of SCaM-4 and SCaM-5 in transgenic tobacco plants triggered spontaneous induction of lesions and induces an array of systemic acquired resistance (SAR)-associated genes. Surprisingly, these transgenic plants have normal levels of endogenous salicylic acid (SA). Furthermore, coexpression of nahG gene did not block the induction of SAR-associated genes in these transgenic plants, indicating that SA is not involved in the SAR gene induction mediated by SCaM-4 or SCaM-5. The transgenic plants exhibit enhanced resistance to a wide spectrum of virulent and avirulent pathogens, including bacteria, fungi, and virus. These results suggest that specific CaM isoforms are components of a SA-independent signal transduction chain leading to disease resistance.

Cyclooxygenase-2/carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells

PubMed Central

Sansone, Pasquale; Piazzi, Giulia; Paterini, Paola; Strillacci, Antonio; Ceccarelli, Claudio; Minni, Francesco; Biasco, Guido; Chieco, Pasquale; Bonafè, Massimiliano

2009-01-01

Inflammation promotes colorectal carcinogenesis. Tumour growth often generates a hypoxic environment in the inner tumour mass. We here report that, in colon cancer cells, the expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) associates with that of the hypoxia response gene carbonic anhydrase-IX (CA-IX). The COX-2 knockdown, achieved by the stable infection of a COX-2 specific short harpin RNA interference (shCOX-2), down-regulates CA-IX gene expression. In colorectal cancer (CRC) cells, PGE2, the main COX-2 gene products, promotes CA-IX gene expression by ERK1/2 activation. In normoxic environment, shCOX-2 infected/CA-IX siRNA transfected CRC cells show a reduced level of active metalloproteinase-2 (MMP-2) that associates with a decreased extracellular matrix invasion capacity. In presence of hypoxia, COX-2 gene expression and PGE2 production increase. The knockdown of COX-2/CA-IX blunts the survival capability of CRC cells in hypoxia. At a high cell density, a culture condition that creates a mild pericellular hypoxic environment, the expression of COX-2/CA-IX genes is increased and triggers the invasive potential of colon cancer cells. In human colon cancer tissues, COX-2/CA-IX protein expression levels, assessed by Western blot and immunohistochemistry, correlate each other and increase with tumour stage. In conclusion, these data indicate that COX-2/CA-IX interplay promotes the aggressive behaviour of CRC cells. PMID:19017360

Photoemission study of CaF2- and SrF2-GaAs(110) interfaces formed at room temperature

NASA Astrophysics Data System (ADS)

Mao, D.; Young, K.; Kahn, A.; Zanoni, R.; McKinley, J.; Margaritondo, G.

1989-06-01

Interfaces formed by evaporating CaF2 or SrF2 on room-temperature GaAs(110) are studied with synchrotron-radiation photoemission spectroscopy. The fluoride films grow uniformly on the GaAs surface. The deposition of CaF2 and SrF2 induces a large initial band bending on p-type GaAs (~0.9 eV) and a small initial band bending on n-type GaAs (~0.25 eV). The valence band is dominated by the F 2p peak which shifts toward high binding energies by ~1.5 eV after the deposition of >=16 Å fluoride. This shift reflects an increase in the valence-band offset between the two materials as the film forms. The final band offsets are estimated at 7.7 and 8.0 eV for CaF2 and SrF2, respectively, and are in qualitative agreement with those expected from the fluoride-Si data. Core-level measurements indicate that no reaction or decomposition of the MF2 molecule takes place at the interface. The F 2s core-level line shape and the increase in the binding-energy separation of F 2s and Ca 3p with increasing coverage suggest the presence of an interface F component. Contrary to the CaF2/Si case, no measurable Ca-substrate bonding effect is observed. The dissociative effect of uv irradiation on the CaF2 film is also investigated.

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.

CA27.29 as a tumour marker for risk evaluation and therapy monitoring in primary breast cancer patients.

PubMed

Rack, Brigitte; Jückstock, Julia; Trapp, Elisabeth; Weissenbacher, Tobias; Alunni-Fabbroni, Marianna; Schramm, Amelie; Widschwendter, Peter; Lato, Krisztian; Zwingers, Thomas; Lorenz, Ralf; Tesch, Hans; Schneeweiss, Andreas; Fasching, Peter; Mahner, Sven; Beckmann, Matthias W; Lichtenegger, Werner; Janni, Wolfgang

2016-10-01

Several trials showed that tumour markers are associated with an impaired prognosis for breast cancer. Whether earlier treatment can improve the course of the disease remains controversial. The SUCCESS Trial compares FEC (500/100/500)-docetaxel (100) vs. FEC (500/100/500)-docetaxel/gemcitabine (75/2000) as well as 2 vs. 5 years of zoledronate in high-risk primary breast cancer patients. In 2669 patients, CA27.29 was measured before and after chemotherapy with the ST AIA-PACK CA27.29 reagent for the AIA-600II automated enzyme immunoassay (Tosoh Bioscience, Belgium). Values above 31 U/ml were considered positive. Of the patients, 7.6 % (n = 202, mean 19, range 3-410) and 19.1 % (n = 511, mean 21, range 3-331) had elevated marker levels before and after chemotherapy, respectively. Of the patients, 4.9 and 78 % showed elevated and low CA27.29, respectively, at both time points. After treatment, 35 % of the pre-therapy positive patients were negative, and 15 % of the initially negative patients became positive. The correlation between both time points was significant (p < 0.0001). No correlations among nodal status, grading, hormonal status, HER2 status and CA27.29 levels were found. However, tumour size (p = 0.02), older age (p < 0.001) and post-menopausal status (p = 0.006) were significantly associated with higher CA27.29 levels. Before treatment, the prevalence of elevated CA27.29 was equally distributed between both treatment arms, whereas after chemotherapy, 13.7 % of the patients in the FEC-doc arm showed an increased level vs. 25.4 % of the patients in the FEC-doc/gemcitabine arm (p < 0.0001). However, we could not show a significant association between the G-CSF application (yes vs. no) and CA27.29 status before/after chemotherapy (p = 0.75). These results indicate a close relationship between CA27.29 levels and tumour mass. Increased values after the completion of chemotherapy might be attributed to treatment effects and should be considered with caution.

Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production

PubMed Central

Sensi, Stefano L.; Yin, Hong Z.; Carriedo, Sean G.; Rao, Shyam S.; Weiss, John H.

1999-01-01

Synaptically released Zn2+ can enter and cause injury to postsynaptic neurons. Microfluorimetric studies using the Zn2+-sensitive probe, Newport green, examined levels of [Zn2+]i attained in cultured cortical neurons on exposure to N-methyl-d-asparte, kainate, or high K+ (to activate voltage-sensitive Ca2+ channels) in the presence of 300 μM Zn2+. Indicating particularly high permeability through Ca2+-permeable α-amino3-hydroxy-5-methyl-4-isoxazolepropionic-acid/kainate (Ca-A/K) channels, micromolar [Zn2+]i rises were observed only after kainate exposures and only in neurons expressing these channels [Ca-A/K(+) neurons]. Further studies using the oxidation-sensitive dye, hydroethidine, revealed Zn2+-dependent reactive oxygen species (ROS) generation that paralleled the [Zn2+]i rises, with rapid oxidation observed only in the case of Zn2+ entry through Ca-A/K channels. Indicating a mitochondrial source of this ROS generation, hydroethidine oxidation was inhibited by the mitochondrial electron transport blocker, rotenone. Additional evidence for a direct interaction between Zn2+ and mitochondria was provided by the observation that the Zn2+ entry through Ca-A/K channels triggered rapid mitochondrial depolarization, as assessed by using the potential-sensitive dye tetramethylrhodamine ethylester. Whereas Ca2+ influx through Ca-A/K channels also triggers ROS production, the [Zn2+]i rises and subsequent ROS production are of more prolonged duration. PMID:10051656

Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

PubMed

Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

2018-03-05

Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

Molecular basis of proton block of L-type Ca2+ channels.

PubMed

Chen, X H; Bezprozvanny, I; Tsien, R W

1996-11-01

Hydrogen ions are important regulators of ion flux through voltage-gated Ca2+ channels but their site of action has been controversial. To identify molecular determinants of proton block of L-type Ca2+ channels, we combined site-directed mutagenesis and unitary current recordings from wild-type (WT) and mutant L-type Ca2+ channels expressed in Xenopus oocytes. WT channels in 150 mM K+ displayed two conductance states, deprotonated (140 pS) and protonated (45 pS), as found previously in native L-type Ca2+ channels. Proton block was altered in a unique fashion by mutation of each of the four P-region glutamates (EI-EIV) that form the locus of high affinity Ca2+ interaction. Glu(E)-->Gln(Q) substitution in either repeats I or III abolished the high-conductance state, as if the titration site had become permanently protonated. While the EIQ mutant displayed only an approximately 40 pS conductance, the EIIIQ mutant showed the approximately 40 pS conductance plus additional pH-sensitive transitions to an even lower conductance level. The EIVQ mutant exhibited the same deprotonated and protonated conductance states as WT, but with an accelerated rate of deprotonation. The EIIQ mutant was unusual in exhibiting three conductance states (approximately 145, 102, 50 pS, respectively). Occupancy of the low conductance state increased with external acidification, albeit much higher proton concentration was required than for WT. In contrast, the equilibrium between medium and high conductance levels was apparently pH-insensitive. We concluded that the protonation site in L-type Ca2+ channels lies within the pore and is formed by a combination of conserved P-region glutamates in repeats I, II, and III, acting in concert. EIV lies to the cytoplasmic side of the site but exerts an additional stabilizing influence on protonation, most likely via electrostatic interaction. These findings are likely to hold for all voltage-gated Ca2+ channels and provide a simple molecular explanation for the modulatory effect of H+ ions on open channel flux and the competition between H+ ions and permeant divalent cations. The characteristics of H+ interactions advanced our picture of the functional interplay between P-region glutamates, with important implications for the mechanism of Ca2+ selectivity and permeation.

Correlation of CA-125 serum level and clinico-pathological characteristic of patients with endometriosis.

PubMed

Karimi-Zarchi, Mojgan; Dehshiri-Zadeh, Najmeh; Sekhavat, Leili; Nosouhi, Fahime

2016-11-01

Cancer antigen 125 (CA-125) is a glycoprotein biomarker that is used in women with pelvic masses such as endometriosis and maybe is useful in practice of patients suspicious to endometriosis. The aim of this study was to evaluate the association between preoperative serum CA-125 levels and clinic pathological characteristic in women with endometriosis, and find out the best serum CA-125 levels cut-off in pre and post menopause women. Serum CA-125 levels in 87 women aged 21-54 years suspected to endometriosis with pelvic pain, dysmenorrhea, or dyspareunia were measured preoperatively. Also the association between clinic pathological characteristic and serum CA-125 level were analyzed. The mean age of women was 32.22±6.91. The mean serum CA-125 level was 49.93±4.30 U/mL. There was a significant correlation between the endometriosis stage, lesion size, adhesion score and preoperative CA-125 plasma concentration. However, we did not found significant differences in age, marital status, patient's complaints, and pelvic pain associated to Ca125 serum level. The suggested preoperative serum cut-off levels in premenopausal and postmenopausal patients were 37 U/ml and 35 U/ml, respectively. According to the results, preoperative serum CA-125 is an important predictor for patients with endometriosis and it should be taken into consideration when surgical management is suspected, especially if stage of disease, lesion size and adhesion score are undertaken.

Fate of Shiga toxin-producing O157:H7 and non-O157:H7 Escherichia coli cells within refrigerated, frozen, or frozen then thawed ground beef patties cooked on a commercial open-flame gas or a clamshell electric grill.

PubMed

Luchansky, John B; Porto-Fett, Anna C S; Shoyer, Bradley A; Phillips, John; Chen, Vivian; Eblen, Denise R; Cook, L Victor; Mohr, Tim B; Esteban, Emilio; Bauer, Nathan

2013-09-01

Both high-fat and low-fat ground beef (percent lean:fat = ca. 70:30 and 93:7, respectively) were inoculated with a 6-strain cocktail of non-O157:H7 Shiga toxin-producing Escherichia coli (STEC) or a five-strain cocktail of E. coli O157:H7 (ca. 7.0 log CFU/g). Patties were pressed (ca. 2.54 cm thick, ca. 300 g each) and then refrigerated (4°C, 18 to 24 h), or frozen (-18°C, 3 weeks), or frozen (-18°C, 3 weeks) and then thawed (4°C for 18 h or 21°C for 10 h) before being cooked on commercial gas or electric grills to internal temperatures of 60 to 76.6°C. For E. coli O157:H7, regardless of grill type or fat level, cooking refrigerated patties to 71.1 or 76.6°C decreased E. coli O157:H7 numbers from an initial level of ca. 7.0 log CFU/g to a final level of ≤1.0 log CFU/g, whereas decreases to ca. 1.1 to 3.1 log CFU/g were observed when refrigerated patties were cooked to 60.0 or 65.5°C. For patties that were frozen or freeze-thawed and cooked to 71.1 or 76.6°C, E. coli O157:H7 numbers decreased to ca. 1.7 or ≤0.7 log CFU/g. Likewise, pathogen numbers decreased to ca. 0.7 to 3.7 log CFU/g in patties that were frozen or freeze-thawed and cooked to 60.0 or 65.5°C. For STEC, regardless of grill type or fat level, cooking refrigerated patties to 71.1 or 76.6°C decreased pathogen numbers from ca. 7.0 to ≤0.7 log CFU/g, whereas decreases to ca. 0.7 to 3.6 log CFU/g were observed when refrigerated patties were cooked to 60.0 or 65.5°C. For patties that were frozen or freeze-thawed and cooked to 71.1 or 76.6°C, STEC numbers decreased to a final level of ca. 1.5 to ≤0.7 log CFU/g. Likewise, pathogen numbers decreased from ca. 7.0 to ca. 0.8 to 4.3 log CFU/g in patties that were frozen or freeze-thawed and cooked to 60.0 or 65.5°C. Thus, cooking ground beef patties that were refrigerated, frozen, or freeze-thawed to internal temperatures of 71.1 and 76.6°C was effective for eliminating ca. 5.1 to 7.0 log CFU of E. coli O157:H7 and STEC per g.

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

PubMed Central

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

2014-01-01

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

Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries.

PubMed

Kansui, Yasuo; Garland, Christopher J; Dora, Kim A

2008-08-01

Increases in global Ca(2+) in the endothelium are a crucial step in releasing relaxing factors to modulate arterial tone. In the present study we investigated spontaneous Ca(2+) events in endothelial cells, and the contribution of smooth muscle cells to these Ca(2+) events, in pressurized rat mesenteric resistance arteries. Spontaneous Ca(2+) events were observed under resting conditions in 34% of cells. These Ca(2+) events were absent in arteries preincubated with either cyclopiazonic acid or U-73122, but were unaffected by ryanodine or nicotinamide. Stimulation of smooth muscle cell depolarization and contraction with either phenylephrine or high concentrations of KCl significantly increased the frequency of endothelial cell Ca(2+) events. The putative gap junction uncouplers carbenoxolone and 18alpha-glycyrrhetinic acid each inhibited spontaneous and evoked Ca(2+) events, and the movement of calcein from endothelial to smooth muscle cells. In addition, spontaneous Ca(2+) events were diminished by nifedipine, lowering extracellular Ca(2+) levels, or by blockers of non-selective Ca(2+) influx pathways. These findings suggest that in pressurized rat mesenteric arteries, spontaneous Ca(2+) events in the endothelial cells appear to originate from endoplasmic reticulum IP(3) receptors, and are subject to regulation by surrounding smooth muscle cells via myoendothelial gap junctions, even under basal conditions.

Overexpression of CaAPX Induces Orchestrated Reactive Oxygen Scavenging and Enhances Cold and Heat Tolerances in Tobacco

PubMed Central

Wang, Jiangying; Wu, Bin; Fan, Zhengqi; Li, Xinlei; Ni, Sui

2017-01-01

Ascorbate peroxidase (APX) acts indispensably in synthesizing L-ascorbate (AsA) which is pivotal to plant stress tolerance by detoxifying reactive oxygen species (ROS). Enhanced activity of APX has been shown to be a key step for genetic engineering of improving plant tolerance. However it needs a deeper understanding on the maintenance of cellular ROS homeostasis in response to stress. In this study, we identified and characterized an APX (CaAPX) gene from Camellia azalea. Quantitative real-time PCR (qRT-PCR) analysis showed that CaAPX was expressed in all tissues and peaked in immature green fruits; the expression levels were significantly upregulated upon cold and hot stresses. Transgenic plants displayed marked enhancements of tolerance under both cold and heat treatments, and plant growth was correlated with CaAPX expression levels. Furthermore, we monitored the activities of several ROS-scavenging enzymes including Cu/Zn-SOD, CAT, DHAR, and MDHAR, and we showed that stress tolerance was synchronized with elevated activities of ROS-scavenging. Moreover, gene expression analysis of ROS-scavenging enzymes revealed a role of CaAPX to orchestrate ROS signaling in response to temperature stresses. Overall, this study presents a comprehensive characterization of cellular response related to CaAPX expression and provides insights to breed crops with high temperature tolerances. PMID:28386551

Overexpression of CaAPX Induces Orchestrated Reactive Oxygen Scavenging and Enhances Cold and Heat Tolerances in Tobacco.

PubMed

Wang, Jiangying; Wu, Bin; Yin, Hengfu; Fan, Zhengqi; Li, Xinlei; Ni, Sui; He, Libo; Li, Jiyuan

2017-01-01

Ascorbate peroxidase (APX) acts indispensably in synthesizing L-ascorbate (AsA) which is pivotal to plant stress tolerance by detoxifying reactive oxygen species (ROS). Enhanced activity of APX has been shown to be a key step for genetic engineering of improving plant tolerance. However it needs a deeper understanding on the maintenance of cellular ROS homeostasis in response to stress. In this study, we identified and characterized an APX ( CaAPX ) gene from Camellia azalea . Quantitative real-time PCR (qRT-PCR) analysis showed that CaAPX was expressed in all tissues and peaked in immature green fruits; the expression levels were significantly upregulated upon cold and hot stresses. Transgenic plants displayed marked enhancements of tolerance under both cold and heat treatments, and plant growth was correlated with CaAPX expression levels. Furthermore, we monitored the activities of several ROS-scavenging enzymes including Cu/Zn-SOD , CAT , DHAR , and MDHAR , and we showed that stress tolerance was synchronized with elevated activities of ROS-scavenging. Moreover, gene expression analysis of ROS-scavenging enzymes revealed a role of CaAPX to orchestrate ROS signaling in response to temperature stresses. Overall, this study presents a comprehensive characterization of cellular response related to CaAPX expression and provides insights to breed crops with high temperature tolerances.

PRODUCTION AND ECONOMIC OPTIMIZATION OF DIETARY PROTEIN AND CARBOHYDRATE IN THE CULTURE OF JUVENILE SEA URCHIN Lytechinus variegatus

PubMed Central

Heflin, Laura E.; Makowsky, Robert; Taylor, J. Christopher; Williams, Michael B.; Lawrence, Addison L.; Watts, Stephen A.

2016-01-01

Juvenile Lytechinus variegatus (ca. 3.95± 0.54 g) were fed one of 10 formulated diets with different protein (ranging from 11- 43%) and carbohydrate (12 or 18%; brackets determined from previous studies) levels. Urchins (n= 16 per treatment) were fed a daily sub-satiation ration equivalent to 2.0% of average body weight for 10 weeks. Our objective was (1) to create predictive models of growth, production and efficiency outcomes and (2) to generate economic analysis models in relation to these dietary outcomes for juvenile L. variegatus held in culture. At dietary protein levels below ca. 30%, models for most growth and production outcomes predicted increased rates of growth and production among urchins fed diets containing 18% dietary carbohydrate levels as compared to urchins fed diets containing 12% dietary carbohydrate. For most outcomes, growth and production was predicted to increase with increasing level of dietary protein up to ca. 30%, after which, no further increase in growth and production were predicted. Likewise, dry matter production efficiency was predicted to increase with increasing protein level up to ca. 30%, with urchins fed diets with 18% carbohydrate exhibiting greater efficiency than those fed diets with 12% carbohydrate. The energetic cost of dry matter production was optimal at protein levels less than those required for maximal weight gain and gonad production, suggesting an increased energetic cost (decreased energy efficiency) is required to increase gonad production relative to somatic growth. Economic analysis models predict when cost of feed ingredients are low, the lowest cost per gram of wet weight gain will occur at 18% dietary carbohydrate and ca. 25- 30% dietary protein. In contrast, lowest cost per gram of wet weight gain will occur at 12% dietary carbohydrate and ca. 35- 40% dietary protein when feed ingredient costs are high or average. For both 18 and 12% levels of dietary carbohydrate, cost per gram of wet weight gain is predicted to be maximized at low dietary protein levels, regardless of feed ingredient costs. These models will compare dietary requirements and growth outcomes in relation to economic costs and provide insight for future commercialization of sea urchin aquaculture. PMID:28082753

PRODUCTION AND ECONOMIC OPTIMIZATION OF DIETARY PROTEIN AND CARBOHYDRATE IN THE CULTURE OF JUVENILE SEA URCHIN Lytechinus variegatus.

PubMed

Heflin, Laura E; Makowsky, Robert; Taylor, J Christopher; Williams, Michael B; Lawrence, Addison L; Watts, Stephen A

2016-10-01

Juvenile Lytechinus variegatus (ca. 3.95± 0.54 g) were fed one of 10 formulated diets with different protein (ranging from 11- 43%) and carbohydrate (12 or 18%; brackets determined from previous studies) levels. Urchins (n= 16 per treatment) were fed a daily sub-satiation ration equivalent to 2.0% of average body weight for 10 weeks. Our objective was (1) to create predictive models of growth, production and efficiency outcomes and (2) to generate economic analysis models in relation to these dietary outcomes for juvenile L. variegatus held in culture. At dietary protein levels below ca. 30%, models for most growth and production outcomes predicted increased rates of growth and production among urchins fed diets containing 18% dietary carbohydrate levels as compared to urchins fed diets containing 12% dietary carbohydrate. For most outcomes, growth and production was predicted to increase with increasing level of dietary protein up to ca. 30%, after which, no further increase in growth and production were predicted. Likewise, dry matter production efficiency was predicted to increase with increasing protein level up to ca. 30%, with urchins fed diets with 18% carbohydrate exhibiting greater efficiency than those fed diets with 12% carbohydrate. The energetic cost of dry matter production was optimal at protein levels less than those required for maximal weight gain and gonad production, suggesting an increased energetic cost (decreased energy efficiency) is required to increase gonad production relative to somatic growth. Economic analysis models predict when cost of feed ingredients are low, the lowest cost per gram of wet weight gain will occur at 18% dietary carbohydrate and ca. 25- 30% dietary protein. In contrast, lowest cost per gram of wet weight gain will occur at 12% dietary carbohydrate and ca. 35- 40% dietary protein when feed ingredient costs are high or average. For both 18 and 12% levels of dietary carbohydrate, cost per gram of wet weight gain is predicted to be maximized at low dietary protein levels, regardless of feed ingredient costs. These models will compare dietary requirements and growth outcomes in relation to economic costs and provide insight for future commercialization of sea urchin aquaculture.

Liquid Biopsy Analysis of FGFR3 and PIK3CA Hotspot Mutations for Disease Surveillance in Bladder Cancer.

PubMed

Christensen, Emil; Birkenkamp-Demtröder, Karin; Nordentoft, Iver; Høyer, Søren; van der Keur, Kirstin; van Kessel, Kim; Zwarthoff, Ellen; Agerbæk, Mads; Ørntoft, Torben Falck; Jensen, Jørgen Bjerggaard; Dyrskjøt, Lars

2017-06-01

Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment. To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations. Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n=216, Cx n=27) and plasma samples (NMIBC n=39, Cx n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied. In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p=0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p=0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study. Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer. Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Direct reduction processes for titanium oxide in molten salt

NASA Astrophysics Data System (ADS)

Suzuki, Ryosuke O.

2007-02-01

Molten salt electrolysis using CaCl2 is employed to produce pure titanium and its alloys directly from TiO2 and a mixture of elemental oxides, respectively, as an alternate to the Kroll process. This is because CaO, which is a reduction by-product, is highly soluble in CaCl2. Good-quality titanium containing only a small amount of residual oxygen has been successfully produced and scaled to industrial levels. Thermochemical and electrochemical bases are reviewed to optimize the process conditions. Several processes using molten salt are being examined for future progress in titanium processing.

Role of Ca++ in Shoot Gravitropism. [avena

NASA Technical Reports Server (NTRS)

Rayle, D. L.

1985-01-01

A cornerstone in the argument that Ca(2+) levels may regulate growth is the finding the EGTA promotes straight growth. The usual explanation for these results is that Ca(2+) chelation from cell walls results in wall loosening and thus accelerated straight growth. The ability of frozen-thawed Avena coleoptile tissue (subjected to 15g tension) to extend in response to EGTA and Quin II was examined. The EGTA when applied in weakly buffered (i.e., 0.1mM) neutral solutions initiates rapid extension. When the buffer strength is increased, similar concentrations of EGTA produce no growth response. This implies when EGTA liberated protons are released upon Ca(2+) chelation they can either initiate acid growth (low buffer conditions) or if consumed (high buffer conditions) have no effect. Thus Ca(2+) chelation in itself apparently does not result in straight growth.

CaP CURE Initiatives and Projects

PubMed Central

Soule, Howard R

2003-01-01

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization’s Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE’s efforts have resulted in a significant increase in federal funding of prostate cancer research programs. PMID:16986049

Calmodulin protects cells from death under normal growth conditions and mitogenic starvation but plays a mediating role in cell death upon B-cell receptor stimulation

PubMed Central

Schmalzigaug, Robert; Ye, Qunrui; Berchtold, Martin W

2001-01-01

Calmodulin (CaM) is the main intracellular Ca2+ sensor protein responsible for mediating Ca2+ triggered processes. Chicken DT40 lymphoma B cells express CaM from the two genes, CaMI and CaMII. Here we report the phenotypes of DT40 cells with the CaMII gene knocked out. The disruption of the CaMII gene causes the intracellular CaM level to decrease by 60%. CaMII−/− cells grow more slowly and die more frequently as compared to wild type (wt) cells but do not exhibit significant differences in their cell cycle profile. Both phenotypes are more pronounced at reduced serum concentrations. Upon stimulation of the B-cell receptor (BCR), the resting Ca2+ levels remain elevated after the initial transient in CaMII−/− cells. Despite higher Ca2+ resting levels, the CaMII−/− cells are partially protected from BCR induced apoptosis indicating that CaM plays a dual role in apoptotic processes. PMID:11454062

Quantitative analysis of the expression and distribution of calcium channel alpha 1 subunit mRNA in the atria and ventricles of the rat heart.

PubMed

Larsen, Janice K; Mitchell, Jennifer W; Best, Philip M

2002-05-01

Two distinct calcium currents are present in mammalian cardiac myocytes. Utilizing quantitative RT-PCR methods, we have analysed the expression patterns and abundance of four calcium channel alpha 1 subunit mRNAs in different regions of the rat heart and compared them to the known density of calcium currents recorded from rat atria. Our results show that Ca(V)1.2 is the most abundant of the four alpha 1 subunit transcripts in the rat heart. The Ca(V)1.2 message is more abundant in ventricle than in atria and does not vary in expression as a function of developmental age. Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2 mRNAs are 10-100 times less abundant than Ca(V)1.2. Interestingly, Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2 are expressed in both atria and ventricle. The abundance of atrial Ca(V)3.1 mRNA does not change significantly during development and remains high in older animals. In contrast, levels of atrial Ca(V)3.2 mRNA are high in embryonic tissue and at 3- and 4-weeks postnatal but become undetectable at 5 weeks. Expression of atrial Ca(V)2.3 mRNA is highest at 4-weeks postnatal and then declines gradually. We have previously documented that the LVA calcium current density is highest within 4-5 weeks after birth and then declines gradually reaching less than 30% of its maximal value at 12-14 weeks. The complex relationship between atrial LVA current density and the abundance of Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2 mRNA suggests that their contribution to the cardiac LVA current may vary as a function of postnatal age. Copyright 2002 Academic Press.

Salt Content Determination for Bentonite Mine Spoil: Saturation Extracts Versus 1:5 Extracts

Treesearch

Marguerite E. Voorhees; Daniel W. Uresk

2004-01-01

The reliability of estimating salt content in saturated extracts from 1:5 (1spoil:5water) extract levels for bentonite mine spoil was examined by regression analyses. Nine chemical variables were examined that included pH, EC, Ca++, Mg++, Na+, K+, HCO3-, SO4-, and Cl-. Ion concentrations from 1:5 extracts were estimated with high predictability for Ca++, Mg++, Na+, SO4...

Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

PubMed

Stepan, Jens; Dine, Julien; Eder, Matthias

2015-01-01

Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

Consequences of phosphorus interactions with calcium, phytase, and cholecalciferol on zootechnical performance and mineral retention in broiler chickens.

PubMed

Delezie, E; Maertens, L; Huyghebaert, G

2012-10-01

The objective was to determine the effect of calcium (Ca), total phosphorus (Ptot), cholecalciferol, and phytase level in the diet on the performance, tibia ash percentage, and Ca and P retention in broilers until slaughter age. Broilers were randomly assigned to 12 treatments, each with 6 replicates, comprising 3 diets differing in Ca and P level: 1) normal Ca and Ptot level (NN); 2) normal Ca and low Ptot level (NL), 3) low Ca and Ptot level (LL). Broilers were also given 2 levels of cholecalciferol and 2 levels of phytase. The normal levels of Ca and Ptot for the starter, grower, and finisher phases were 0.90, 0.82, 0.74% and 0.67, 0.62, 0.57%, respectively. The low Ca and Ptot levels for the 3 phases were 0.67, 0.60, 0.52% and 0.57, 0.51, 0.46%, respectively. Broilers of the NL treatment obtained the lowest BW, whereas BW of the NN and LL groups were comparable. Cholecalciferol significantly affected the BW, with differences up to 2.6 and 1.2% for the starter and grower phases, respectively. The highest cholecalciferol effect was found in combination with the NN treatment. The percentage of retained Ca increased from 33% to 41% and 48% when the imbalanced diet was replaced by the NN and LL balanced diets, respectively. P release from phytate was 64 and 67% for the NL and LL diets, respectively. Phytase and cholecalciferol had significantly favorable effects on retention values but these effects were dependent on Ca and Ptot levels and their ratio. In conclusion, both diets with the balanced Ca/Ptot ratio resulted in the best performance, highest tibia ash percentage and P release from phytate. A reduction of the Aviagen (2009) recommended P requirements by 25 to 30% and Ca by 15 to 20% over the various phases did not negatively affect performance, bone development, and improved Ca and Ptot retention. The effects of supplementing cholecalciferol and phytase were additive but not significant and no synergism between both was present.

Altering the level of calcium changes the physical properties and digestibility of casein-based emulsion gels.

PubMed

McIntyre, Irene; O Sullivan, Michael; O Riordan, Dolores

2017-04-19

Casein-based emulsion gels prepared with different types of lipid (i.e. milk fat or rapeseed oil) were formulated with high (774 mg Ca per 100 g) or low (357 mg Ca per 100 g) calcium levels by blending acid and rennet casein. Their physicochemical characteristics (i.e. composition, texture, microstructure & water mobility) and in vitro digestibility were compared to conventionally formulated high-calcium (723 mg Ca per 100 g) emulsion gels made from rennet casein with calcium chelating salts (CCS). CCS-free, high-calcium emulsion gels were significantly (p ≤ 0.05) softer than those with low calcium levels (possibly due to their shorter manufacture time and higher pH) and showed the highest rates of disintegration during simulated gastric digestion. Despite having a higher moisture to protein ratio, the high-calcium emulsion gels containing CCS had broadly similar hardness values to those of high-calcium concentration prepared without CCS, but had higher cohesiveness. The high-calcium matrices containing CCS had quite a different microstructure and increased water mobility compared to those made without CCS and showed the slowest rate (p ≤ 0.05) of disintegration in the gastric environment. Gastric resistance was not affected by the type of lipid phase. Conversely, fatty acid release was similar for all emulsion gels prepared from milk fat, however, high-calcium emulsion gels (CCS-free) prepared from rapeseed oil showed higher lipolysis. Results suggest that food matrix physical properties can be modified to alter resistance to gastric degradation which may have consequences for the kinetics of nutrient release and delivery of bioactives sensitive to the gastric environment.

Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

PubMed Central

Dimke, Henrik; Desai, Prajakta; Borovac, Jelena; Lau, Alyssa; Pan, Wanling; Alexander, R. Todd

2016-01-01

Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones. PMID:23283989

Structural and functional characterization of the recombinant thioredoxin reductase from Candida albicans as a potential target for vaccine and drug design.

PubMed

Godoy, Janine Silva Ribeiro; Kioshima, Érika Seki; Abadio, Ana Karina Rodrigues; Felipe, Maria Sueli Soares; de Freitas, Sonia Maria; Svidzinski, Terezinha Inez Estivalet

2016-05-01

The thioredoxin system plays a critical role in maintaining the cytoplasm redox state, participating in functions that are important to the cellular viability of fungi. Although functional and structural information on targets in human pathogenic fungi has been scarcely described in the literature, such studies are essential for in silico drug design and biotechnological applications. Therefore, the aims of the present study were to produce recombinant proteins of the thioredoxin system from Candida albicans and evaluate their possible use as prophylactic or alternative therapies against the most important pathogenic fungus associated with nosocomial infections. We focused on biochemical and structural analyses of recombinant thioredoxin reductase from C. albicans with His-tag (CaTrxR-His) for further biotechnology applications. Heterologous CaTrxR-His was efficiently expressed in the soluble fraction of the Escherichia coli lysate. CaTrxR-His was obtained with a high level of purity and presented specific enzymatic activity. Conformational changes of the protein were observed at different pHs and temperatures, with higher thermal stability at pH 8.0. The CaTrxR-His vaccine was shown to effectively induce high levels of CaTrxR-specific immunoglobulin G antibodies in Balb/c mice and reduce the renal fungal burden of experimental disseminated candidiasis in mice. These data may greatly impact future development strategies for vaccine and drug designs against C. albicans infection.

