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Sample records for 15-3 ca 19-9

  1. A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the Differential Diagnosis of the Pancreatic Lesion

    PubMed Central

    Skulimowski, Aleksander; Durczyński, Adam; Kumor, Anna; Poznańska, Grażyna; Oleśna, Aleksandra; Rut, Joanna

    2017-01-01

    Background. Proper diagnosis of pancreatic lesion etiology is a challenging clinical dilemma. Studies suggest that surgery for suspected pancreatic ductal adenocarcinoma (PDAC) reveals a benign lesion in 5% to 13% of cases. The aim of our study was to assess whether routinely used biomarkers such as CA19-9, Ca125, Ca15-3, and CEA, when combined, can potentially yield an accurate test predicting pancreatic lesion etiology. Methods. We retrospectively analyzed data of 326 patients who underwent a diagnostic process due to pancreatic lesions of unknown etiology. Results. We found statistically significant differences in mean levels of all biomarkers. In logistic regression model, we applied levels CA19-9, Ca125, and Ca15-3 as variables. Two validation methods were used, namely, random data split into training and validation groups and bootstrapping. Afterward, we built ROC curve using the model that we had created, reaching AUC = 0,801. With an optimal cut-off point, it achieved specificity of 81,2% and sensitivity of 63,10%. Our proposed model has superior diagnostic accuracy to both CA19-9 (p = 0,0194) and CA125 (p = 0,0026). Conclusion. We propose a test that is superior to CA19-9 in a differential diagnosis of pancreatic lesion etiology. Although our test fails to reach exceptionally high accuracy, its feasibility and cost-effectiveness make it clinically useful. PMID:28356610

  2. Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C

    PubMed Central

    ASSMAR, Mehdi; YEGANEH, Sara; MANSOURGHANAEI, Fariborz; AMIRMOZAFARI, Nour

    2016-01-01

    Background: This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. Methods: This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. Results: No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis (P>0.05). In patients with hepatitis B, increase in CA125 were observed (P=0.03). In hepatitis C patients, there was an increase in AFP levels (P=0.03). Conclusion: The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase. PMID:28053931

  3. The diagnostic value of CA 27-29, CA 15-3, mucin-like carcinoma antigen, carcinoembryonic antigen and CA 19-9 in breast and gastrointestinal malignancies.

    PubMed

    Frenette, P S; Thirlwell, M P; Trudeau, M; Thomson, D M; Joseph, L; Shuster, J S

    1994-01-01

    In the past decade, considerable interest has arisen for defining the role of various tumor markers in the diagnosis of cancer. This cross-sectional study evaluates four breast cancer markers (CA 27-29, CA 15-3, MCA and CEA) and two gastrointestinal (GI) markers (CA 19-9 and CEA) in 213 patients. Receiver operating curves (ROC) revealed a sensitivity for the 90% specificity cutoff for breast cancers compared to breast benign diseases of 70% for CA 27-29, 67.5% for CA 15-3, 52.5% for MCA and 40% for CEA. When GI tumors were compared to benign GI disease, the sensitivity for 90% specificity was 40.3% for CEA and 32.3% for CA 19-9. Comparison of breast cancer and GI malignancies with other malignancies leads to a marked shift of the ROC curve to the right and loss of specificity. Late stage for all breast and GI tumor markers was found to be a predictor of high serum antigen level (p < 0.001). The presence of liver metastases in breast cancer was associated with abnormal levels of CA 27-29 (p = 0.028). Pancreas adenocarcinomas had a higher CA 19-9 antigen level (p < 0.001) than other GI malignancies. CA 27-29 appears to be at least as sensitive and specific as CA 15-3 in patients with breast cancer. None of the above markers retain their specificity when compared with a control group consisting of other malignancies.

  4. CA 19-9 (Cancer Antigen 19-9)

    MedlinePlus

    ... monitor a person who has been diagnosed with pancreatic cancer and is undergoing treatment. CA 19-9 is ... tumor marker : To monitor a person's response to pancreatic cancer treatment and/or cancer progression To watch for ...

  5. Assessment of average of normals (AON) procedure for outlier-free datasets including qualitative values below limit of detection (LoD): an application within tumor markers such as CA 15-3, CA 125, and CA 19-9.

    PubMed

    Usta, Murat; Aral, Hale; Mete Çilingirtürk, Ahmet; Kural, Alev; Topaç, Ibrahim; Semerci, Tuna; Hicri Köseoğlu, Mehmet

    2016-11-01

    Average of normals (AON) is a quality control procedure that is sensitive only to systematic errors that can occur in an analytical process in which patient test results are used. The aim of this study was to develop an alternative model in order to apply the AON quality control procedure to datasets that include qualitative values below limit of detection (LoD). The reported patient test results for tumor markers, such as CA 15-3, CA 125, and CA 19-9, analyzed by two instruments, were retrieved from the information system over a period of 5 months, using the calibrator and control materials with the same lot numbers. The median as a measure of central tendency and the median absolute deviation (MAD) as a measure of dispersion were used for the complementary model of AON quality control procedure. The ubias values, which were determined for the bias component of the measurement uncertainty, were partially linked to the percentages of the daily median values of the test results that fall within the control limits. The results for these tumor markers, in which lower limits of reference intervals are not medically important for clinical diagnosis and management, showed that the AON quality control procedure, using the MAD around the median, can be applied for datasets including qualitative values below LoD.

  6. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  7. 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

  8. CA19-9: A promising tumor marker for pancreatic carcinoma

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

    1984-01-01

    In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA.

  9. Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease.

    PubMed

    Hong, Ji Young; Jang, Sun Hee; Kim, Song Yee; Chung, Kyung Soo; Song, Joo Han; Park, Moo Suk; Kim, Young Sam; Kim, Se Kyu; Chang, Joon; Kang, Young Ae

    2016-01-01

    Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p<0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p=0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p=0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.

  10. Two cases of the same family with the unusual elevation of CA19-9 levels.

    PubMed

    Uyanik, Metin; Sertoglu, Erdim; Serdar, Muhittin A; Aydin, Fevzi N; Ozgurtas, Taner; Kurt, Ismail

    2014-01-01

    Introdução: O antigénio carbohidrato (CA19-9) presente no soro é um marcador amplamente utilizado na prática clínica e apresenta pequenos aumentos em algumas doenças benignas. Aqui relatamos dois casos saudáveis, uma mãe e a sua filha, com níveis CA19-9 um pouco elevados.Casos Clínicos: A mãe, com um nível CA19-9 elevado (89,90 U/mL; limite superior do intervalo normal (ULNR) < 37 U/mL) foi encaminhada ao nosso departamento para avaliação. Um aumento semelhante foi incidentalmente determinado na sua filha. O nível de CA19-9 da filha era 123,92 U/mL. Os restantes parametros laboratoriais avaliados, estudos imagiológicos e avaliações clínicas revelaram-se dentro dos limites da normalidade. Não foi encontrada, qualquer patologia que justifique elevado nível de CA19-9. A fim de evitar erros de laboratório ou possíveis interferências, as amostras foram analisadas em quatro plataformas de imunoensaios diferentes, em duplicado.Conclusão: As pessoas saudáveis podem ter níveis da CA19-9 superiores aos limites de referência. Portanto, os médicos precisam estar cientes dessas situações raras, sem falhar o diagnóstico de doenças malignas.

  11. CA 19-9 as a Predictor for Response and Survival in Advanced Pancreatic Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Koom, Woong Sub; Seong, Jinsil Kim, Yong Bae; Pyun, Hae Ok; Song, Si Young

    2009-03-15

    Purpose: To investigate the significance of carbohydrate antigen 19-9 (CA 19-9) levels for predicting response and survival in pancreatic cancer (PC) treated with concurrent chemoradiotherapy. Methods and Materials: We retrospectively reviewed data from 69 patients with PC between 1999 and 2005. All patients had elevated CA 19-9 levels before treatment. CA 19-9 levels (pre- and posttreatment CA 19-9) and their decline were analyzed for radiologic response and overall survival. Results: Seventeen patients (25%) had a 50% or greater reduction in tumor size within 3 months of chemoradiotherapy (1 complete response, 16 partial responses). CA 19-9 decline was significantly correlated with radiologic response (p = 0.03). The median survival time (MST) was 12 months (range, 4-48 months), and 1-year survival rate was 44%. Pretreatment CA 19-9 > 1,200 U/mL (MST, 13 vs. 8 months; p = 0.002), posttreatment CA 19-9 >100 U/mL (MST, 17 vs. 10 months; p = 0.0003), and CA 19-9 decline {<=}40% (MST, 13 vs. 10 months; p = 0.005) were the strongest and most unfavorable prognostic factors. In addition, patients with multiple unfavorable CA 19-9 levels had significantly worse outcomes than those without. Conclusions: CA 19-9 decline shows a correlation with radiologic response. The combination of pretreatment CA 19-9 >1,200 U/mL, posttreatment CA 19-9 >100 U/mL, and CA 19-9 decline {<=}40% may possibly serve as a surrogate marker for poor survival in advanced PC receiving chemoradiotherapy.