Multicenter Evaluation of the Bruker MALDI Biotyper CA System for the Identification of Clinically Important Bacteria and Yeasts.

PubMed

Wilson, Deborah A; Young, Stephen; Timm, Karen; Novak-Weekley, Susan; Marlowe, Elizabeth M; Madisen, Neil; Lillie, Jennifer L; Ledeboer, Nathan A; Smith, Rebecca; Hyke, Josh; Griego-Fullbright, Christen; Jim, Patricia; Granato, Paul A; Faron, Matthew L; Cumpio, Joven; Buchan, Blake W; Procop, Gary W

2017-06-01

A report on the multicenter evaluation of the Bruker MALDI Biotyper CA System (MBT-CA; Bruker Daltonics, Billerica, MA) for the identification of clinically important bacteria and yeasts. In total, 4,399 isolates of medically important bacteria and yeasts were assessed in the MBT-CA. These included 2,262 aerobic gram-positive (AGP) bacteria, 792 aerobic gram-negative (AGN) bacteria 530 anaerobic (AnA) bacteria, and 815 yeasts (YSTs). Three processing methods were assesed. Overall, 98.4% (4,329/4,399) of all bacterial and yeast isolates were correctly identified to the genus and species/species complex level, and 95.7% of isolates were identified with a high degree of confidence. The percentage correctly identified and the percentage identified correctly with a high level of confidence, respectively, were as follows: AGP bacteria (98.6%/96.5%), AGN bacteria (98.5%/96.8%), AnA bacteria (98.5%/97.4%), and YSTs (97.8%/87.6%). The extended direct transfer method was only minimally superior to the direct transfer method for bacteria (89.9% vs 86.8%, respectively) but significantly superior for yeast isolates (74.0% vs 48.9%, respectively). The Bruker MALDI Biotyper CA System accurately identifies most clinically important bacteria and yeasts and has optional processing methods to improve isolate characterization. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Interactions between calcium and phosphorus in the regulation of the production of fibroblast growth factor 23 in vivo

PubMed Central

Quinn, Stephen J.; Thomsen, Alex R. B.; Pang, Jian L.; Kantham, Lakshmi; Bräuner-Osborne, Hans; Pollak, Martin; Goltzman, David

2013-01-01

Calcium and phosphorus homeostasis are highly interrelated and share common regulatory hormones, including FGF23. However, little is known about calcium's role in the regulation of FGF23. We sought to investigate the regulatory roles of calcium and phosphorus in FGF23 production using genetic mouse models with targeted inactivation of PTH (PTH KO) or both PTH and the calcium-sensing receptor (CaSR; PTH-CaSR DKO). In wild-type, PTH KO, and PTH-CaSR DKO mice, elevation of either serum calcium or phosphorus by intraperitoneal injection increased serum FGF23 levels. In PTH KO and PTH-CaSR DKO mice, however, increases in serum phosphorus by dietary manipulation were accompanied by severe hypocalcemia, which appeared to blunt stimulation of FGF23 release. Increases in dietary phosphorus in PTH-CaSR DKO mice markedly decreased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] despite no change in FGF23, suggesting direct regulation of 1,25(OH)2D3 synthesis by serum phosphorus. Calcium-mediated increases in serum FGF23 required a threshold level of serum phosphorus of about 5 mg/dl. Analogously, phosphorus-elicited increases in FGF23 were markedly blunted if serum calcium was less than 8 mg/dl. The best correlation between calcium and phosphorus and serum FGF23 was found between FGF23 and the calcium × phosphorus product. Since calcium stimulated FGF23 production in the PTH-CaSR DKO mice, this effect cannot be mediated by the full-length CaSR. Thus the regulation of FGF23 by both calcium and phosphorus appears to be fundamentally important in coordinating the serum levels of both mineral ions and ensuring that the calcium × phosphorus product remains within a physiological range. PMID:23233539

Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients.

PubMed

MacLean, G D; Reddish, M A; Longenecker, B M

1997-01-01

The TRUQUANT BR radioimmunoassay, which uses monoclonal antibody B27.29 to quantitate CA27.29 mucin antigen (MUC-1 gene product) in serum, has recently received Food and Drug Administration approval for predicting recurrent breast cancer in patients with stage II and III disease. The purpose of this study was to determine whether the new radioimmunoassay for serum MUC-1 has prognostic significance for patients with metastatic adenocarcinoma receiving active specific immunotherapy (ASI). Using 40 U/ml as the upper limit of "normal," patients with metastatic breast and ovarian cancer with a preimmunotherapy serum CA27.29 mucin > 40 U/ml (CA27.29 Hi patients) had a poorer survival than CA27.29 Lo patients (< or = 40 U/ml) after ASI. There was no significant correlation between preimmunotherapy CA27.29 serum levels and measurable tumor burden. The preimmunotherapy CA27.29 serum level was a predictor of poor survival of metastatic colorectal and pancreatic cancer patients independent of other prognostic factors. There seemed to be two populations of pancreatic cancer patients, separated at 60 U/ml serum CA27.29 (CA27.29 Hi versus Lo patients). A CA27.29 serum level of 22 U/ml separated patients with CA27.29 Hi vs. Lo colorectal cancer. Patients with CA27.29 Lo colorectal and pancreatic cancer survived longer after ASI compared with patients with CA27.29 Hi colorectal and pancreatic cancer, respectively. We suggest that various CA27.29 serum levels define poor prognosis patients (CA27.29 Hi secretors) versus good prognosis patients (CA27.29 Lo secretors) for different cancer types.

Imperforate hymen with elevated serum CA 125 and CA 19-9 levels.

PubMed

Sak, Muhammet Erdal; Evsen, Mehmet Siddik; Soydinc, Hatice Ender; Sak, Sibel; Yalinkaya, Ahmet

2013-01-01

To report the clinical characteristics of 14 patients with imperforate hymen and their levels of tumor markers (CA 19-9 and CA 125). Fourteen patients with imperforate hymen who followed-up between September 2006 and September 2010 in the Department of Obstetrics and Gynecology, Dicle University School of Medicine, Diyarbakir, Turkey, were evaluated retrospectively. The clinical features and the management of the patients are discussed. The mean age of the patients was 13.8 years. All patients had primary amenorrhea and pelvic pain. The most common clinical symptoms were cryptomenorrhea in 14 patients, pelvic pain in 11, palpable abdominal mass in 6, voiding difficulties in 7, and defecation problems in 2. In 6 patients with palpable pelvic mass, the mean + standard deviation values of tumor markers were as follows: CA 125, 84.0 +/- 23.7 and CA 19-9, 162 +/- 189. One week after surgery we measured CA 125 and CA 19-9 levels once again. The postoperative mean CA 125 level was 13.8 +/- 3.6, and the mean postoperative CA 19-9 level was 17.5 +/- 3.5. Preoperative levels of CA 125 and CA 19-9 were significantly higher than those of the postoperative period (p < 0.001 for both comparisons). Six patients were treated by T-shaped incision and 8 patients by a central surgical incision through the hymenal membrane. Diagnosis of imperforate hymen is very important before undergoing surgery in a different clinic. Many patients have seen several doctors before receiving a clear diagnosis and have had tumor markers evaluated because the presence of pelvic mass in patients suggests the possibility of a gynecologic malignancy. Imperforate hymen is one of the benign conditions that increase serum CA 125 and CA 19-9 levels and which is not listed in the classical medical textbooks. These markers are not needed for the diagnosis.

Photosynthesis is improved by exogenous calcium in heat-stressed tobacco plants.

PubMed

Tan, Wei; Meng, Qing wei; Brestic, Marian; Olsovska, Katarina; Yang, Xinghong

2011-11-15

Effects of exogenous calcium chloride (CaCl(2)) (20 mM) on photosynthetic gas exchange, photosystem II photochemistry, and the activities of antioxidant enzymes in tobacco plants under high temperature stress (43°C for 2 h) were investigated. Heat stress resulted in a decrease in net photosynthetic rate (P(n)), stomatal conductance as well as the apparent quantum yield (AQY) and carboxylation efficiency (CE) of photosynthesis. Heat stress also caused a decrease of the maximal photochemical efficiency of primary photochemistry (F(v)/F(m)). On the other hand, CaCl(2) application improved P(n), AQY, and CE as well as F(v)/F(m) under high temperature stress. Heat stress reduced the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), whereas the activities of these enzymes either decreased less or increased in plants pretreated with CaCl(2); glutathione reductase (GR) activity increased under high temperature, and it increased more in plants pretreated with CaCl(2). There was an obvious accumulation of H(2)O(2) and O(2)(-) under high temperature, but CaCl(2) application decreased the contents of H(2)O(2) and O(2)(-) under heat stress conditions. Heat stress induced the level of heat shock protein 70 (HSP70), while CaCl(2) pretreatment enhanced it. These results suggested that photosynthesis was improved by CaCl(2) application in heat-stressed plants and such an improvement was associated with an improvement in stomatal conductance and the thermostability of oxygen-evolving complex (OEC), which might be due to less accumulation of reactive oxygen species. Copyright © 2011 Elsevier GmbH. All rights reserved.

Methylation of the PMEPA1 gene, a negative regulator of the androgen receptor in prostate cancer.

PubMed

Sharad, Shashwat; Ravindranath, Lakshmi; Haffner, Michael C; Li, Hua; Yan, Wusheng; Sesterhenn, Isabell A; Chen, Yongmei; Ali, Amina; Srinivasan, Alagarsamy; McLeod, David G; Yegnasubramanian, Srinivasan; Srivastava, Shiv; Dobi, Albert; Petrovics, Gyorgy

2014-06-01

The prostate transmembrane protein androgen induced 1 (PMEPA1) gene is highly expressed in prostate epithelial cells and is a direct transcriptional target for the androgen receptor (AR). AR protein levels are controlled by the AR-PMEPA1 negative feedback loop through NEDD4-E3 ligase. Reduced expression of PMEPA1 observed in prostate tumors, suggests that loss of PMEPA1 may play critical roles in prostate tumorigenesis. This study focuses on epigenetic mechanisms of reduced PMEPA1 expression in the cancer of the prostate (CaP). Benign (n = 77) and matched malignant (n = 77) prostate epithelial cells were laser capture micro-dissected from optimum cutting temperature embedded frozen prostate sections from 42 Caucasian American (CA) and 35 African American (AA) cases. Purified DNA specimens were analyzed for CpG methylation of the PMEPA1 gene. PMEPA1 mRNA expression levels were evaluated by qRT-PCR. Analysis of PMEPA1 methylation and mRNA expression in the same tumor cell populations indicated a significant inverse correlation between mRNA expression and methylation in CaP (P = 0.0115). We noted higher frequency of CpG methylation within the evaluated first intronic region of the PMEPA1 gene in prostate tumors of CA men as compared with AA. In CaP cell lines, PMEPA1 expression was induced and AR protein levels were diminished in response to treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (decitabine). Cell culture-based studies demonstrated that decitabine restores PMEPA1 expression in AR-positive CaP cell lines. This report reveals the potential role of PMEPA1 gene methylation in the regulation of AR stability. Thus, downregulation of PMEPA1 may result in increased AR protein levels and function in CaP cells, contributing to prostate tumorigenesis.

Methylation of the PMEPA1 gene, a negative regulator of the androgen receptor in prostate cancer

PubMed Central

Sharad, Shashwat; Ravindranath, Lakshmi; Haffner, Michael C; Li, Hua; Yan, Wusheng; Sesterhenn, Isabell A; Chen, Yongmei; Ali, Amina; Srinivasan, Alagarsamy; McLeod, David G; Yegnasubramanian, Srinivasan; Srivastava, Shiv; Dobi, Albert; Petrovics, Gyorgy

2014-01-01

The prostate transmembrane protein androgen induced 1 (PMEPA1) gene is highly expressed in prostate epithelial cells and is a direct transcriptional target for the androgen receptor (AR). AR protein levels are controlled by the AR-PMEPA1 negative feedback loop through NEDD4-E3 ligase. Reduced expression of PMEPA1 observed in prostate tumors, suggests that loss of PMEPA1 may play critical roles in prostate tumorigenesis. This study focuses on epigenetic mechanisms of reduced PMEPA1 expression in the cancer of the prostate (CaP). Benign (n = 77) and matched malignant (n = 77) prostate epithelial cells were laser capture micro-dissected from optimum cutting temperature embedded frozen prostate sections from 42 Caucasian American (CA) and 35 African American (AA) cases. Purified DNA specimens were analyzed for CpG methylation of the PMEPA1 gene. PMEPA1 mRNA expression levels were evaluated by qRT-PCR. Analysis of PMEPA1 methylation and mRNA expression in the same tumor cell populations indicated a significant inverse correlation between mRNA expression and methylation in CaP (P = 0.0115). We noted higher frequency of CpG methylation within the evaluated first intronic region of the PMEPA1 gene in prostate tumors of CA men as compared with AA. In CaP cell lines, PMEPA1 expression was induced and AR protein levels were diminished in response to treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (decitabine). Cell culture-based studies demonstrated that decitabine restores PMEPA1 expression in AR-positive CaP cell lines. This report reveals the potential role of PMEPA1 gene methylation in the regulation of AR stability. Thus, downregulation of PMEPA1 may result in increased AR protein levels and function in CaP cells, contributing to prostate tumorigenesis. PMID:24694733

Trace element evidence for a depleted component intrinsic to the Hawaiian plume

NASA Astrophysics Data System (ADS)

DeFelice, C.; Mallick, S.; Saal, A. E.; Huang, S.

2017-12-01

The Hawaii Scientific Drilling Project (HSDP) recovered 3.5 km of Mauna Kea post-shield and shield stage basalts to investigate the geochemical evolution of a Hawaiian shield stage volcano and to constrain the geochemical structure of Hawaiian plume. A group of tholeiitic lavas from 1760-1810 meters below sea level (mbsl) have higher CaO content at given MgO content and are called high-CaO basalts. Isotopes of Pb, Sr, Hf, and Nd of these basalts show they are the most depleted shield basalts ever recovered in Hawaii. Their 206Pb/204Pb-208Pb/204Pb values indicate that they are not related to Pacific MORB. Their Ba/Th values (115-160) are characteristic of Hawaiian plume material and they are isotopically similar to Hawaiian rejuvenated stage lavas. To further investigate this relationship, we compare high-CaO basalts to the Honolulu Volcanics, a set of rejuvenated stage lavas. To determine their possible petrogenetic relation, we calculate their parental melt composition by adding or removing olivine until their geochemical composition is in equilibrium with Fo90. The High-CaO basalt parent magma composition has a much flatter REE pattern and much lower absolute REE contents than that of the Honolulu lavas. Batch melting forward models are calculated to determine potential sources that could contribute to both the Honolulu Volcanics and high-CaO basalts petrogenesis. Both parental magma compositions can be recreated by melting the same rejuvenated-stage source composition to varying degrees. Honolulu Volcanics are the result of a low degree of melting of the rejuvenated source, while higher degrees of melting reproduce the high-CaO basalts. The High-CaO basalts, erupted during shield-stage volcanism, show that the depleted component that rejuvenated stage basalts form from can be sampled during the most voluminous stage of volcanism, and is likely intrinsic to the plume.

Effect of calcium and phosphorus, residual lactose, and salt-to-moisture ratio on the melting characteristics and hardness of cheddar cheese during ripening.

PubMed

Chevanan, N; Muthukumarappan, K

2007-05-01

Meltability, melt profile parameters, and hardness of cheddar cheese prepared with varying levels of calcium (Ca) and phosphorus (P) content, residual lactose content, and salt-to-moisture ratio were studied at 0, 1, 2, 4, 6, and 8 mo of ripening. Meltability, melt profile parameters, and hardness of cheddar cheeses measured at 0, 1, 2, 4, 6, and 8 mo of ripening showed significant interaction between the levels of Ca and P, residual lactose, salt-to-moisture ratio, and ripening time for most of the properties studied. cheddar cheese prepared with high Ca and P (0.67% Ca and 0.53% P) resulted in up to 6.2%, 4.5%, 9.6%, 5.0%, and 22.8% increase in softening time, softening temperature, melting time, melting temperature, and hardness, respectively, and 23.5%, 9.6%, and 3.2% decrease in meltability, flow rate, and extent of flow, respectively, compared to the cheddar cheese prepared with low Ca and P (0.53% Ca and 0.39% P). cheddar cheese prepared with high lactose (1.4%) content resulted in up to 7.7%, 7.0%, 4.9%, 4.2%, and 24.6% increase in softening time, softening temperature, melting time, melting temperature, and hardness, respectively, and 14.7%, 12.7%, and 2.8% decrease in meltability, flow rate, and extent of flow respectively compared to the cheddar cheese prepared with low lactose (0.78%) content. cheddar cheese prepared with high salt-to-moisture ratio (6.4%) resulted in up to 21.8%, 11.3%, 12.9%, 4.1%, and 29.4% increase in softening time, softening temperature, melting time, melting temperature, and hardness, respectively, and 13.2%, 28.6%, and 2.6% decrease in meltability, flow rate, and extent of flow, respectively, compared to the cheddar cheese prepared with low salt-to-moisture ratio (4.8%) during ripening.

Dietary calcium intake is associated with adiposity, metabolic profile, inflammatory state and blood pressure, but not with erythrocyte intracellular calcium and endothelial function in healthy pre-menopausal women.

PubMed

da Silva Ferreira, Thaís; Torres, Márcia Regina Simas Gonçalves; Sanjuliani, Antonio Felipe

2013-09-28

Recent studies have suggested that dietary Ca may have beneficial effects on adiposity, insulin resistance, dyslipidaemia and blood pressure (BP). One potential mechanism underlying these benefits involves modifications in intracellular Ca concentration ([Ca2+]i). The present study aimed to evaluate the associations of dietary Ca with adiposity, erythrocyte [Ca2+]i, metabolic profile, BP, inflammatory state and endothelial function in healthy pre-menopausal women. In the present cross-sectional study, seventy-six women aged 18–50 years were submitted to the evaluation of dietary intake, anthropometric parameters, body composition, erythrocyte [Ca2+]i, biochemical variables, endothelial function and BP. A FFQ was used to assess usual dietary intake. Endothelial function was evaluated by serum concentrations of adhesion molecules and by the peripheral arterial tonometry (PAT) method, using Endo-PAT 2000®. Participants were allocated into two groups according to Ca intake: low-Ca group (LCG; n 32; < 600 mg/d) and high-Ca group (HCG; n 44; ≥ 600 mg/d). Women in the LCG compared with those in the HCG exhibited, after adjustments for potential confounders, higher values of BMI, waist circumference, waist:height ratio, percentage of body fat, insulin, homeostasis model assessment of insulin resistance, leptin, diastolic and mean BP; and lower levels of HDL-cholesterol, adiponectin and vascular cell adhesion molecule 1. Endothelial function assessed by PAT and [Ca2+]i was similar in both groups. Subjects in the HCG had lower OR for prevalent overweight, obesity, abdominal obesity, insulin resistance, HDL-cholesterol < 600 mg/l and systolic BP >120 mmHg. The findings of the present study suggest that high Ca intake is inversely associated with some cardiovascular risk factors.

Diastolic scattered light fluctuation, resting force and twitch force in mammalian cardiac muscle

PubMed Central

Lakatta, E. G.; Lappé, D. L.

1981-01-01

1. When coherent light was passed through isolated isometric cardiac muscles during the diastolic or resting period, intensity fluctuations were observed in the scattered field. The frequency of these intensity fluctuations (f½) varied with many experimental interventions known to enhance Ca2+ flux into the cell. 2. In rat muscles stimulated at low frequencies (0.1 ± 2.0 min-1) stepwise increases (0.4-10 mm) of [Ca2+] in the bathing fluid ([Ca2+]e), or addition of ouabain (10-6-6 × 10-4 m) to the perfusate caused stepwise increases in f½. These were paralleled by increments in resting force (RF) such that the changes in f½ and RF were highly correlated. Substitution of K+ for Na+ in the perfusate resulted in parallel transients in RF and f½. 3. In contrast to the rat, most cat muscles stimulated at low frequencies in the steady state exhibited neither diastolic intensity fluctuations nor Ca2+-dependent changes in RF in [Ca2+]e of 10 mm or less; when [Ca2+]e was increased to 12-32 mm, however, steady-state Ca2+-dependent f½ and RF were observed. In a given [Ca2+]e reduction of [Na+]e increased f½. In the transient state following cessation of regular stimulation at more rapid rates (12-96 min-1) intensity fluctuations were present in all [Ca2+]e and decayed with time (seconds to minutes); the f½ and time course of the decay of the fluctuations were determined by the rate of prior stimulation and [Ca2+]e. 4. Maximum potentiation of twitch force in response to the above inotropic interventions was associated with an optimal level of f½ which was similar in both species; when higher levels of f½ were produced by more intense inotropic intervention, twitch force declined. Over the range of inotropic intervention up to and including that at which maximum twitch potentiation occurred, the increase in diastolic f½ predicted the extent of twitch potentiation with a high degree of accuracy (r > 0.97) both in the transient and steady states. 5. In contrast to the other inotropic interventions studied, catecholamines were unique in that neither f½ nor RF increased over a full range of concentrations that resulted in maximum potentiation of the twitch. 6. It is concluded from these observations that f½ reflects diastolic Ca2+-dependent myofilament interaction; the increase in the extent of this interaction by inotropic interventions that do not alter the affinity of the myofilaments for Ca2+ probably reflects an increase in diastolic myoplasmic [Ca2+], an optimal level of which is associated with maximal potentiation of twitch force; the difference in f½ in rat and cat muscles under a given set of in vitro conditions may be related to the marked species difference in the effectiveness of excitation—contraction coupling. PMID:7310715

Near-membrane [Ca2+] transients resolved using the Ca2+ indicator FFP18.

PubMed

Etter, E F; Minta, A; Poenie, M; Fay, F S

1996-05-28

(Ca2+)-sensitive processes at cell membranes involved in contraction, secretion, and neurotransmitter release are activated in situ or in vitro by Ca2+ concentrations ([Ca2+]) 10-100 times higher than [Ca2+] measured during stimulation in intact cells. This paradox might be explained if the local [Ca2+] at the cell membrane is very different from that in the rest of the cell. Soluble Ca2+ indicators, which indicate spatially averaged cytoplasmic [Ca2+], cannot resolve these localized, near-membrane [Ca2+] signals. FFP18, the newest Ca2+ indicator designed to selectively monitor near-membrane [Ca2+], has a lower Ca2+ affinity and is more water soluble than previously used membrane-associating Ca2+ indicators. Images of the intracellular distribution of FFP18 show that >65% is located on or near the plasma membrane. [Ca2+] transients recorded using FFP18 during membrane depolarization-induced Ca2+ influx show that near-membrane [Ca2+] rises faster and reaches micromolar levels at early times when the cytoplasmic [Ca2+], recorded using fura-2, has risen to only a few hundred nanomolar. High-speed series of digital images of [Ca2+] show that near-membrane [Ca2+], reported by FFP18, rises within 20 msec, peaks at 50-100 msec, and then declines. [Ca2+] reported by fura-2 rose slowly and continuously throughout the time images were acquired. The existence of these large, rapid increases in [Ca2+] directly beneath the surface membrane may explain how numerous (Ca2+)-sensitive membrane processes are activated at times when bulk cytoplasmic [Ca2+] changes are too small to activate them.

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

PubMed

Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

2017-06-01

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

Redistribution of carbon flux in Torulopsis glabrata by altering vitamin and calcium level.

PubMed

Liu, Liming; Li, Yin; Zhu, Yang; Du, Guocheng; Chen, Jian

2007-01-01

Manipulation of cofactor (thiamine, biotin and Ca(2+)) levels as a potential tool to redistribute carbon flux was studied in Torulopsis glabrata. With sub-optimization of vitamin in fermentation medium, the carbon flux was blocked at the key node of pyruvate, and 69 g/L pyruvate was accumulated. Increasing the concentrations of thiamine and biotin could selectively open the valve of carbon flux from pyruvate to pyruvate dehydrogenase complex, the pyruvate carboxylase (PC) pathway and the channel into the TCA cycle, leading to the over-production of alpha-ketoglutarate. In addition, the activity of PC was enhanced with Ca(2+) present in fermentation medium. By combining high concentration's vitamins and CaCO(3) as the pH buffer, a batch culture was conducted in a 7-L fermentor, with the pyruvate concentration decreased to 21.8 g/L while alpha-ketoglutarate concentration increased to 43.7 g/L. Our study indicated that the metabolic flux could be redistributed to overproduce desired metabolites with manipulating the cofactor levels. Furthermore, the manipulation of vitamin level provided an alternative tool to realize metabolic engineering goals.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

PubMed

Gutiérrez-Repiso, Carolina; Soriguer, Federico; Rojo-Martínez, Gemma; García-Fuentes, Eduardo; Valdés, Sergio; Goday, Albert; Calle-Pascual, Alfonso; López-Alba, Alfonso; Castell, Conxa; Menéndez, Edelmiro; Bordiú, Elena; Delgado, Elías; Ortega, Emilio; Pascual-Manich, Gemma; Urrutia, Inés; Mora-Peces, Inmaculada; Vendrell, Joan; Vázquez, José Antonio; Franch, Josep; Girbés, Juan; Castaño, Luis; Serrano-Ríos, Manuel; Martínez-Larrad, María Teresa; Catalá, Miguel; Carmena, Rafael; Gomis, Ramón; Casamitjana, Roser; Gaztambide, Sonia

2014-09-01

Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations. Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, <25 kg/m(2); overweight, 25-29.9 kg/m(2); and obese, >30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol intake were associated with being metabolically healthy. Olive oil intake was negatively associated with the prevalence of CA. Smoking, physical activity level, and alcohol intake contribute to the explanation of the prevalence of CA in the Spanish population, as in the US population. However in Spain, olive oil intake contributes significantly to the explanation of the variance in the prevalence of CA. Copyright © 2014 Elsevier B.V. All rights reserved.

Acute exposure to progesterone attenuates cardiac contraction by modifying myofilament calcium sensitivity in the female mouse heart

PubMed Central

Feridooni, Hirad A.; MacDonald, Jennifer K.; Ghimire, Anjali; Pyle, W. Glen

2017-01-01

Acute application of progesterone attenuates cardiac contraction, although the underlying mechanisms are unclear. We investigated whether progesterone modified contraction in isolated ventricular myocytes and identified the Ca2+ handling mechanisms involved in female C57BL/6 mice (6–9 mo; sodium pentobarbital anesthesia). Cells were field-stimulated (4 Hz; 37°C) and exposed to progesterone (0.001–10.0 μM) or vehicle (35 min). Ca2+ transients (fura-2) and cell shortening were recorded simultaneously. Maximal concentrations of progesterone inhibited peak contraction by 71.4% (IC50 = 160 ± 50 nM; n = 12) and slowed relaxation by 75.4%. By contrast, progesterone had no effect on amplitudes or time courses of underlying Ca2+ transients. Progesterone (1 µM) also abbreviated action potential duration. When the duration of depolarization was controlled by voltage-clamp, progesterone attenuated contraction and slowed relaxation but did not affect Ca2+ currents, Ca2+ transients, sarcoplasmic reticulum (SR) content, or fractional release of SR Ca2+. Actomyosin MgATPase activity was assayed in myofilaments from hearts perfused with progesterone (1 μM) or vehicle (35 min). While maximal responses to Ca2+ were not affected by progesterone, myofilament Ca2+ sensitivity was reduced (EC50 = 0.94 ± 0.01 µM for control, n = 7 vs. 1.13 ± 0.05 μM for progesterone, n = 6; P < 0.05) and progesterone increased phosphorylation of myosin binding protein C. The effects on contraction were inhibited by lonaprisan (progesterone receptor antagonist) and levosimendan (Ca2+ sensitizer). Unlike results in females, progesterone had no effect on contraction or myofilament Ca2+ sensitivity in age-matched male mice. These data indicate that progesterone reduces myofilament Ca2+ sensitivity in female hearts, which may exacerbate manifestations of cardiovascular disease late in pregnancy when progesterone levels are high. NEW & NOTEWORTHY We investigated myocardial effects of acute application of progesterone. In females, but not males, progesterone attenuates and slows cardiomyocyte contraction with no effect on calcium transients. Progesterone also reduces myofilament calcium sensitivity in female hearts. This may adversely affect heart function, especially when serum progesterone levels are high in pregnancy. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/acute-progesterone-modifies-cardiac-contraction/. PMID:27793852

Calcium buffering properties of sarcoplasmic reticulum and calcium-induced Ca2+ release during the quasi-steady level of release in twitch fibers from frog skeletal muscle

PubMed Central

Fénelon, Karine; Lamboley, Cédric R.H.; Carrier, Nicole

2012-01-01

Experiments were performed to characterize the properties of the intrinsic Ca2+ buffers in the sarcoplasmic reticulum (SR) of cut fibers from frog twitch muscle. The concentrations of total and free calcium ions within the SR ([CaT]SR and [Ca2+]SR) were measured, respectively, with the EGTA/phenol red method and tetramethylmurexide (a low affinity Ca2+ indicator). Results indicate SR Ca2+ buffering was consistent with a single cooperative-binding component or a combination of a cooperative-binding component and a linear binding component accounting for 20% or less of the bound Ca2+. Under the assumption of a single cooperative-binding component, the most likely resting values of [Ca2+]SR and [CaT]SR are 0.67 and 17.1 mM, respectively, and the dissociation constant, Hill coefficient, and concentration of the Ca-binding sites are 0.78 mM, 3.0, and 44 mM, respectively. This information can be used to calculate a variable proportional to the Ca2+ permeability of the SR, namely d[CaT]SR/dt ÷ [Ca2+]SR (denoted release permeability), in experiments in which only [CaT]SR or [Ca2+]SR is measured. In response to a voltage-clamp step to −20 mV at 15°C, the release permeability reaches an early peak followed by a rapid decline to a quasi-steady level that lasts ∼50 ms, followed by a slower decline during which the release permeability decreases by at least threefold. During the quasi-steady level of release, the release amplitude is 3.3-fold greater than expected from voltage activation alone, a result consistent with the recruitment by Ca-induced Ca2+ release of 2.3 SR Ca2+ release channels neighboring each channel activated by its associated voltage sensor. Release permeability at −60 mV increases as [CaT]SR decreases from its resting physiological level to ∼0.1 of this level. This result argues against a release termination mechanism proposed in mammalian muscle fibers in which a luminal sensor of [Ca2+]SR inhibits release when [CaT]SR declines to a low level. PMID:23008434

Calcium buffering properties of sarcoplasmic reticulum and calcium-induced Ca(2+) release during the quasi-steady level of release in twitch fibers from frog skeletal muscle.

PubMed

Fénelon, Karine; Lamboley, Cédric R H; Carrier, Nicole; Pape, Paul C

2012-10-01

Experiments were performed to characterize the properties of the intrinsic Ca(2+) buffers in the sarcoplasmic reticulum (SR) of cut fibers from frog twitch muscle. The concentrations of total and free calcium ions within the SR ([Ca(T)](SR) and [Ca(2+)](SR)) were measured, respectively, with the EGTA/phenol red method and tetramethylmurexide (a low affinity Ca(2+) indicator). Results indicate SR Ca(2+) buffering was consistent with a single cooperative-binding component or a combination of a cooperative-binding component and a linear binding component accounting for 20% or less of the bound Ca(2+). Under the assumption of a single cooperative-binding component, the most likely resting values of [Ca(2+)](SR) and [Ca(T)](SR) are 0.67 and 17.1 mM, respectively, and the dissociation constant, Hill coefficient, and concentration of the Ca-binding sites are 0.78 mM, 3.0, and 44 mM, respectively. This information can be used to calculate a variable proportional to the Ca(2+) permeability of the SR, namely d[Ca(T)](SR)/dt ÷ [Ca(2+)](SR) (denoted release permeability), in experiments in which only [Ca(T)](SR) or [Ca(2+)](SR) is measured. In response to a voltage-clamp step to -20 mV at 15°C, the release permeability reaches an early peak followed by a rapid decline to a quasi-steady level that lasts ~50 ms, followed by a slower decline during which the release permeability decreases by at least threefold. During the quasi-steady level of release, the release amplitude is 3.3-fold greater than expected from voltage activation alone, a result consistent with the recruitment by Ca-induced Ca(2+) release of 2.3 SR Ca(2+) release channels neighboring each channel activated by its associated voltage sensor. Release permeability at -60 mV increases as [Ca(T)](SR) decreases from its resting physiological level to ~0.1 of this level. This result argues against a release termination mechanism proposed in mammalian muscle fibers in which a luminal sensor of [Ca(2+)](SR) inhibits release when [Ca(T)](SR) declines to a low level.

Exogenous Calcium Alleviates Photoinhibition of PSII by Improving the Xanthophyll Cycle in Peanut (Arachis Hypogaea) Leaves during Heat Stress under High Irradiance

PubMed Central

Yang, Sha; Wang, Fang; Guo, Feng; Meng, Jing-Jing; Li, Xin-Guo; Dong, Shu-Ting; Wan, Shu-Bo

2013-01-01

Peanut is one of the calciphilous plants. Calcium (Ca) serves as a ubiquitous central hub in a large number of signaling pathways. The effect of exogenous calcium nitrate [Ca(NO3)2] (6 mM) on the dissipation of excess excitation energy in the photosystem II (PSII) antenna, especially on the level of D1 protein and the xanthophyll cycle in peanut plants under heat (40°C) and high irradiance (HI) (1 200 µmol m−2 s−1) stress were investigated. Compared with the control plants [cultivated in 0 mM Ca(NO3)2 medium], the maximal photochemical efficiency of PSII (Fv/Fm) in Ca2+-treated plants showed a slighter decrease after 5 h of stress, accompanied by higher non-photochemical quenching (NPQ), higher expression of antioxidative genes and less reactive oxygen species (ROS) accumulation. Meanwhile, higher content of D1 protein and higher ratio of (A+Z)/(V+A+Z) were also detected in Ca2+-treated plants under such stress. These results showed that Ca2+ could help protect the peanut photosynthetic system from severe photoinhibition under heat and HI stress by accelerating the repair of D1 protein and improving the de-epoxidation ratio of the xanthophyll cycle. Furthermore, EGTA (a chelant of Ca ion), LaCl3 (a blocker of Ca2+ channel in cytoplasmic membrane), and CPZ [a calmodulin (CaM) antagonist] were used to analyze the effects of Ca2+/CaM on the variation of (A+Z)/(V+A+Z) (%) and the expression of violaxanthin de-epoxidase (VDE). The results indicated that CaM, an important component of the Ca2+ signal transduction pathway, mediated the expression of the VDE gene in the presence of Ca to improve the xanthophyll cycle. PMID:23940721

Functional roles of the pepper RING finger protein gene, CaRING1, in abscisic acid signaling and dehydration tolerance.

PubMed

Lim, Chae Woo; Hwang, Byung Kook; Lee, Sung Chul

2015-09-01

Plants are constantly exposed to a variety of biotic and abiotic stresses, which include pathogens and conditions of high salinity, low temperature, and drought. Abscisic acid (ABA) is a major plant hormone involved in signal transduction pathways that mediate the defense response of plants to abiotic stress. Previously, we isolated Ring finger protein gene (CaRING1) from pepper (Capsicum annuum), which is associated with resistance to bacterial pathogens, accompanied by hypersensitive cell death. Here, we report a new function of the CaRING1 gene product in the ABA-mediated defense responses of plants to dehydration stress. The expression of the CaRING1 gene was induced in pepper leaves treated with ABA or exposed to dehydration or NaCl. Virus-induced gene silencing of CaRING1 in pepper plants exhibited low degree of ABA-induced stomatal closure and high levels of transpirational water loss in dehydrated leaves. These led to be more vulnerable to dehydration stress in CaRING1-silenced pepper than in the control pepper, accompanied by reduction of ABA-regulated gene expression and low accumulation of ABA and H2O2. In contrast, CaRING1-overexpressing transgenic plants showed enhanced sensitivity to ABA during the seedling growth and establishment. These plants were also more tolerant to dehydration stress than the wild-type plants because of high ABA accumulation, enhanced stomatal closure and increased expression of stress-responsive genes. Together, these results suggest that the CaRING1 acts as positive factor for dehydration tolerance in Arabidopsis by modulating ABA biosynthesis and ABA-mediated stomatal closing and gene expression.

Expression of the high capacity calcium-binding domain of calreticulin increases bioavailable calcium stores in plants

NASA Technical Reports Server (NTRS)

Wyatt, Sarah E.; Tsou, Pei-Lan; Robertson, Dominique; Brown, C. S. (Principal Investigator)

2002-01-01

Modulation of cytosolic calcium levels in both plants and animals is achieved by a system of Ca2+-transport and storage pathways that include Ca2+ buffering proteins in the lumen of intracellular compartments. To date, most research has focused on the role of transporters in regulating cytosolic calcium. We used a reverse genetics approach to modulate calcium stores in the lumen of the endoplasmic reticulum. Our goals were two-fold: to use the low affinity, high capacity Ca2+ binding characteristics of the C-domain of calreticulin to selectively increase Ca2+ storage in the endoplasmic reticulum, and to determine if those alterations affected plant physiological responses to stress. The C-domain of calreticulin is a highly acidic region that binds 20-50 moles of Ca2+ per mole of protein and has been shown to be the major site of Ca2+ storage within the endoplasmic reticulum of plant cells. A 377-bp fragment encoding the C-domain and ER retention signal from the maize calreticulin gene was fused to a gene for the green fluorescent protein and expressed in Arabidopsis under the control of a heat shock promoter. Following induction on normal medium, the C-domain transformants showed delayed loss of chlorophyll after transfer to calcium depleted medium when compared to seedlings transformed with green fluorescent protein alone. Total calcium measurements showed a 9-35% increase for induced C-domain transformants compared to controls. The data suggest that ectopic expression of the calreticulin C-domain increases Ca2+ stores, and that this Ca2+ reserve can be used by the plant in times of stress.

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

PubMed

García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

2017-12-01

The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

PubMed

Wang, Qian; Huang, Lihong; Yue, Jianbo

2017-06-01

High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of the Mineral Content of Tap Water and Bottled Waters

PubMed Central

Azoulay, Arik; Garzon, Philippe; Eisenberg, Mark J

2001-01-01

OBJECTIVES Because of growing concern that constituents of drinking water may have adverse health effects, consumption of tap water in North America has decreased and consumption of bottled water has increased. Our objectives were to 1) determine whether North American tap water contains clinically important levels of calcium (Ca2+), magnesium (Mg2+), and sodium (Na+) and 2) determine whether differences in mineral content of tap water and commercially available bottled waters are clinically important. DESIGN We obtained mineral analysis reports from municipal water authorities of 21 major North American cities. Mineral content of tap water was compared with published data regarding commercially available bottled waters and with dietary reference intakes (DRIs). MEASUREMENTS AND MAIN RESULTS Mineral levels varied among tap water sources in North America and among bottled waters. European bottled waters generally contained higher mineral levels than North American tap water sources and North American bottled waters. For half of the tap water sources we examined, adults may fulfill between 8% and 16% of their Ca2+ DRI and between 6% and 31% of their Mg2+ DRI by drinking 2 liters per day. One liter of most moderate mineralization European bottled waters contained between 20% and 58% of the Ca2+ DRI and between 16% and 41% of the Mg2+ DRI in adults. High mineralization bottled waters often contained up to half of the maximum recommended daily intake of Na+. CONCLUSION Drinking water sources available to North Americans may contain high levels of Ca2+, Mg2+, and Na+ and may provide clinically important portions of the recommended dietary intake of these minerals. Physicians should encourage patients to check the mineral content of their drinking water, whether tap or bottled, and choose water most appropriate for their needs. PMID:11318912

The influences of the AMO and NAO on the sedimentary infill in an Azores Archipelago lake since ca. 1350 CE

NASA Astrophysics Data System (ADS)

Hernández, Armand; Sáez, Alberto; Bao, Roberto; Raposeiro, Pedro M.; Trigo, Ricardo M.; Doolittle, Sara; Masqué, Pere; Rull, Valentí; Gonçalves, Vítor; Vázquez-Loureiro, David; Rubio-Inglés, María J.; Sánchez-López, Guiomar; Giralt, Santiago

2017-07-01

The location of the Azores Archipelago in the North Atlantic makes this group of islands an excellent setting to study the long-term behavior of large oceanic and atmospheric climate dynamic patterns, such as the Atlantic Multidecadal Oscillation (AMO) and the North Atlantic Oscillation (NAO). Here, we present the impacts of these patterns on Lake Empadadas (Azores Archipelago) from the Medieval Climate Anomaly (MCA) - Little Ice Age (LIA) transition to the present based on sedimentological, geochemical and biological characterizations of the sedimentary record. Multivariate analyses of a number of proxies including X-ray fluorescence (XRF), X-ray diffraction (XRD), total organic and inorganic carbon (TOC and TIC) and diatom life forms abundance reveal that the sedimentary infill evolution has been controlled by (i) fluctuations in the lake level and (ii) variations in organic matter accumulation. Both processes are governed by climate variability and modulated by anthropogenic activities associated with changes on the lake catchment. Changes in these two sedimentary processes have been used to infer five stages: (i) the MCA-LIA transition (ca. 1350-1450 CE) was characterized by a predominantly positive AMO phase, which led to intermediate lake levels and high organic matter concentration; (ii) the first half of the LIA (ca. 1450-1600 CE) was characterized by predominant lowstand conditions and intermediate organic matter deposition mainly related to negative AMO phases; (iii) the second half of the LIA (ca. 1600-1850 CE) was characterized by negative AMO and NAO phases, implying intermediate lake levels and high organic matter deposition; (iv) the Industrial era (ca. 1850-1980 CE) was characterized by the lowest lake level and organic matter accumulation associated with negative AMO phases; and (v) the period spanning between 1980 CE and the present reveals the highest lake levels and low organic matter deposition, being associated with very positive AMO conditions. At decadal-to-centennial scales, the influence of the AMO on Azorean climate plays a larger role than previously thought. In fact, the AMO appears to exert a stronger influence compared to the NAO, which is the main mode of climate variability at shorter time scales.

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca²⁺ handling in smooth muscle cells.

PubMed

Ma, Yu-Guang; Zhang, Yin-Bin; Bai, Yun-Gang; Dai, Zhi-Jun; Liang, Liang; Liu, Mei; Xie, Man-Jiang; Guan, Hai-Tao

2016-04-12

Vascular dysfunction is a distinctive phenotype in diabetes mellitus. Current treatments mostly focus on the tight glycemic control and few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. As a classical natural medicine, berberine has been explored as a possible therapy for DM. In addition, it is reported that berberine has an extra-protective effect in diabetic vascular dysfunction. However, little is known whether the berberine treatment could ameliorate the smooth muscle contractility independent of a functional endothelium under hyperglycemia. Furthermore, it remains unknown whether berberine affects the arterial contractility by regulating the intracellular Ca(2+) handling in vascular smooth cells (VSMCs) under hyperglycemia. Sprague-Dawley rats were used to establish the diabetic model with a high-fat diet plus injections of streptozotocin (STZ). Berberine (50, 100, and 200 mg/kg/day) were intragastrically administered to control and diabetic rats for 8 weeks since the injection of STZ. The intracellular Ca(2+) handling of isolated cerebral VSMCs was investigated by recording the whole-cell L-type Ca(2+) channel (CaL) currents, assessing the protein expressions of CaL channel, and measuring the intracellular Ca(2+) in response to caffeine. Our results showed that chronic administration of 100 mg/kg/day berberine not only reduced glucose levels, but also inhibited the augmented contractile function of cerebral artery to KCl and 5-hydroxytryptamine (5-HT) in diabetic rats. Furthermore, chronic administration of 100 mg/kg/day berberine significantly inhibited the CaL channel current densities, reduced the α1C-subunit expressions of CaL channel, decreased the resting intracellular Ca(2+) ([Ca(2+)]i) level, and suppressed the Ca(2+) releases from RyRs in cerebral VSMCs isolated from diabetic rats. Correspondingly, acute application of 10 μM berberine could directly inhibit the hyperglycemia-induced CaL currents and suppress the hyperglycemia-induced Ca(2+) releases from RyRs in cerebral VSMCs isolated from normal control rats. Our study indicated that berberine alleviated the cerebral arterial contractility in the rat model of streptozotocin-induced diabetes via regulating the intracellular Ca(2+) handling of smooth muscle cells.

Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

PubMed

Hu, Hai-Jie; Mao, Hui; Tan, Yong-Qiong; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

2016-01-01

To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P < 0.001), preoperative CA 125 levels ≤26 U/ml (OR 8.209, 95 % CI 2.624-25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma. Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in Drosophila

PubMed Central

Liao, Pin-Chao; Tandarich, Lauren C.

2017-01-01

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using the Drosophila third instar larval nervous system as the in vivo model, we found that ROS inhibited mitochondrial axonal transport more specifically, primarily due to reduced flux and velocity, but did not affect transport of other organelles. To understand the mechanisms underlying these effects, we examined Ca2+ levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca2+ levels, and that experimental reduction of Ca2+ to physiological levels rescued ROS-induced defects in mitochondrial transport in primary neuron cell cultures. In addition, in vivo activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca2+ and JNK signaling play roles in mediating these effects. In addition to transport defects, ROS produces imbalances in mitochondrial fission-fusion and metabolic state, indicating that mitochondrial transport, fission-fusion steady state, and metabolic state are closely interrelated in the response to ROS. PMID:28542430

Dendritic excitability modulates dendritic information processing in a purkinje cell model.

PubMed

Coop, Allan D; Cornelis, Hugo; Santamaria, Fidel

2010-01-01

Using an electrophysiological compartmental model of a Purkinje cell we quantified the contribution of individual active dendritic currents to processing of synaptic activity from granule cells. We used mutual information as a measure to quantify the information from the total excitatory input current (I(Glu)) encoded in each dendritic current. In this context, each active current was considered an information channel. Our analyses showed that most of the information was encoded by the calcium (I(CaP)) and calcium activated potassium (I(Kc)) currents. Mutual information between I(Glu) and I(CaP) and I(Kc) was sensitive to different levels of excitatory and inhibitory synaptic activity that, at the same time, resulted in the same firing rate at the soma. Since dendritic excitability could be a mechanism to regulate information processing in neurons we quantified the changes in mutual information between I(Glu) and all Purkinje cell currents as a function of the density of dendritic Ca (g(CaP)) and Kca (g(Kc)) conductances. We extended our analysis to determine the window of temporal integration of I(Glu) by I(CaP) and I(Kc) as a function of channel density and synaptic activity. The window of information integration has a stronger dependence on increasing values of g(Kc) than on g(CaP), but at high levels of synaptic stimulation information integration is reduced to a few milliseconds. Overall, our results show that different dendritic conductances differentially encode synaptic activity and that dendritic excitability and the level of synaptic activity regulate the flow of information in dendrites.

Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

PubMed

Hou, M F; Chen, Y L; Tseng, T F; Lin, C M; Chen, M S; Huang, C J; Huang, Y S; Hsieh, J S; Huang, T J; Jong, S B; Huang, Y F

1999-09-01

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

ATP promotes cell survival via regulation of cytosolic [Ca2+] and Bcl-2/Bax ratio in lung cancer cells

PubMed Central

Song, Shanshan; Jacobson, Krista N.; McDermott, Kimberly M.; Reddy, Sekhar P.; Cress, Anne E.; Tang, Haiyang; Dudek, Steven M.; Black, Stephen M.; Garcia, Joe G. N.; Makino, Ayako

2015-01-01

Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger elevated in the tumor microenvironment. ATP regulates cell functions by acting on purinergic receptors (P2X and P2Y) and activating a series of intracellular signaling pathways. We examined ATP-induced Ca2+ signaling and its effects on antiapoptotic (Bcl-2) and proapoptotic (Bax) proteins in normal human airway epithelial cells and lung cancer cells. Lung cancer cells exhibited two phases (transient and plateau phases) of increase in cytosolic [Ca2+] ([Ca2+]cyt) caused by ATP, while only the transient phase was observed in normal cells. Removal of extracellular Ca2+ eliminated the plateau phase increase of [Ca2+]cyt in lung cancer cells, indicating that the plateau phase of [Ca2+]cyt increase is due to Ca2+ influx. The distribution of P2X (P2X1-7) and P2Y (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11) receptors was different between lung cancer cells and normal cells. Proapoptotic P2X7 was nearly undetectable in lung cancer cells, which may explain why lung cancer cells showed decreased cytotoxicity when treated with high concentration of ATP. The Bcl-2/Bax ratio was increased in lung cancer cells following treatment with ATP; however, the antiapoptotic protein Bcl-2 demonstrated more sensitivity to ATP than proapoptotic protein Bax. Decreasing extracellular Ca2+ or chelating intracellular Ca2+ with BAPTA-AM significantly inhibited ATP-induced increase in Bcl-2/Bax ratio, indicating that a rise in [Ca2+]cyt through Ca2+ influx is the critical mediator for ATP-mediated increase in Bcl-2/Bax ratio. Therefore, despite high ATP levels in the tumor microenvironment, which would induce cell apoptosis in normal cells, the decreased P2X7 and elevated Bcl-2/Bax ratio in lung cancer cells may enable tumor cells to survive. Increasing the Bcl-2/Bax ratio by exposure to high extracellular ATP may, therefore, be an important selective pressure promoting transformation and cancer progression. PMID:26491047

From harmful Microcystis blooms to multi-functional core-double-shell microsphere bio-hydrochar materials.

PubMed

Bi, Lei; Pan, Gang

2017-11-13

Harmful algal blooms (HABs) induced by eutrophication is becoming a serious global environmental problem affecting public health and aquatic ecological sustainability. A novel strategy for the utilization of biomass from HABs was developed by converting the algae cells into hollow mesoporous bio-hydrochar microspheres via hydrothermal carbonization method. The hollow microspheres were used as microreactors and carriers for constructing CaO 2 core-mesoporous shell-CaO 2 shell microspheres (OCRMs). The CaO 2 shells could quickly increase dissolved oxygen to extremely anaerobic water in the initial 40 min until the CaO 2 shells were consumed. The mesoporous shells continued to act as regulators restricting the release of oxygen from CaO 2 cores. The oxygen-release time using OCRMs was 7 times longer than when directly using CaO 2 . More interestingly, OCRMs presented a high phosphate removal efficiency (95.6%) and prevented the pH of the solution from rising to high levels in comparison with directly adding CaO 2 due to the OH - controlled-release effect of OCRMs. The distinct core-double-shell micro/nanostructure endowed the OCRMs with triple functions for oxygen controlled-release, phosphorus removal and less impact on water pH. The study is to explore the possibility to prepare smarter bio-hydrochar materials by utilizing algal blooms.

Systems Modeling of Ca2+ Homeostasis and Mobilization in Platelets Mediated by IP3 and Store-Operated Ca2+ Entry

PubMed Central

Dolan, Andrew T.; Diamond, Scott L.

2014-01-01

Resting platelets maintain a stable level of low cytoplasmic calcium ([Ca2+]cyt) and high dense tubular system calcium ([Ca2+]dts). During thrombosis, activators cause a transient rise in inositol trisphosphate (IP3) to trigger calcium mobilization from stores and elevation of [Ca2+]cyt. Another major source of [Ca2+]cyt elevation is store-operated calcium entry (SOCE) through plasmalemmal calcium channels that open in response to store depletion as [Ca2+]dts drops. A 34-species systems model employed kinetics describing IP3-receptor, DTS-plasmalemma puncta formation, SOCE via assembly of STIM1 and Orai1, and the plasmalemma and sarco/endoplasmic reticulum Ca2+-ATPases. Four constraints were imposed: calcium homeostasis before activation; stable in zero extracellular calcium; IP3-activatable; and functional SOCE. Using a Monte Carlo method to sample three unknown parameters and nine initial concentrations in a 12-dimensional space near measured or expected values, we found that model configurations that were responsive to stimuli and demonstrated significant SOCE required high inner membrane electric potential (>−70 mV) and low resting IP3 concentrations. The absence of puncta in resting cells was required to prevent spontaneous store depletion in calcium-free media. Ten-fold increases in IP3 caused saturated calcium mobilization. This systems model represents a critical step in being able to predict platelets’ phenotypes during hemostasis or thrombosis. PMID:24806937

Variability in GCSE Controlled Assessments Subject to High Levels of Control: Ipsos MORI's "Evaluation of the Introduction of Controlled Assessment" (2011) and Its Implications for Controlled Assessments in English Literature

ERIC Educational Resources Information Center

Vowles, C. G.

2012-01-01

Controlled assessment (CA) was introduced as a valid and reliable replacement for coursework in GCSE English and English Literature assessments in 2009. I argue that CA lacks clear definition, typically mimics externally-assessed public examinations and, when interrogated through the Crooks eight-link chain model, is undermined by several threats…

Thematic accuracy assessment of the 2011 National Land Cover Database (NLCD)

USGS Publications Warehouse

Wickham, James; Stehman, Stephen V.; Gass, Leila; Dewitz, Jon; Sorenson, Daniel G.; Granneman, Brian J.; Poss, Richard V.; Baer, Lori Anne

2017-01-01

Accuracy assessment is a standard protocol of National Land Cover Database (NLCD) mapping. Here we report agreement statistics between map and reference labels for NLCD 2011, which includes land cover for ca. 2001, ca. 2006, and ca. 2011. The two main objectives were assessment of agreement between map and reference labels for the three, single-date NLCD land cover products at Level II and Level I of the classification hierarchy, and agreement for 17 land cover change reporting themes based on Level I classes (e.g., forest loss; forest gain; forest, no change) for three change periods (2001–2006, 2006–2011, and 2001–2011). The single-date overall accuracies were 82%, 83%, and 83% at Level II and 88%, 89%, and 89% at Level I for 2011, 2006, and 2001, respectively. Many class-specific user's accuracies met or exceeded a previously established nominal accuracy benchmark of 85%. Overall accuracies for 2006 and 2001 land cover components of NLCD 2011 were approximately 4% higher (at Level II and Level I) than the overall accuracies for the same components of NLCD 2006. The high Level I overall, user's, and producer's accuracies for the single-date eras in NLCD 2011 did not translate into high class-specific user's and producer's accuracies for many of the 17 change reporting themes. User's accuracies were high for the no change reporting themes, commonly exceeding 85%, but were typically much lower for the reporting themes that represented change. Only forest loss, forest gain, and urban gain had user's accuracies that exceeded 70%. Lower user's accuracies for the other change reporting themes may be attributable to the difficulty in determining the context of grass (e.g., open urban, grassland, agriculture) and between the components of the forest-shrubland-grassland gradient at either the mapping phase, reference label assignment phase, or both. NLCD 2011 user's accuracies for forest loss, forest gain, and urban gain compare favorably with results from other land cover change accuracy assessments.

Gonadotrophin-releasing hormone agonist combined with high-intensity focused ultrasound ablation for adenomyosis: a clinical study.

PubMed

Guo, Y; Duan, H; Cheng, J; Zhang, Y

2017-08-01

This study was to investigate the clinical efficacy of a gonadotrophin-releasing hormone agonist (GnRH-a) combined with high-intensity focused ultrasound (HIFU) ablation treatment for adenomyosis. A non-randomized prospective study. Gynaecological Minimally Invasive Centre in a single hospital. Patients with adenomyosis. Seventy-nine patients with adenomyosis were enrolled, including 55 patients in the control group treated with only HIFU and 24 patients in the study group treated with GnRH-a combined with HIFU. All the patients follow up 6 months after the HIFU procedure. The related parameters in the two groups were assessed before and 3 months as well as 6 months after treatment including serum levels of tumor marker and cytokine, volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrheal scores. Differences between the group treated with HIFU alone and the group treated with GnRH-a combined with HIFU. Before HIFU treatment, no significant difference was observed in serum levels of CA125, CA19-9, and interleukin-6 (IL-6), the volumes of uterine, adenomyotic lesion, and menstrual blood, as well as dysmenorrhea scores between the two groups. (P > 0.05). The serum CA125 levels significantly decreased in both groups after HIFU, but the serum CA125 levels in the study group were still significantly lower than those in the control group (P < 0.05). The volume of uterine and adenomyotic lesion significantly decreased in both groups after HIFU procedure, and decreased even more in the study group 3 and 6 months after treatment (P < 0.05). Dysmenorrhea scores and menstruation volumes significantly decreased in both groups after HIFU treatment. Moreover in the study group were significantly lower than those in the control group after 3 and 6 months (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. The short-term follow-up results indicate that the combination of GnRH-a and HIFU treatment significantly decreased serum CA125 levels, volumes of uterine, adenomyotic lesion and menstrual blood, as well as dysmenorrhea scores, and improved the clinical outcomes compared with the HIFU ablation alone in patients with adenomyosis. However, the further follow-up is needed to explore the long-term effects. A combination of GnRH-a with HIFU in the treatment of adenomyosis significantly decreased serum CA125 levels, uterine and adenomyotic lesion volumes, dysmenorrhea scores, and menstrual blood volumes. © 2017 Royal College of Obstetricians and Gynaecologists.

Calcium requirements of the modern broiler chicken as influenced by dietary protein and age.

PubMed

Driver, J P; Pesti, G M; Bakalli, R I; Edwards, H M

2005-10-01

Two experiments were conducted to examine the calcium requirements of broiler chickens fed corn-soybean meal diets. Experiment 1 used a 6 x 2 x 2 factorial arrangement and was conducted with broilers in floor pens during the grower phase (19 to 42 d). Diets were mixed with 6 levels of dietary Ca (0.325, 0.4, 0.475, 0.55, 0.625, and 0.9%) and 17 or 23% CP and fed to males and females separately. Experiment 2 was a 6 x 2 factorial design conducted using Petersime battery brooders during the starter phase (0 to 16 d). The same 6 levels of dietary Ca used in experiment 1 were fed separately to each sex, but only at the 23% level of CP. The diets used in both experiments were formulated to contain 0.45% nonphytin phosphorus. In experiment 1, grower chickens did not demonstrate significant body weight gain (BWG) or feed conversion ratio (FCR) response (g of feed per g of gain) to the different levels of Ca at either level of protein. The percentage tibia ash did not respond to increasing Ca levels beyond 0.625% Ca at either protein level. In experiment 2, BWG increased linearly up to 0.55 and 0.625% dietary Ca for males and females, respectively. Feed conversion ratio decreased linearly with increasing dietary Ca up to 0.625% Ca, and tibia ash was highest at 0.9% Ca for both sexes. These results suggest that the current NRC Ca requirements for the broiler starter (1.0%) are sufficient for maximum bone ash, but that Ca requirements for grower birds (0.9%) may be excessive for optimum BWG, FCR, and tibia ash.

A Putative Chloroplast-Localized Ca(2+)/H(+) Antiporter CCHA1 Is Involved in Calcium and pH Homeostasis and Required for PSII Function in Arabidopsis.

PubMed

Wang, Chao; Xu, Weitao; Jin, Honglei; Zhang, Taijie; Lai, Jianbin; Zhou, Xuan; Zhang, Shengchun; Liu, Shengjie; Duan, Xuewu; Wang, Hongbin; Peng, Changlian; Yang, Chengwei

2016-08-01

Calcium is important for chloroplast, not only in its photosynthetic but also nonphotosynthetic functions. Multiple Ca(2+)/H(+) transporters and channels have been described and studied in the plasma membrane and organelle membranes of plant cells; however, the molecular identity and physiological roles of chloroplast Ca(2+)/H(+) antiporters have remained unknown. Here we report the identification and characterization of a member of the UPF0016 family, CCHA1 (a chloroplast-localized potential Ca(2+)/H(+) antiporter), in Arabidopsis thaliana. We observed that the ccha1 mutant plants developed pale green leaves and showed severely stunted growth along with impaired photosystem II (PSII) function. CCHA1 localizes to the chloroplasts, and the levels of the PSII core subunits and the oxygen-evolving complex were significantly decreased in the ccha1 mutants compared with the wild type. In high Ca(2+) concentrations, Arabidopsis CCHA1 partially rescued the growth defect of yeast gdt1Δ null mutant, which is defective in a Ca(2+)/H(+) antiporter. The ccha1 mutant plants also showed significant sensitivity to high concentrations of CaCl2 and MnCl2, as well as variation in pH. Taken these results together, we propose that CCHA1 might encode a putative chloroplast-localized Ca(2+)/H(+) antiporter with critical functions in the regulation of PSII and in chloroplast Ca(2+) and pH homeostasis in Arabidopsis. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Regulation of Hippocampal α1d Adrenergic Receptor mRNA by Corticosterone in Adrenalectomized Rats

PubMed Central

Day, Heidi E.W.; Kryskow, Elisa M.; Watson, Stanley J.; Akil, Huda; Campeau, Serge

2008-01-01

The hippocampal formation receives extensive noradrenergic projections and expresses high levels of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Considerable evidence suggests that the noradrenergic system influences hippocampal corticosteroid receptors. However, there is relatively little data describing the influence of glucocorticoids on noradrenergic receptors in the hippocampal formation. α1d adrenergic receptor (ADR) mRNA is expressed at high levels in the hippocampal formation, within cells that express MR or GR. In order to determine whether expression of α1d ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7 or 14 days. Levels of α1d ADR mRNA were profoundly decreased in hippocampal subfields CA1, CA2 and CA3 and the medial and lateral blades of the dentate gyrus, as early as 1 day after ADX, as determined by in situ hybridization. The effect was specific for the hippocampal formation, with levels of α1d mRNA unaltered by ADX in the lateral amygdala, reticular thalamic nucleus, retrosplenial cortex or primary somatosensory cortex. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 days. Corticosterone replacement prevented the ADX-induced decrease in hippocampal α1d ADR mRNA, with the magnitude of effect depending on corticosterone dose and hippocampal subregion. These data indicate that α1d ADR mRNA expression in the hippocampal formation is highly sensitive to circulating levels of corticosterone, and provides further evidence for a close interaction between glucocorticoids and the noradrenergic system in the hippocampus. PMID:18534559

Prediction of possible CaMnO3 modifications using an ab initio minimization data-mining approach.

PubMed

Zagorac, Jelena; Zagorac, Dejan; Zarubica, Aleksandra; Schön, J Christian; Djuris, Katarina; Matovic, Branko

2014-10-01

We have performed a crystal structure prediction study of CaMnO3 focusing on structures generated by octahedral tilting according to group-subgroup relations from the ideal perovskite type (Pm\\overline 3 m), which is the aristotype of the experimentally known CaMnO3 compound in the Pnma space group. Furthermore, additional structure candidates have been obtained using data mining. For each of the structure candidates, a local optimization on the ab initio level using density-functional theory (LDA, hybrid B3LYP) and the Hartree--Fock (HF) method was performed, and we find that several of the modifications may be experimentally accessible. In the high-pressure regime, we identify a post-perovskite phase in the CaIrO3 type, not previously observed in CaMnO3. Similarly, calculations at effective negative pressure predict a phase transition from the orthorhombic perovskite to an ilmenite-type (FeTiO3) modification of CaMnO3.

P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells.

PubMed

Gailly, P; Szutkowska, M; Olinger, E; Debaix, H; Seghers, F; Janas, S; Vallon, V; Devuyst, O

2014-11-01

Luminal nucleotide stimulation is known to reduce Na(+) transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca(2+) transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca(2+) transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca(2+) concentration ([Ca(2+)]i) may control NCC transcription, we overexpressed the Ca(2+)-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca(2+). Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from -1 to -2,200 bp was not regulated by changes in [Ca(2+)]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca(2+) signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca(2+) concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA.

Effect of fluoride and low versus high levels of dietary calcium on mRNA expression of osteoprotegerin and osteoprotegerin ligand in the bone of rats.

PubMed

Yu, Jun; Gao, Yanhui; Sun, Dianjun

2013-06-01

The ratio of osteoprotegerin ligand (OPGL) to osteoprotegerin (OPG) determines the delicate balance between bone resorption and synthesis. The main objective of the present study is to investigate the possible role of OPGL and OPG in the bone metabolism of rats exposed to fluoride and the protective or aggravating effect of calcium (Ca). In a 6-month study, 270 weanling male Sprague-Dawley rats weighing between 70 and 90 g were divided randomly into six groups of 45 rats in each group. Three groups (groups I, III, and V)served as controls and drank deionized water and were fed purified rodent diets containing either 1,000 mg Ca/kg (low Ca), 5,000 mg Ca/kg (normal Ca), or 20,000 mg Ca/kg (high Ca). The three experimental groups (groups II, IV, and VI) were given the same diets but they drank water containing 100 mg F ion/L (from NaF). Every 2 months 15 rats were randomly selected from each group and sacrificed for the study. The ratio of OPGL mRNA to OPG mRNA was significantly increased by the sixth month in the distal femur joints of the F-exposed rats. Serum tartrate-resistant acid phosphatase activity and serum calcitonin activity in the F-exposed groups was increased, although changes were not apparent in the serum alkaline phosphatase or Gla-containing proteins, especially in the low calcium and high calcium diet F-exposed groups. The results indicated that OPG and OPGL may play important roles in skeletal fluorosis, and that fluoride may enhance osteoclast formation and induce osteoclastic bone destruction. A high Ca diet did not play a protective role, but rather may aggravate the damage of fluoride.

Ca2+ spike initiation from sensitized inositol 1,4,5-trisphosphate-sensitive Ca2+ stores in megakaryocytes.

PubMed

Ikeda, M; Kurokawa, K; Maruyama, Y

1994-06-01

Ca(2+)-mediated Ca2+ spikes were analysed in fura-2-loaded megakaryocytes. Direct Ca2+ loading using whole-cell dialysis induced an all-or-none Ca2+ spike on top of a tonic increase in cellular Ca2+ concentration ([Ca2+]i) with a latency of 3-7 s. The latency decreased with increasingly higher concentrations of Ca2+ in the dialysing solution. Spike size and its initiation did not correlate with the tonic level of [Ca2+]i. Thapsigargin completely abolished the Ca(2+)-induced spike initiation, suggesting that Ca2+ spikes originate from thapsigargin-sensitive Ca2+ pools. An inhibitor of phosphatidylinositide-specific phospholipase C (PLC), 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate prolonged the latency without changes of spike size in most cases (6/9 cells), but abolished the spike initiation in the other cells (3/9). The results suggest that an increase in [Ca2+]i charges up the inositol-1,4,5-trisphosphate-(InsP3)- and thapsigargin-sensitive Ca2+ pools which progressively sensitize to low or slightly elevated levels of InsP3 by the action of Ca(2+)-dependent PLC until a critical Ca2+ content is reached, and then the Ca2+ spike is triggered. Thus, the limiting step of Ca2+ spike triggering is the initial filling process and the level of InsP3 in megakaryocytes.