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

    PubMed Central

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

    2015-01-01

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

  13. Patients with normal-range CA19-9 levels represent a distinct subgroup of pancreatic cancer patients

    PubMed Central

    Luo, Guopei; Jin, Kaizhou; Guo, Meng; Cheng, He; Liu, Zuqiang; Xiao, Zhiwen; Lu, Yu; Long, Jiang; Liu, Liang; Xu, Jin; Liu, Chen; Gao, Yutang; Ni, Quanxing; Yu, Xianjun

    2017-01-01

    Pancreatic cancer remains a lethal disease that responds poorly to multiple types of treatment. Therefore, the identification of distinct subgroups that exhibit unique therapeutic responses is an urgent requirement. In the present multicenter study (1,912 cases), the differences between the therapeutic responses and clinical characteristics of two subgroups of pancreatic cancer, carbohydrate antigen 19–9 (CA19-9)-normal (baseline serum level, ≤37 U/ml) and CA19-9-elevated (baseline serum level, >37 U/ml), were analyzed. CA19-9-normal expression was identified to be an independent prognostic factor for patients with stage I–II [hazard ratio (HR)=0.77; P=0.037] and stage III–IV (HR=0.68; P<0.001) pancreatic cancer. The 5-year survival rate of the stage III–IV CA19-9-normal subgroup was increased compared with the stage I–II CA19-9-elevated subgroup (15.4 vs. 13.8%). In the stage I–II CA19-9-normal and CA19-9-elevated subgroups, gemcitabine-based chemotherapy was a significant positive prognostic factor for survival (CA19-9-normal, HR=0.54, P=0.013; CA19-9-elevated, HR=0.55, P<0.001). However, among stage III–IV patients, the CA19-9-normal subgroup exhibited a poor response to gemcitabine-based chemotherapy (HR=0.77; P=0.165), while the CA19-9-elevated subgroup exhibited a favorable response, resulting in a lower rate of mortality (HR=0.70; P<0.001) compared with no chemotherapy. It was concluded that CA19-9-normal pancreatic cancer is a less aggressive subgroup; however, advanced CA19-9-normal pancreatic cancer exhibits a poorer response to gemcitabine-based chemotherapy. PMID:28356973

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

    PubMed Central

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

    2012-01-01

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

  15. Pancreatic Tuberculosis with Markedly Elevated CA 19-9 Levels: A Diagnostic Pitfall

    PubMed Central

    Kaur, Manveen; Dalal, Varsha; Bhatnagar, Amar; Siraj, Fouzia

    2016-01-01

    Despite the high prevalence of tuberculosis (TB) in developing countries, isolated pancreatic TB is rare and is usually seen in immunocompromised patients. It presents with non-specific signs and symptoms and may mimic malignancy both clinically and radiologically. Cytologic and histologic confirmation is required to establish the definitive diagnosis. We present a case of a 25-year-old male with a pancreatic mass and markedly elevated serum cancer antigen (CA) 19-9 levels raising the suspicion of malignancy but with a histopathologic picture of TB. This case suggests that clinicians should have a heightened suspicion of pancreatic TB when faced with discrete pancreatic lesions even though elevated tumor markers may indicate malignancy. It is important to perform appropriate diagnostic testing and initiate antitubercular therapy early. PMID:27974961

  16. CA 19-9 Level as Indicator of Early Distant Metastasis and Therapeutic Selection in Resected Pancreatic Cancer

    SciTech Connect

    Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae; Lee, Woo Jin; Woo, Sang Myung; Yoo, Tae; Moon, Sung Ho; Kim, Seong Hoon; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-12-01

    Purpose: In patients with pancreatic cancer treated with curative resection, we evaluated the effect of clinicopathologic parameters on early distant metastasis within 6 months (DM{sup 6m}) to identify patients who might benefit from surgery. Methods and Materials: The study involved 84 patients with pancreatic cancer who had undergone curative resection between August 2001 and April 2009. The parameters of gender, age, tumor size, histologic differentiation, T classification, N classification, pre- and postoperative carbohydrate antigen (CA) 19-9 level, resection margin, and adjuvant chemoradiotherapy were analyzed to identify the risk factors associated with DM{sup 6m}. Results: Of the 84 patients, locoregional recurrence developed in 35 (41.7%) and distant metastasis in 58 (69%). Of the 58 patients with distant metastasis, DM{sup 6m} had developed in 27 (46.6%). Multivariate analysis showed that preoperative CA 19-9 level was significantly associated with DM{sup 6m} (p < .05). Of all 84 patients, DM{sup 6m} was observed in 9.1%, 50%, and 80% of those with a preoperative CA 19-9 level of {<=}100 U/mL, 101-400 U/mL, and >400 U/mL, respectively (p < .001). Conclusions: The preoperative CA 19-9 level might be a useful predictor of DM{sup 6m} and to identify those who would benefit from surgical resection.

  17. Serum CA549 in primary breast cancer: comparison with CA15.3 and MCA.

    PubMed Central

    Gion, M.; Plebani, M.; Mione, R.; Penzo, C.; Meo, S.; Burlina, A.

    1994-01-01

    We carried out a comparison of three commonly used mucin markers, CA549, CA15.3 and MCA. Serum samples from 184 healthy women and 237 patients with primary breast cancer were evaluated. The markers were measured using commercially available immunometric assays. Like CA15.3 and MCA, CA549 was significantly associated with tumour size and lymph node status, being an effective indicator of tumour bulk. CA549 was significantly correlated with both CA15.3 and MCA. Positive/negative concordance rate was very good (93.7%) between CA549 and MCA. Conversely, CA15.3 was positive and CA549 negative in 20.4% of cases. Axillary status was not significantly different in the latter group of patients and in cases in which CA15.3 and CA549 showed concordant results. From the present findings we draw the following major conclusions: 1. CA549 and MCA are highly correlated and their association should not provide additional information; however, they should not be considered interchangeable since they may behave differently in individual cases. 2. CA549 and CA15.3, although well correlated, are discordant in a significant number of cases. Longitudinal studies are needed to verify the usefulness of the association between the two markers. 3. The three evaluated mucin markers are not interchangeable in individual patients; if a patient is monitored with a marker, she should be followed up with the same marker. PMID:8142260

  18. Applying PET to Broaden the Diagnostic Utility of the Clinically Validated CA19.9 Serum Biomarker for Oncology

    PubMed Central

    Viola-Villegas, Nerissa Therese; Rice, Samuel L.; Carlin, Sean; Wu, Xiaohong; Evans, Michael J.; Sevak, Kuntal K.; Drobjnak, Marija; Ragupathi, Govind; Sawada, Ritsuko; Scholz, Wolfgang W.; Livingston, Philip O.; Lewis, Jason S.

    2014-01-01

    Despite their considerable advantages, many circulating biomarkers have well-documented limitations. One prominent shortcoming in oncology is a high frequency of false-positive indications for malignant disease in upfront diagnosis. Because one common cause of false positivism is biomarker production from benign disorders in unrelated host tissues, we hypothesized that probing the sites of biomarker secretion with an imaging tool could be a broadly useful strategy to deconvolute the meaning of foreboding but inconclusive circulating biomarker levels. Methods In preparation to address this hypothesis clinically, we developed 89Zr-5B1, a fully human, antibody-based radiotracer targeting tumor-associated CA19.9 in the preclinical setting. Results 89Zr-5B1 localized to multiple tumor models representing diseases with undetectable and supraphysiologic serum CA19.9 levels. Among these, 89Zr-5B1 detected orthotopic models of pancreatic ductal adenocarcinoma, an elusive cancer for which the serum assay is measured in humans but with limited specificity in part because of the frequency of CA19.9 secretion from benign hepatic pathologies. Conclusion In this report, a general strategy to supplement some of the shortcomings of otherwise highly useful circulating biomarkers with immunoPET is described. To expedite the clinical validation of this model, a human monoclonal antibody to CA19.9 (a highly visible but partially flawed serum biomarker for several cancers) was radiolabeled and evaluated, and the compelling preclinical evidence suggests that the radiotracer may enhance the fidelity of diagnosis and staging of pancreatic ductal adenocarcinoma, a notoriously occult cancer. PMID:24029655

  19. Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy

    PubMed Central

    Bernhard, J; Dietrich, D; Glimelius, B; Hess, V; Bodoky, G; Scheithauer, W; Herrmann, R

    2010-01-01

    Background: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. Methods: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00–CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. Results: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of ⩾50% vs <50%. Conclusion: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account. PMID:20877359

  20. Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9.

    PubMed Central

    Nilsson, O.; Johansson, C.; Glimelius, B.; Persson, B.; Nørgaard-Pedersen, B.; Andrén-Sandberg, A.; Lindholm, L.