Excessive fructose intake causes 1,25-(OH)2D3-dependent inhibition of intestinal and renal calcium transport in growing rats

PubMed Central

Douard, Veronique; Sabbagh, Yves; Lee, Jacklyn; Patel, Chirag; Kemp, Francis W.; Bogden, John D.; Lin, Sheldon

2013-01-01

We recently discovered that chronic high fructose intake by lactating rats prevented adaptive increases in rates of active intestinal Ca2+ transport and in levels of 1,25-(OH)2D3, the active form of vitamin D. Since sufficient Ca2+ absorption is essential for skeletal growth, our discovery may explain findings that excessive consumption of sweeteners compromises bone integrity in children. We tested the hypothesis that 1,25-(OH)2D3 mediates the inhibitory effect of excessive fructose intake on active Ca2+ transport. First, compared with those fed glucose or starch, growing rats fed fructose for 4 wk had a marked reduction in intestinal Ca2+ transport rate as well as in expression of intestinal and renal Ca2+ transporters that was tightly associated with decreases in circulating levels of 1,25-(OH)2D3, bone length, and total bone ash weight but not with serum parathyroid hormone (PTH). Dietary fructose increased the expression of 24-hydroxylase (CYP24A1) and decreased that of 1α-hydroxylase (CYP27B1), suggesting that fructose might enhance the renal catabolism and impair the synthesis, respectively, of 1,25-(OH)2D3. Serum FGF23, which is secreted by osteocytes and inhibits CYP27B1 expression, was upregulated, suggesting a potential role of bone in mediating the fructose effects on 1,25-(OH)2D3 synthesis. Second, 1,25-(OH)2D3 treatment rescued the fructose effect and normalized intestinal and renal Ca2+ transporter expression. The mechanism underlying the deleterious effect of excessive fructose intake on intestinal and renal Ca2+ transporters is a reduction in serum levels of 1,25-(OH)2D3. This finding is significant because of the large amounts of fructose now consumed by Americans increasingly vulnerable to Ca2+ and vitamin D deficiency. PMID:23571713

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.

Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women's Health Initiative calcium/vitamin D randomized trial.

PubMed

Schnatz, Peter F; Jiang, Xuezhi; Vila-Wright, Sharon; Aragaki, Aaron K; Nudy, Matthew; O'Sullivan, David M; Jackson, Rebecca; LeBlanc, Erin; Robinson, Jennifer G; Shikany, James M; Womack, Catherine R; Martin, Lisa W; Neuhouser, Marian L; Vitolins, Mara Z; Song, Yiqing; Kritchevsky, Stephen; Manson, JoAnn E

2014-08-01

The objective of this study was to evaluate whether increased serum 25-hydroxyvitamin D3 (25OHD3) concentrations, in response to calcium/vitamin D (CaD) supplementation, are associated with improved lipids in postmenopausal women. The parent trial was a double-blind, randomized, placebo-controlled, parallel-group trial designed to test the effects of CaD supplementation (1,000 mg of elemental calcium + 400 IU of vitamin D3 daily) versus placebo in postmenopausal women. Women from the general community, including multiple sites in the United States, were enrolled between 1993 and 1998. This cohort included 300 white, 200 African-American, and 100 Hispanic participants who were randomly selected from the Women's Health Initiative CaD trial. Serum 25OHD3 and lipid (fasting plasma triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], and calculated low-density lipoprotein cholesterol [LDL-C]) levels were assessed before and after CaD randomization. There was a 38% increase in mean serum 25OHD3 concentrations after 2 years (95% CI, 1.29-1.47, P < 0.001) for women randomized to CaD (24.3 ng/mL postrandomization mean) compared with placebo (18.2 ng/mL). Women randomized to CaD had a 4.46-mg/dL mean decrease in LDL-C (P = 0.03). Higher concentrations of 25OHD3 were associated with higher HDL-C levels (P = 0.003), along with lower LDL-C and TG levels (P = 0.02 and P < 0.001, respectively). Supplemental CaD significantly increases 25OHD3 concentrations and decreases LDL-C. Women with higher 25OHD3 concentrations have more favorable lipid profiles, including increased HDL-C, lower LDL-C, and lower TG. These results support the hypothesis that higher concentrations of 25OHD3, in response to CaD supplementation, are associated with improved LDL-C.

Sarcoplasmic reticulum buffering of myoplasmic calcium in bovine coronary artery smooth muscle.

PubMed Central

Sturek, M; Kunda, K; Hu, Q

1992-01-01

1. We tested the hypothesis that the sarcoplasmic reticulum (SR) buffers (attenuates) the increase in averaged myoplasmic free [Ca2+] (Ca(im)) resulting from Ca2+ influx. 2. Fura-2 measurements of Ca(im) were obtained in single smooth muscle cells freshly dispersed from bovine coronary artery. 3. Caffeine (5 x 10(-3) M) elicited a transient increase in Ca(im) and depleted the SR Ca2+ store. In the continued presence of caffeine or 10(-5) M-ryanodine SR buffering of Ca(im) was inhibited. Subsequent exposure to high extracellular [K+] (greater than 30 mM, equimolar Na+ removal) elicited a 2-fold more rapid and 2-fold greater peak increase in Ca(im) than high K+ elicited when SR buffering of Ca(im) was normal. The augmented increase in Ca(im) was inhibited 35% by 10(-5) M-diltiazem, 65% by 2 x 10(-4) M-LaCl3, and 87% in Ca(2+)-free external solution. 4. When Ca(im) buffering capacity was increased by partially depleting the SR with a transient (1 min) exposure to caffeine, subsequent exposure to 80 nM-K+ solution increased Ca(im) almost 2-fold more slowly than 80 mM-K+ before depletion of Ca2+ from the SR. However, the influxing Ca2+ was sequestered by the SR and refilled it, as evident by the subsequent caffeine-induced Ca(im) transient being identical to the first. Increasing extracellular [K+] (thus, increasing depolarization and Na+ removal) caused proportional increases in Ca(im) and the subsequent caffeine-induced Ca(im) transients were proportionally larger, indicating a graded filling of the SR by Ca2+ influx. 5. Diltiazem (10(-5) M) inhibited the refilling of the SR achieved by 80 mM-K+, by 26%. Refilling was inhibited 76% by 80 mM-K+, Ca(2+)-free solution, indicating the fraction of refilling dependent on influx of Ca2+ through voltage-gated Ca2+ channels, leak channels, and other influx pathways. Mild depolarization with 35 mM-K+ (no Na+ removal) often caused no increase in Ca(im), but influx through voltage-gated Ca2+ channels occurred because the SR Ca2+ store was refilled. Also, 10(-5) M-diltiazem or 10(-6) M-TA3090 inhibited the refilling to levels attributable only to leak influx of Ca2+. 6. All data support our hypothesis that the SR significantly attenuates the amount of Ca2+ influx that accumulates to increase Ca(im).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1403813

The Effects of Calcitonin on the Development of and Ca2+ Levels in Heat-shocked Bovine Preimplantation Embryos In Vitro

PubMed Central

KAMANO, Shumpei; IKEDA, Shuntaro; SUGIMOTO, Miki; KUME, Shinichi

2014-01-01

Intracellular calcium homeostasis is essential for proper cell function. We investigated the effects of heat shock on the development of and the intracellular Ca2+ levels in bovine preimplantation embryos in vitro and the effects of calcitonin (CT), a receptor-mediated Ca2+ regulator, on heat shock-induced events. Heat shock (40.5 C for 10 h between 20 and 30 h postinsemination) of in vitro-produced bovine embryos did not affect the cleavage rate; however, it significantly decreased the rates of development to the 5- to 8-cell and blastocyst stages as compared with those of the control cultured for the entire period at 38.5 C (P < 0.05). The relative intracellular Ca2+ levels at the 1-cell stage (5 h after the start of heat shock), as assessed by Fluo-8 AM, a fluorescent probe for Ca2+, indicated that heat shock significantly lowered the Ca2+ level as compared with the control level. Semiquantitative reverse transcription PCR and western blot analyses revealed the expression of CT receptor in bovine preimplantation embryos. The addition of CT (10 nM) to the culture medium ameliorated the heat shock-induced impairment of embryonic development beyond the 5- to 8-cell stage. The Ca2+ level in the heat-shocked embryos cultured with CT was similar to that of the control embryos, suggesting that heat shock lowers the Ca2+ level in fertilized embryos in vitro and that a lower Ca2+ level is implicated in heat shock-induced impairment of embryonic development. Intracellular Ca2+-mobilizing agents, e.g., CT, may effectively circumvent the detrimental effects of heat shock on early embryonic development. PMID:24899099

Effect of a dairy- and calcium-rich diet on weight loss and appetite during energy restriction in overweight and obese adults: a randomized trial.

PubMed

Jones, K W; Eller, L K; Parnell, J A; Doyle-Baker, P K; Edwards, A L; Reimer, R A

2013-04-01

A diet rich in dairy and calcium (Ca) has been variably associated with improvements in body composition and decreased risk of type 2 diabetes. Our objective was to determine if a dietary pattern high in dairy and Ca improves weight loss and subjective appetite to a greater extent than a low dairy/Ca diet during energy restriction in overweight and obese adults with metabolic syndrome. A total of 49 participants were randomized to one of two treatment groups: Control (low dairy, ≈ 700 mg/day Ca, -500 kcal/day) or Dairy/Ca (high dairy, ≈ 1400 mg/day Ca, -500 kcal/day) for 12 weeks. Body composition, subjective ratings of appetite, food intake, plasma satiety hormones, glycemic response and inflammatory cytokines were measured. Control (-2.2 ± 0.5 kg) and Dairy/Ca (-3.3 ± 0.6 kg) had similar weight loss. Based on self-reported energy intake, the percentage of expected weight loss achieved was higher with Dairy/Ca (82.1 ± 19.4%) than Control (32.2 ± 7.7%; P=0.03). Subjects in the Dairy/Ca group reported feeling more satisfied (P=0.01) and had lower dietary fat intake (P=0.02) over 12 weeks compared with Control. Compared with Control, Dairy/Ca had higher plasma levels of peptide tyrosine tyrosine (PYY, P=0.01) during the meal tolerance test at week 12. Monocyte chemoattractant protein-1 was reduced at 30 min with Dairy/Ca compared with Control (P=0.04). In conclusion, a dairy- and Ca-rich diet was not associated with greater weight loss than control. Modest increases in plasma PYY concentrations with increased dairy/Ca intake, however, may contribute to enhanced sensations of satisfaction and reduced dietary fat intake during energy restriction.

Constraining Ecosystem Gross Primary Production and Transpiration with Measurements of Photosynthetic 13CO2 Discrimination

NASA Astrophysics Data System (ADS)

Blonquist, J. M.; Wingate, L.; Ogeé, J.; Bowling, D. R.

2011-12-01

The stable carbon isotope composition of atmospheric CO2 (δ13Ca) can provide useful information on water use efficiency (WUE) dynamics of terrestrial ecosystems and potentially constrain models of CO2 and water fluxes at the land surface. This is due to the leaf-level relationship between photosynthetic 13CO2 discrimination (Δ), which influences δ13Ca, and the ratio of leaf intercellular to atmospheric CO2 mole fractions (Ci / Ca), which is related to WUE and is determined by the balance between C assimilation (CO2 demand) and stomatal conductance (CO2 supply). We used branch-scale Δ derived from tunable diode laser absorption spectroscopy measurements collected in a Maritime pine forest to estimate Ci / Ca variations over an entire growing season. We combined Ci / Ca estimates with rates of gross primary production (GPP) derived from eddy covariance (EC) to estimate canopy-scale stomatal conductance (Gs) and transpiration (T). Estimates of T were highly correlated to T estimates derived from sapflow data (y = 1.22x + 0.08; r2 = 0.61; slope P < 0.001) and T predictions from an ecosystem model (MuSICA) (y = 0.88x - 0.05; r2 = 0.64; slope P < 0.001). As an alternative to estimating T, Δ measurements can be used to estimate GPP by combining Ci / Ca estimates with Gs estimates from sapflow data. Estimates of GPP were determined in this fashion and were highly correlated to GPP values derived from EC (y = 0.82 + 0.07; r2 = 0.61; slope P < 0.001) and GPP predictions from MuSICA (y = 1.10 + 0.42; r2 = 0.50; slope P < 0.001). Results demonstrate that the leaf-level relationship between Δ and Ci / Ca can be extended to the canopy-scale and that Δ measurements have utility for partitioning ecosystem-scale CO2 and water fluxes.

Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model

PubMed Central

Lu, Luyao; Xia, Ling; Zhu, Xiuwei

2012-01-01

Cardiac cells with heart failure are usually characterized by impairment of Ca2+ handling with smaller SR Ca2+ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca2+ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca2+ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca2+ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca2+ dynamics is unstable and Ca2+ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level. PMID:23056145

Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis

PubMed Central

O’Brien, Darragh P.; Durand, Dominique; Voegele, Alexis; Hourdel, Véronique; Davi, Marilyne; Chamot-Rooke, Julia; Vachette, Patrice; Brier, Sébastien; Ladant, Daniel

2017-01-01

Once translocated into the cytosol of target cells, the catalytic domain (AC) of the adenylate cyclase toxin (CyaA), a major virulence factor of Bordetella pertussis, is potently activated by binding calmodulin (CaM) to produce supraphysiological levels of cAMP, inducing cell death. Using a combination of small-angle X-ray scattering (SAXS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), and synchrotron radiation circular dichroism (SR-CD), we show that, in the absence of CaM, AC exhibits significant structural disorder, and a 75-residue-long stretch within AC undergoes a disorder-to-order transition upon CaM binding. Beyond this local folding, CaM binding induces long-range allosteric effects that stabilize the distant catalytic site, whilst preserving catalytic loop flexibility. We propose that the high enzymatic activity of AC is due to a tight balance between the CaM-induced decrease of structural flexibility around the catalytic site and the preservation of catalytic loop flexibility, allowing for fast substrate binding and product release. The CaM-induced dampening of AC conformational disorder is likely relevant to other CaM-activated enzymes. PMID:29287065

Calcium Metabolism in Newborn Infants THE INTERRELATIONSHIP OF PARATHYROID FUNCTION AND CALCIUM, MAGNESIUM, AND PHOSPHORUS METABOLISM IN NORMAL, “SICK,” AND HYPOCALCEMIC NEWBORNS

PubMed Central

David, Louis; Anast, Constantine S.

1974-01-01

Serum immunoreactive parathyroid hormone (iPTH) and plasma total calcium, ionized calcium, magnesium, and phosphorus levels were determined during the first 9 days of life in 137 normal term infants, 55 “sick” infants, and 43 hypocalcemic (Ca <7.5 mg/100 ml; Ca++<4.0 mg/100 ml) infants. In the cord blood, elevated levels of plasma Ca++ and Ca were observed, while levels of serum iPTH were either undetectable or low. In normal newborns during the first 48 h of life there was a decrease in plasma Ca and Ca++, while the serum iPTH level in most samples remained undetectable or low; after 48 h there were parallel increases in plasma Ca and Ca++ and serum iPTH levels. Plasma Mg and P levels increased progressively after birth in normal infants. In the sick infants, plasma Ca, Ca++ and P levels were significantly lower than in the normal newborns, while no significant differences were found in the plasma Mg levels. The general pattern of serum iPTH levels in the sick infants was similar to that observed in the normal group, though there was a tendency for the increase in serum iPTH to occur earlier and for the iPTH levels to be higher in the sick infants. In the hypocalcemic infants, plasma Mg levels were consistently lower than in the normal infants after 24 h of age, while no significant differences were found in the plasma P levels. Hyperphosphatemia was uncommon and did not appear to be a contributing factor in the pathogenesis of hypocalcemia in most infants. Most of the hypocalcemic infants, including those older than 48 h, had inappropriately low serum iPTH levels. Evidence obtained from these studies indicates that parathyroid secretion is normally low in the early new born period and impaired parathyroid function, characterized by undetectable or low serum iPTH, is present in most infants with neonatal hypocalcemia. Additional unknown factors appear to contribute to the lowering of plasma Ca in the neonatal period. The net effect of unknown plasma hypocalcemic factor(s) on the one hand and parathyroid activity on the other may account for differences in plasma Ca levels observed between normal, sick, and hypocalcemic infants. Depressed plasma Mg is frequently present in hypocalcemic infants. To what degree the hypomagnesemia reflects parathyroid insufficiency or the converse, to what degree parathyroid insufficiency and hypocalcemia are secondary to hypomagnesemia, is uncertain. PMID:4858778

Cellular distribution of calmodulin and calmodulin-binding proteins in Vicia faba L

NASA Technical Reports Server (NTRS)

Ling, V.; Assmann, S. M.

1992-01-01

The distribution of calmodulin (CaM) and CaM-binding proteins within Vicia faba was investigated. Both CaM and CaM-binding proteins were found to be differentially distributed among organs, tissues, and protoplast types. CaM levels, on a per protein basis, were found to be the highest in leaf epidermis, containing 3-fold higher levels of CaM than in total leaf. Similarly, guard cell and epidermal cell protoplasts were also found to have higher levels of CaM than mesophyll cell protoplasts. 125I-CaM blot overlay assays were performed to qualitatively examine CaM-binding proteins in these protoplast types as well as in whole tissues and organs. CaM-binding proteins with Mr 52,000, 78,000, and 115,000 were common in all metabolically active plant parts. Unique CaM-binding protein bands were detected in guard cell protoplasts (Mr 39,000, 88,000), stems (Mr 45,000, 60,000, 64,000), and roots (Mr 62,000), suggesting the presence of specialized CaM-dependent processes in these cells and organs.

Segregation of Calcium Isotopes in the Atmospheres of CP Stars as a Consequence of Light-Induced Drift

NASA Astrophysics Data System (ADS)

Parkhomenko, A. I.; Shalagin, A. M.

2018-06-01

A mechanism for the segregation of calcium isotopes in the atmospheres of chemically peculiar (CP) stars due to light-induced drift (LID) of singly charged 48Ca+ ions is discussed. One peculiarity of Ca+ is that an adequate description of the effect of LID requires taking into account several energy levels of Ca+, and thus several pairs of relative differences ( ν i - ν k )/ ν i for the transport frequencies for collisions of levels i and k with neutral atoms (hydrogen, helium). The known real (calculated ab initio) interaction potentials are used to numerically calculate the factors ( ν i - ν k )/ ν i for several states of Ca+ for collisions with H and He atoms. These computations show that, at the temperatures characteristic of the atmospheres of CP stars, T = 6600-12 000 K, fairly high values are obtained for Ca+ ions, ( ν i - ν k )/ ν i ≈ 0.4-0.6. Simple, transparent computations demonstrate that the LID rates of Ca+ ions in the atmospheres of cool CP stars ( T eff = 6600 K) exceed the drift rate due to light pressure by two orders of magnitude. The LID is directed upward in the stellar atmosphere, and the heavy isotope 48Ca is pushed into upper layers of the atmosphere. This can explain the observed predominance of the heavy isotope 48Ca in the upper atmospheric layers of CP stars; according to the radiative-diffusion theory, the action of light pressure alone (in the absence of LID) would lead to sinking of the isotope 48Ca deeper into stellar atmosphere, following the lighter main isotope 40Ca. The 48Ca+ LIDrate decreases and its drift rate due to light pressure increases with growth of the effective temperatures in the atmospheres of CP stars. The manifestations of LID and light pressure are roughly comparable in the atmospheres of CP stars with effective temperatures near T eff = 9500 K.

Carbonic anhydrase 2-like in the giant clam, Tridacna squamosa: characterization, localization, response to light, and possible role in the transport of inorganic carbon from the host to its symbionts.

PubMed

Ip, Yuen K; Koh, Clarissa Z Y; Hiong, Kum C; Choo, Celine Y L; Boo, Mel V; Wong, Wai P; Neo, Mei L; Chew, Shit F

2017-12-01

The fluted giant clam, Tridacna squamosa , lives in symbiosis with zooxanthellae which reside extracellularly inside a tubular system. Zooxanthellae fix inorganic carbon (C i ) during insolation and donate photosynthate to the host. Carbonic anhydrases catalyze the interconversion of CO 2 and HCO3-, of which carbonic anhydrase 2 (CA2) is the most ubiquitous and involved in many biological processes. This study aimed to clone a CA2 homolog ( CA2-like ) from the fleshy and colorful outer mantle as well as the thin and whitish inner mantle of T. squamosa , to determine its cellular and subcellular localization, and to examine the effects of light exposure on its gene and protein expression levels. The cDNA coding sequence of CA2-like from T. squamosa comprised 789 bp, encoding 263 amino acids with an estimated molecular mass of 29.6 kDa. A phenogramic analysis of the deduced CA2-like sequence denoted an animal origin. CA2-like was not detectable in the shell-facing epithelium of the inner mantle adjacent to the extrapallial fluid. Hence, CA2-like is unlikely to participate directly in light-enhanced calcification. By contrast, the outer mantle, which contains the highest density of tertiary tubules and zooxanthellae, displayed high level of CA2-like expression, and CA2-like was localized to the tubule epithelial cells. More importantly, exposure to light induced significant increases in the protein abundance of CA2-like in the outer mantle. Hence, CA2-like could probably take part in the increased supply of inorganic carbon (C i ) from the host clam to the symbiotic zooxanthellae when the latter conduct photosynthesis to fix C i during light exposure. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Structural, dynamical & electronic properties of CaCuO{sub 2}

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

Agrawal, B.K.; Agrawal, S.

1994-12-31

The scalar relativistic version of an accurate first principles full potential self- consistent linearized muffin tin orbital (LMTO) method has been employed for describing the physical properties of the parent system of the high-Tc oxide superconductors, i.e., CaCuO2. The presently employed modified version of the LMTO method is quite fast and goes beyond the usual LMTO-ASA method in the sense that it permits a completely general shape of the potential and the charge density. Also, in contrast to LMTO-ASA, the present method is also capable of treating distorted lattice structures accurately. The calculated values of the lattice parameters of puremore » CaCuO2 lie within 3% of the experimentally measured values for the Sr-doped system Ca(.86)Sr(.14)CuO(2). The computed electronic structures and the density of states is quite similar to those of the other oxide superconductors, except of their three- dimensional character because of the presence of strong coupling between the closely spaced CuO2 layers. The van Hove singularity peak appears slightly below the Fermi level and a small concentration of oxygenation /or/ substitutional doping may pin it as the Fermi level. The calculated frequencies for some symmetric frozen phonons for undoped CaCuO2 are quite near to the measured data for the Sr-doped CaCuO2.« less

Reduction of CaO and MgO Slag Components by Al in Liquid Fe

NASA Astrophysics Data System (ADS)

Mu, Haoyuan; Zhang, Tongsheng; Fruehan, Richard J.; Webler, Bryan A.

2018-05-01

This study documents laboratory-scale observations of reactions between Fe-Al alloys (0.1 to 2 wt pct Al) with slags and refractories. Al in steels is known to reduce oxide components in slag and refractory. With continued development of Al-containing Advanced High-Strength Steel (AHSS) grade, the effects of higher Al must be examined because reduction of components such as CaO and MgO could lead to uncontrolled modification of non-metallic inclusions. This may lead to castability or in-service performance problems. In this work, Fe-Al alloys and CaO-MgO-Al2O3 slags were melted in an MgO crucible and samples were taken at various times up to 60 minutes. Inclusions from these samples were characterized using an automated scanning electron microscope equipped with energy dispersive x-ray analysis (SEM/EDS). Initially Al2O3 inclusions were modified to MgAl2O4, then MgO, then MgO + CaO-Al2O3-MgO liquid inclusions. Modification of the inclusions was faster at higher Al levels. Very little Ca modification was observed except at 2 wt pct Al level. The thermodynamic feasibility of inclusion modification and some of the mass transfer considerations that may have led to the differences in the Mg and Ca modification behavior were discussed.

Structural, dynamical and electronic properties of CaCuO2

NASA Technical Reports Server (NTRS)

Agrawal, Bal K.; Agrawal, Savitri

1995-01-01

The scalar relativistic version of an accurate first principles full potential self-consistent linearized muffin tin orbital (LMTO) method has been employed for describing the physical properties of the parent system of the high-T(sub c) oxide superconductors, i.e., CaCuO2. The presently employed modified version of the LMTO method is quite fast and goes beyond the usual LMTO ASA method in the sense that it permits a completely general shape of the potential and the charge density. Also, in contrast to LMTO ASA, the present method is also capable of treating distorted lattice structures accurately. The calculated values of the lattice parameters of pure CaCuO2 lie within 3% of the experimentally measured values for the Sr-doped system Ca(0.86)Sr(0.14)CuO(2). The computed electronic structures and the density of states is quite similar to those of the other oxide superconductors, except of their three- dimensional character because of the presence of strong coupling between the closely spaced CuO2 layers. The van Hove singularity peak appears slightly below the Fermi level and a small concentration of oxygenation /or/ substitutional doping may pin it at the Fermi level. The calculated frequencies for some symmetric frozen phonons for undoped CaCuO2 are quite near to the measured data for the Sr-doped CaCuO2.

High-density lipoproteins induce a rapid and transient release of Ca2+ in cultured fibroblasts.

PubMed Central

Pörn, M I; Akerman, K E; Slotte, J P

1991-01-01

Several different cell types showed increased rates of proliferation and cholesterol mobilization in response to treatment with high-density lipoprotein (HDL). This would suggest that one main function of HDL is the activation of signal pathways in cells. In the current study we have used the fluorescent indicator fura-2 to monitor the level of cytosolic Ca2+ ([Ca2+]i) in human skin fibroblasts. Exposure of subconfluent as well as confluent fibroblasts to HDL3 (20-60 micrograms/ml) resulted in a rapid and transient increase in [Ca2+]i. Sequential additions of HDL3 resulted in diminished rises in [Ca2+]i. The transient rise in [Ca2+]i was observed with HDL prepared from plasma either by conventional ultracentrifugation or by precipitation with dextran sulphate. Chelation of the extracellular Ca2+ with EGTA prior to the addition of HDL3 did not prevent the HDL3-induced rise in [Ca2+]i, suggesting that the mobilized Ca2+ was derived mainly from intracellular stores. Covalent modification of the apoproteins of HDL3 with dimethyl suberimidate or tetranitromethane did not inhibit the HDL3-induced rise in [Ca2+]i. This indicates that the binding of HDL3 to cell surface receptors may not be necessary for the mobilization of intracellular Ca2+. Moreover, the Ca(2+)-releasing effect of HDL3 was not inhibited by the presence of albumin (1%, w/v) in the extracellular medium, suggesting that non-esterified fatty acids were not the cause of the increased [Ca2+]i. The exposure of fibroblasts to lysophosphatidic acid, a potent mitogen and Ca(2+)-releasing agent, before addition of HDL3 completely inhibited the HDL3-induced rise in [Ca2+]i. Furthermore, phorbol 12-myristate 13-acetate blocked the HDL3-induced rise in [Ca2+]i. The results of this study imply that exposure of cells to HDL generates an intracellular signal which is induced by a component of the lipid fraction. PMID:1930148

Hypervitaminosis D mediates compensatory Ca2+ hyperabsorption in TRPV5 knockout mice.

PubMed

Renkema, Kirsten Y; Nijenhuis, Tom; van der Eerden, Bram C J; van der Kemp, Annemiete W C M; Weinans, Harrie; van Leeuwen, Johannes P T M; Bindels, René J M; Hoenderop, Joost G J

2005-11-01

Vitamin D plays an important role in Ca(2+) homeostasis by controlling Ca(2+) (re)absorption in intestine, kidney, and bone. The epithelial Ca(2+) channel TRPV5 mediates the Ca(2+) entry step in active Ca(2+) reabsorption. TRPV5 knockout (TRPV5(-/-)) mice show impaired Ca(2+) reabsorption, hypercalciuria, hypervitaminosis D, and intestinal hyperabsorption of Ca(2+). Moreover, these mice demonstrate upregulation of intestinal TRPV6 and calbindin-D(9K) expression compared with wild-type mice. For addressing the role of the observed hypervitaminosis D in the maintenance of Ca(2+) homeostasis and the regulation of expression levels of the Ca(2+) transport proteins in kidney and intestine, TRPV5/25-hydroxyvitamin-D(3)-1alpha-hydroxylase double knockout (TRPV5(-/-)/1alpha-OHase(-/-)) mice, which show undetectable serum 1,25(OH)(2)D(3) levels, were generated. TRPV5(-/-)/1alpha-OHase(-/-) mice displayed a significant hypocalcemia compared with wild-type mice (1.10 +/- 0.02 and 2.54 +/- 0.01 mM, respectively; P < 0.05). mRNA levels of renal calbindin-D(28K) (7 +/- 2%), calbindin-D(9K) (32 +/- 4%), Na(+)/Ca(2+) exchanger (12 +/- 2%), and intestinal TRPV6 (40 +/- 8%) and calbindin-D(9K) (26 +/- 4%) expression levels were decreased compared with wild-type mice. Hyperparathyroidism and rickets were present in TRPV5(-/-)/1alpha-OHase(-/-) mice, more pronounced than observed in single TRPV5 or 1alpha-OHase knockout mice. It is interesting that a renal Ca(2+) leak, as demonstrated in TRPV5(-/-) mice, persisted in TRPV5(-/-)/1alpha-OHase(-/-) mice, but a compensatory upregulation of intestinal Ca(2+) transporters was abolished. In conclusion, the elevation of serum 1,25(OH)(2)D(3) levels in TRPV5(-/-) mice is responsible for the upregulation of intestinal Ca(2+) transporters and Ca(2+) hyperabsorption. Hypervitaminosis D, therefore, is of crucial importance to maintain normocalcemia in impaired Ca(2+) reabsorption in TRPV5(-/-) mice.

Metabolomic assessment reveals an elevated level of glucosinolate content in CaCl₂ treated broccoli microgreens.

PubMed

Sun, Jianghao; Kou, Liping; Geng, Ping; Huang, Huilian; Yang, Tianbao; Luo, Yaguang; Chen, Pei

2015-02-18

Preharvest calcium application has been shown to increase broccoli microgreen yield and extend shelf life. In this study, we investigated the effect of calcium application on its metabolome using ultra-high-performance liquid chromatography with mass spectrometry. The data collected were analyzed using principal component analysis and orthogonal projection to latent structural discriminate analysis. Chemical composition comparison shows that glucosinolates, a very important group of phytochemicals, are the major compounds enhanced by preharvest treatment with 10 mM calcium chloride (CaCl2). Aliphatic glucosinolates (glucoerucin, glucoiberin, glucoiberverin, glucoraphanin, pentyl glucosinolate, and hexyl glucosinolate) and indolic glucosinolates (glucobrassicin, neoglucobrassicin, and 4-hydroxyglucobrassicin) were increased significantly in the CaCl2 treated microgreens using metabolomic approaches. Targeted glucosinolate analysis using the ISO 9167-1 method was further employed to confirm the findings. Results indicate that glucosinolates can be considered as a class of compounds that are responsible for the difference between two groups and a higher glucosinolate level was found in CaCl2 treated groups at each time point after harvest in comparison with the control group.

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

PubMed

Schmidt, T; Rein, D T; Foth, D; Eibach, H W; Kurbacher, C M; Mallmann, P; Römer, T

2001-08-01

To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. Two prospective open-label studies with longitudinal follow-up in the second trial. Academic Department of Obstetrics and Gynecology, University of Cologne. Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.

Calcium/calmodulin-dependent kinase II and nitric oxide synthase 1-dependent modulation of ryanodine receptors during β-adrenergic stimulation is restricted to the dyadic cleft.