    1992-01-01

    A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer. PMID:1739620

  1. Laparoscopic resection of a benign true cyst of the spleen with the harmonic scalpel producing high levels of CA 19-9 and carcinoembryonic antigen.

    PubMed

    Sardi, A; Ojeda, H F; King, D

    1998-12-01

    Primary true cysts of the spleen constitute 10 per cent of all nonparasitic cysts of the spleen. These cysts have been managed with total or partial splenectomy or marsupialization. Previous series reported elevated serum levels of CA 19-9 and carcinoembryonic antigen (CEA). A 16-year-old male presented with left upper quadrant pain and was found to have a mass on palpation. An ultrasound and a CT scan of the abdomen showed a 20-cm cystic lesion in the spleen. The CA 19-9 and CEA serum levels were 1264 units/ml (nl <33 units/ml) and 7.5 ng/ml (nl <3.1 ng/ml), respectively. Laparoscopic resection of the cyst using the harmonic scalpel was performed. The pathology showed a benign true epithelial cyst of the spleen, with strongly immunoperoxidase stains for keratin, CA 19-9, and CEA. Levels of CA 19-9 and CEA in the cystic fluid were 48,275 units/ml and 96.6 ng/ml, respectively. This is the first case reported in the literature of a true benign splenic cyst producing high levels of CEA and CA 19-9 in serum and cystic fluid. The patient was discharged home on the 1st postoperative day without problems and returned to his normal daily activities with the 1st week after surgery. The CA 19-9 and CEA serum levels returned to normal levels.

  2. Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 {<=}90 U/mL and Comparison to the CONKO-001 Trial

    SciTech Connect

    Berger, Adam C.; Winter, Kathryn; Hoffman, John P.; Regine, William F.; Abrams, Ross A.; Safran, Howard; Benson, Alan B.; MacDonald, John; Willett, Christopher G.

    2012-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of {<=}90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable ({<=}90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of {>=}90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 {>=}90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values {>=}90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).

  3. ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma

    PubMed Central

    Lin, Chao; Wu, Wen-Chuan; Zhao, Guo-Chao; Wang, Dan-Song; Lou, Wen-Hui; Jin, Da-Yong

    2016-01-01

    Abstract Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19-9 and radiological means, whereas some patients do not have elevated levels of CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify potential serum biomarkers for CA19-9 negative PDAC. A total of 114 serum samples were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9 positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the first 12 samples from each group were used for isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were selected for validation by enzyme-linked immunosorbent assay (ELISA) with the rest specimens. Using the iTRAQ approach, a total of 5 proteins were identified as significantly different between CA19-9 negative PDAC patients and healthy subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and transferrin (TF) were selected to validate the proteomic results by ELISA in a further 78 serum specimens. It revealed that TF significantly correlated with the degree of histological differentiation (P = 0.042), and univariate and multivariate analyses indicated that TF is an independent prognostic factor for survival (hazard ratio, 0.302; 95% confidence interval, 0.118–0.774; P = 0.013) of patients with PDAC after curative surgery. ITRAQ-based quantitative proteomics revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers. PMID:27495108

  4. Combination of preoperative CEA and CA19-9 improves prediction outcomes in patients with resectable pancreatic adenocarcinoma: results from a large follow-up cohort

    PubMed Central

    Zhou, Guofeng; Liu, Xiaoyu; Wang, Xiaoyi; Jin, Dayong; Chen, Yi; Li, Guoping; Li, Changyu; Fu, Deliang; Xu, Wanghong; Wang, Xiaolin

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with a 5-year survival rate of <7%. Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) are often used to predict the outcome of the malignancy independently. However, the joint prognostic effect of the two tumor biomarkers has not been well determined. The study assessed the joint role of preoperative CA19-9 and CEA in the prognostic prediction of resectable PDAC in a large cohort of patients. The study enrolled 460 eligible patients who were ready to undergo surgery for PDAC. Restricted cubic spline and direct-adjusted survival curve revealed the nonlinear association between the biomarker levels and prognosis of patients. Combination of preoperative CA19-9 and CEA effectively improved the prognostic prediction. About 100 U/mL of CA19-9 and 10 μg/mL of CEA were revealed as potential assistant index for prognostic prediction in patients with resectable PDAC and may be used as one of the criteria to assess the resectability of PDAC. PMID:28280354

  5. Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer.

    PubMed

    Kallioniemi, O P; Oksa, H; Aaran, R K; Hietanen, T; Lehtinen, M; Koivula, T

    1988-08-01

    Serum CA 15-3 values were determined in 177 patients with primary breast cancer and in 41 with non-malignant breast disease. Increased preoperative serum CA 15-3 values (greater than 38 U ml-1) were observed in 7%, 17%, 64% and 67% of patients with stage I, II, III and IV disease, respectively and in none of the patients with benign breast disease. Patients with elevated serum CA 15-3 values had poor 3-year cumulative survival (27%). In the postoperative follow-up 9% of patients with no clinical evidence of disease, 33% with a single metastasis and 67% with two or more metastases had elevated values. Increasing or decreasing serum CA 15-3 values correlated with the clinical outcome in 26 out of 27 cases (96%), whereas serum values remaining in the reference range had no predictive value. At the time of recurrence elevated serum CA 15-3 values were also observed in patients with normal preoperative values. Increased serum CA 15-3 values preceded the clinical detection of tumour recurrence by up to 13 months. In conclusion, serum CA 15-3 levels had prognostic value in breast cancer, reflected the extent of clinically detectable disease and the presence of occult metastatic disease. Further research is warranted on the benefits of CA 15-3 assays in relation to adjuvant chemotherapy as well as the earlier detection and treatment of metastatic disease.

  6. Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer

    PubMed Central

    Xing, Lingxi; Shi, Qiusheng; Zheng, Kailiang; Shen, Ming; Ma, Jing; Li, Fan; Liu, Yang; Lin, Lizhou; Tu, Wenzhi; Duan, Yourong; Du, Lianfang

    2016-01-01

    Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer. PMID:27446491

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

    PubMed Central

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

    2017-01-01

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

  8. 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.

  9. Combination Twist1 and CA15-3 in axillary lymph nodes for breast cancer prognosis

    PubMed Central

    Jiang, Xiaowei; Guo, Dan; Li, Wenfang; Yu, Tianwu; Zhou, Jian; Gong, Jianping

    2017-01-01

    Twist1 overexpression is involved in epithelial-mesenchymal transition resulting in migration and metastasis of breast cancer. Carcinoma antigen 15–3 (CA15-3) is widely used to monitor the prognosis for patients after treatment. However, the significance of Twist1 in axillary lymph nodes (ALN) and CA15-3 for co-examination for survival rates remains to be elucidated. The present study aimed to explore the role of the combination of Twist1 expression in metastasized ALN and the serum level of CA15-3 in evaluating the prognosis of patients with breast cancer. cluster of differentiation (CD)44, CD24, aldehyde dehydrogenase (ALDH)1 and Twist1 expression in normal and metastasized ALN from 102 patients with breast cancer were detected using laser confocal microscopy and the expression of the genes evaluated by reverse transcription-quantitative polymerase chain reaction; E-cadherin, N-cadherin and vimentin expression was also tested by western blotting. The serum concentrations of CA15-3 prior to and following surgery were analyzed by chemiluminescence immunoassay. The expression of CD44, ALDH1 and Twist1 mRNA in the primary breast cancer tissues and involved ALN was upregulated compared with the normal ALN (P<0.05). The proteins N-cadherin and vimentin of the involved ALN were poorly expressed compared with breast cancer tissues, however E-cadherin protein expression was higher in metastasized and normal ALN compared with primary cancer tissues (P<0.05). Of the 102 patients, the serum CA15-3 levels of the patients in stages I and II were significantly lower compared with stages III and IV (P<0.05). Twist1+/CA15-3+, HER2-negative/Twist1+/CA15-3+ and Triple-receptor negative/Twist1+/CA15-3+ groups displayed a shorter progression-free survival compared with others. The results of the present study demonstrated that CD44, ALDH1 and Twist1 were significantly overexpressed in involved ALN. The serum levels of CA15-3 in those patients were clearly increased and the survival

  10. Enzyme-linked PNA lectin binding assay compared with CA19-9 and CEA radioimmunoassay as a diagnostic blood test for pancreatic cancer.

    PubMed Central

    Ching, C. K.; Rhodes, J. M.

    1989-01-01

    Previous studies have shown that sera from patients with pancreatic cancer often contain a mucus glycoprotein that expresses the oncofetal antigen galactose 1-3, N-acetyl galactosamine, which is the T blood group antigen and the binding site for the lectin peanut agglutinin (PNA). An enzyme-linked lectin assay has been developed to quantify PNA-binding glycoproteins in serum and has been evaluated as a serological test for pancreatic cancer. Sera were studied from 53 patients with pancreatic cancer and 154 controls, including benign obstructive jaundice, acute and chronic pancreatitis, chronic liver disease and inflammatory bowel disease. The enzyme-linked peanut lectin assay proved highly reproducible and has 77% sensitivity and 83% specificity for pancreatic cancer, results that are very similar to those achieved in the same sera by CA19-9 radioimmunoassay (75% sensitivity, 82% specificity with the upper limit of normal set at 37 u ml-1). CEA assay proved less useful (60% sensitivity, 47% specificity). In this study better results were obtained if an upper limit of normal of 50 u ml-1 was used for CA19-9 (75% sensitivity, 92% specificity). Combination of CA19-9 assay with the upper limit set at 50 u ml-1 and the peanut lectin assay improved the sensitivity to 85% with only a slight fall in specificity (85%). These results compare well with published results for ultrasound and CT scanning. PMID:2736232

  11. Palliative Gastrectomy Prolongs Survival of Metastatic Gastric Cancer Patients with Normal Preoperative CEA or CA19-9 Values: A Retrospective Cohort Study

    PubMed Central

    Chiu, Chang-Fang; Yang, Horng-Ren; Yang, Mei-Due; Jeng, Long-Bin; Yang, Tse-Yen; Sargeant, Aaron M.

    2016-01-01

    Background. Palliative gastrectomy has been suggested to improve survival of patients with metastatic gastric cancer, but limitations in study design and availability of robust prognostic factors have cast doubt on the overall merit of this procedure. Methods. The characteristics and clinical outcomes of 173 patients diagnosed between 2008 and 2012 were analyzed to determine the value of palliative gastrectomy and to identify potential prognostic factors. Results. Median overall patient survival was 6.5 months. To attenuate potential selection bias, patients with adequate performance and survival time of ≥ 2 months since diagnosis were included for risk factor analysis (n = 137). The median overall survival was longer for patients who were younger than 60 years, had better performance status (8.7 versus 6.4 months, P = 0.015), received systemic chemotherapy, or had palliative gastrectomy in univariate analyses. Gastrectomy (P = 0.002) remained statistically significant in multivariate analyses. Subgroup analysis showed that patients aged < 60 years, CEA < 5 ng/mL or CA19-9 < 35 U/mL, obtained a survival advantage from palliative gastrectomy. In fact, palliative gastrectomy doubled overall survival for patients who had normal CEA and/or normal CA19-9. Conclusions. Palliative gastrectomy prolongs the survival of metastatic gastric cancer patients with normal CEA and/or CA19-9 level at the time of diagnosis. PMID:27990157

  12. Palliative Gastrectomy Prolongs Survival of Metastatic Gastric Cancer Patients with Normal Preoperative CEA or CA19-9 Values: A Retrospective Cohort Study.

    PubMed

    Chiu, Chang-Fang; Yang, Horng-Ren; Yang, Mei-Due; Jeng, Long-Bin; Yang, Tse-Yen; Sargeant, Aaron M; Bai, Li-Yuan

    2016-01-01

    Background. Palliative gastrectomy has been suggested to improve survival of patients with metastatic gastric cancer, but limitations in study design and availability of robust prognostic factors have cast doubt on the overall merit of this procedure. Methods. The characteristics and clinical outcomes of 173 patients diagnosed between 2008 and 2012 were analyzed to determine the value of palliative gastrectomy and to identify potential prognostic factors. Results. Median overall patient survival was 6.5 months. To attenuate potential selection bias, patients with adequate performance and survival time of ≥ 2 months since diagnosis were included for risk factor analysis (n = 137). The median overall survival was longer for patients who were younger than 60 years, had better performance status (8.7 versus 6.4 months, P = 0.015), received systemic chemotherapy, or had palliative gastrectomy in univariate analyses. Gastrectomy (P = 0.002) remained statistically significant in multivariate analyses. Subgroup analysis showed that patients aged < 60 years, CEA < 5 ng/mL or CA19-9 < 35 U/mL, obtained a survival advantage from palliative gastrectomy. In fact, palliative gastrectomy doubled overall survival for patients who had normal CEA and/or normal CA19-9. Conclusions. Palliative gastrectomy prolongs the survival of metastatic gastric cancer patients with normal CEA and/or CA19-9 level at the time of diagnosis.

  13. 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.

  14. CA15.3 Serum Concentrations in Older Women with Infiltrating Ductal Carcinomas of the Breast

    PubMed Central

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Padín-Iruegas, María Elena; Arias, José Ignacio; Herranz, Michel

    2014-01-01

    Breast cancer is currently becoming a disease of the elderly. We have studied the relation between CA 15.3 serum concentrations and clinical-pathological parameters in 69 women with IDC aged over 70 years (76.3 ± 4.2; range: 71–88; median 76). A group of 205 women with the same tumor but aged <70 years (62.8 ± 4.0; range: 55–70; median 63) was also considered for comparison. Tumor size, axillary lymph node involvement, distant metastasis and histological grade were taken account. Serum CA 15.3 was determined by luminescence assay. CA 15.3 serum concentrations ranged between 6 and 85 U/mL (median 22.9 U/mL), and were higher only in patients with greater (qualitative and quantitative; p: 0.041) tumor size. Our results show that in women with IDCs, and aged over 70 years, serum CA 15.3 serum concentrations are associated exclusively with a greater tumor size, being these findings different to those described in women with the same subtype of tumor considered as a whole or with lower age. PMID:25365176

  15. CA15.3 serum concentrations in older women with infiltrating ductal carcinomas of the breast.

    PubMed

    Ruibal, Álvaro; Aguiar, Pablo; Del Río, María Carmen; Padín-Iruegas, María Elena; Arias, José Ignacio; Herranz, Michel

    2014-10-31

    Breast cancer is currently becoming a disease of the elderly. We have studied the relation between CA 15.3 serum concentrations and clinical-pathological parameters in 69 women with IDC aged over 70 years (76.3±4.2; range: 71-88; median 76). A group of 205 women with the same tumor but aged <70 years (62.8±4.0; range: 55-70; median 63) was also considered for comparison. Tumor size, axillary lymph node involvement, distant metastasis and histological grade were taken account. Serum CA 15.3 was determined by luminescence assay. CA 15.3 serum concentrations ranged between 6 and 85 U/mL (median 22.9 U/mL), and were higher only in patients with greater (qualitative and quantitative; p: 0.041) tumor size. Our results show that in women with IDCs, and aged over 70 years, serum CA 15.3 serum concentrations are associated exclusively with a greater tumor size, being these findings different to those described in women with the same subtype of tumor considered as a whole or with lower age.

  16. [Endometrial cancer associated with an increase of CA 15 3 and CA 125 in tamoxifen treated patients with breast cancer].

    PubMed

    Mekić-Abazović, Alma; Beculić, Hakija; Musić, Miralem; Fajkić, Almir; Dervisević, Senad

    2011-02-01

    The study presents a case of endometrial cancer in a breast cancer patient treated with tamoxifen. The disease occured with elevated values of CA 125 and CA 15_3 tumour markers without any other signs. Additional diagnostic analyses were performed showing a "de novo" endometrial cancer rather than metastatic breast cancer. The patient underwent surgery and radiotherapy. Thereafter, the values of tumour markers were in the reference values.

  17. Site-specifically labeled CA19.9-targeted immunoconjugates for the PET, NIRF, and multimodal PET/NIRF imaging of pancreatic cancer

    PubMed Central

    Houghton, Jacob L.; Zeglis, Brian M.; Abdel-Atti, Dalya; Aggeler, Robert; Sawada, Ritsuko; Agnew, Brian J.; Scholz, Wolfgang W.; Lewis, Jason S.

    2015-01-01

    Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs (ssDFO-5B1, ssFL-5B1, and ssdual-5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9-positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The ssdual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation. PMID:26668398

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

    PubMed Central

    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. PMID:25469301

  19. Multicenter evaluation of the Bayer Immuno I CA 15-3 assay.

    PubMed

    Cheli, C D; Morris, D L; Kish, L; Goldblatt, J; Neaman, I; Allard, W J; Yeung, K K; Wu, A H; Moore, R; Chan, D W; Fritsche, H A; Schwartz, M K; Very, D L

    1998-04-01

    We conducted a multicenter evaluation of the analytical and clinical features of the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay pooled across four evaluation sites and three lots of reagent produced total CV < or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%). Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR 27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL); values were similar for all methods. Longitudinal monitoring of healthy women yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the analytical features, intermethod correlation, and long-term performance characteristics that are essential for longitudinal monitoring of breast cancer patients.