PubMed

Dries, Eef; Santiago, Demetrio J; Johnson, Daniel M; Gilbert, Guillaume; Holemans, Patricia; Korte, Sanne M; Roderick, H Llewelyn; Sipido, Karin R

2016-10-15

The dyadic cleft, where coupled ryanodine receptors (RyRs) reside, is thought to serve as a microdomain for local signalling, as supported by distinct modulation of coupled RyRs dependent on Ca 2+ /calmodulin-dependent kinase II (CaMKII) activation during high-frequency stimulation. Sympathetic stimulation through β-adrenergic receptors activates an integrated signalling cascade, enhancing Ca 2+ cycling and is at least partially mediated through CaMKII. Here we report that CaMKII activation during β-adrenergic signalling is restricted to the dyadic cleft, where it enhances activity of coupled RyRs thereby contributing to the increase in diastolic events. Nitric oxide synthase 1 equally participates in the local modulation of coupled RyRs. In contrast, the increase in the Ca 2+ content of the sarcoplasmic reticulum and related increase in the amplitude of the Ca 2+ transient are primarily protein kinase A-dependent. The present data extend the concept of microdomain signalling in the dyadic cleft and give perspectives for selective modulation of RyR subpopulations and diastolic events. In cardiac myocytes, β-adrenergic stimulation enhances Ca 2+ cycling through an integrated signalling cascade modulating L-type Ca 2+ channels (LTCCs), phospholamban and ryanodine receptors (RyRs). Ca 2+ /calmodulin-dependent kinase II (CaMKII) and nitric oxide synthase 1 (NOS1) are proposed as prime mediators for increasing RyR open probability. We investigate whether this pathway is confined to the high Ca 2+ microdomain of the dyadic cleft and thus to coupled RyRs. Pig ventricular myocytes are studied under whole-cell voltage-clamp and confocal line-scan imaging with Fluo-4 as a [Ca 2+ ] i indicator. Following conditioning depolarizing pulses, spontaneous RyR activity is recorded as Ca 2+ sparks, which are assigned to coupled and non-coupled RyR clusters. Isoproterenol (ISO) (10 nm) increases Ca 2+ spark frequency in both populations of RyRs. However, CaMKII inhibition reduces spark frequency in coupled RyRs only; NOS1 inhibition mimics the effect of CaMKII inhibition. Moreover, ISO induces the repetitive activation of coupled RyR clusters through CaMKII activation. Immunostaining shows high levels of CaMKII phosphorylation at the dyadic cleft. CaMKII inhibition reduces I CaL and local Ca 2+ transients during depolarizing steps but has only modest effects on amplitude or relaxation of the global Ca 2+ transient. In contrast, protein kinase A (PKA) inhibition reduces spark frequency in all RyRs concurrently with a reduction of sarcoplasmic reticulum Ca 2+ content, Ca 2+ transient amplitude and relaxation. In conclusion, CaMKII activation during β-adrenergic stimulation is restricted to the dyadic cleft microdomain, enhancing LTCC-triggered local Ca 2+ release as well as spontaneous diastolic Ca 2+ release whilst PKA is the major pathway increasing global Ca 2+ cycling. Selective CaMKII inhibition may reduce potentially arrhythmogenic release without negative inotropy. © 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel

NASA Technical Reports Server (NTRS)

Yamaguchi, T.; Ye, C.; Chattopadhyay, N.; Sanders, J. L.; Vassilev, P. M.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

2000-01-01

Human promyelocytic leukemia cells (HL-60) have been used widely as a model for studying the differentiation of hematopoietic progenitor cells in vitro. After treatment with phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], HL-60 cells differentiate into cells with the phenotype of monocytes/macrophages. We previously showed that peripheral blood monocytes and the murine J774 monocytic cell line express the CaR, and myeloid progenitors in the bone marrow and myeloid cells in peripheral blood other than monocytes express lower levels of the CaR. Therefore, we investigated whether undifferentiated HL-60 cells express a functional G protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) and if the expression of the CaR increases as these cells differentiate along the monocytic lineage. The use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by sequencing of the amplified products, identified an authentic CaR transcript in undifferentiated HL-60 cells. Both immunocytochemistry and Western blot analysis using a CaR-specific antiserum detected low levels of CaR protein expression in undifferentiated HL-60 cells. The levels of CaR protein increased considerably following treatment of the cells with PMA (50 nM) or 1,25(OH)(2)D(3) (100 nM) for 5 days. Northern analysis using a CaR-specific riboprobe identified CaR transcripts in undifferentiated HL-60 cells, but CaR mRNA levels did not change appreciably after treatment with either agent, suggesting that upregulation of CaR protein occurs at a translational level. PMA-treated HL-60 cells expressed a nonselective cation channel (NCC), and the calcimimetic CaR activator, NPS R-467, but not its less active stereoisomer, NPS S-467, as well as the polycationic CaR agonist, neomycin, activated this NCC, demonstrating that the CaR expressed in these cells is functionally active. Therefore, HL-60 cells exhibit an increase in CaR protein expression, occurring at a translational level during their differentiation into cells with a monocyte/macrophage phenotype in response to treatment with PMA or 1, 25(OH)(2)D(3), which is functionally linked to activation of a nonselective cation channel.

Differential expression and functional analysis of three calmodulin isoforms in germinating pea (Pisum sativum L.) seeds.

PubMed

Duval, Frédéric D; Renard, Michelle; Jaquinod, Michel; Biou, Valérie; Montrichard, Françoise; Macherel, David

2002-11-01

Implication of the ubiquitous, highly conserved, Ca2+ sensor calmodulin (CaM) in pea seed germination has been investigated. Mass spectrometry analysis of purified CaM revealed the coexistence in seeds of three protein isoforms, diverging from each other by single amino acid substitution in the N-terminal alpha-helix. CaM was shown to be encoded by a small multigenic family, and full-length cDNAs of the three isoforms (PsCaM1, 2 and 3) were isolated to allow the design of specific primers in more divergent 5' and 3' untranslated regions. Expression studies, performed by semiquantitative RT-PCR, demonstrated differential expression patterns of the three transcripts during germination. PsCaM1 and 2 were detected at different levels in dry axes and cotyledons, and they accumulated during imbibition and prior to radicle protrusion. In contrast, PsCaM3 appeared only upon radicle protrusion, then gradually increased in both tissues. To characterise the biochemical properties of the CaM isoforms, functional analyses were conducted in vitro using recombinant Strep-tagged proteins (CaM1-ST, CaM2-ST and CaM3-ST) expressed in Escherichia coli. Gel mobility shift assays revealed that CaM1-ST exhibited a stoichiometric binding of a synthetic amphiphilic CaM kinase II peptide while CaM2-ST and CaM3-ST affinities for the same peptide were reduced. Affinity differences were also observed for CaM isoform binding to Trp-3, an idealised helical CaM-binding peptide. However, the three proteins activated in the same way the CaM-dependent pea NAD kinase. Finally, the significance of the single substitutions upon CaM interaction with its targets is discussed in a structural context.

Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats.

PubMed

Kumar, Pardeep; Taha, Asia; Kumar, Nitin; Kumar, Vinod; Baquer, Najma Zaheer

2015-01-01

Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells.

PubMed

Engbers, Jordan D T; Anderson, Dustin; Asmara, Hadhimulya; Rehak, Renata; Mehaffey, W Hamish; Hameed, Shahid; McKay, Bruce E; Kruskic, Mirna; Zamponi, Gerald W; Turner, Ray W

2012-02-14

Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca(2+)-activated K(+) channels are known to control spike frequency in central neurons, Ca(2+)-activated K(+) channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca(2+) channels at the nanodomain level to support a previously undescribed transient voltage- and Ca(2+)-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca(2+) influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.

Influence of dietary magnesium on mineral, ascorbic acid and glutathione concentrations in tissues of a freshwater fish, the common carp.

PubMed

Dabrowska, H; Dabrowski, K

1990-01-01

Supplementation with dietary Mg at a minimum level of 0.06% seems to be essential to prevent the hypercalcinosis of the kidney and hepatopancreas in a fish, the common carp. Mg deficiency appears to have no effect on the Mg level in kidneys and hepatic tissue, whereas the Fe level in those tissues was significantly diminished by increasing dietary Mg supplementation up to 3.2 g.kg-1. Both hypercalcinosis and accumulation of Fe in soft tissues were more pronounced in fish offered diets high in protein (44%) compared to fish on low dietary protein (25%). The ascorbic acid in the hepatopancreas and kidney was greatly depleted in fish fed the high-protein diets, and this depletion did not correlate with the dietary Mg level nor with a high level of tissue Ca. However, the increased Ca concentration in the kidney coincided with the greatest depletion of ascorbate in fish fed a high-protein diet. The concentration of ascorbate in the brain was much less affected by a low level of vitamin C in the diets than in other tissues. Depletion of ascorbate in soft tissues did not correspond to fish growth but might be rather related to the metabolic rate imposed by the dietary nutrients. It is suggested that the Mg and ascorbic acid requirements in the carp are considerably elevated by the increased dietary protein level.

Forest calcium depletion and biotic retention along a soil nitrogen gradient

USGS Publications Warehouse

Perakis, Steven S.; Sinkhorn, Emily R.; Catricala, Christina; Bullen, Thomas D.; Fitzpatrick, John A.; Hynicka, Justin D.; Cromack, Kermit

2013-01-01

High nitrogen (N) accumulation in terrestrial ecosystems can shift patterns of nutrient limitation and deficiency beyond N toward other nutrients, most notably phosphorus (P) and base cations (calcium [Ca], magnesium [Mg], and potassium [K]). We examined how naturally high N accumulation from a legacy of symbiotic N fixation shaped P and base cation cycling across a gradient of nine temperate conifer forests in the Oregon Coast Range. We were particularly interested in whether long-term legacies of symbiotic N fixation promoted coupled N and organic P accumulation in soils, and whether biotic demands by non-fixing vegetation could conserve ecosystem base cations as N accumulated. Total soil N (0–100 cm) pools increased nearly threefold across the N gradient, leading to increased nitrate leaching, declines in soil pH from 5.8 to 4.2, 10-fold declines in soil exchangeable Ca, Mg, and K, and increased mobilization of aluminum. These results suggest that long-term N enrichment had acidified soils and depleted much of the readily weatherable base cation pool. Soil organic P increased with both soil N and C across the gradient, but soil inorganic P, biomass P, and P leaching loss did not vary with N, implying that historic symbiotic N fixation promoted soil organic P accumulation and P sufficiency for non-fixers. Even though soil pools of Ca, Mg, and K all declined as soil N increased, only Ca declined in biomass pools, suggesting the emergence of Ca deficiency at high N. Biotic conservation and tight recycling of Ca increased in response to whole-ecosystem Ca depletion, as indicated by preferential accumulation of Ca in biomass and surface soil. Our findings support a hierarchical model of coupled N–Ca cycling under long-term soil N enrichment, whereby ecosystem-level N saturation and nitrate leaching deplete readily available soil Ca, stimulating biotic Ca conservation as overall supply diminishes. We conclude that a legacy of biological N fixation can increase N and P accumulation in soil organic matter to the point that neither nutrient is limiting to subsequent non-fixers, while also resulting in natural N saturation that intensifies base cation depletion and deficiency.

The Social and Spatial Patterning of Life Stress Among Immigrants in Canada.

PubMed

Wang, Lu; Palacios, Elmer Lara

2017-06-01

While much literature has examined immigrants' health in Canada, less attention has focused specifically on the life stress, an important yet understudied post-migration challenge which may lead to poor coping strategies and negative health consequences. For this study, the pooled 2009-2014 Canadian Community Health Survey (CCHS) was analyzed, using multilevel logistic regression to examine the compositional effects (at an individual level) and areal effects (at a CMA/CA level) on reported high life stress. Separate models have been run for immigrants and non-immigrants for comparative purposes. The results reveal different ways in which select individual socioeconomic and lifestyle factors affect life stress. A statistically significant yet small areal effect at the CMA/CA level on life stress was identified for both immigrants and non-immigrants. When comparing immigrants to non-immigrants, factors such as smoking, length of residency in Canada, and mental health status were found to be particularly informative for predicting high life stress among immigrants. A Healthy Immigrant Effect (HIE) is partially evident, as immigrants with a longer stay in Canada are more likely to be highly stressed than recent arrivals. The areal effect on variances in high life stress is minimal, suggesting the importance of focusing on individual-level effects as stress predictors.

Laser cytometric analysis of FIV-induced injury in astroglia.

PubMed

Zenger, E; Collisson, E W; Barhoumi, R; Burghardt, R C; Danave, I R; Tiffany-Castiglioni, E

1995-02-01

Glia are the predominant brain cells infected by the lentiviruses human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). The importance of astrocytes in maintenance of central nervous system homeostasis suggests that astrocytes are likely to play a strategic role in the progression of neurological disease in lentiviral-infected patients. In consideration of this postulate, the ability of FIV to cause injury by infection of cultured feline astroglia was examined via vital fluorescence assays. Intracellular Ca2+ homeostasis, plasma membrane permeability and fluidity, and cytosolic glutathione (GSH) levels were evaluated. Although basal intracellular Ca2+ was not significantly different between groups, FIV-infected astroglia displayed both a significant delay in development of peak Ca2+ levels following ionophore application and a decrease in the amount of Ca2+ released from intracellular stores. Plasma membrane lipid mobility was increased in FIV-infected cells within 24 h of infection. Glutathione levels were affected in a dose dependent fashion. With a standard viral inoculum there was a decrease in GSH which became significant after 8 days postinfection. With a high inoculum dose there was rapid loss of cell viability with an increase in GSH in surviving cells. We have identified several cellular processes altered in FIV-infected astroglia and our findings suggest that FIV-infection of feline astroglia affects cellular membranes, both structurally and functionally.

Trace metal determination in natural waters by automated solid phase extraction system and ICP-MS: the influence of low level Mg and Ca.

PubMed

Wang, Bo-Shian; Lee, Chih-Ping; Ho, Tung-Yuan

2014-10-01

A fully automated high pressure pretreatment system with Nobias Chelate-PA1 resin (PA1) was developed for trace metal determination by ICP-MS in natural waters. By varying the concentrations of Mg and Ca to mimic the concentrations in the eluate obtained by PA1 or iminodiacetate type resins, the overall analytical performance of the system was assessed for the determination of Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Cd, Ag, Pb and REE. Comparing with the low mM level Mg and Ca (both ranging from 1 to 4mM) eluted by iminodiacetate type resins, the eluate obtained by PA1 contains sub-μM level Mg and Ca, which remarkably decrease matrix effect in ICP-MS analysis and significantly improve the analytical performance. With recovery better than 90% for most the trace metals examined, the accuracy was further verified through the analysis of five natural water reference materials with salinity spanning from 0 to 35‰. We have successfully applied the pretreatment system to determine trace metals in the seawater samples collected in the Western Philippine Sea through Taiwan GEOTRACES cruise. Copyright © 2014 Elsevier B.V. All rights reserved.

XES studies of density of states of high temperature superconductors

NASA Technical Reports Server (NTRS)

Jasiolek, Gabriel

1990-01-01

X-ray emission spectroscopic studies concerning the superconducting crystals, thin films and ceramics of the Y-Ba-Cu-O, Tm-Ba-Cu-O, Bi-Sr-Ca-Cu-O, Bi-Pb-Sr-Ca-Cu-O and T1-Ba-Ca-Cu-O types are presented. The contributions of the 13d(9)L, 13d(10)L, 13d(10)LL and 13d(10)L(2) configurations, where L denotes a ligand hole at the oxygen orbitals in the spectroscopic pattern of these superconductors are discussed. An attempt to connect the x-ray 'as registered' Cu L emission spectra with the density of states close to the Fermi level, considering an influence of the CuL3 absorption edge, is presented. The corrected intensity distributions below the Fermi level are found to correspond to the theoretical density of states. Furthermore, an approach to the average valence of copper based on the account of the self-absorption and fluorescence effects and on the configurations listed above is shown. The average valence of copper in the materials investigated is estimated to lie in the range of +2.10 to 2.32 when the formal trivalent copper is considered as that characterized by the 13d(9)L configuration. The density of states at the Fermi level was estimated to be 2.4 states/eV-cell for a Bi-Sr-Ca-Cu-O crystal and 3.6 states/eV-cell for a Tl-Ba-Ca-Cu-O ceramic.

XES studies of density of states of high temperature superconductors

NASA Technical Reports Server (NTRS)

Jasiolek, Gabriel

1991-01-01

X-ray emission spectroscopic studies concerning the superconducting crystals, thin films, and ceramics of the Y-Ba-Cu-O, Tm-Ba-Cu-O, Bi-Sr-Ca-Cu-O, Bi-Pb-Sr-Ca-Cu-O, and Tl-Ba-Ca-Cu-O types are presented. The contributions of the 13d(9)L, 13d(10)L, 13d(10)LL, and 13d(10)L(2) configurations, where L denotes a ligand hole at the oxygen orbitals in the spectroscopic pattern of these superconductors are discussed. An attempt to connect the x-ray 'as registered' Cu L(alpha) emission spectra with the density of states close to the Fermi level, considering an influence of the CuL3 absorption edge, is presented. The corrected intensity distributions below the Fermi level are found to correspond to the theoretical density of states. Furthermore, an approach to the average valence of copper basing on the account of the self-absorption and fluorescence effects and on the configurations listed above is shown. The average valence of copper in the materials investigated is estimated to lie in the range of +2.10 to 2.32 when the formal trivalent copper is considered as that characterized by the 13d(9)L configuration. The density of states at the Fermi level was estimated to be 2.4 states/eV-cell for a Bi-Sr-Ca-Cu-O crystal and 3.6 states/eV-cell for a Tl-Ba-Ca-CU-O ceramic.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels.

PubMed

Bache, Matthias; Reddemann, Rolf; Said, Harun M; Holzhausen, Hans-Jürgen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Hänsgen, Gabriele; Dunst, Jürgen; Vordermark, Dirk

2006-12-01

The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO(2)), the hypoxia-related markers hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1alpha, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO(2)), HIF-1alpha and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1alpha expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO(2) correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1alpha or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1alpha, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1{alpha}-related markers, and hemoglobin levels

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

Bache, Matthias; Reddemann, Rolf; Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle

2006-12-01

Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO{sub 2}), the hypoxia-related markers hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1{alpha}, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO{sub 2}), HIF-1{alpha}more » and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1{alpha} expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO{sub 2} correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1{alpha} or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1{alpha}, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.« less

Accumulation of Palmitoylcarnitine and Its Effect on Pro-Inflammatory Pathways and Calcium Influx in Prostate Cancer.

PubMed

Al-Bakheit, Ala'a; Traka, Maria; Saha, Shikha; Mithen, Richard; Melchini, Antonietta

2016-10-01

Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between β-oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development. Levels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC-MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca(2+) ) influx was investigated in in vitro models of prostate cancer. We observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro-inflammatory cytokine IL-6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca(2+) influx in PC3 cells, but not in DU145, BPH-1, or PNT1A cells. This pattern of Ca(2+) influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response. This study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro-inflammatory pathways, (ii) Ca(2+) influx, and (iii) DHT-like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326-1337, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

Serum uric acid level and cardiovascular risks in hemodialysis patients: an Algerian cohort study.

PubMed

Gouri, Adel; Dekaken, Aoulia; Bentorki, Ahmed Aimen; Touaref, Amel; Yakhlef, Amina; Kouicem, Nabila

2014-01-01

Elevated serum uric acid (SUA) was usually associated with an increased risk of cardiovascular events and mortality in the general population. However, there are few reports concerning the clinical impact and the pathogenic role of uric acid (UA) in hemodialysis (HD) patients. The aim of the study was to investigate the relationship between SUA and various cardiovascular (CV) risk factors in HD patients. This retrospective, observational cohort study includes 45 HD patients with a mean age of 51.26 +/- 15.21 years. The differences of the CV risk factors between the patients according to their SUA levels were investigated. Age, cardiovascular diseases (CVD), increased creatinine, fasting blood glucose (FBG), corrected calcium (cCa), phosphate (P), cCa x P product, and LDL cholesterol levels were associated with lower SUA levels, whereas a higher SUA level was associated with diabetes mellitus (DM), hypertension, and increased triglycerides level (p < 0.01). In multiple regression analysis, history of diabetes (beta = 0.360, p < 0.05), reduced corrected serum calcium (cCa) (beta = -1.456, p < 0.01), and phosphate (P) levels (beta = -1.752, p < 0.01) were predictive of an increased SUA concentration. Despite what has been demonstrated in the general population and DM patients, a lower SUA level in HD patients was associated with higher cardiovascular risk factors and high co-morbidity burden. Moreover, higher SUA concentrations may be cardioprotective in dialysis patients.

Serum uric acid level and cardiovascular risks in hemodialysis patients: an Algerian cohort study.

PubMed

Gouri, Adel; Dekaken, Aoulia; Bentorki, Ahmed Aimen; Touaref, Amel; Yekhlef, Amina; Sekkache, Fouzia; Kouicem, Nabila

2013-09-01

Elevated Serum Uric Acid (SUA) was usually associated with an increased risk of cardiovascular events and mortality in general population. However, there are few reports concerning the clinical impact and the pathogenic role of Uric Acid (UA) in Hemodialysis (HD) patients. The aim of the study was to investigate the relationship between SUA and various Cardiovascular (CV) risk factors in HD patients. This retrospective; observational cohort study includes 45 HD patients with a mean age of 51.26+/-15.21 years. The differences of the CV risk factors between the patients according to their SUA levels were investigated. Age, Cardiovascular Diseases (CVD), increased creatinine, Fasting Blood Glucose (FBG), Corrected Calcium (cCa), Phosphate (P), cCa x P product and LDL cholesterol levels were associated with lower SUA levels, whereas higher SUA level was associated with Diabetes Mellitus (DM), hypertension and increased triglycerides level (p<0.01). In multiple regression analysis, history of diabetes (beta= 0.360, p<0.05), reduced corrected serum calcium (cCa) (beta = -1.456, p<0.01) and Phosphate (P) levels (beta= -1.752, p<0.01) were predictive of an increased SUA concentration. Despite from what has been demonstrated in the general population and DM patients, a lower SUA level in HD patients was associated with higher cardiovascular risk factors and high co-morbidity burden. Moreover, higher SUA concentrations may be cardioprotective in dialysis patients.

A spatially explicit representation of conservation agriculture for application in global change studies.

PubMed

Prestele, Reinhard; Hirsch, Annette L; Davin, Edouard L; Seneviratne, Sonia I; Verburg, Peter H

2018-05-10

Conservation agriculture (CA) is widely promoted as a sustainable agricultural management strategy with the potential to alleviate some of the adverse effects of modern, industrial agriculture such as large-scale soil erosion, nutrient leaching and overexploitation of water resources. Moreover, agricultural land managed under CA is proposed to contribute to climate change mitigation and adaptation through reduced emission of greenhouse gases, increased solar radiation reflection, and the sustainable use of soil and water resources. Due to the lack of official reporting schemes, the amount of agricultural land managed under CA systems is uncertain and spatially explicit information about the distribution of CA required for various modeling studies is missing. Here, we present an approach to downscale present-day national-level estimates of CA to a 5 arcminute regular grid, based on multicriteria analysis. We provide a best estimate of CA distribution and an uncertainty range in the form of a low and high estimate of CA distribution, reflecting the inconsistency in CA definitions. We also design two scenarios of the potential future development of CA combining present-day data and an assessment of the potential for implementation using biophysical and socioeconomic factors. By our estimates, 122-215 Mha or 9%-15% of global arable land is currently managed under CA systems. The lower end of the range represents CA as an integrated system of permanent no-tillage, crop residue management and crop rotations, while the high estimate includes a wider range of areas primarily devoted to temporary no-tillage or reduced tillage operations. Our scenario analysis suggests a future potential of CA in the range of 533-1130 Mha (38%-81% of global arable land). Our estimates can be used in various ecosystem modeling applications and are expected to help identifying more realistic climate mitigation and adaptation potentials of agricultural practices. © 2018 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Mechanism of Ca2+-influx and Ca2+/calmodulin-dependent protein kinase IV activity during in utero hypoxia in cerebral cortical neuronal nuclei of the guinea pig fetus at term.

PubMed

Vibert, Yanick M; Ashraf, Qazi M; Mishra, Om P; Delivoria-Papadopoulos, Maria

2008-08-08

Previously we showed that following hypoxia there is an increase in nuclear Ca(2+)-influx and Ca(2+)/calmodulin-dependent protein kinase IV activity (CaMK IV) in the cerebral cortex of term guinea pig fetus. The present study tests the hypothesis that clonidine administration will prevent hypoxia-induced increased neuronal nuclear Ca(2+)-influx and increased CaMK IV activity, by blocking high-affinity Ca(2+)-ATPase. Studies were conducted in 18 pregnant guinea pigs at term, normoxia (Nx, n=6), hypoxia (Hx, n=6) and clonidine with Hx (Hx+Clo, n=6). The pregnant guinea pig was exposed to a decreased FiO(2) of 0.07 for 60 min. Clonidine, an imidazoline inhibitor of high-affinity Ca(2+)-ATPase, was administered 12.5 microg/kg IP 30 min prior to hypoxia. Hypoxia was determined biochemically by ATP and phosphocreatine (PCr) levels. Nuclei were isolated and ATP-dependent (45)Ca(2+)-influx was determined. CaMK IV activity was determined by (33)P-incorporation into syntide 2 for 2 min at 37 degrees C in a medium containing 50mM HEPES (pH 7.5), 2mM DTT, 40muM syntide 2, 0.2mM (33)P-ATP, 10mM magnesium acetate, 5 microM PKI 5-24, 2 microM PKC 19-36 inhibitor peptides, 1 microM microcystine LR, 200 microM sodium orthovanadate and either 1mM EGTA (for CaMK IV-independent activity) or 0.8mM CaCl(2) and 1mM calmodulin (for total activity). ATP (mumoles/gbrain) values were significantly different in the Nx (4.62+/-0.2), Hx (1.65+/-0.2, p<0.05 vs. Nx), and Hx+Clo (1.92+/-0.6, p<0.05 vs. Nx). PCr (mumoles/g brain) values in the Nx (3.9+/-0.1), Hx (1.10+/-0.3, p<0.05 vs. Nx), and Hx+Clo (1.14+/-0.3, p<0.05 vs. Nx). There was a significant difference between nuclear Ca(2+)-influx (pmoles/mg protein/min) in Nx (3.98+/-0.4), Hx (10.38+/-0.7, p<0.05 vs. Nx), and Hx+Clo (7.35+/-0.9, p<0.05 vs. Nx, p<0.05 vs. Hx), and CaM KIV (pmoles/mg protein/min) in Nx (1314.00+/-195.4), Hx (2315.14+/-148.5, p<0.05 vs. Nx), and Hx+Clo (1686.75+/-154.3, p<0.05 vs. Nx, p<0.05 vs. Hx). We conclude that the mechanism of hypoxia-induced increased nuclear Ca(2+)-influx is mediated by high-affinity Ca(2+)-ATPase and that CaMK IV activity is nuclear Ca(2+)-influx-dependent. We speculate that hypoxia-induced alteration of high-affinity Ca(2+)-ATPase is a key step that triggers nuclear Ca(2+)-influx, leading to CREB protein-mediated increased expression of apoptotic proteins and hypoxic neuronal death.

New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space

NASA Astrophysics Data System (ADS)

Kvetnansky, R.; Noskov, V. B.; Blazicek, P.; Macho, L.; Grigoriev, A. I.; Goldstein, D. S.; Kopin, I. J.

In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.

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

A pH-Sensitive, Biobased Calcium Carbonate Aragonite Nanocrystal as a Novel Anticancer Delivery System

PubMed Central

Ismail, Maznah; Tengku Ibrahim, Tengku Azmi; Zakaria, Zuki Abu Bakar

2013-01-01

The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO3/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO3/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO3/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO3 nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy. PMID:24324966

Supplementation with Ca salts of soybean oil interacts with concentrate level in grazing dairy cows: milk production and milk composition.

PubMed

Macedo, Fernanda Lopes; de Souza, Jonas; Batistel, Fernanda; Chagas, Lucas Jado; Santos, Flávio Augusto Portela

2016-12-01

In this study, we investigated the associative effects of concentrate levels and Ca salts of soybean oil (CSSO) supplementation on milk production, milk composition, and milk fatty acids of mid-lactation dairy cows grazing on tropical pasture. Twenty-four Jersey × Holstein cows were used in a randomized block design and assigned to four treatments arranged in a 2 × 2 factorial design. Factors evaluated were concentrate levels (low, 3 kg/day vs. high, 7 kg/day of concentrate) and CSSO supplementation (without CSSO vs. with 250 g CSSO cow/day). All cows grazed on elephant grass (Pennisetum purpureum cv. Cameroon) and received the supplemental treatments for a 90-day period. Interactions between concentrate level and CSSO were detected for milk yield, milk yield components, energy-corrected milk (ECM) and 3.5 % fat-corrected milk (FCM). Milk yield increased when CSSO was fed in a low concentrate level, while it decreased milk production in a high concentrate level. Yields of fat, protein, lactose, 3.5 % FCM, and ECM were not affected with CSSO in the low concentrate, but reduced in the high concentrate level. CSSO increased proportions of monounsaturated milk FA, C18:2 trans-10 cis-12, and polyunsaturated FA, and reduced proportions of saturated milk FA in milk. In conclusion, feeding the high level of concentrate was an effective strategy to improve milk yield and solid production. CSSO supplementation increased milk production when fed at low concentrate level but did not affect yield of solids.

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.

Factors Modulating Post-Activation Potentiation of Jump, Sprint, Throw, and Upper-Body Ballistic Performances: A Systematic Review with Meta-Analysis.

PubMed

Seitz, Laurent B; Haff, G Gregory

2016-02-01

Although post-activation potentiation (PAP) has been extensively examined following the completion of a conditioning activity (CA), the precise effects on subsequent jump, sprint, throw, and upper-body ballistic performances and the factors modulating these effects have yet to be determined. Moreover, weaker and stronger individuals seem to exhibit different PAP responses; however, how they respond to the different components of a strength-power-potentiation complex remains to be elucidated. This meta-analysis determined (1) the effect of performing a CA on subsequent jump, sprint, throw, and upper-body ballistic performances; (2) the influence of different types of CA, squat depths during the CA, rest intervals, volumes of CA, and loads during the CA on PAP; and (3) how individuals of different strength levels respond to these various strength-power-potentiation complex components. A computerized search was conducted in ADONIS, ERIC, SPORTDiscus, EBSCOhost, Google Scholar, MEDLINE, and PubMed databases up to March 2015. The analysis comprised 47 studies and 135 groups of participants for a total of 1954 participants. The PAP effect is small for jump (effect size [ES] = 0.29), throw (ES = 0.26), and upper-body ballistic (ES = 0.23) performance activities, and moderate for sprint (ES = 0.51) performance activity. A larger PAP effect is observed among stronger individuals and those with more experience in resistance training. Plyometric (ES = 0.47) CAs induce a slightly larger PAP effect than traditional high-intensity (ES = 0.41), traditional moderate-intensity (ES = 0.19), and maximal isometric (ES = -0.09) CAs, and a greater effect after shallower (ES = 0.58) versus deeper (ES = 0.25) squat CAs, longer (ES = 0.44 and 0.49) versus shorter (ES = 0.17) recovery intervals, multiple- (ES = 0.69) versus single- (ES = 0.24) set CAs, and repetition maximum (RM) (ES = 0.51) versus sub-maximal (ES = 0.34) loads during the CA. It is noteworthy that a greater PAP effect can be realized earlier after a plyometric CA than with traditional high- and moderate-intensity CAs. Additionally, shorter recovery intervals, single-set CAs, and RM CAs are more effective at inducing PAP in stronger individuals, while weaker individuals respond better to longer recovery intervals, multiple-set CAs, and sub-maximal CAs. Finally, both weaker and stronger individuals express greater PAP after shallower squat CAs. Performing a CA elicits small PAP effects for jump, throw, and upper-body ballistic performance activities, and a moderate effect for sprint performance activity. The level of potentiation is dependent on the individual's level of strength and resistance training experience, the type of CA, the depth of the squat when this exercise is employed to elicit PAP, the rest period between the CA and subsequent performance, the number of set(s) of the CA, and the type of load used during the CA. Finally, some components of the strength-power-potentiation complex modulate the PAP response of weaker and stronger individuals in a different way.

Spermatozoa in the sperm-peak-fraction of the boar ejaculate show a lower flow of Ca(2+) under capacitation conditions post-thaw which might account for their higher membrane stability after cryopreservation.

PubMed

Hossain, Md Sharoare; Johannisson, Anders; Siqueira, Amanda Pimenta; Wallgren, Margareta; Rodriguez-Martinez, Heriberto

2011-10-01

Boar spermatozoa collected in the ejaculate sperm peak-portion (P1, first 10 mL of the sperm-rich fraction, SRF), had shown a higher resilience to freezing and thawing compared to spermatozoa from the rest of the ejaculate (2nd portion of the SRF plus the post-sperm-rich fraction, PSRF), even when using a simplified freezing technique, as long as spermatozoa were incubated in their own seminal plasma (SP). This experiment studied the stability of P1- and SRF-P1 boar spermatozoa frozen in MiniFlatPacks (MFP), post-thaw, using flow cytometry. Since spermatozoa from either portion showed similar cryosurvival and low proportions of unstable membranes (<3%, annexin-V/propidium iodide staining), and only a tendency for SRF-P1 live spermatozoa to depict acrosome exocytosis (FITC-PNA/PI/H33342); they were explored for Ca(2+) contents using a Fluo-4 probe under in vitro capacitating conditions (mBO+ medium), as well they were tested for their ability to sustain a short Ca(2+)-ionophore (A23187) in vitro challenge. The proportions of live spermatozoa depicting high Ca(2+)-levels were initially <2% but increased over incubation time, particularly in SRF-P1(P<0.05), while proportions of live spermatozoa with low Ca(2+)-levels were basically constant over incubation time (~11-14%), for either portion. Incubation in capacitation medium did not modify the proportions of low-Ca(2+) but dramatically increased the proportions of high-Ca(2+) spermatozoa (P<0.001) already after 15 min exposure, highest for SRF-P1 spermatozoa. While the proportion of live spermatozoa with intact acrosome was significantly decreased among SRF-P1 (P<0.001), that of P1-spermatozoa remained unchanged, probably owing to the lowest relative content of cytosolic Ca(2+). The results suggest that spermatozoa in the P1-portion are more resilient to express acrosome exocytosis post-thaw compared to those bathing in the rest of the SRF-fraction when cryopreserved using a simplified technique, in MFPs. Copyright © 2011 Elsevier B.V. All rights reserved.

Hydrogen peroxide-induced DNA damage is independent of nuclear calcium but dependent on redox-active ions.