  20. Decreased serum CA19-9 is associated with improvement of insulin resistance and metabolic control in patients with obesity and type 2 diabetes after Roux-en-Y gastric bypass

    PubMed Central

    Tu, Yinfang; Yu, Haoyong; Zhang, Pin; Di, Jianzhong; Han, Xiaodong; Wu, Songhua; Bao, Yuqian; Jia, Weiping

    2014-01-01

    Aims/Introduction Patients with type 2 diabetes are known to show elevated serum levels of carbohydrate antigen 19-9 (CA19-9). The aim of the present study was to investigate the possible relationships of CA19-9 with metabolic control, insulin resistance (IR), and pancreatic β-cell function in patients with obesity and type 2 diabetes who underwent Roux-En-Y gastric bypass (RYGB). Materials and Methods The present study included 81 healthy volunteers, and 33 patients diagnosed with obesity and type 2 diabetes who underwent RYGB. Anthropometry, serum levels of CA19-9, glucose and lipid metabolic profiles, and serum insulin levels were determined at baseline and at 12 weeks after RYGB. Results Changes in CA19-9 were significantly and positively correlated with changes in fasting plasma glucose (r = 0.552, P = 0.001), 2-h post-challenge plasma glucose levels (r = 0.623, P = 0.000), glycated hemoglobin levels (r = 0.819, P = 0.000), glycated albumin levels (r = 0.711, P = 0.000), total cholesterol (r = 0.449, P = 0.009) and the Homeostasis Model of Assessment-IR index (r = 0.407, P = 0.019). Furthermore, a multiple stepwise regression analysis showed that the changes in serum levels of CA19-9 were independently and significantly associated with changes in glycated hemoglobin (β = 0.598, P = 0.000), fasting plasma glucose (β = 0.309, P = 0.000) and Homeostasis Model of Assessment-IR (β = 0.235, P = 0.010) after adjusting for confounding factors. Conclusions CA19-9 could be an effective indicator of IR, and glycemic and lipid metabolism in patients with obesity and type 2 diabetes after rapid metabolic control by RYGB. Additionally, CA19-9 might be a marker with which to evaluate the short-term effects of glycolipid toxicity on IR in these patients. PMID:25422770

  1. A new competitive enzyme linked immunosorbent assay (MRP83-CA15-3) for MUC1 measurement in breast cancer.

    PubMed

    Mohammadnejad, J; Rasaee, Mohammad J; Saqhafi, B; Rajabibazl, M; Rahbarizadeh, F; Omidfar, K; Paknejad, M

    2006-01-01

    A new competitive enzyme linked immunosorbent assay was developed in this study. Monoclonal antibody (PR81) against the tandem repeat of the core protein was prepared, characterized, purified, and conjugated to HRP. This antibody exhibited no cross reactions with proteins such as bovine serum albumin, keyhole limpet homocyanin, human serum albumin, casein, human milk fat globin (HMFG), and peptone. The native cancerous MUC1 protein was purified from ascites fluid of a patient suffering from small cell lung carcinoma by immunoaffinity chromatography and used as a standard preparation in the assay buffer. The standard curve was constructed following a competitive procedure in the range of 0-200 U/mL. The level of MUC1 in normal and cancerous samples was compared following this procedure and using available CA15-3 EIA (Can Ag), as well as LIAISON CA15-3 commercial kits. The correlation coefficient between the procedure reported in this work (MRP83-CA15-3) and CA15-3 EIA (Can Ag) was 0.68 and was 0.95 with the LIAISON CA15-3 kit. We concluded that the present assay can detect MUC1 in breast cancer patients with great sensitivity and accuracy.

  2. Comparison of CEA, MCA, CA 15-3 and CA 27-29 in follow-up and monitoring therapeutic response in breast cancer patients.

    PubMed

    Lauro, S; Trasatti, L; Bordin, F; Lanzetta, G; Bria, E; Gelibter, A; Reale, M G; Vecchione, A

    1999-01-01

    In order to define the most useful tumor marker panel in breast cancer patients' follow-up and in monitoring treatment response, serological levels of CEA, MCA, Ca 15-3 and Ca 27-29 were evaluated in 220 patients. 180 patients had no evidence of disease (NED) after primary treatment, and 40 had metastases at first diagnosis time; in a 4 years follow-up, 30 of the NED patients relapsed, and were then included in the group of metastatic patients subjected to anticancer treatment. Overall sensitivity in metastatic patients was: CEA 40%, MCA 35%, Ca 15-3 79%, Ca 27-29 70%, with the highest percentages and mean values in liver and bone localizations. Combination of Ca 15-3 and Ca 27-29 improved sensitivity in bone lesion (85% vs 80%), in locoregional relapses only association with CEA increased sensitivity (60% vs 40%). Ca 15-3 and Ca 27-29 values increased on average 3 months before clinical diagnosis. In treated patients there was a better correlation with a clinical course of disease for Ca 15-3 and Ca 27-29 (both 81%) as compared to the other determined markers.

  3. Sensitive electrochemiluminescence detection for CA15-3 based on immobilizing luminol on dendrimer functionalized ZnO nanorods.

    PubMed

    Jiang, Xinya; Wang, Haijun; Yuan, Ruo; Chai, Yaqin

    2015-01-15

    In this study, we constructed a novel electrochemiluminescence (ECL) immunosensor for sensitive and selective detection of carbohydrate antigen 15-3 (CA15-3) by using polyamidoamine (PAMAM)-functionalized ZnO nanorods (ZNs-PAMAM) as carriers. PAMAM dendrimers with hyper-branched and three-dimensional structure were used as linked reagents for co-immobilization of luminol and CA15-3 detection antibody on the ZNs to prepare the signal probe. In addition, ZNs could hasten the decomposition of H2O2 to generate various reactive oxygen species (ROSs) which accelerated the ECL reaction of luminol with amplified ECL intensity. Compared with luminol in the detection solution, the ECL efficiencies of luminol could be improved by immobilizing luminol on the electrode due to the smaller distance between luminescence reagent and the electrode surface. Moreover, the electrodepositing gold nanoparticles (AuNPs) on the bare glass carbon electrode (GCE) with enhanced surface area could capture a large amount of primary anti-CA15-3 to improve the sensitivity of the immunosensor. Under the optimized experimental conditions, a wide linear range of 0.1-120 U mL(-1) was acquired with a relatively low detection limit of 0.033 U mL(-1) (S/N=3) for CA15-3.

  4. Metastatic recurrence in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore.

    PubMed

    Hiroshima, Yukihiko; Maawy, Ali; Zhang, Yong; Murakami, Takashi; Momiyama, Masashi; Mori, Ryutaro; Matsuyama, Ryusei; Katz, Matthew H G; Fleming, Jason B; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Endo, Itaru; Hoffman, Robert M; Bouvet, Michael

    2014-01-01

    The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.

  5. Study of serum tumor markers CEA, CA 15.3 and CA 27.29 as diagnostic parameters in patients with breast carcinoma.

    PubMed

    Rodríguez de Paterna, L; Arnaiz, F; Estenoz, J; Ortuño, B; Lanzós, E

    1995-01-01

    Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determination of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker. The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.

  6. Ultrasensitive photoelectrochemical immunoassay for CA19-9 detection based on CdSe@ZnS quantum dots sensitized TiO2NWs/Au hybrid structure amplified by quenching effect of Ab2@V(2+) conjugates.

    PubMed

    Zhu, Hua; Fan, Gao-Chao; Abdel-Halim, E S; Zhang, Jian-Rong; Zhu, Jun-Jie

    2016-03-15

    A novel, enhanced photoelectrochemical immunoassay was established for sensitive and specific detection of carbohydrate antigen 19-9 (CA19-9, Ag). In this protocol, TiO2 nanowires (TiO2NWs) were first decorated with Au nanoparticles to form TiO2NWs/Au hybrid structure, and then coated with CdSe@ZnS quantum dots (QDs) via the layer-by-layer method, producing TiO2NWs/Au/CdSe@ZnS sensitized structure, which was employed as the photoelectrochemical matrix to immobilize capture CA19-9 antibodies (Ab1); whereas, bipyridinium (V(2+)) molecules were labeled on signal CA19-9 antibodies (Ab2) to form Ab2@V(2+) conjugates, which were used as signal amplification elements. The TiO2NWs/Au/CdSe@ZnS sensitized structure could adequately absorb light energy and dramatically depress electron-hole recombination, resulting in evidently enhanced photocurrent intensity of the immunosensing electrode. While target Ag were detected, the Ab2@V(2+) conjugates could significantly decrease the photocurrent detection signal because of strong electron-withdrawing property of V(2+) coupled with evident steric hindrance of Ab2. Thanks to synergy effect of TiO2NWs/Au/CdSe@ZnS sensitized structure and quenching effect of Ab2@V(2+) conjugates, the well-established photoelectrochemical immunoassay exhibited a low detection limit of 0.0039 U/mL with a wide linear range from 0.01 U/mL to 200 U/mL for target Ag detection. This proposed photoelectrochemical protocol also showed good reproducibility, specificity and stability, and might be applied to detect other important biomarkers.

  7. Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics

    PubMed Central

    Yoneyama, Toshihiro; Ohtsuki, Sumio; Honda, Kazufumi; Kobayashi, Makoto; Iwasaki, Motoki; Uchida, Yasuo; Okusaka, Takuji; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Kaneda, Takashi; Kato, Takao; Yagihara, Kazuhiro; Fujita, Shigeyuki; Huang, Wilber; Yamada, Tesshi; Tachikawa, Masanori; Terasaki, Tetsuya

    2016-01-01

    Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19–9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of

  8. Measurements of Dipole Excitations in ^48Ca Between Eγ = 9.5 and 15.3 MeV

    NASA Astrophysics Data System (ADS)

    Tompkins, J. R.; Arnold, C. W.; Karwowski, H. J.; Rich, G. C.; Howell, C. R.; Sobotka, L. G.

    2010-02-01

    ^48Ca photodisintegration cross sections were measured using γ-ray beams of 34 different energies between 9.5 and 15.3 MeV generated with the TUNL High-Intensity γ-ray Source (HIγS). The cross sections were measured with a 2.7 g ^48Ca target enriched to 92% using an array of ^3He proportional-counters embedded in thermalizing polyethylene. The absolute cross sections for the ^48Ca(γ,n) reaction were obtained by normalization to the well known ^2H(γ,n) reaction cross sections. Single neutron emission is the dominant channel in this energy range and its detection provides a measurement of dipole excitation strength such as the previously identified M1 strength at Eγ = 10.22 MeV,footnotetextW.Steffen et al. Nucl. Phys. A 404, 413 (1983). for which a new value will be presented. Structures on the low-energy tail of the E1 GDR were also observed and will be presented. )

  9. Nomograms for Predicting the Prognostic Value of Pre-Therapeutic CA15-3 and CEA Serum Levels in TNBC Patients.

    PubMed

    Dai, Danian; Chen, Bo; Tang, Hailin; Wang, Bin; Zhao, Zhiping; Xie, Xiaoming; Wei, Weidong

    2016-01-01

    Previous studies have indicated that carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are both independent prognostic factors in breast cancer. However, the utility of CEA and CA15-3 levels as conventional cancer biomarkers in patients with triple-negative breast cancer (TNBC) remains controversial. The current study was performed to explore the predictive value of pre-therapeutic serum CEA and CA15-3 levels, and nomograms were developed including these serum cancer biomarkers to improve the prognostic evaluation of TNBC patients. Pre-therapeutic CA15-3 and CEA concentrations were measured in 247 patients with stage I-IV TNBC. Kaplan-Meier analysis showed that TNBC patients with high levels of both CEA and CA15-3 had shorter overall survival (OS) and disease-free survival (DFS) rates than those in the low-level groups (p<0.05). Multivariate analysis suggested that pre-therapeutic CA15-3 and CEA levels are independent predictive elements for OS (p = 0.022 and p = 0.040, respectively) and DFS (p = 0.023 and p = 0.028, respectively). In addition, novel nomograms were established and validated to provide personal forecasts of OS and DFS for patients with TNBC. These novel nomograms may help physicians to select the optimal treatment plans to ensure the best outcomes for TNBC patients.

  10. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  11. 22 CFR 19.9-1 - Entitlement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) A pension benefit under this section is treated the same as a survivor annuity for purposes of § 19... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Entitlement. 19.9-1 Section 19.9-1 Foreign... FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.9-1 Entitlement. (a) Unless otherwise...

  12. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Performance. 19.9 Section 19.9 Mineral... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap...

  13. Optofluidic ring resonator sensor for sensitive label-free detection of breast cancer antigen CA15-3 in human serum

    NASA Astrophysics Data System (ADS)

    Zhu, Hongying; Dale, Paul S.; Fan, Xudong

    2009-05-01

    Breast cancer is the most frequently diagnosed malignancy in women worldwide. Because of its great impact on society, a lot of research funding has been used to develop novel detection tools for aiding breast cancer diagnosis and prognosis. In this work, we demonstrated a simple, fast, and sensitive detection of circulating breast cancer biomarker CA15-3 with opto-fluidic ring resonator (OFRR) sensors. The OFRR sensor employs a thin-walled capillary with wall thickness less than 4 μm. The circular cross section of the capillary forms the optical ring resonator, in which the light circulates in the form of whispering gallery modes (WGMs). The capillary wall is thin enough that the evanescent field of the WGM extends into the capillary core and responds to refractive index changes in the capillary core or close to its interior surface. The WGM spectral position will change when the biomolecules bind to the surface, yielding quantitative and kinetic information about the biomolecule interaction. Here, the direct immunoassay method was employed for the detection of CA15-3 antigen without any signal amplification steps. The sensor performance in both PBS buffer and human serum were investigated, respectively. The experimental detection limit was 5 units/mL in PBS buffer and 30 units/mL for CA15-3 spiked in serum, both of which satisfied clinical diagnosis requirements. The potential use of the OFRR as the point-of-care device for breast cancer detection was tested by measuring the CA15-3 level in blood samples collected from stage IV breast cancer patients and the results were compared with standard clinical test.

  14. Determination of serum CRP, VEGF, Leptin, CK-MB, CA-15-3 and IL-6 levels for malignancy prediction in adnexal masses

    PubMed Central

    Şen, Serhat; Kuru, Oğuzhan; Akbayır, Özgür; Oğuz, Hilal; Yasasever, Vildan; Berkman, Sinan

    2011-01-01

    Objective Investigation of serum markers which could be used in the malignancy prediction of adnexal masses. Material and Methods Vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), leptin, C-reactive protein (CRP), creatine-kinase-MB (CK-MB) and cancer antigen 15-3 (CA 15-3) levels were determined prospectively in serum samples that were obtained from patients who underwent surgery for an adnexal mass and who were referred to Istanbul University, Faculty of Medicine, Department of Obstetrics and Gynecology, between 2009 and 2011, and then were compared with the serum samples of completely healthy outpatient patients as a control group. Based onto the ovarian cancer status, cases were divided into four groups: 13 patients were included in the early-stage malignant group, 12 patients were included in the advanced-stage malignant group, 25 in the benign group and 19 in the healthy control group. Patients with only epithelial ovarian cancer were included into the cancer group. Ethics Commitee approval was obtained for this study. The budget was supported by the Istanbul University Scientific Research Projects Unit. Results Results related with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and odds ratio (OR), respectively, and the following values were calculated: 48%, 95%, 92%, 59% and +OR 9.6 −OR 0.5 for CA; 15-3; 52%, 75%, 72%, 55%, +OR 2.08 −OR 0.64 for leptin; 72%, 70%, 75%, 66% 2.4-0.5 for IL-6; 24%, 80%, 60%, 45%, 1.2-0.92 for VEGF; 68%, 30%, 55%, 43%, 0.97–1.06 for CRP; and 8%, 70%, 25%, 38%, 026–1.31 for CK-MB. Conclusion CA 15-3, IL-6, Leptin, VEGF and CRP were effective in the prediction of benign and malignant masses; however they may be more suitable in selected cases as they have a limited use because of their inadequate potential regarding sensitivity and specificity. PMID:24591997

  15. An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. Expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases.

    PubMed

    Terada, Tadashi

    2013-01-01

    There have no comprehensive immunohistochemical studies of primary signet ring cell carcinoma (SRCC) in the stomach and colorectum. The author examined the expression of nine common antigens (EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63) in the non-tumorous normal epithelium of the stomach and colorectum and in 42 cases of primary SRCC of the stomach (30 cases) and colorectum (12 cases). The normal epithelium of the stomach and colon consistently (100%) expressed EMA, CEA, CA19-9, CDX-2, and Ki-67 (labeling <15%). Normal epithelium of these locations never expressed p53, TTF-1, vimentin, and p63. In the primary gastric SRCC, the expression percentage of EMA was 57% (17/30), CEA 100% (30/30), CA19-9 100% (30/30), CDX-2 43% (13/30), p53 83% (25/30), Ki-67 100% (30/30) (labeling index= 36 ± 23 %), TTF-1 0% (0/30), vimentin 0% (0/30), and p63 0% (0/30). In primary colorectal SRCC, the expression percentage of EMA was 25% (3/12), CEA 100% (12/12), CA19-9 100% (12/12), CDX-2 93% (28/30), p53 75% (9/12), Ki-67 100% (30/30) (labeling index= 47% ± 26 %), TTF-1 0% (0/12), vimentin 0% (0/12), and p63 0% (0/12). A comparative statistical analysis showed significant difference in EMA (gastric SRCC 57% vs colorectal SRCC 25%) and CDX-2 (43% vs 93%). There were no significant differences in the other seven antigens' expression between primary gastric SRCC and primary colorectal SRCC. These findings provide much knowledge of primary SRCC of the stomach and colorectum. The data indicated primary gastric SRCC frequently express EMA but not CDX-2 whereas primary colorectal SRCC frequently express CDX-2 but not EMA. These findings also suggest that EMA and CDX-2 are down-regulated during the gastric SRCC carcinogenesis. This down regulations may be associated with the malignant transformation of gastric SRCC. The data of colorectal SRCC suggest EMA is markedly down-regulated and also suggest that this EMA down-regulation may be associated with the