PubMed Central

Jornot, L; Petersen, H; Junod, A F

1998-01-01

In cells undergoing oxidative stress, DNA damage may result from attack by .OH radicals produced by the Fenton reaction, and/or by nucleases activated by nuclear calcium. In the present study, the participation of these two mechanisms was investigated in HeLa cells. Nuclear-targeted aequorin was used for selectively monitoring Ca2+ concentrations within the nuclei ([Ca2+]n), in conjunction with the cell-permeant calcium chelator bis-(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid acetoxymethyl ester (BAPTA/AM), the lipid-soluble broad-spectrum metal chelator with low affinity for Ca2+ and Mg2+ N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and the high-affinity iron/copper chelator 1, 10-phenanthroline (PHE). In Ca2+-containing medium, H2O2 induced extensive DNA strand breaks and an increase in [Ca2+]n that was almost identical to that observed in the cytosol ([Ca2+]c). In cells bathed in Ca2+-free/EGTA medium, in which the increases in [Ca2+]n and [Ca2+]c due to H2O2 were significantly reduced, similar levels of DNA fragmentation also occurred. In cells preloaded with BAPTA/AM or TPEN, the small increase of [Ca2+]n normally elicited by H2O2 in Ca2+-free medium was completely buffered, and DNA damage was largely prevented. On the other hand, pretreatment with PHE did not affect the calcium response in the nuclei, but completely prevented DNA strand breakage induced by H2O2. Re-addition of 100 microM CuSO4 and 100 microM FeSO4 to TPEN- and PHE-treated cells prior to H2O2 challenge reversed the effect of TPEN and PHE, whereas 1 mM was necessary to negate the effect of BAPTA/AM. The levels of DNA strand breakage observed, however, did not correlate with the amounts of 8-hydroxy 2'-deoxyguanosine (8-OHdG): H2O2 did not produce 8-OHdG, whereas PHE alone slightly increased 8-OHdG levels. CuSO4 and FeSO4 enhanced the effects of PHE, particularly in the presence of H2O2. Exposure of cells to a mixture of CuSO4/FeSO4 also resulted in a significant increase in 8-OHdG levels, which was prevented in cells preloaded with BAPTA/AM. Similar results were obtained in a cell-free system using isolated calf thymus DNA exposed to CuSO4/FeSO4, regardless of whether H2O2 was present or not. These results suggest that BAPTA/AM prevents H2O2-induced DNA damage by acting as an iron/copper chelator. These data also indicate that caution must be exercised in using Ca2+ chelating agents as evidence for a role in cellular Ca2+ levels in experimental conditions in which transition-metal-ion-mediated oxidant production is also occurring. PMID:9742216

Effect of parathyroid hormone and uremic sera on the autoagglutination and sedimentation of human red blood cells.

PubMed

Earon, Y; Blum, M; Bogin, E

1983-12-30

Parathyroid hormone (PTH) caused a dramatic acceleration of erythrocyte sedimentation rate (ESR). This effect was calcium dependent and was partially reversed by verapamil. It was not mimicked by 5 mumol/l calcium ionophore A-23187. Following the removal of PTH from the cell suspension the ESR returned to normal. PTH also caused haemagglutination, the reaction was Ca2+ dependent, pH dependent and was partially reversed by verapamil. High levels of Ca2+ ionophore A-23187 mimicked this phenomenon. Magnesium ions even at concentrations of 5 mmol/l did not replace Ca2+, while Ca2+ at concentrations of 3 mmol/l and above caused haemagglutination. The glycolytic inhibitor NaF at levels of 1 mmol/l did not inhibit haemagglutination. The polyamines pertusin and spermidin, prostaglandins PGE2 and PGF, and the calcium hormone calcitonin, did not reproduce the PTH effect. Dialysate from serum of patients with chronic renal failure and hyperparathyroidism caused haemagglutination, while dialysate from patients with chronic renal failure following parathyroidectomy and normal individuals did not cause this phenomenon. It seems that abnormal erythrocyte behaviour seen in patients with chronic renal failure is caused by PTH which leads to modified Ca2+ metabolism in these cells.

Implication of Ca2+ in the regulation of replicative life span of budding yeast.

PubMed

Tsubakiyama, Ryohei; Mizunuma, Masaki; Gengyo, Anri; Yamamoto, Josuke; Kume, Kazunori; Miyakawa, Tokichi; Hirata, Dai

2011-08-19

In eukaryotic cells, Ca(2+)-triggered signaling pathways are used to regulate a wide variety of cellular processes. Calcineurin, a highly conserved Ca(2+)/calmodulin-dependent protein phosphatase, plays key roles in the regulation of diverse biological processes in organisms ranging from yeast to humans. We isolated a mutant of the SIR3 gene, implicated in the regulation of life span, as a suppressor of the Ca(2+) sensitivity of zds1Δ cells in the budding yeast Saccharomyces cerevisiae. Therefore, we investigated a relationship between Ca(2+) signaling and life span in yeast. Here we show that Ca(2+) affected the replicative life span (RLS) of yeast. Increased external and intracellular Ca(2+) levels caused a reduction in their RLS. Consistently, the increase in calcineurin activity by either the zds1 deletion or the constitutively activated calcineurin reduced RLS. Indeed, the shortened RLS of zds1Δ cells was suppressed by the calcineurin deletion. Further, the calcineurin deletion per se promoted aging without impairing the gene silencing typically observed in short-lived sir mutants, indicating that calcineurin plays an important role in a regulation of RLS even under normal growth condition. Thus, our results indicate that Ca(2+) homeostasis/Ca(2+) signaling are required to regulate longevity in budding yeast.

The protective effect of supplemental calcium on colonic permeability depends on a calcium phosphate-induced increase in luminal buffering capacity.

PubMed

Schepens, Marloes A A; ten Bruggencate, Sandra J M; Schonewille, Arjan J; Brummer, Robert-Jan M; van der Meer, Roelof; Bovee-Oudenhoven, Ingeborg M J

2012-04-01

An increased intestinal permeability is associated with several diseases. Previously, we have shown that dietary Ca decreases colonic permeability in rats. This might be explained by a calcium-phosphate-induced increase in luminal buffering capacity, which protects against an acidic pH due to microbial fermentation. Therefore, we investigated whether dietary phosphate is a co-player in the effect of Ca on permeability. Rats were fed a humanised low-Ca diet, or a similar diet supplemented with Ca and containing either high, medium or low phosphate concentrations. Chromium-EDTA was added as an inert dietary intestinal permeability marker. After dietary adaptation, short-chain fructo-oligosaccharides (scFOS) were added to all diets to stimulate fermentation, acidify the colonic contents and induce an increase in permeability. Dietary Ca prevented the scFOS-induced increase in intestinal permeability in rats fed medium- and high-phosphate diets but not in those fed the low-phosphate diet. This was associated with higher faecal water cytotoxicity and higher caecal lactate levels in the latter group. Moreover, food intake and body weight during scFOS supplementation were adversely affected by the low-phosphate diet. Importantly, luminal buffering capacity was higher in rats fed the medium- and high-phosphate diets compared with those fed the low-phosphate diet. The protective effect of dietary Ca on intestinal permeability is impaired if dietary phosphate is low. This is associated with a calcium phosphate-induced increase in luminal buffering capacity. Dragging phosphate into the colon and thereby increasing the colonic phosphate concentration is at least part of the mechanism behind the protective effect of Ca on intestinal permeability.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer

PubMed Central

Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor

2004-01-01

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030

Potentiation of inositol trisphosphate-induced Ca2+ mobilization in Xenopus oocytes by cytosolic Ca2+.

PubMed Central

Yao, Y; Parker, I

1992-01-01

1. The ability of cytosolic Ca2+ ions to modulate inositol 1,4,5-trisphosphate (Insp3)-induced Ca2+ liberation from intracellular stores was studied in Xenopus oocytes using light flash photolysis of caged InsP3. Changes in cytosolic free Ca2+ level were effected by inducing Ca2+ entry through ionophore and voltage-gated plasma membrane channels and by injection of Ca2+ through a micropipette. Their effects on Ca2+ liberation were monitored by video imaging of Fluo-3 fluorescence and by voltage clamp recording of Ca(2+)-activated membrane Cl- currents. 2. Treatment of oocytes with the Ca2+ ionophores A23187 and ionomycin caused a transient elevation of cytosolic Ca2+ level when cells were bathed in Ca(2+)-free solution, which probably arose because of release of Ca2+ from intracellular stores. 3. Membrane current and Fluo-3 Ca2+ signals evoked by photoreleased InsP3 in ionophore-treated oocytes were potentiated when the intracellular Ca2+ level was elevated by raising the Ca2+ level in the bathing solution. 4. Responses to photoreleased InsP3 were similarly potentiated following activation of Ca2+ entry through voltage-gated Ca2+ channels expressed in the plasma membrane. 5. Ca(2+)-activated membrane currents evoked by depolarization developed a delayed 'hump' component during sustained photorelease of InsP3, probably because Ca2+ ions entering through the membrane channels triggered liberation of Ca2+ from intracellular stores. 6. Ba2+ and Sr2+ ions were able to substitute for Ca2+ in potentiating InsP3-mediated Ca2+ liberation. 7. Gradual photorelease of InsP3 by weak photolysis light evoked Ca2+ liberation that began at particular foci and then propagated throughout, but not beyond that area of the oocyte exposed to the light. Local elevations of intracellular Ca2+ produced by microinjection of Ca2+ acted as new foci for the initiation of Ca2+ liberation by InsP3. 8. In resting oocytes, intracellular injections of Ca2+ resulted only in localized elevation of intracellular Ca2+, and did not evoke propagating waves. 9. The results show that cytosolic Ca2+ ions potentiate the ability of InsP3 to liberate Ca2+ from intracellular stores. This process may be important for the positive feedback mechanism underlying the generation of Ca2+ spikes and waves, and for interactions between the InsP3 pathway and Ca2+ ions entering cells through voltage- and ligand-gated channels. Images Fig. 5 PMID:1284567

Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

PubMed

Wang, Jun-Ke; Hu, Hai-Jie; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

2017-07-11

To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

Bergamot essential oil differentially modulates intracellular Ca2+ levels in vascular endothelial and smooth muscle cells: a new finding seen with fura-2.

PubMed

You, Ji H; Kang, Purum; Min, Sun Seek; Seol, Geun Hee

2013-04-01

In this study, we compared the effect of the essential oil of Citrus bergamia Risso [bergamot, bergamot essential oil (BEO)] on the intracellular Ca levels in vascular endothelial (EA) and mouse vascular smooth muscle (MOVAS) cells, using the fura-2 fluorescence technique. BEO caused an initial transient increase in intracellular Ca concentration ([Ca]i) in EA cells, followed by a decrease, whereas it induced a sustained increase in [Ca]i in MOVAS cells. Linalyl acetate (LA) as a major component of BEO-induced [Ca]i mobilization was similar to BEO in EA cells. The increase of [Ca]i by LA was higher in EA cells than in MOVAS cells. [Ca]i rise induced by extracellular Ca application was significantly blocked by BEO or LA in EA cells but not in MOVAS cells, suggesting that BEO and LA block Ca influx in EA cells. The present results suggest that BEO and LA differentially modulate intracellular Ca levels in vascular endothelial and smooth muscle cells. In addition, blockade of Ca influx by BEO and LA in EA cells may explain the protective effects of BEO on endothelial dysfunction associated with cardiovascular disease.

Effect of increasing the colloidal calcium phosphate of milk on the texture and microstructure of yogurt.

PubMed

Ozcan, T; Horne, D; Lucey, J A

2011-11-01

The effect of increasing the colloidal calcium phosphate (CCP) content on the physical, rheological, and microstructural properties of yogurt was investigated. The CCP content of heated (85°C for 30 min) milk was increased by increasing the pH by the addition of alkali (NaOH). Alkalized milk was dialyzed against pasteurized skim milk at approximately 4°C for 72 h to attempt to restore the original pH and soluble Ca content. By adjustment of the milk to pH values 7.45, 8.84, 10.06, and 10.73, the CCP content was increased to approximately 107, 116, 123, and 128%, respectively, relative to the concentration in heated milk. During fermentation of milk, the storage modulus (G') and loss tangent values of yogurts were measured using dynamic oscillatory rheology. Large deformation rheological properties were also measured. The microstructure of yogurt was observed using fluorescence microscopy, and whey separation was determined. Acid-base titration was used to evaluate changes in the CCP content in milk. Total Ca and casein-bound Ca increased with an increase in the pH value of alkalization. During acidification, elevated buffering occurred in milk between pH values 6.7 to 5.2 with an increase in the pH of alkalization. When acidified milk was titrated with alkali, elevated buffering occurred in milk between pH values 5.6 to 6.4 with an increase in the pH of alkalization. The high residual pH of milk after dialysis could be responsible for the decreased contents of soluble Ca in these milks. The pH of gelation was higher in all dialyzed samples compared with the heated control milk, and the gelation pH was higher with an increase in CCP content. The sample with highest CCP content (128%) exhibited gelation at very high pH (6.3), which could be due to alkali-induced CN micellar disruption. The G' values at pH 4.6 were similar in gels with CCP levels up to 116%; at higher CCP levels, the G' values at pH 4.6 greatly decreased. Loss tangent values at pH 5.1 were similar in all samples except in gels with a CCP level of 128%. For dialyzed milk, the whey separation levels were similar in gels made from milk with up to 107% CCP but increased at higher CCP levels. Microstructure of yogurt gels made from milk with 100 to 107% CCP was similar but very large clusters were observed in gels made from milk with higher CCP levels. By dialyzing heated milk against pasteurized milk, we may have retained some heat-induced Ca phosphate on micelles that normally dissolves on cooling because, during dialysis, pasteurized milk provided soluble Ca ions to the heated milk system. Yogurt texture was significantly affected by increasing the casein-bound Ca (and total Ca) content of milk as well as by the alkalization procedure involved in that approach. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Performance of a new carbon dioxide absorbent, Yabashi lime® as compared to conventional carbon dioxide absorbent during sevoflurane anesthesia in dogs.

PubMed

Kondoh, Kei; Atiba, Ayman; Nagase, Kiyoshi; Ogawa, Shizuko; Miwa, Takashi; Katsumata, Teruya; Ueno, Hiroshi; Uzuka, Yuji

2015-08-01

In the present study, we compare a new carbon dioxide (CO2) absorbent, Yabashi lime(®) with a conventional CO2 absorbent, Sodasorb(®) as a control CO2 absorbent for Compound A (CA) and Carbon monoxide (CO) productions. Four dogs were anesthetized with sevoflurane. Each dog was anesthetized with four preparations, Yabashi lime(®) with high or low-flow rate of oxygen and control CO2 absorbent with high or low-flow rate. CA and CO concentrations in the anesthetic circuit, canister temperature and carbooxyhemoglobin (COHb) concentration in the blood were measured. Yabashi lime(®) did not produce CA. Control CO2 absorbent generated CA, and its concentration was significantly higher in low-flow rate than a high-flow rate. CO was generated only in low-flow rate groups, but there was no significance between Yabashi lime(®) groups and control CO2 absorbent groups. However, the CO concentration in the circuit could not be detected (≤5ppm), and no change was found in COHb level. Canister temperature was significantly higher in low-flow rate groups than high-flow rate groups. Furthermore, in low-flow rate groups, the lower layer of canister temperature in control CO2 absorbent group was significantly higher than Yabashi lime(®) group. CA and CO productions are thought to be related to the composition of CO2 absorbent, flow rate and canister temperature. Though CO concentration is equal, it might be safer to use Yabashi lime(®) with sevoflurane anesthesia in dogs than conventional CO2 absorbent at the point of CA production.

Effects of cadmium, calcium, age and parity on bone mineral, density and strength in female rats

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

Hammond, B.F.

Weanling female rats were fed diets containing one of three levels of calcium and one of four levels of cadmium in the drinking water. Approximately 10 animals from each group were sacrificed after the first pregnancy and the remaining animals after the fourth pregnancy. Reproductive performance, plasma and bone Ca and P and bone density and strength were measured. After the first pregnancy, offspring of dams treated with 5 or 10 ppM Cd were smaller at birth than offspring of dams treated with 0 or 1 ppM Cd. Offspring of dams fed 5 or 10 ppM Cd or the 0.3%more » Ca diet had decreased weaning weight regardless of parity. Cadmium treatment had no effect on the plasma Ca or the Ca-P ratio. At Cd levels of 5 or 10 ppM the plasma P was increased. The 0.3% Ca diet depressed the plasma Ca and the 0.9% Ca diet elevated the plasma Ca and depressed the plasma P when compared to the 0.6% diet. Parity did not affect plasma Ca but, after four pregnancies, plasma P was decreased. Plasma Ca of mature dams was higher than that of adolescent dams but plasma P was unaffected. Bone mineral, density and strength were decreased by the 0.3% Ca diet especially when Cd levels reached 10 ppM. Increasing dietary Ca above normal increased femur Ca of dams fed 1 ppM Cd but did not increase the Ca of the femur of dams given higher levels of Cd. After the first pregnancy, femur Ca of mature dams was greater than that of adolescent dams. After the fourth pregnancy, femurs of mature dams were less strong than those of adolescent dams; however, the density was the same. Increasing dietary Ca above 0.6% lessened the detrimental effects of 5 ppM Cd ingestion on bone density. Mature dams were less affected by the 0.3% Ca 10 ppM Cd treatment than were adolescent dams. 60 refs., 3 figs., 26 tabs.« less

Maternal high-salt diet altered PKC/MLC20 pathway and increased ANG II receptor-mediated vasoconstriction in adult male rat offspring.

PubMed

Li, Weisheng; Lv, Juanxiu; Wu, Jue; Zhou, Xiuwen; Jiang, Lin; Zhu, Xiaolin; Tu, Qing; Tang, Jiaqi; Liu, Yanping; He, Axin; Zhong, Yuan; Xu, Zhice

2016-07-01

High-salt diet (HSD) is associated with cardiovascular diseases. This study aims at ascertaining the influence of maternal HSD on offspring's angiotensin II (ANG II)-mediated vasoconstriction and the underlying mechanisms. In comparison to a normal-salt diet, HSD used in pregnancy in rats changed the ultrastructures of the coronary artery (CA) in 5-month-old male offspring, and increased ANG II-mediated CA contractility. Measurement of [Ca(2+) ]i in CA using fluorescent fura-2, a Ca(2+) indicator, showed that ANG II-mediated increases in [Ca(2+) ]i were the same between HSD and normal-salt diet groups, but the ratio of diameter change/[Ca(2+) ]i induced by ANG II were significantly higher in HSD groups. Angiotensin II receptor type 1, not angiotensin II receptor type 2, caused ANG II-mediated vasoconstriction. Protein kinase C (PKC) inhibitor GF109203X attenuated the ANG II-mediated vasoconstriction, PKC agonist phorbol12,13-dibutyrate produced a greater contraction. There was an increase in PKCβ mRNA and the corresponding protein abundance in the offspring, whereas other PKC subunits PKCα, PKCδ, and PKCε did not change. Moreover, 20 kDa myosin light chain phosphorylation levels were increased in HSD group. Maternal HSD affected the developmental programing for the offspring CA, with increased ANG II-mediated vasoconstrictions. The angiotensin II receptor type 1-PKC-20 kDa myosin light chain phosphorylation pathway was the possible mediated cellular mechanism. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entorhinal theta-frequency input to the dentate gyrus trisynaptically evokes hippocampal CA1 LTP

PubMed Central

Stepan, Jens; Dine, Julien; Fenzl, Thomas; Polta, Stephanie A.; von Wolff, Gregor; Wotjak, Carsten T.; Eder, Matthias

2012-01-01

There exists substantial evidence that some forms of explicit learning in mammals require long-term potentiation (LTP) at hippocampal CA3-CA1 synapses. While CA1 LTP has been well characterized at the monosynaptic level, it still remains unclear how the afferent systems to the hippocampus can initiate formation of this neuroplastic phenomenon. Using voltage-sensitive dye imaging (VSDI) in a mouse brain slice preparation, we show that evoked entorhinal cortical (EC) theta-frequency input to the dentate gyrus highly effectively generates waves of neuronal activity which propagate through the entire trisynaptic circuit of the hippocampus (“HTC-Waves”). This flow of activity, which we also demonstrate in vivo, critically depends on frequency facilitation of mossy fiber to CA3 synaptic transmission. The HTC-Waves are rapidly boosted by the cognitive enhancer caffeine (5 μM) and the stress hormone corticosterone (100 nM). They precisely follow the rhythm of the EC input, involve high-frequency firing (>100 Hz) of CA3 pyramidal neurons, and induce NMDA receptor-dependent CA1 LTP within a few seconds. Our study provides the first experimental evidence that synchronous theta-rhythmical spiking of EC stellate cells, as occurring during EC theta oscillations, has the capacity to drive induction of CA1 LTP via the hippocampal trisynaptic pathway. Moreover, we present data pointing to a basic filter mechanism of the hippocampus regarding EC inputs and describe a methodology to reveal alterations in the “input–output relationship” of the hippocampal trisynaptic circuit. PMID:22988432

Enhancement of redox- and phase-stability of thermoelectric CaMnO3-δ by substitution

NASA Astrophysics Data System (ADS)

Thiel, Philipp; Populoh, Sascha; Yoon, Songhak; Weidenkaff, Anke

2015-09-01

Redox Reactivity and structural phase transitions have a major impact on transport and me-chemical properties of thermoelectric CaMnO3-δ. In this study series of Ca1-xAxMn1-yByO3-δ (0≤x,y≤0.8) compounds, each with A-site (Dy3+, Yb3+) or B-site (Nb5+, Ta5+ and Mo6+, W6+) substitution, were synthesized and crystallographically analyzed. It was found that the high-temperature oxygen content is widely independent from the substituent. Subsequently, with increasing temperature the differences in the Seebeck coefficient vanish above 1200 K. With increasing substitution the orthorhombic distortion of the perovskite-like phase increases. The orthorhombic distortion and the upper temperature limit of the stability of the orthorhombic crystal structure show an almost linear dependency. Accordingly, the mechanical stability of all-oxides thermoelectric converters at temperatures exceeding 1000 K will be increased employing materials with high substitution level and substituents inducing a high orthorhombic distortion.

Physiological and Molecular Biological Characterization of Intracellular Carbonic Anhydrase from the Marine Diatom Phaeodactylum tricornutum1

PubMed Central

Satoh, Dan; Hiraoka, Yasutaka; Colman, Brian; Matsuda, Yusuke

2001-01-01

A single intracellular carbonic anhydrase (CA) was detected in air-grown and, at reduced levels, in high CO2-grown cells of the marine diatom Phaeodactylum tricornutum (UTEX 642). No external CA activity was detected irrespective of growth CO2 conditions. Ethoxyzolamide (0.4 mm), a CA-specific inhibitor, severely inhibited high-affinity photosynthesis at low concentrations of dissolved inorganic carbon, whereas 2 mm acetazolamide had little effect on the affinity for dissolved inorganic carbon, suggesting that internal CA is crucial for the operation of a carbon concentrating mechanism in P. tricornutum. Internal CA was purified 36.7-fold of that of cell homogenates by ammonium sulfate precipitation, and two-step column chromatography on diethylaminoethyl-sephacel and p-aminomethylbenzene sulfone amide agarose. The purified CA was shown, by SDS-PAGE, to comprise an electrophoretically single polypeptide of 28 kD under both reduced and nonreduced conditions. The entire sequence of the cDNA of this CA was obtained by the rapid amplification of cDNA ends method and indicated that the cDNA encodes 282 amino acids. Comparison of this putative precursor sequence with the N-terminal amino acid sequence of the purified CA indicated that it included a possible signal sequence of up to 46 amino acids at the N terminus. The mature CA was found to consist of 236 amino acids and the sequence was homologous to β-type CAs. Even though the zinc-ligand amino acid residues were shown to be completely conserved, the amino acid residues that may constitute a CO2-binding site appeared to be unique among the β-CAs so far reported. PMID:11500545

Adjusting CA19-9 values to predict malignancy in obstructive jaundice: Influence of bilirubin and C-reactive protein

PubMed Central

La Greca, Gaetano; Sofia, Maria; Lombardo, Rosario; Latteri, Saverio; Ricotta, Agostino; Puleo, Stefano; Russello, Domenico

2012-01-01

AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ). METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment. RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively. CONCLUSION: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice. PMID:22919247

Ca2+ influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery

PubMed Central

Ihara, Eikichi; Derkach, Dmitry N; Hirano, Katsuya; Nishimura, Junji; Nawata, Hajime; Kanaide, Hideo

2001-01-01

To determine the mechanism of bradykinin-induced production of endothelium-derived contracting factors, we monitored the changes in cytosolic Ca2+ concentration ([Ca2+]i) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca2+]i of smooth muscle cells and force in porcine interlobar renal arterial strips using front-surface fluorometry of fura-2. In the presence of Nω-nitro-l-arginine methyl ester, bradykinin caused an endothelium-dependent transient elevation of [Ca2+]i and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H2/thromboxane A2 receptor antagonist. In the absence of extracellular Ca2+, bradykinin failed to induce contraction. However, replenishing extracellular Ca2+ to 0.75 mm and higher induced an instantaneous contraction. However, replenishing Ca2+per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10−5m 1-(β-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365) or 0.2 mm Ni2+ abolished the contraction induced by bradykinin in the presence of extracellular Ca2+. Treatment with 10−5m indomethacin completely inhibited the contractile response induced by Ca2+ replenishment, regardless of the timing of its application, before or after the application of bradykinin. In endothelial cells in the valvular strips, bradykinin caused a transient [Ca2+]i elevation in the presence of 1.25 mm extracellular Ca2+, but [Ca2+]i returned to the resting level within 10 min. Neither 10−5m SKF96365 nor 0.2 mm Ni2+ had any effect on the peak [Ca2+]i elevation, but decreased [Ca2+]i in the declining phase. In the absence of extracellular Ca2+, bradykinin induced a transient [Ca2+]i elevation to a level similar to that seen in the presence of 1.25 mm extracellular Ca2+. However, [Ca2+]i then rapidly returned to the prestimulation level within 5 min. Subsequent Ca2+ replenishment to 0.75 mm and higher in the presence of bradykinin elevated [Ca2+]i to significantly higher levels than the resting level seen in the media containing 1.25 mm Ca2+. In conclusion, Ca2+ influx in the endothelial cells is essential for bradykinin to induce endothelium-dependent contraction in the porcine interlobar renal artery. PMID:11483701

The role of calcium, silicon and salicylic acid treatment in protection of canola plants against boron toxicity stress.

PubMed

Metwally, Ashraf M; Radi, Abeer A; El-Shazoly, Rasha M; Hamada, Afaf M

2018-01-22

Boron (B) toxicity often limits crop yield and the quality of production in agricultural areas. Here, we investigated the effects of calcium (Ca), silicon (Si) and salicylic acid (SA) on development of B toxicity, B allocation in canola (Brassica napus cultivar Sarw 4) and its role in non-enzymatic antioxidants in relation to yield of this cultivar under B toxicity. Canola seedlings were subjected to four B levels induced by boric acid in the absence or presence of Ca, Si and SA. The results showed that Ca, Si and SA addition ameliorated the inhibition in canola growth, water content (WC), and improved siliqua number, siliqua weight and seed index. The B content in shoots and roots and total B accumulation in the whole plant were increased in control plants under B-toxicity-stress, and these parameters were significantly decreased by addition of Ca, Si and SA. The shoot ascorbate pool (ascorbate, AsA, and dehydroascorbate, DHA), α-tocopherol and phenolics (free and bound) were increased under B toxicity, and were significantly decreased in most cases by addition of Ca, Si and SA, except α-tocopherol, which increased at low B levels (0, 25 and 50 mg kg soil -1 ). The glutathione content did not obviously change by B stress, while added Ca, Si and SA inhibited its accumulation under B stress. In addition, B toxicity reduced the shoot flavonoids content; however, this reduction was not alleviated by the use of Ca, Si and SA treatments. It could be concluded that growth and yield of canola plants grown under high B concentration improved after external application of Ca, Si or SA.

Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+ channel gene expression

PubMed Central

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

1999-01-01

We investigated whether insulin-like growth factor-1 (IGF-1), an endogenous potent activator of skeletal muscle proliferation and differentiation, enhances L-type Ca2+ channel gene expression resulting in increased functional voltage sensors in single skeletal muscle cells. Charge movement and inward Ca2+ current were recorded in primary cultured rat myoballs using the whole-cell configuration of the patch-clamp technique. Ca2+ current and maximum charge movement (Qmax) were potentiated in cells treated with IGF-1 without significant changes in their voltage dependence. Peak Ca2+ current in control and IGF-1-treated cells was -7·8 ± 0·44 and -10·5 ± 0·37 pA pF−1, respectively (P < 0·01), whilst Qmax was 12·9 ± 0·4 and 22·0 ± 0·3 nC μF−1, respectively (P < 0·01). The number of L-type Ca2+ channels was found to increase in the same preparation. The maximum binding capacity (Bmax) of the high-affinity radioligand [3H]PN200-110 in control and IGF-1-treated cells was 1·21 ± 0·25 and 3·15 ± 0·5 pmol (mg protein)−1, respectively (P < 0·01). No significant change in the dissociation constant for [3H]PN200-110 was found. Antisense RNA amplification showed a significant increase in the level of mRNA encoding the L-type Ca2+ channel α1-subunit in IGF-1-treated cells. This study demonstrates that IGF-1 regulates charge movement and the level of L-type Ca2+ channel α1-subunits through activation of gene expression in skeletal muscle cells. PMID:10087334

Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools.

PubMed

Pan, Xiaoyu; Chen, Jiechun; Wang, Weijie; Chen, Ling; Wang, Lin; Ma, Quan; Zhang, Jianbo; Chen, Lichao; Wang, Gang; Zhang, Meixi; Wu, Hao; Cheng, Ruochuan

2017-02-07

Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.

Prognostic Value of the Interaction between Galectin-3 and Antigen Carbohydrate 125 in Acute Heart Failure

PubMed Central

Núñez, Julio; Rabinovich, Gabriel A.; Sandino, Justo; Mainar, Luis; Palau, Patricia; Santas, Enrique; Villanueva, Maria Pilar; Núñez, Eduardo; Bodí, Vicent; Chorro, Francisco J.; Miñana, Gema; Sanchis, Juan

2015-01-01

Aims Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125. Methods and Results We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints. Conclusion In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml). PMID:25875367

CaI and SrI molecules for iodine determination by high-resolution continuum source graphite furnace molecular absorption spectrometry: Greener molecules for practical application.

PubMed

Zanatta, Melina Borges Teixeira; Nakadi, Flávio Venâncio; da Veiga, Márcia Andreia Mesquita Silva

2018-03-01

A new method to determine iodine in drug samples by high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) has been developed. The method measures the molecular absorption of a diatomic molecule, CaI or SrI (less toxic molecule-forming reagents), at 638.904 or 677.692nm, respectively, and uses a mixture containing 5μg of Pd and 0.5μg of Mg as chemical modifier. The method employs pyrolysis temperatures of 1000 and 800°C and vaporization temperatures of 2300 and 2400°C for CaI and SrI, respectively. The optimized amounts of Ca and Sr as molecule-forming reagents are 100 and 150µg, respectively. On the basis of interference studies, even small chlorine concentrations reduce CaI and SrI absorbance significantly. The developed method was used to analyze different commercial drug samples, namely thyroid hormone pills with three different iodine amounts (15.88, 31.77, and 47.66µg) and one liquid drug with 1% m v -1 active iodine in their compositions. The results agreed with the values informed by the manufacturers (95% confidence level) regardless of whether CaI or SrI was determined. Therefore, the developed method is useful for iodine determination on the basis of CaI or SrI molecular absorption. Copyright © 2017 Elsevier B.V. All rights reserved.

Calcium Signaling Regulates Trafficking of Familial Hypocalciuric Hypercalcemia (FHH) Mutants of the Calcium Sensing Receptor

PubMed Central

Grant, Michael P.; Stepanchick, Ann

2012-01-01

Calcium-sensing receptors (CaSRs) regulate systemic Ca2+ homeostasis. Loss-of-function mutations cause familial benign hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). FHH/NSHPT mutations can reduce trafficking of CaSRs to the plasma membrane. CaSR signaling is potentiated by agonist-driven anterograde CaSR trafficking, leading to a new steady state level of plasma membrane CaSR, which is maintained, with minimal functional desensitization, as long as extracellular Ca2+ is elevated. This requirement for CaSR signaling to drive CaSR trafficking to the plasma membrane led us to reconsider the mechanism(s) contributing to dysregulated trafficking of FHH/NSHPT mutants. We simultaneously monitored dynamic changes in plasma membrane levels of CaSR and intracellular Ca2+, using a chimeric CaSR construct, which allowed explicit tracking of plasma membrane levels of mutant or wild-type CaSRs in the presence of nonchimeric partners. Expression of mutants alone revealed severe defects in plasma membrane targeting and Ca2+ signaling, which were substantially rescued by coexpression with wild-type CaSR. Biasing toward heterodimerization of wild-type and FHH/NSHPT mutants revealed that intracellular Ca2+ oscillations were insufficient to rescue plasma membrane targeting. Coexpression of the nonfunctional mutant E297K with the truncation CaSRΔ868 robustly rescued trafficking and Ca2+ signaling, whereas coexpression of distinct FHH/NSHPT mutants rescued neither trafficking nor signaling. Our study suggests that rescue of FHH/NSHPT mutants requires a steady state intracellular Ca2+ response when extracellular Ca2+ is elevated and argues that Ca2+ signaling by wild-type CaSRs rescues FHH mutant trafficking to the plasma membrane. PMID:23077345

Ca2+/Calmodulin-Dependent Protein Kinase Kinases (CaMKKs) Effects on AMP-Activated Protein Kinase (AMPK) Regulation of Chicken Sperm Functions.