  16. Role of Urinary and Serum Carbohydrate Antigen 19-9 as a Biomarker in Diagnosis of Adult Giant Hydronephrosis

    PubMed Central

    Tomar, Vinay; Yadav, Sher Singh; Vyas, Nachiket; Yadav, Suresh; Sathian, Brijesh

    2016-01-01

    Introduction The most common cause of adult Giant Hydronephrosis (GH) is congenital Uretero-Pelvic Junction (UPJ) obstruction. Conventional imaging modalities, like Intravenous Urography (IVU) and Computed Tomography Urography (CTU) and radionuclide renal scan can be fallacious. Serum carbohydrate antigen 19-9 (CA19-9) is a useful tumour marker for gastrointestinal and pancreatic cancer. Only a few studies and case reports have shown raised serum levels due to benign hydronephrosis and GH. Aim To investigate the prognostic role of urine and serum CA19-9 in the diagnosis and follow-up of adult GH due to UPJ obstruction. Materials and Methods The present hospital based observational study was conducted on 24 adult patients (Group 1) with unilateral GH due to UPJ obstruction. Twenty four healthy adults were included as control (Group 2). Serum and voided urine samples were collected to evaluate Carbohydrate Antigen (CA) 19-9 in each group. During surgery, urine from the affected pelvis was collected to determine CA19-9 level. Patients were followed up after surgery at 3 and 9 months with serum and voided urine samples for CA19-9 level. Results Preoperative Serum and voided urine CA19-9 were significantly greater in Group1 than in controls, which significantly correlated inversely with preoperative percentage renal function and glomerular filtration rate. Postoperative improvement in renal function significantly correlated inversely with serum and voided urine CA19-9 at 3 and 9 months. Conclusion Voided urine CA19-9 can be a non-invasive clinical marker in adult GH due to UPJ obstruction. The clinical implications of these data for diagnosis and follow-up of these patients are significant. Our findings suggest, significant decrease in urinary Ca19-9 level during follow-up is predictive of excellent surgical outcome and resolution of renal damage. PMID:27790508

  17. Photoluminescence properties and application of yellow Ca0.65Si10Al2O0.7N15.3:xEu2+ phosphors for white LEDs

    NASA Astrophysics Data System (ADS)

    Wang, Baochen; Liu, Yangai; Chen, Jian; Mi, Ruiyu; Xia, Yufei; Huang, Zhaohui; Fang, Minghao; Mei, Lefu

    2017-02-01

    A series of yellow-emitting oxynitride Ca0.65Si10Al2O0.7N15.3:xEu2+ phosphors with α-sialon structure were synthesized. The phase composition and crystal structure were identified by X-ray diffraction and the Rietveld refinement. The excitation and emission spectra, reflectance spectra and thermal stability were investigated in detail, respectively. Results show that Ca0.65Si10Al2O0.7N15.3:0.12Eu2+ phosphors can be efficiently excited by UV-Vis light in the broad range of 290-450 nm and exhibit broad emission spectra peaking at 550-575 nm. The concentration quenching mechanism are discussed in detail and determined to be the dipole-dipole interaction. When the temperature increased to 150 °C, the emission intensity of Ca0.65Si10Al2O0.7N15.3:0.12Eu2+ phosphor is 88.46% of the initial value at room temperature. White LED was fabricated with N-UV LED chip combined with blue Ca3Si2O4N2:Ce3+ and yellow Ca0.65Si10Al2O0.7N15.3:Eu2+ phosphors. The color rendering index and correlated color temperature of this white LED were measured to 78.94 and 6728.12 K, respectively. All above results demonstrate that the as-prepared Ca0.65Si10Al2O0.7N15.3:xEu2+ may serve as a potential yellow phosphor for N-UV w-LEDs.

  18. 22 CFR 19.9-4 - Effect on annuitant.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Effect on annuitant. 19.9-4 Section 19.9-4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.9-4 Effect on annuitant. Any pension...

  19. 12 CFR 19.9 - Ex parte communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Ex parte communications. 19.9 Section 19.9 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY RULES OF PRACTICE AND PROCEDURE Uniform Rules of Practice and Procedure § 19.9 Ex parte communications. (a) Definition—(1)...

  20. Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

    PubMed Central

    Su, Si-Biao; Qin, Shan-Yu; Chen, Wen; Luo, Wei; Jiang, Hai-Xing

    2015-01-01

    AIM: To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools. RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95%CI: 0.80-0.83); specificity, 0.81 (95%CI: 0.79-0.82); positive likelihood ratio, 4.08 (95%CI: 3.39-4.91); negative likelihood ratio, 0.24 (95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31 (95%CI: 14.40-25.90). The area under the ROC curve was 0.88. No significant publication bias was detected. CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy. PMID:25892884

  1. 22 CFR 19.9-4 - Effect on annuitant.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Effect on annuitant. 19.9-4 Section 19.9-4 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.9-4 Effect on annuitant. Any pension payable to a former spouse under this section...

  2. Ciliated hepatic foregut cyst with high intra-cystic carbohydrate antigen 19-9 level.

    PubMed

    Ben Ari, Ziv; Cohen-Ezra, Oranit; Weidenfeld, Jonathan; Bradichevsky, Tania; Weitzman, Ella; Rimon, Uri; Inbar, Yael; Amitai, Michal; Bar-Zachai, Barak; Eshkenazy, Roni; Ariche, Arie; Azoulay, Daniel

    2014-11-21

    A ciliated hepatic foregut cyst (CHFC) is a rare foregut developmental malformation usually diagnosed in adulthood. Five percent of reported cases of CHFC transform into squamous cell carcinoma. We report the presentation, evaluation, and surgical management of a symptomatic 45-year-old male found to have a 6.2 cm CHFC. Contrast tomography-guided fine-needle aspiration demonstrated columnar, ciliated epithelium consistent with the histologic diagnosis of CHFC. The intracystic levels of carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were extremely high (978118 U/mL and 973 μg/L, respectively). Histologically, the wall of the cyst showed characteristic pseudopapillae lined with a ciliated stratified columnar epithelium, underlying smooth muscle, an outer fibrous layer and no atypia. Immunohistochemistry for CA19-9 and CEA was positive. This is the first case report of a CHFC in which levels of CA 19-9 and CEA were measured. Our findings suggest that a large sized multilocular cyst and elevated cyst CA19-9 and CEA levels do not exclude a CHFC from consideration in the diagnosis. CHFCs should be included in the differential diagnosis of hepatic lesions. Accurate diagnosis of a CHFC is necessary given its potential for malignant transformation, and surgical excision is recommended.

  3. Identification of a panel of complex autoantigens (LGALS3, PHB2, MUC1, and GK2) in combination with CA15-3 for the diagnosis of early-stage breast cancer.

    PubMed

    Zuo, Xiaoxiao; Chen, Ling; Liu, Lifeng; Zhang, Zhe; Zhang, Xiaojin; Yu, Qing; Feng, Lu; Zhao, Xinhan; Qin, Tianjie

    2016-01-01

    Currently, there is no effective single antigen and there are only a very limited number of complex antigens for the diagnosis of early-stage breast cancer (BC). In this study, we used serological analysis of recombinant cDNA expression libraries (SEREX) in combination with phage display technology to screen complex autoantigens from the sera of BC patients. The cDNA expression library was constructed using tissue samples of three patients with BC at as early as stage T1N0M0. The serum samples of ten patients, including the three patients who provided tissue samples, as well as five healthy human subjects as controls were used to screen the library. All seven autoantigens were identified from the library by four rounds of screening and matched the existing genes after a blast search using NCBI-BLAST. Then, the expression conditions of the autoantibodies of the seven autoantigens and anti-CA15-3 in the sera from 100 BC patients and 50 healthy donors were examined by gray values. The data were analyzed by the area under the receiver operating characteristic (ROC) curve and logistic regression diagnostic models. In the end, a panel of complex autoantigens consisting of B11 (LGALS3), B18 (PHB2), B119 (MUC1), B130 (GK2), and CA15-3, which had a sensitivity of 87 % and a specificity of 76 %, were identified. The area under the curve (AUC) of the complex antigens was 0.872, which is significantly greater than that of anti-CA15-3 alone (AUC = 0.634) for the diagnosis of BC. Thus, this panel of complex antigens provides a promising strategy for the diagnosis of early-stage BC.

  4. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    PubMed Central

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M.