PubMed

Nguyen, Thi Mong Diep; Combarnous, Yves; Praud, Christophe; Duittoz, Anne; Blesbois, Elisabeth

2016-01-01

Sperm require high levels of energy to ensure motility and acrosome reaction (AR) accomplishment. The AMP-activated protein kinase (AMPK) has been demonstrated to be strongly involved in the control of these properties. We address here the question of the potential role of calcium mobilization on AMPK activation and function in chicken sperm through the Ca(2+)/calmodulin-dependent protein kinase kinases (CaMKKs) mediated pathway. The presence of CaMKKs and their substrates CaMKI and CaMKIV was evaluated by western-blotting and indirect immunofluorescence. Sperm were incubated in presence or absence of extracellular Ca(2+), or of CaMKKs inhibitor (STO-609). Phosphorylations of AMPK, CaMKI, and CaMKIV, as well as sperm functions were evaluated. We demonstrate the presence of both CaMKKs (α and β), CaMKI and CaMKIV in chicken sperm. CaMKKα and CaMKI were localized in the acrosome, the midpiece, and at much lower fluorescence in the flagellum, whereas CaMKKβ was mostly localized in the flagellum and much less in the midpiece and the acrosome. CaMKIV was only present in the flagellum. The presence of extracellular calcium induced an increase in kinases phosphorylation and sperm activity. STO-609 reduced AMPK phosphorylation in the presence of extracellular Ca(2+) but not in its absence. STO-609 did not affect CaMKIV phosphorylation but decreased CaMKI phosphorylation and this inhibition was quicker in the presence of extracellular Ca(2+) than in its absence. STO-609 efficiently inhibited sperm motility and AR, both in the presence and absence of extracellular Ca(2+). Our results show for the first time the presence of CaMKKs (α and β) and one of its substrate, CaMKI in different subcellular compartments in germ cells, as well as the changes in the AMPK regulation pathway, sperm motility and AR related to Ca(2+) entry in sperm through the Ca(2+)/CaM/CaMKKs/CaMKI pathway. The Ca(2+)/CaMKKs/AMPK pathway is activated only under conditions of extracellular Ca(2+) entry in the cells.

Neuroprotective Effect of Ginseng against Alteration of Calcium Binding Proteins Immunoreactivity in the Mice Hippocampus after Radiofrequency Exposure

PubMed Central

Maskey, Dhiraj

2013-01-01

Calcium binding proteins (CaBPs) such as calbindin D28-k, parvalbumin, and calretinin are able to bind Ca2+ with high affinity. Changes in Ca2+ concentrations via CaBPs can disturb Ca2+ homeostasis. Brain damage can be induced by the prolonged electromagnetic field (EMF) exposure with loss of interacellular Ca2+ balance. The present study investigated the radioprotective effect of ginseng in regard to CaBPs immunoreactivity (IR) in the hippocampus through immunohistochemistry after one-month exposure at 1.6 SAR value by comparing sham control with exposed and ginseng-treated exposed groups separately. Loss of dendritic arborization was noted with the CaBPs in the Cornu Ammonis areas as well as a decrease of staining intensity of the granule cells in the dentate gyrus after exposure while no loss was observed in the ginseng-treated group. A significant difference in the relative mean density was noted between control and exposed groups but was nonsignificant in the ginseng-treated group. Decrease in CaBP IR with changes in the neuronal staining as observed in the exposed group would affect the hippocampal trisynaptic circuit by alteration of the Ca2+ concentration which could be prevented by ginseng. Hence, ginseng could contribute as a radioprotective agent against EMF exposure, contributing to the maintenance of Ca2+ homeostasis by preventing impairment of intracellular Ca2+ levels in the hippocampus. PMID:24069603

Comparative carcass and tissue nutrient composition of transgenic Yorkshire pigs expressing phytase in the saliva and conventional Yorkshire pigs.

PubMed

Forsberg, C W; Meidinger, R G; Ajakaiye, A; Murray, D; Fan, M Z; Mandell, I B; Phillips, J P

2014-10-01

A transgenic line of Yorkshire (YK) pigs named the Cassie (CA) line was produced with a low copy number phytase transgene inserted in the genome. The transgenic line efficiently digests P, Ca, and other major minerals of plant dietary origin. The objectives of this study were to 1) compare carcass and tissue nutrient composition and meat quality traits for third generation hemizygous CA line market BW finisher pigs (n = 24) with age-matched conventional YK finisher pigs (n = 24) and 2) examine effects of outbreeding with high-index conventional YK boars on modifying carcass leanness from the third to sixth generations in CA line finisher boars (n = 73) and gilts (n = 103). Cassie boars (n = 12) and CA gilts (n = 12) were fed diets without supplemental P and comparable numbers of age-matched YK boars and gilts fed diets containing supplement P were raised throughout the finisher phase. The pigs were slaughtered and then fabricated into commercial pork primals before meat composition and quality evaluation. Proximate and major micronutrient composition was determined on tissues including fat, kidney, lean, liver, and skin. The main difference observed was greater (P = 0.033) crude fat content in CA boar carcasses and increased (P < 0.04) leaf lard in both CA boars and gilts but no differences were observed (P = 0.895 and P = 0.223, respectively) in carcass backfat thickness as compared with YK pigs. There were no substantive differences in tissue composition, except for CA boar kidneys. Numerous changes in the mineral, fatty acid, and indispensable AA composition for CA boar kidneys were not apparent in CA gilts. These changes may point to adaptive physiological changes in the boar kidney necessary for homeostatic regulation of mineral retention related to phytase action rather than to insertion of the transgene. However, from a meat composition perspective, transgenic expression of phytase in the CA line of YK pigs had little overall effect on meat composition. Outbreeding of high-index CA gilts with high-index commercial YK boars linearly reduced (P = 0.002) back fat thickness with a corresponding linear increase (P = 0.001) in lean yield in finisher CA gilts, although no change in these parameters was observed in CA finisher boars. The increase in lean yield in CA gilts by selective breeding without affecting the level of salivary phytase activity documents the value of conventional genetic selection in conjunction with genetic modification.

Gromwell (Lithospermum erythrorhizon) supplementation enhances epidermal levels of ceramides, glucosylceramides, β-glucocerebrosidase, and acidic sphingomyelinase in NC/Nga mice.

PubMed

Kim, Jungmin; Cho, Yunhi

2013-10-01

We have previously reported that dietary gromwell (Lithospermum erythrorhizon; LE) prevents the development of atopic dermatitis (AD) with increased epidermal levels of total ceramide (Cer), the major lipid maintaining epidermal barrier. In this study, we investigated whether the increased level of total Cer induced by dietary LE would be related to the altered metabolism of glucosylceramide (GlcCer) and sphingomyelin (SM), two major precursor lipids in Cer generation. NC/Nga mice, an animal model of AD, were fed a control diet (group CA: atopic control) or a diet with 70% ethanol LE extracts (1% in diet; group LE) for 10 weeks. Individual species of Cer, GlcCer, and SM were analyzed by high-performance thin layer chromatography. In the epidermis of group CA, total Cer (including Cer2 and Cer5-7) and total GlcCer (including GlcCer-B/C/D) were significantly reduced; these levels in group LE were increased to levels similar to the normal control group of BALB/c mice (group C). In addition, protein expressions and activities of β-glucocerebrosidase (β-GlcCer'ase) and acidic sphingomyelinase (aSMase), enzymes for GlcCer or SM hydrolysis, respectively, were increased in group LE. However, alterations of Cer1, Cer3/4, GlcCer-A, and all SM species (including SM1-3) were not significant among groups C, CA, and LE. Dietary gromwell increases GlcCer-B/C/D, and further enhances the generation of Cer2 and Cer5-7 with high protein expressions and activities of β-GlcCer'ase and aSMase.

Dietary calcium intake and renin angiotensin system polymorphisms alter the blood pressure response to aerobic exercise: a randomized control design.

PubMed

Pescatello, Linda S; Turner, Debbie; Rodriguez, Nancy; Blanchard, Bruce E; Tsongalis, Gregory J; Maresh, Carl M; Duffy, Valerie; Thompson, Paul D

2007-01-04

Dietary calcium intake and the renin angiotensin system (RAS) regulate blood pressure (BP) by modulating calcium homeostasis. Despite similar BP regulatory effects, the influence of dietary calcium intake alone and combined with RAS polymorphisms on the BP response following acute aerobic exercise (i.e., postexercise hypotension) has not been studied. Thus, we examined the effect of dietary calcium intake and selected RAS polymorphisms on postexercise hypotension. Subjects were men (n = 50, 43.8 +/- 1.3 yr) with high BP (145.3 +/- 1.5/85.9 +/- 1.1 mm Hg). They completed three experiments: non-exercise control and two cycle bouts at 40% and 60% of maximal oxygen consumption (VO2max). Subjects provided 3 d food records on five protocol-specific occasions. Dietary calcium intake was averaged and categorized as low (<880 mg/d = LowCa) or high (> or = 880 mg/d = HighCa). RAS polymorphisms (angiotensin converting enzyme insertion/deletion, ACE I/D; angiotensin II type 1 receptor, AT1R A/C) were analyzed with molecular methods. Genotypes were reduced from three to two: ACE II/ID and ACE DD; or AT1R AA and AT1R CC/AC. Repeated measure ANCOVA tested if BP differed among experiments, dietary calcium intake level and RAS polymorphisms. Systolic BP (SBP) decreased 6 mm Hg after 40% and 60% VO2max compared to non-exercise control for 10 h with LowCa (p < 0.01), but not with HighCa (p > or = 0.05). Under these conditions, diastolic BP (DBP) did not differ between dietary calcium intake levels (p > or = 0.05). With LowCa, SBP decreased after 60% VO2max versus non-exercise control for 10 h among ACE II/ID (6 mm Hg) and AT1R AA (8 mm Hg); and by 8 mm Hg after 40% VO2max among ACE DD and AT1R CC/CA (p < 0.01). With HighCa, SBP (8 mm Hg) and DBP (4 mm Hg) decreased after 60% VO2max compared to non-exercise control for 10 h (p < 0.05), but not after 40% VO2max (p > or = 0.05). SBP decreased after exercise compared to non-exercise control among men with low but not high dietary calcium intake. Dietary calcium intake interacted with the ACE I/D and AT1R A/C polymorphisms to further modulate postexercise hypotension. Interactions among dietary calcium intake, exercise intensity and RAS polymorphisms account for some of the variability in the BP response to exercise.

Single Nisoldipine-Sensitive Calcium Channels in Smooth Muscle Cells Isolated from Rabbit Mesenteric Artery

NASA Astrophysics Data System (ADS)

Worley, Jennings F.; Deitmer, Joachim W.; Nelson, Mark T.

1986-08-01

Single smooth muscle cells were enzymatically isolated from the rabbit mesenteric artery. At physiological levels of external Ca, these cells were relaxed and contracted on exposure to norepinephrine, caffeine, or high levels of potassium. The patch-clamp technique was used to measure unitary currents through single channels in the isolated cells. Single channels were selective for divalent cations and exhibited two conductance levels, 8 pS and 15 pS. Both types of channels were voltage-dependent, and channel activity occurred at potentials positive to -40 mV. The activity of both channel types was almost completely inhibited by 50 nM nisoldipine. These channels appear to be the pathways for voltage-dependent Ca influx in vascular smooth muscle and may be the targets of the clinically used dihydropyridines.

The influence of dietary and supplemental calcium on postprandial effects of a high-fat meal on lipaemia, glycaemia, C-reactive protein and adiponectin in obese women.

PubMed

Ferreira, Thaís da S; Antunes, Vanessa P; Leal, Priscila M; Sanjuliani, Antonio F; Klein, Márcia R S T

2017-10-01

Non-fasting hypertriacylglycerolaemia is a risk factor for CVD and the amount of fat in a meal seems to be the main factor influencing postprandial lipaemia. Although several studies suggest that Ca can increase faecal fat excretion, it is not known whether Ca can decrease postprandial TAG. This study aimed to evaluate the influence of dietary Ca (DC) and supplemental Ca (SC) on lipaemia, glucose metabolism, C-reactive protein (CRP) and adiponectin during postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (approximately 2900 kJ; 48 % fat): high DC (547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (42 mg DC). Blood samples were collected in the fasting period and at minutes 120 and 240 after meals to evaluate total cholesterol and fractions, TAG, glucose, insulin, high-sensitivity CRP and adiponectin. Serum levels of TAG and insulin increased significantly after all test meals. Only after HSCM total cholesterol did not present a significant increase and LDL-cholesterol had a significant decrease. Postprandial glucose, HDL-cholesterol, CRP and adiponectin did not present significant changes after the three test meals. The comparative analysis of the effects of the three test meals on serum lipids, glucose, insulin, CRP and adiponectin revealed no significant meal-by-time interaction. These results suggest that in obese women challenged with a high-fat meal DC and SC do not interfere with postprandial lipaemia, glucose metabolism, CRP and adiponectin.

The therapeutic response of CDDO-Me in the esophageal squamous cell carcinoma (ESCC) cells is mediated by CaMKIIα.

PubMed

Wang, Yan-Yang; Zhou, Shun; Zhao, Ren; Hai, Ping; Zhe, Hong

2016-01-01

CDDO-Me has exhibited a potent anticancer effect in human esophageal squamous cell carcinoma (ESCC) cells in our previous study, but the molecular interactome remains elusive. We applied the approach of stable-isotope labeling by amino acids in cell culture (SILAC) to assess the proteomic responses of CDDO-Me treatment in human ESCC Ec109 cells. The data were subsequently validated using Western blot assay. The results of our study revealed that CDDO-Me increased the expression level of 543 protein molecules, but decreased the expression level of 709 protein molecules in Ec109 cells. Among these modulated protein molecules, calcium/calmodulin-dependent protein kinase type II subunit α (CaMKIIα) was highly expressed in all tested ESCC cell lines, whereas its expression levels were substantially lower in normal control cell line. Its silencing by small interfering RNA inhibited CDDO-Me induced apoptosis and autophagy in ESCC cells. Collectively, these data demonstrate that the therapeutic response of CDDO-Me in the human ESCC cells is mediated by CaMKIIα.

Maturation and long-term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility

PubMed Central

Goyal, Ravi; Mittal, Ashwani; Chu, Nina; Arthur, Rebecca Afiba; Zhang, Lubo

2010-01-01

In the developing fetus, cerebral arteries (CA) show striking differences in signal transduction mechanisms compared with the adult, and these differences are magnified in response to high-altitude long-term hypoxia (LTH). In addition, in the mature organism, cerebrovascular acclimatization to LTH may be associated with several clinical problems, the mechanisms of which are unknown. Because PKC plays a key role in regulating CA contractility, in fetal and adult cerebral arteries, we tested the hypothesis that LTH differentially regulates the PKC-mediated Ca2+ sensitization pathways and contractility. In four groups of sheep [fetal normoxic (FN), fetal hypoxic (FH), adult normoxic (AN), and adult hypoxic (AH)], we examined, simultaneously, responses of CA tension and intracellular Ca2+ concentration and measured CA levels of PKC, ERK1/2, RhoA, 20-kDa myosin light chain, and the 17-kDa PKC-potentiated myosin phosphatase inhibitor CPI-17. The PKC activator phorbol 12,13-dibutyrate (PDBu) produced robust contractions in all four groups. However, PDBu-induced contractions were significantly greater in AH CA than in the other groups. In all CA groups except AH, in the presence of MEK inhibitor (U-0126), the PDBu-induced contractions were increased a further 20–30%. Furthermore, in adult CA, PDBu led to increased phosphorylation of ERK1, but not ERK2; in fetal CA, the reverse was the case. PDBu-stimulated ERK2 phosphorylation also was significantly greater in FH than FN CA. Also, although RhoA/Rho kinase played a significant role in PDBu-mediated contractions of FN CA, this was not the case in FH or either adult group. Also, whereas CPI-17 had a significant role in adult CA contractility, this was not the case for the fetus. Overall, in ovine CA, the present study demonstrates several important maturational and LTH acclimatization changes in PKC-induced contractile responses and downstream pathways. The latter may play a key role in the pathophysiologic disorders associated with acclimatization to high altitude. PMID:20702800

Maturation and long-term hypoxia-induced acclimatization responses in PKC-mediated signaling pathways in ovine cerebral arterial contractility.

PubMed

Goyal, Ravi; Mittal, Ashwani; Chu, Nina; Arthur, Rebecca Afiba; Zhang, Lubo; Longo, Lawrence D

2010-11-01

In the developing fetus, cerebral arteries (CA) show striking differences in signal transduction mechanisms compared with the adult, and these differences are magnified in response to high-altitude long-term hypoxia (LTH). In addition, in the mature organism, cerebrovascular acclimatization to LTH may be associated with several clinical problems, the mechanisms of which are unknown. Because PKC plays a key role in regulating CA contractility, in fetal and adult cerebral arteries, we tested the hypothesis that LTH differentially regulates the PKC-mediated Ca(2+) sensitization pathways and contractility. In four groups of sheep [fetal normoxic (FN), fetal hypoxic (FH), adult normoxic (AN), and adult hypoxic (AH)], we examined, simultaneously, responses of CA tension and intracellular Ca(2+) concentration and measured CA levels of PKC, ERK1/2, RhoA, 20-kDa myosin light chain, and the 17-kDa PKC-potentiated myosin phosphatase inhibitor CPI-17. The PKC activator phorbol 12,13-dibutyrate (PDBu) produced robust contractions in all four groups. However, PDBu-induced contractions were significantly greater in AH CA than in the other groups. In all CA groups except AH, in the presence of MEK inhibitor (U-0126), the PDBu-induced contractions were increased a further 20-30%. Furthermore, in adult CA, PDBu led to increased phosphorylation of ERK1, but not ERK2; in fetal CA, the reverse was the case. PDBu-stimulated ERK2 phosphorylation also was significantly greater in FH than FN CA. Also, although RhoA/Rho kinase played a significant role in PDBu-mediated contractions of FN CA, this was not the case in FH or either adult group. Also, whereas CPI-17 had a significant role in adult CA contractility, this was not the case for the fetus. Overall, in ovine CA, the present study demonstrates several important maturational and LTH acclimatization changes in PKC-induced contractile responses and downstream pathways. The latter may play a key role in the pathophysiologic disorders associated with acclimatization to high altitude.

4f and 5d energy levels of the divalent and trivalent lanthanide ions in M{sub 2}Si{sub 5}N{sub 8} (M=Ca, Sr, Ba)

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

Kate, O.M. ten, E-mail: o.m.tenkate@tudelft.nl; Energy Materials and Devices, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, Den Dolech 2, 5600MB Eindhoven; Zhang, Z.

Optical data of Sm, Tb and Yb doped Ca{sub 2}Si{sub 5}N{sub 8} and Sr{sub 2}Si{sub 5}N{sub 8} phosphors that have been prepared by solid-state synthesis, are presented. Together with luminescence data from literature on Ce{sup 3+} and Eu{sup 2+} doping in the M{sub 2}Si{sub 5}N{sub 8} (M=Ca, Sr, Ba) hosts, energy level schemes were constructed showing the energy of the 4f and 5d levels of all divalent and trivalent lanthanide ions relative to the valence and conduction band. The schemes were of great help in interpreting the optical data of the lanthanide doped phosphors and allow commenting on the valencemore » stability of the ions, as well as the stability against thermal quenching of the Eu{sup 2+}d-f emission. Tb{sup 3+} substitutes on both a high energy and a low energy site in Ca{sub 2}Si{sub 5}N{sub 8}, due to which excitation at 4.77 eV led to emission from both the {sup 5}D{sub 3} and {sup 5}D{sub 4} levels, while excitation at 4.34 eV gave rise to mainly {sup 5}D{sub 4} emission. Doping with Sm resulted in typical Sm{sup 3+}f-f line absorption, as well as an absorption band around 4.1 eV in Ca{sub 2}Si{sub 5}N{sub 8} and 3.6 eV in Sr{sub 2}Si{sub 5}N{sub 8} that could be identified as the Sm{sup 3+} charge transfer band. Yb on the other hand was incorporated in both the divalent and the trivalent state in Ca{sub 2}Si{sub 5}N{sub 8}. - Graphical abstract: Energy level schemes showing the 4f ground states of the trivalent ( Black-Down-Pointing-Small-Triangle ) and divalent ( Black-Up-Pointing-Small-Triangle ) lanthanide ions and lowest energy 5d states of the trivalent ({nabla}) and divalent ({Delta}) ions with respect to the valence and conduction bands of Ca{sub 2}Si{sub 5}N{sub 8} (left) and Sr{sub 2}Si{sub 5}N{sub 8} (right). Highlights: Black-Right-Pointing-Pointer Construction of energy level schemes of all lanthanides within the M{sub 2}Si{sub 5}N{sub 8} hosts. Black-Right-Pointing-Pointer Construction was done by analyzing existing as well as new spectroscopic data. Black-Right-Pointing-Pointer Tb{sup 3+}d-f emission from two different Ca sites in Ca{sub 2}Si{sub 5}N{sub 8} has been observed. Black-Right-Pointing-Pointer Observation of the Sm{sup 3+} charge transfer band in Ca{sub 2}Si{sub 5}N{sub 8} and Sr{sub 2}Si{sub 5}N{sub 8}. Black-Right-Pointing-Pointer Ytterbium has been found in the divalent and trivalent state in Ca{sub 2}Si{sub 5}N{sub 8}.« less

Ovarian Cancer, Stem Cells, and Bioreactors

DTIC Science & Technology

2009-10-01

also indirectly assessed by measuring CEA and CA125 levels in the circulating medium. CEA and CA125, belonging to the CEA antigen family, are...with OVC#6 could not be detected. The low level of CA125 may be due to a dilution of the protein in the circulating medium as protein concentrations...lower than 8.7U/ml are below the assay sensitivity. Unfortunately, we have been unable to obtain the CA125 circulating level for either patient so

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

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

Kayaaltı, Zeliha, E-mail: kayaalti@ankara.edu.tr; Akyüzlü, Dilek Kaya; Söylemezoğlu, Tülin

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metalmore » trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. • Individuals with the DMT1 IVS4+44 CC genotype had higher blood iron, lead and cadmium levels. • Individuals with DMT1 IVS4+44 CC genotype may be more susceptible for metal toxicity.« less

Does the Loss of Stromal Caveolin-1 Remodel the Tumor Microenvironment by Activating Src-Mediated PEAK1 and PI3K Pathways

DTIC Science & Technology

2017-11-01

and PI3K Pathways? PRINCIPAL INVESTIGATOR: MARIANA REIS SOBREIRO PhD CONTRACTING ORGANIZATION: Cedars-Sinai Medical Center Los Angeles, CA 90048...BEVERLY BLVD LOS ANGELES CA 90048-1804 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical...oncosomes ( LO ). LO internalization induces reprogramming of human normal prostate fibroblasts, as reflected by high levels of α-SMA, IL6, and MMP9. In

Down-regulation of activity and expression of three transport-related proteins in the gills of the euryhaline green crab, Carcinus maenas, in response to high salinity acclimation.

PubMed

Jillette, Nathaniel; Cammack, Lauren; Lowenstein, Margaret; Henry, Raymond P

2011-02-01

The euryhaline green crab, Carcinus maenas, undergoes an annual cycle of salinity exposure, having to adapt to low salinity during its annual spring migration into estuaries, and then having to re-adapt to high salinity when it moves off-shore at the end of summer. Most studies have focused on low salinity acclimation, the activation of osmoregulatory mechanisms, and the induction of transport protein and transport-related enzyme activity and gene expression. In this study we followed the changes in hemolymph osmolality, carbonic anhydrase activity, and mRNA expression of three proteins through a complete cycle of low (15 ppt) and high (32 ppt) salinity acclimation. One week of low salinity acclimation resulted in hemolymph osmoregulation and a four-fold induction of branchial carbonic anhydrase activity. Relative mRNA expression increased for two CA isoforms (CAc 100-fold, and CAg 7-fold) and the α-subunit of the Na/K-ATPase (8-fold). Upon re-exposure to high salinity, hemolymph osmolality increased to 32 ppt acclimated levels by 6 h, and mRNA levels returned to high salinity, baseline levels within 1 week. However, CA activity remained unchanged in response to high salinity exposure for the first week and then gradually declined to baseline levels over 4 weeks. The relative timing of these changes suggests that while whole-organism physiological adaptations and regulation at the gene level can be very rapid, changes at the level of protein expression and turnover are much slower. It is possible that the high metabolic cost of protein synthesis and/or processing could be the underlying reason for long biological life spans of physiologically important proteins. Published by Elsevier Inc.

Cloning, Expression Analysis and Enzyme Activity Assays of the α-Carbonic Anhydrase Gene from Chlamydomonas sp. ICE-L.

PubMed

Qu, Changfeng; He, Yingying; Zheng, Zhou; An, Meiling; Li, Lulu; Wang, Xixi; He, Xiaodong; Wang, Yibin; Liu, Fangming; Miao, Jinlai

2018-01-01

The α-carbonic anhydrase (α-CA) is a zinc ion-containing enzyme that catalyzes the hydration of carbon dioxide. In this paper, a full-length α-CA gene was cloned from Chlamydomonas sp. ICE-L using RT-PCR and RACE-PCR for bioinformatic analysis. The α-CA open reading frame obtained by PCR was cloned into a vector and transformed into Escherichia coli to generate α-CA-producing bacteria. The α-CA was highly expressed upon induction with isopropyl-β-d-thiogalactoside (IPTG) at a final concentration of 0.8 mM. A single band with a molecular weight of approximate 40 kDa expressed in the recombinant E. coli strain harboring the α-CA vector was observed in SDS-PAGE analysis. The carbon dioxide hydration activity and esterase activity of α-CA expressed by the recombinant strain were 0.404 U/mg and 0.319 U, respectively. In addition, three conditions, temperature, salinity and UVB radiation exposure, were selected to analyze α-CA transcription levels by qRT-PCR. The results suggested UVB exposure increased the expression of relative mRNA; meanwhile, the α-CA mRNA expression was rapidly induced by temperature and salinity stress, indicating that Chlamydomonas sp. ICE-L might modulate the α-CA mRNA expression to adapt to the extreme environments.

Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes.

PubMed

Gutiérrez, Tomás; Parra, Valentina; Troncoso, Rodrigo; Pennanen, Christian; Contreras-Ferrat, Ariel; Vasquez-Trincado, César; Morales, Pablo E; Lopez-Crisosto, Camila; Sotomayor-Flores, Cristian; Chiong, Mario; Rothermel, Beverly A; Lavandero, Sergio

2014-11-07

Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca(2+) release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood. In the present study we investigated insulin-dependent mitochondrial Ca(2+) signaling in normal and norepinephrine or insulin like growth factor-1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca(2+)-fluorescent probes we showed that insulin increases mitochondrial Ca(2+) levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca(2+) uniporter, as well as by siRNA-dependent mitochondrial Ca(2+) uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor-1-stimulated cells. This resulted in a reduction in mitochondrial Ca(2+) uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca(2+) uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling. Mitochondrial Ca(2+) uptake is a key event in insulin signaling and metabolism in cardiomyocytes.

Ga(+) Basicity and Affinity Scales Based on High-Level Ab Initio Calculations.

PubMed

Brea, Oriana; Mó, Otilia; Yáñez, Manuel

2015-10-26

The structure, relative stability and bonding of complexes formed by the interaction between Ga(+) and a large set of compounds, including hydrocarbons, aromatic systems, and oxygen-, nitrogen-, fluorine and sulfur-containing Lewis bases have been investigated through the use of the high-level composite ab initio Gaussian-4 theory. This allowed us to establish rather accurate Ga(+) cation affinity (GaCA) and Ga(+) cation basicity (GaCB) scales. The bonding analysis of the complexes under scrutiny shows that, even though one of the main ingredients of the Ga(+) -base interaction is electrostatic, it exhibits a non-negligible covalent character triggered by the presence of the low-lying empty 4p orbital of Ga(+) , which favors a charge donation from occupied orbitals of the base to the metal ion. This partial covalent character, also observed in AlCA scales, is behind the dissimilarities observed when GaCA are compared with Li(+) cation affinities, where these covalent contributions are practically nonexistent. Quite unexpectedly, there are some dissimilarities between several Ga(+) -complexes and the corresponding Al(+) -analogues, mainly affecting the relative stability of π-complexes involving aromatic compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic characteristics of fluid inclusions in sphalerite from the Silesian-Cracow ores, Poland

USGS Publications Warehouse

Kozlowski, A.; Leach, D.L.; Viets, J.G.

1996-01-01

Fluid inclusion studies in sphalerite from early-stage Zn-Pb mineralization in the Silesian-Cracow region (southern Poland), yielded homogenization temperatures (Th) from 80 to 158??C. Vertical thermal gradient of the parent fluids was 6 to 10??C, and the ore crystallization temperature ranges varied from <10??C at deep levels to 25??C at shallow levels. The peculiarities of formation of primary and secondary fluid inclusions from organic-matter-bearing water-dominated medium, position of the inclusions in crystals, features of secondary inclusions, the inclusion refilling phenomena, their formation on recrystallization of ores, and Th distribution in single fissure fillings were considered. The ore-forming fluids were liquid-hydrocarbon-bearing aqueous solutions of Na-Ca-Cl type with lower Ca contents in the south and higher Ca contents in the north of the region. The ore-forming fluids had salinities from nul to about 23 weight percent of NaCl equivalent. Three types of fluids were recognized, that mixed during ore precipitation: a) ascending fluids of low-to-moderate salinity and high, b) formation brines of high salinity and moderate Th, and c) descending waters of low salinity and low-to-moderate Th.

Spontaneous Ca2+ sparks and Ca2+ homeostasis in a minimal model of permeabilized ventricular myocytes

PubMed Central

Hartman, Jana M.; Sobie, Eric A.

2010-01-01

Many issues remain unresolved concerning how local, subcellular Ca2+ signals interact with bulk cellular concentrations to maintain homeostasis in health and disease. To aid in the interpretation of data obtained in quiescent ventricular myocytes, we present here a minimal whole cell model that accounts for both localized (subcellular) and global (cellular) aspects of Ca2+ signaling. Using a minimal formulation of the distribution of local [Ca2+] associated with a large number of Ca2+-release sites, the model simulates both random spontaneous Ca2+ sparks and the changes in myoplasmic and sarcoplasmic reticulum (SR) [Ca2+] that result from the balance between stochastic release and reuptake into the SR. Ca2+-release sites are composed of clusters of two-state ryanodine receptors (RyRs) that exhibit activation by local cytosolic [Ca2+] but no inactivation or regulation by luminal Ca2+. Decreasing RyR open probability in the model causes a decrease in aggregate release flux and an increase in SR [Ca2+], regardless of whether RyR inhibition is mediated by a decrease in RyR open dwell time or an increase in RyR closed dwell time. The same balance of stochastic release and reuptake can be achieved, however, by either high-frequency/short-duration or low-frequency/long-duration Ca2+ sparks. The results are well correlated with recent experimental observations using pharmacological RyR inhibitors and clarify those aspects of the release-reuptake balance that are inherent to the coupling between local and global Ca2+ signals and those aspects that depend on molecular-level details. The model of Ca2+ sparks and homeostasis presented here can be a useful tool for understanding changes in cardiac Ca2+ release resulting from drugs, mutations, or acquired diseases. PMID:20852058

Experimental study on nonmonotonicity of Capillary Desaturation Curves in a 2-D pore network

NASA Astrophysics Data System (ADS)

Rodríguez de Castro, Antonio; Shokri, Nima; Karadimitriou, Nikolaos; Oostrom, Mart; Joekar-Niasar, Vahid

2015-10-01

Immiscible displacement in porous media is important in many applications such as soil remediation and enhanced oil recovery. When gravitational forces are negligible, two-phase immiscible displacement at the pore level is controlled by capillary and viscous forces whose relative importance is quantified through the dimensionless capillary number Ca and the viscosity ratio M between liquid phases. Depending on the values of Ca and M, capillary fingering, viscous fingering, or stable displacement may be observed resulting in a variety of patterns affecting the phase entrapment. The Capillary Desaturation Curve (CDC), which represents the relationship between the residual oil saturation and Ca, is an important relation to describe the phase entrapment at a given Ca. In the present study, we investigated the CDC as influenced by the viscosity ratio. To do so, we have conducted a comprehensive series of experiments using a high-resolution microscope and state-of-art micromodels to investigate the dynamics and patterns of phase entrapment at different Ca and M. By postprocessing of the experimental high-resolution images, we calculated the CDC and quantified the effects of the Ca and M on the phase entrapment and number of blobs trapped in the micromodel and their size distributions during immiscible two-phase flow. Our results show that CDCs are not necessarily monotonic for all M, and the physical mechanisms causing this nonmonotonic behavior are discussed.

Effect of lime and wood ash on the nixtamalization of maize and tortilla chemical and nutritional characteristics.

PubMed

Pappa, María Renée; de Palomo, Patricia Palacios; Bressani, Ricardo

2010-06-01

The objective of the study was to obtain information on the chemical composition, functional properties, sensory quality and protein value of tortillas made from the nixtamalization of maize using either lime or wood ashes. The Ca, K, Mg, Fe, and Zn content of lime and wood ashes showed lime to be high in Ca content while wood ash contained more K and about 71% of the Ca content of lime. Both contained relatively high levels of Mg, Fe and Zn, but more so in the wood ashes. The level of reagent for nixtamalization was set at 0.8% of the maize weight. All other processing conditions were kept constant. The pH of the cooking solution was 12.0 for lime and 10.9 for wood ash. The moisture content of maize at 60 min of cooking was 45.8% for both treatments, however after 12 h of soaking, moisture level was 51.0% for the lime treatment and only 46.8% for the ash treatment. Solids (2.4%) in the lime cooking liquor were higher than in the wood ash liquor (1.0%). Chemical composition changes were similar between treatments in masa and tortilla; however, both masa and tortillas absorbed relatively high levels of all minerals including Fe and Zn from the wood ash treatment. The different treatment influenced functional properties particularly hardness and color. Tortilla characteristics were also similar. Protein quality of both alkali cooked products was lower than that of raw corn, more so the product from the wood ash treatment. Although some differences were observed in the sensory studies, human subjects did not dislike the wood ash made tortillas.

Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca2+ overload and ER stress during hyperglycemia.

PubMed

Biswas, Raktim; Ahn, Jin Chul; Moon, Jeong Hwan; Kim, Jungbin; Choi, Young-Hoon; Park, So Young; Chung, Phil-Sang

2018-05-09

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca 2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm 2 ) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm 2 ) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca 2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation. Copyright © 2018. Published by Elsevier B.V.

Hydrochemical water evolution in the Aral Sea Basin. Part I: Unconfined groundwater of the Amu Darya Delta - Interactions with surface waters

NASA Astrophysics Data System (ADS)

Schettler, Georg; Oberhänsli, Hedi; Stulina, Galina; Mavlonov, Aslon A.; Naumann, Rudolf

2013-07-01

The Aral Sea, which has been affected by lake level lowering of approximately 25 m and a salinity increase from 10 to >100 g/l since 1963, represents, along with the Amu Dary Delta a dynamic hydrological system under an arid climate regime. The system receives river water inflow at high seasonal and inter-annual variability from remote alpine source areas. In the Amu Darya Delta, there is a distinct salinity contrast between the low-salinity river water (∼1 g/l) and the salinity of the unconfined GW (GWunconf: 10-95 g/l). The GWunconf levels are predominantly controlled by the seepage of the river water inflow and GW discharge into the shrinking Aral Sea. In June 2009 and August 2009, we sampled water from various sources including surface waters, GWunconf, lake water and soil leachates for chemical analyses. Evaporative enrichment, precipitation/dissolution of gypsum and precipitation of calcite drive the GWunconf to an NaCl(SO4) water type presenting a positive correlation between Na and SO4. We model the hydrochemical evolution of the GWunconf in a box model which considers the capillary rise of near-surface GW, the precipitation of minerals in the unsaturated horizon and the seasonal re-flushing of adhesive residual brines and soluble salts. The model documents a rapid increase in salinity over a few annual cycles. Furthermore, the model simulations demonstrate the importance of the aeolian redistribution of soluble salts on the hydrochemical GW evolution. In a lab experiment, halite, hexahydrite and starkeyite are precipitated during the late stages of evaporative enrichment from a representative local brine. Processes specific to different water compartments plausibly explain the variations of selected element ratios. For example, the precipitation of low-Sr calcite in irrigation canals and natural river branches of the delta lowers Ca/Sr. The dissolution of gypsum in soils (Ca/Sr mole ratio ∼ 150) and the possible precipitation of SrSO4 associated with Sr-depletion in adhesive residual brines increases Ca/Sr in seepage and re-increases Ca/Sr in the unconfined GW. Aral Sea water, which receives high-Ca/Sr surface and groundwater inflow, developed due to continued precipitation of high-Ca/Sr calcite the almost lowest Ca/Sr ratio (∼25) over time. We observed spatial variations in the GWunconf composition: (i) ammonium levels increase strongly due to interaction with lake sediments rich in organic matter and (ii) distinct increases in levels of nitrate, U, Mo and Se locally reflect oxygenation when GW levels decrease. The Amu Darya Delta acts as a sink for boron (uptake via terrestrial vegetation) and a source for bromide (release by degradation of organically-bound Br). Our results concerning the hydrochemical evolution of the GWunconf and additional data from the Aral Sea constrain the parameter ‘GW discharge’ in water budget models of the lake and improve the basis for palaeoclimatic interpretations of sediment records from the Aral Sea.

Iron, zinc and calcium dialyzability from extruded product based on whole grain amaranth (Amaranthus caudatus and Amaranthus cruentus) and amaranth/Zea mays blends.

PubMed

Galan, María Gimena; Drago, Silvina Rosa; Armada, Margarita; José, Rolando González

2013-06-01

Amaranth is a Native American grain appreciated for its high nutritional properties including high mineral content. The aim of this study was to evaluate the availability of Fe, Zn and Ca from extruded products made with two varieties of amaranth and their mixtures with maize at two levels of replacement. Mineral availability was estimated using dialyzability method. The contents of Fe (64.0-84.0 mg/kg), Ca (1977.5-2348.8 mg/kg) and Zn (30.0-32.1 mg/kg) were higher in amaranth than in maize products (6.2, 19.1, 9.7 mg/kg, respectively). Mineral availability was in the range of (2.0-3.6%), (3.3-11.1%) and (1.6-11.4%) for Fe, Ca and Zn, respectively. Extruded amaranth and amaranth/maize products provide higher amount of Fe and Ca than extruded maize. Extruded amaranth products and amaranth addition to maize could be an interesting way to increase nutritional value of extruded products.

High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity.

PubMed

Farghaly, Hanan Sayed Mohamed; Ashry, Israa El-Sayed Mohamed; Hareedy, Mohammad Salem

2018-06-06

Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization. Our aim was to characterize the role of NF-kB during digoxin toxicity and to assess its correlation with Cav 1.2 in healthy mice in vivo. To address these questions, digoxin was administered in doses of 0.1, 1 or 5 mg/kg orally daily for seven days to the animals. Serum digoxin, serum calcium, atrial and ventricular calcium levels were measured. We, also, looked for NF-kB and CaV1.2 channel expression in cardiac muscle of mice. Digoxin at a dose of 0.1 mg/kg did not enhance serum, atrial, and ventricular Ca+2 levels, but were increased when digoxin dose of 1 and 5 mg/kg were administered. Histologically, myocardial necrosis and cellular infiltration on day 7 were significantly more severe in the 5 mg/kg/day digoxin group. Immunohistochemical studies showed more expression of both NF-kB and CaV1.2 in 1 and 5 mg/kg/day digoxin groups. These data suggest that NF-kB may be responsible for digoxin toxicity, at least partially via modulation of CaV1.2 and intracellular calcium homeostasis in the myocardium. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Tumor type M2 pyruvate kinase expression in advanced breast cancer.

PubMed

Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, P E; Wernecke, K D; Possinger, K

2000-01-01

Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls. Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA). In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly. Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.

Effects of sodium chloride salting and substitution with potassium chloride on whey expulsion of Cheddar cheese.

PubMed

Lu, Y; McMahon, D J

2015-01-01

A challenge in manufacturing reduced-sodium cheese is that whey expulsion after salting decreases when less salt is applied. Our objectives were (1) to determine whether changing the salting method would increase whey syneresis when making a lower sodium cheese and (2) to better understand factors contributing to salt-induced curd syneresis. Unsalted milled Cheddar curds were salted using different salting intervals (5 or 10 min), different salting levels (20, 25, or 30g/kg), different numbers of applications when using only 20g/kg salt (1, 2, or 3 applications), and salting with the equivalent of 30g/kg NaCl using a 2:1 molar ratio of NaCl and KCl. Whey from these curds was collected every 5 or 10 min until 30 or 40 min after the start of salting, and curds were subsequently pressed for 3h. Additional trials were conducted in which salted milled Cheddar cheese curd was immersed at 22°C for 6h in various solutions to determine how milled curd pieces respond to different levels of salt and Ca. The use of 10-min intervals delayed whey syneresis without influencing total whey expulsion or cheese composition after pressing. Lowering the salt level reduced whey expulsion, resulting in cheeses with higher moisture and slightly lower pH. Adding salt faster did not increase whey expulsion in reduced-salt cheese. Partial substitution with KCl restored the extent of whey expulsion. When salted milled curd was immersed in a 30g/L salt solution, there was a net influx of salt solution into the curd and curd weight increased. When curd was immersed in 60g/L salt solution, a contraction of curd occurred. Curd shrinkage was more pronounced as the salt solution concentration was increased to 90 and 120g/L. Increasing the Ca concentration in test solutions (such that both serum and total Ca in the curd increased) also promoted curd contraction, resulting in lower curd moisture and pH and less weight gain by the curd. The proportion of Ca in the curd that was bound to the para-casein protein matrix changed with the Ca content of the test solution. Compared with test solutions containing 10g/L Ca, at low Ca levels (i.e., 1 and 5g/L) the proportion of bound Ca was lower, whereas at 20g/L Ca, the proportion of bound Ca was higher. Both Ca and salt concentration influence the physicochemical properties of the protein matrix such that at low concentrations the curd expands, whereas at high concentrations the curd contracts and expels whey. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Validation of the Conversion between the Mini-Mental State Examination and Montreal Cognitive assessment in Korean Patients with Parkinson’s Disease

PubMed Central

Kim, Ryul; Kim, Han-Joon; Kim, Aryun; Jang, Mi-Hee; Kim, Hyun Jeong; Jeon, Beomseok

2018-01-01

Objective Two conversion tables between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) have recently been established for Parkinson’s disease (PD). This study aimed to validate them in Korean patients with PD and to evaluate whether they could be influenced by educational level. Methods A total of 391 patients with PD who undertook both the Korean MMSE and the Korean MoCA during the same session were retrospectively assessed. The mean, median, and root mean squared error (RMSE) of the difference between the true and converted MMSE scores and the intraclass correlation coefficient (ICC) were calculated according to educational level (6 or fewer years, 7–12 years, or 13 or more years). Results Both conversions had a median value of 0, with a small mean and RMSE of differences, and a high correlation between the true and converted MMSE scores. In the classification according to educational level, all groups had roughly similar values of the median, mean, RMSE, and ICC both within and between the conversions. Conclusion Our findings suggest that both MMSE-MoCA conversion tables are useful instruments for transforming MoCA scores into converted MMSE scores in Korean patients with PD, regardless of educational level. These will greatly enhance the utility of the existing cognitive data from the Korean PD population in clinical and research settings. PMID:29316782

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.

Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders.

PubMed

Tanwar, Jyoti; Trebak, Mohamed; Motiani, Rajender K

2017-01-01

Store-operated Ca 2+ entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca 2+ storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca 2+ levels and transmits the message to plasma membrane Ca 2+ channels constituted by Orai family members (Orai1/2/3) resulting in Ca 2+ influx into the cells. This increase in cytosolic Ca 2+ in turn activates a variety of signaling cascades to regulate a plethora of cellular functions. Evidence from the literature suggests that SOCE dysregulation is associated with several pathophysiologies, including vascular disorders. Interestingly, recent studies have suggested that STIM proteins may also regulate vascular functions independent of their contribution to SOCE. In this updated book chapter, we will focus on the physiological role of STIM and Orai proteins in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in vascular disease.

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats☆

PubMed Central

Janata, Andreas; Magnet, Ingrid A.M.; Uray, Thomas; Stezoski, Jason P.; Janesko-Feldman, Keri; Tisherman, Samuel A.; Kochanek, Patrick M.; Drabek, Tomas

2014-01-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. PMID:24530249

The role of low levels of fullerene C60 nanocrystals on enhanced learning and memory of rats through persistent CaMKII activation.

PubMed

Chen, Liang; Miao, Yanyan; Chen, Lin; Xu, Jing; Wang, Xinxing; Zhao, Han; Shen, Yi; Hu, Yi; Bian, Yunpeng; Shen, Yuanyuan; Chen, Jutao; Zha, Yingying; Wen, Long-Ping; Wang, Ming

2014-11-01

Engineered nanomaterials are known to exhibit diverse and sometimes unexpected biological effects. Fullerene nanoparticles have been reported to specifically bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca(2+) signal transduction and critical for synaptic plasticity, but the functional consequence of that modulation is unknown. Here we show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through intrahippocampal infusion and without any obvious cytotoxicity in hippocampal neuronal cells, enhance the long-term potentiation (LTP) of rats. Intraperitoneal injection of 320 μg/kg of Nano C60, once daily for 10 days, also enhanced spatial memory of rats in addition to an increase of LTP. In parallel, both the IH and IP administration of Nano C60 increased the autonomous activity and the level of threonine 286 (T286) autophosphorylation of CaMKII, enhanced post-synaptic AMPA/NMDA ratio, and triggered time-dependent activation of ERK and CREB. Our results reveal a striking and highly unexpected ability of Nano C60 in positively modulating learning and memory, an effect that is most likely manifested through locking CaMKII in an active conformation, and may have significant implications for the potential therapeutic applications of fullerene C60, a classic engineered nanomaterial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prostate Cancer Information Available in Health-Care Provider Offices: An Analysis of Content, Readability, and Cultural Sensitivity.

PubMed

Choi, Seul Ki; Seel, Jessica S; Yelton, Brooks; Steck, Susan E; McCormick, Douglas P; Payne, Johnny; Minter, Anthony; Deutchki, Elizabeth K; Hébert, James R; Friedman, Daniela B

2018-07-01

Prostate cancer (PrCA) is the most common cancer affecting men in the United States, and African American men have the highest incidence among men in the United States. Little is known about the PrCA-related educational materials being provided to patients in health-care settings. Content, readability, and cultural sensitivity of materials available in providers' practices in South Carolina were examined. A total of 44 educational materials about PrCA and associated sexual dysfunction was collected from 16 general and specialty practices. The content of the materials was coded, and cultural sensitivity was assessed using the Cultural Sensitivity Assessment Tool. Flesch Reading Ease, Flesch-Kincaid Grade Level, and the Simple Measure of Gobbledygook were used to assess readability. Communication with health-care providers (52.3%), side effects of PrCA treatment (40.9%), sexual dysfunction and its treatment (38.6%), and treatment options (34.1%) were frequently presented. All materials had acceptable cultural sensitivity scores; however, 2.3% and 15.9% of materials demonstrated unacceptable cultural sensitivity regarding format and visual messages, respectively. Readability of the materials varied. More than half of the materials were written above a high-school reading level. PrCA-related materials available in health-care practices may not meet patients' needs regarding content, cultural sensitivity, and readability. A wide range of educational materials that address various aspects of PrCA, including treatment options and side effects, should be presented in plain language and be culturally sensitive.

AltitudeOmics: cerebral autoregulation during ascent, acclimatization, and re-exposure to high altitude and its relation with acute mountain sickness.

PubMed

Subudhi, Andrew W; Fan, Jui-Lin; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Julian, Colleen G; Lovering, Andrew T; Panerai, Ronney B; Roach, Robert C

2014-04-01

Cerebral autoregulation (CA) acts to maintain brain blood flow despite fluctuations in perfusion pressure. Acute hypoxia is thought to impair CA, but it is unclear if CA is affected by acclimatization or related to the development of acute mountain sickness (AMS). We assessed changes in CA using transfer function analysis of spontaneous fluctuations in radial artery blood pressure (indwelling catheter) and resulting changes in middle cerebral artery blood flow velocity (transcranial Doppler) in 21 active individuals at sea level upon arrival at 5,260 m (ALT1), after 16 days of acclimatization (ALT16), and upon re-exposure to 5,260 m after 7 days at 1,525 m (POST7). The Lake Louise Questionnaire was used to evaluate AMS symptom severity. CA was impaired upon arrival at ALT1 (P < 0.001) and did not change with acclimatization at ALT16 or upon re-exposure at POST7. CA was not associated with AMS symptoms (all R < 0.50, P > 0.05). These findings suggest that alterations in CA are an intrinsic consequence of hypoxia and are not directly related to the occurrence or severity of AMS.

Determination of serum calcium levels by 42Ca isotope dilution inductively coupled plasma mass spectrometry.

PubMed

Han, Bingqing; Ge, Menglei; Zhao, Haijian; Yan, Ying; Zeng, Jie; Zhang, Tianjiao; Zhou, Weiyan; Zhang, Jiangtao; Wang, Jing; Zhang, Chuanbao

2017-11-27

Serum calcium level is an important clinical index that reflects pathophysiological states. However, detection accuracy in laboratory tests is not ideal; as such, a high accuracy method is needed. We developed a reference method for measuring serum calcium levels by isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS), using 42Ca as the enriched isotope. Serum was digested with 69% ultrapure nitric acid and diluted to a suitable concentration. The 44Ca/42Ca ratio was detected in H2 mode; spike concentration was calibrated by reverse IDMS using standard reference material (SRM) 3109a, and sample concentration was measured by a bracketing procedure. We compared the performance of ID ICP-MS with those of three other reference methods in China using the same serum and aqueous samples. The relative expanded uncertainty of the sample concentration was 0.414% (k=2). The range of repeatability (within-run imprecision), intermediate imprecision (between-run imprecision), and intra-laboratory imprecision were 0.12%-0.19%, 0.07%-0.09%, and 0.16%-0.17%, respectively, for two of the serum samples. SRM909bI, SRM909bII, SRM909c, and GBW09152 were found to be within the certified value interval, with mean relative bias values of 0.29%, -0.02%, 0.10%, and -0.19%, respectively. The range of recovery was 99.87%-100.37%. Results obtained by ID ICP-MS showed a better accuracy than and were highly correlated with those of other reference methods. ID ICP-MS is a simple and accurate candidate reference method for serum calcium measurement and can be used to establish and improve serum calcium reference system in China.

Increased extracellular and intracellular Ca{sup 2+} lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

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

Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp; Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp; Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421

2015-02-20

Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub o} and [Ca{sup 2+}]{sub i}) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation, which suggested that increases in [Ca{sup 2+}]{sub o} caused by bone resorption maymore » accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca{sup 2+}]{sub i} (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca{sup 2+}]{sub o} (addition of CaCl{sub 2}) leads to increases in [Ca{sup 2+}]{sub i}. Flow cytometric methods revealed that high [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK independently of intracellular Ca{sup 2+}. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca{sup 2+} provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca{sup 2+}, which results in BMSC proliferation. - Highlights: • Both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation in BMSCs. • High [Ca{sup 2+}]{sub i} enhanced the proliferation of BMSCs but not adipocyte differentiation. • High [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK in BMSCs. • Inhibition of ERK enhanced the differentiation of BMSCs into adipocytes. • High [Ca{sup 2+}]{sub o}-mediated suppression of ERK may be a new therapy target for anemia.« less

The Calcium-Sensing Receptor in Health and Disease.

PubMed

Díaz-Soto, G; Rocher, A; García-Rodríguez, C; Núñez, L; Villalobos, C

2016-01-01

The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca 2+ and by other physiological cations including Mg 2+ , amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca 2+ homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca 2+ absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca 2+ metabolism. CaSR agonists (calcimimetics) and antagonists (calcilytics) are in use or under intense research for treatment of hyperparathyroidism secondary to kidney failure and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR extends to other tissues and systems beyond the extracellular Ca 2+ homeostatic system including the cardiovascular system, the airways, and the nervous system where it may play physiological functions yet to be fully understood. As a consequence, CaSR has been recently involved in different pathologies including uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's disease. Finally, the CaSR has been shown to play a critical role in cancer either contributing to bone metastasis and/or acting as a tumor suppressor in some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as oncogene in others (breast and prostate cancers). Here we review the role of CaSR in health and disease in calciotropic tissues and others beyond the extracellular calcium homeostatic system. Copyright © 2016 Elsevier Inc. All rights reserved.

Turbine Engine Lubricant Reclamation.

DTIC Science & Technology

1983-06-01

results indicate no differences in additive/degradation product removal by varying the basic material level or between Ca(OH)2 and MgO. Data indicates...0H) 2 ɘ.09 .o difference in removal by changing Ca(OH) 2 treat- . ment level by HPLC and TLC. Thin Layer Chromatography Oil + adsorbents Oil + Ca(0H...2.1%) 0.17 3% by weight 0.17 4% by weight 0.16 No difference in removal by changing Ca(OH)2 treat- ment level by HPLC and TLC. Thin Layer

Risk Assessment Among Prostate Cancer Patients Receiving Primary Androgen Deprivation Therapy

PubMed Central

Cooperberg, Matthew R.; Hinotsu, Shiro; Namiki, Mikio; Ito, Kazuto; Broering, Jeanette; Carroll, Peter R.; Akaza, Hideyuki

2009-01-01

Purpose Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients. Methods Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments. Results J-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA—scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage—predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84. Conclusion The novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations. PMID:19667269

Valence-band and core-level photoemission study of single-crystal Bi2CaSr2Cu2O8 superconductors

NASA Astrophysics Data System (ADS)

Shen, Z.-X.; Lindberg, P. A. P.; Wells, B. O.; Mitzi, D. B.; Lindau, I.; Spicer, W. E.; Kapitulnik, A.

1988-12-01

High-quality single crystals of Bi2CaSr2Cu2O8 superconductors have been prepared and cleaved in ultrahigh vacuum. Low-energy electron diffraction measurements show that the surface structure is consistent with the bulk crystal structure. Ultraviolet photoemission and x-ray photoemission experiments were performed on these well-characterized sample surfaces. The valence-band and the core-level spectra obtained from the single-crystal surfaces are in agreement with spectra recorded from polycrystalline samples, justifying earlier results from polycrystalline samples. Cu satellites are observed both in the valence band and Cu 2p core level, signaling the strong correlation among the Cu 3d electrons. The O 1s core-level data exhibit a sharp, single peak at 529-eV binding energy without any clear satellite structures.

Deformation processed Al/Ca nano-filamentary composite conductors for HVDC applications

NASA Astrophysics Data System (ADS)

Czahor, C. F.; Anderson, I. E.; Riedemann, T. M.; Russell, A. M.

2017-07-01

Efficient long-distance power transmission is necessary as the world continues to implement renewable energy sources, often sited in remote areas. Light, strong, high-conductivity materials are desirable for this application to reduce both construction and operational costs. In this study an Al/Ca (11.5% vol.) composite with nano-filamentary reinforcement was produced by powder metallurgy then extruded, swaged, and wire drawn to a maximum true strain of 12.7. The tensile strength increased exponentially as the filament size was reduced to the sub-micron level. In an effort to improve the conductor’s ability to operate at elevated temperatures, the deformation-processed wires were heat-treated at 260°C to transform the Ca-reinforcing filaments to Al2Ca. Such a transformation raised the tensile strength by as much as 28%, and caused little change in ductility, while the electrical conductivity was reduced by only 1% to 3%. Al/Al2Ca composites are compared to existing conductor materials to show how implementation could affect installation and performance.

Leaching Characteristics of Calcium and Strontium from Phosphogypsum Under Acid Rain.

PubMed

Wang, Mei; Luo, Houqiao; Chen, Yong; Yang, Jinyan

2018-02-01

Phosphogypsum (PG) stored close to phosphorus chemical plants has caused worldwide environmental problems. Column leaching experiments were conducted to evaluate Ca and Sr leaching from PG under simulated acid rain at pH levels typical for rain in the study region (Shifang, China). High concentrations of Ca and Sr in leachates in the first five leaching events could pollute the soil and groundwater around the PG. Leachates pH was lower than and had no correlation with simulated rain pH. No correlations between simulated rain pH and cumulative Ca and Sr content in leachates were noted. Around 2.0%-2.2% of Ca and 0.5%-0.6% of Sr were leached out from PG by the simulated summer rainfall in Shifang. Electrical conductivity values, Ca and Sr concentrations at bottom sections of PG columns were higher than those of top sections, while pH values showed a reverse trend. More precautions should be taken to protect the environment around PG stacks.

Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma

PubMed Central

Daft, Paul G.; Yuan, Kaiyu; Warram, Jason M.; Klein, Michael J.; Siegal, Gene P.; Zayzafoon, Majd

2013-01-01

Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is alpha-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients and is expressed in varying levels in different human osteosarcoma cell lines (HOS, MG-63, MNNG/HOS and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by shRNA in MG-63 and 143B cells resulted in decreased proliferation (50 and 41%), migration (22 and 25%) and invasion (95 and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%) and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), while α-CaMKII overexpression resulted in tumor formation in a previously non-tumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. PMID:23364534

Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma.

PubMed

Daft, Paul G; Yuan, Kaiyu; Warram, Jason M; Klein, Michael J; Siegal, Gene P; Zayzafoon, Majd

2013-04-01

Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca(2+)/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca(2+)-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by short hairpin RNA (shRNA) in MG-63 and 143B cells resulted in decreased proliferation (50% and 41%), migration (22% and 25%), and invasion (95% and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%), and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. ©2013 AACR.

Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques

PubMed Central

Gilad, Ron; Williams, James C.; Usman, Kalba D.; Holland, Ronen; Golan, Shay; Ruth, Tor; Lifshitz, David

2017-01-01

Introduction and Objective Stone analysis should be performed in all first-time stone formers. The preferred analytical procedures are Fourier-transform infrared spectroscopy (FT-IR) or X-ray diffraction (XRD). However, due to limited resources, chemical analysis (CA) is still in use throughout the world. The aim of the study was to compare FT-IR and CA in well matched stone specimens and characterize the pros and cons of CA. Methods In a prospective bi-center study, urinary stones were retrieved from 60 consecutive endoscopic procedures. In order to assure that identical stone samples were sent for analyses, the samples were analyzed initially by micro-computed tomography to assess uniformity of each specimen before submitted for FTIR and CA. Results Overall, the results of CA did not match with the FTIR results in 56% of the cases. In 16% of the cases CA missed the major stone component and in 40% the minor stone component. 37 of the 60 specimens contained CaOx as major component by FTIR, and CA reported major CaOx in 47/60, resulting in high sensitivity, but very poor specificity. CA was relatively accurate for UA and cystine. CA missed struvite and calcium phosphate as a major component in all cases. In mixed stones the sensitivity of CA for the minor component was poor, generally less than 50%. Conclusions Urinary stone analysis using CA provides only limited data that should be interpreted carefully. Urinary stone analysis using CA is likely to result in clinically significant errors in its assessment of stone composition. Although the monetary costs of CA are relatively modest, this method does not provide the level of analytical specificity required for proper management of patients with metabolic stones. PMID:26956131

CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells.

PubMed

Frigo, Daniel E; Howe, Matthew K; Wittmann, Bryan M; Brunner, Abigail M; Cushman, Ian; Wang, Qianben; Brown, Myles; Means, Anthony R; McDonnell, Donald P

2011-01-15

While patients with advanced prostate cancer initially respond favorably to androgen ablation therapy, most experience a relapse of the disease within 1-2 years. Although hormone-refractory disease is unresponsive to androgen-deprivation, androgen receptor (AR)-regulated signaling pathways remain active and are necessary for cancer progression. Thus, both AR itself and the processes downstream of the receptor remain viable targets for therapeutic intervention. Microarray analysis of multiple clinical cohorts showed that the serine/threonine kinase Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) is both highly expressed in the prostate and further elevated in prostate cancers. Using cellular models of prostate cancer, we have determined that androgens (a) directly increase the expression of a CaMKKβ splice variant and (b) increase functional CaMKKβ protein levels as determined by the phosphorylation of both CaMKI and AMP-activated protein kinase (AMPK), two of CaMKKβ's primary substrates. Importantly, inhibition of the CaMKKβ-AMPK, but not CaMKI, signaling axis in prostate cancer cells by pharmacological inhibitors or siRNA-mediated knockdown blocks androgen-mediated migration and invasion. Conversely, overexpression of CaMKKβ alone leads to both increased AMPK phosphorylation and cell migration. Given the key roles of CaMKKβ and AMPK in the biology of prostate cancer cells, we propose that these enzymes are potential therapeutic targets in prostate cancer. © 2010 AACR.

Regulation of the voltage-gated Ca2+ channel CaVα2δ-1 subunit expression by the transcription factor Egr-1.

PubMed

González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Gómez-Mora, Kimberly; Felix, Ricardo

2018-04-23

It is well known that the Ca V α 2 δ auxiliary subunit regulates the density of high voltage-activated Ca 2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of Ca V α 2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of Ca V α 2 δ. Overexpression and knockdown analysis of Egr-1 showed significant changes in the transcriptional activity of the Ca V α 2 δ promoter. Egr-1 also regulated the expression of Ca V α 2 δ at the level of protein. Also, functional studies showed that Egr-1 knockdown significantly decreases Ca 2+ currents in dorsal root ganglion (DRG) neurons, while overexpression of the transcription factor increased Ca 2+ currents in the F11 cell line, a hybrid of DRG and N18TG2 neuroblastoma cells. Studying the effects of Egr-1 on the transcriptional expression of Ca V α 2 δ could help to understand the regulatory mechanisms of this protein in both health and disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

PubMed

Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

2017-06-02

Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

NASA Astrophysics Data System (ADS)

Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

2017-05-01

In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

Increased collagen maturity with sildenafil citrate: experimental high risk colonic anastomosis model.

PubMed

Cakir, Tebessum; Ozer, Ilter; Bostanci, Erdal Birol; Keklik, Tulay Timucin; Ercin, Ugur; Bilgihan, Ayse; Akoglu, Musa

2015-01-01

Inadequate healing and high anastomosis leak rates at rectal anastomosis may be due to lack of supportive serosal layer and technical difficulty of low anterior resections. Positive effects of sildenafil on wound healing were observed. The aim of this study was to simulate rectal anastomosis as a technical insufficient anastomosis and investigate the effects of sildenafil on anastomosis healing. Colonic anastomoses were carried out in 64 rats and randomized into four groups, CA-S, complete anastomoses without sildenafil (10 mg/kg for 5 days); CA+S, complete anastomoses with sildenafil; IA-S, incomplete anastomoses without sildenafil; IA+S, incomplete anastomoses with sildenafil. Half of the rats in every group were sacrificed on post-operative day (POD) 3, half of them sacrificed on POD 7. Tissues from the anastomoses were used for functional, histochemical, biochemical investigations. Sildenafil treatment resulted in increased bursting pressures in IA+S on POD 7 (p=0.010). Collagen maturity was higher in IA+S on POD 3 and POD 7, CA+S on POD 7 (p=0.010; p=0.010; p<0.007). Collagen content was higher in IA+S on POD 7 (p<0.001). Glutathione, hydroxyproline levels were similar. Malondialdehyde levels were lower in IA+S on POD 3 (p<0.001). Epithelization score was higher in IA+S on POD 7 (p=0.007). Inflammation score was higher in CA-S group on POD 3 and POD 7 (p<0.001; p<0.001). Neutrophil score was lower in CA+S on POD 3 (p=0.005). An increase in collagen content, maturity, and epithelization, a decrease in neutrophil infiltration, oxidative stress and better mechanical strength were observed with the administration of sildenafil. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas

PubMed Central

Rovira, Meritxell; Scott, Sherri-Gae; Liss, Andrew S.; Jensen, Jan; Thayer, Sarah P.; Leach, Steven D.

2009-01-01

The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium, and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have not previously been isolated in a manner that allows formal assessment of their progenitor capacities. We have found that a subset of adult CA/TD cells are characterized by high levels of ALDH1 enzymatic activity, related to high-level expression of both Aldh1a1 and Aldh1a7. This allows their isolation by FACS using a fluorogenic ALDH1 substrate. FACS-isolated CA/TD cells are relatively depleted of transcripts associated with differentiated pancreatic cell types. In contrast, they are markedly enriched for transcripts encoding Sca1, Sdf1, c-Met, Nestin, and Sox9, markers previously associated with progenitor populations in embryonic pancreas and other tissues. FACS-sorted CA/TD cells are uniquely able to form self-renewing “pancreatospheres” in suspension culture, even when plated at clonal density. These spheres display a capacity for spontaneous endocrine and exocrine differentiation, as well as glucose-responsive insulin secretion. In addition, when injected into cultured embryonic dorsal pancreatic buds, these adult cells display a unique capacity to contribute to both the embryonic endocrine and exocrine lineages. Finally, these cells demonstrate dramatic expansion in the setting of chronic epithelial injury. These findings suggest that CA/TD cells are indeed capable of progenitor function and may contribute to the maintenance of tissue homeostasis in adult mouse pancreas. PMID:20018761

Origins of intracellular calcium mobilization evoked by infrared laser stimulation

NASA Astrophysics Data System (ADS)

Olsovsky, Cory A.; Tolstykh, Gleb P.; Ibey, Bennett L.; Beier, Hope T.

2015-03-01

Cellular delivery of pulsed IR laser energy has been shown to stimulate action potentials in neurons. The mechanism for this stimulation is not completely understood. Certain hypotheses suggest the rise in temperature from IR exposure could activate temperature- or pressure-sensitive channels, or create pores in the cellular outer membrane. Studies using intensity-based Ca2+-responsive dyes show changes in Ca2+ levels after various IR stimulation parameters; however, determination of the origin of this signal proved difficult. An influx of larger, typically plasma-membrane-impermeant ions has been demonstrated, which suggests that Ca2+ may originate from the external solution. However, activation of intracellular signaling pathways, possibly indicating a more complex role of increasing Ca2+ concentration, has also been shown. By usingCa2+ sensitive dye Fura-2 and a high-speed ratiometric imaging system that rapidly alternates the excitation wavelengths, we have quantified the Ca2+ mobilization in terms of influx from the external solution and efflux from intracellular organelles. CHO-K1 cells, which lack voltage-gated Ca2+ channels, and NG-108 neuroblastoma cells, which do not produce action potentials in an early undifferentiated state, are used to determine the origin of the Ca2+ signals and investigate the role these mechanisms may play in IR neural stimulation.