    2016-01-01

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date. PMID:27306770

  5. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    SciTech Connect

    Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  6. An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

    PubMed Central

    Gan, Ning; Zhou, Jing; Xiong, Ping; Li, Tianhua; Jiang, Shan; Cao, Yuting; Jiang, Qianli

    2013-01-01

    The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe3O4). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. PMID:23685872

  7. Predictive Value of Carcinoembryonic and Carbohydrate Antigen 19-9 Related to Some Clinical, Endoscopic and Histological Colorectal Cancer Characteristics

    PubMed Central

    Milosavljević, Tomica; Stojanović, Dragoš; Gluvić, Zoran; Dugalić, Predrag; Ilić, Ivan; Vidaković, Radosav

    2016-01-01

    Summary Background Colorectal cancer (CRC) is an important oncological and public health problem worldwide, including Serbia. Unfortunately, half of the patients are recognized in an advanced stage of the disease, therefore, early detection through specific tumor biomarkers, such as carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA 19-9), is the only way to cope with CRC expansion. Methods Our cross-sectional study evaluated the influence of some clinical, endoscopic and histological characteristics of CRC on CEA and CA 19-9 serum levels, to determine whether these biomarkers could be related to CRC detection. The study included 372 participants: 181 suffered from CRC and 191 participants were controls. Endoscopic and histological examinations were used for CRC diagnosis, while additional ultrasound and abdominal computerised tomography imaging were used for staging the disease. Measurement of CEA and CA 19-9 was performed after CRC confirmation. Results Age, gender, tumor localization, macro-morphological and histological characteristics did not influence biomarkers serum levels. Both were significantly higher (p<0.01) in patients with Dukes D stage of CRC compared with controls. Sensitivity (76.8%) and specificity (76.6%) of CEA alone were higher than for CA 19-9, but with no statistical significance. Furthermore, sensitivity of CEA alone in the Dukes A/B group was similar to the entire CRC patient group. Conclusions Although not recommended as a screening method for the general population, elevated values of each biomarker indicate further diagnostic procedures and their simultaneous testing can improve the diagnostic sensitivity in early detection of CRC, as shown by the united analysis (AUC 0.842). PMID:28356884

  8. Urinary bladder urothelial carcinoma with concurrent plasmacytoid and micropapillary differentiations: A report of two cases with an emphasis on serum carbohydrate antigen 19-9.

    PubMed

    Makise, Naohiro; Morikawa, Teppei; Takeshima, Yuta; Fujimura, Tetsuya; Homma, Yukio; Fukayama, Masashi

    2015-09-01

    We report two cases of urinary bladder urothelial carcinoma (UC). In both, histological examination of a transurethral resection specimen of the bladder tumor revealed UC with plasmacytoid and micropapillary differentiations. In Case 1, residual plasmacytoid UC deeply invaded the extravesical fat tissue of the radical cystectomy specimen, and metastatic carcinoma was found in almost all the dissected lymph nodes. Despite adjuvant chemotherapy and radiotherapy, the patient died 25 months postdiagnosis. Elevated serum carbohydrate antigen 19-9 (CA19-9) returned to near normal levels after radical cystectomy, but they increased shortly before death. In Case 2, no residual carcinoma was found in the radical cystectomy specimen or lymph nodes. Postoperative serum CA19-9 was maintained at normal levels, and the patient remains alive without recurrence or metastasis. Although plasmacytoid and micropapillary UC are known aggressive variants of UC, plasmacytoid UC may be more aggressive. Serum CA19-9 could serve as a useful biomarker to monitor progression of plasmacytoid UC.

  9. A novel sandwich electrochemiluminescence immunosensor for ultrasensitive detection of carbohydrate antigen 19-9 based on immobilizing luminol on Ag@BSA core/shell microspheres.

    PubMed

    Zhang, Amin; Xiang, Hongkun; Zhang, Xin; Guo, Weiwei; Yuan, Enhui; Huang, Chusen; Jia, Nengqin

    2016-01-15

    A novel sandwich-type electrochemiluminescence immunosensor based on immobilizing luminol on Ag@BSA core/shell microspheres (Ag@BSA-luminol) for ultrasensitive detection of tumor marker carbohydrate antigen 19-9 (CA19-9) has been developed. Herein, magnetic carbon nanotubes (MAGCNTs) decorated with polyethylenimine (PEI) was used to construct the base of the immunosensor. MAGCNTs with prominent electrical conductivity and high surface area could be beneficial for promoting the electron transfer and loading plenty of primary antibodies (Ab1) via glutaraldehyde (GA). Meanwhile, the magnetic property of MAGCNTs makes it easy to be attached to the surface of magnetic glass carbon electrode (MGCE) through magnetism interaction, which provides an outstanding platform for this immunosensor. Moreover, Ag@BSA microspheres with large surface area, good stability, and excellent biocompatibility were desirable candidates for effective cross-link of CA19-9 detection antibodies (Ab2). A more interesting thing was that ELISA color reaction was used as an ultrasensitive strategy for identifying Ab2 was successfully coated on Ag@BSA with the naked eye. Additionally, we immobilized the luminol on the surface of Ag@BSA to prepare the target immunosensor. Immobilization of luminol on the surface of Ag@BSA could decrease the distance between luminophores and the electrode surface, leading to great enhancement of the ECL intensity of luminol in the present of hydrogen peroxide (H2O2). Under the optimal conditions, the intensity of the ECL immunosensor increased linearly with the logarithm of CA19-9 concentration in a wide linear range from 0.0005 to 150UmL(-1) with a detection limit of 0.0002UmL(-1) (S/N=3). All the results suggested the prepared CA19-9 immunosensor displayed high sensitivity, excellent stability and good specificity. The developed method opened a new avenue to clinical bioassay.

  10. 47 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Definitions. 15.3 Section 15.3 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.3 Definitions. (a... may or may not contain digital circuitry. This definition does not include CPU boards, as defined...

  11. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND....15-3 Responsibility. (a) With the knowledge and approval of the master, the senior member of...

  12. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

    SciTech Connect

    Yoo, Tae; Lee, Woo Jin; Woo, Sang Myung; Kim, Tae Hyun; Han, Sung-Sik; Park, Sang-Jae; Moon, Sung Ho; Shin, Kyung Hwan; Kim, Sang Soo; Hong, Eun Kyung; Kim, Dae Yong; Park, Joong-Won

    2011-11-15

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM{sup 3m}), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, and CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM{sup 3m}, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2-31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM{sup 3m} occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level ({<=}400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM{sup 3m} (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p < 0.05 for all three parameters). Conclusion: For patients with localized and unresectable pancreatic cancer, pretreatment CA 19-9 level could be helpful in predicting tumor response, DM{sup 3m}, and overall survival and identifying patients who will benefit from CRT.

  13. CA15-3 — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: This gene encodes a membrane-bound protein that is a member of the mucin family. Mucins are O-glycosylated proteins that play an essential role in forming protective mucous barriers on epithelial surfaces. These proteins also play a role in intracellular signaling. This protein is expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues including lung, breast stomach and pancreas. This protein is proteolytically cleaved into alpha and beta subunits that form a heterodimeric complex. The N-terminal alpha subunit functions in cell-adhesion and the C-terminal beta subunit is involved in cell signaling. Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. This gene is known to contain a highly polymorphic variable number tandem repeats (VNTR) domain. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Feb 2011

  14. Silver-functionalized g-C3N4 nanohybrids as signal-transduction tags for electrochemical immunoassay of human carbohydrate antigen 19-9.

    PubMed

    Sun, Ai-Li; Qi, Qing-An

    2016-07-21

    A simple and feasible electrochemical immunosensing platform was developed for highly efficient screening of a disease-related protein (human carbohydrate antigen 19-9, CA 19-9 used in this case) using silver-functionalized g-C3N4 nanosheets (Ag/g-C3N4) as signal-transduction tags. Initially, Ag/g-C3N4 nanohybrids were synthesized by combining thermal polymerization of the melamine precursor with the photo-assisted reduction method. Thereafter, the as-synthesized Ag/g-C3N4 nanohybrids were utilized for the labeling of the anti-CA 19-9 detection antibody by using a typical carbodiimide coupling method. The assay was carried out on a capture antibody-modified glassy carbon electrode in a sandwich-type detection mode. The detectable signal mainly derived from the voltammetric characteristics of the immobilized nanosilver particles on the g-C3N4 nanosheets within the applied potentials. Under the optimal conditions, the voltammetric peak currents increased with the increasing amount of target CA 19-9, and exhibited a wide linear range from 5.0 mU mL(-1) to 50 U mL(-1) with a detection limit of 1.2 mU mL(-1). Our strategy also displayed good reproducibility, precision and specificity. The results of the analysis of clinical serum specimens were in good accordance with the results obtained by an enzyme-linked immunosorbent assay (ELISA) method. The newly developed immunosensing system is promising for enzyme-free and cost-effective analysis of low-abundance proteins.

  15. 7 CFR 15.3 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Discrimination prohibited. 15.3 Section 15.3... Discrimination prohibited. (a) General. No person in the United States shall, on the ground of race, color, or... discrimination under any program or activity of the applicant or recipient to which these regulations...

  16. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory §...

  17. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory §...

  18. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin.

    PubMed

    Yan, Tianlian; Ke, Yini; Chen, Yi; Xu, Chengfu; Yu, Chaohui; Li, Youming

    2017-01-01

    Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19-9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time.

  19. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures...

  20. Serological characteristics of autoimmune pancreatitis and its differential diagnosis from pancreatic cancer by using a combination of carbohydrate antigen 19-9, globulin, eosinophils and hemoglobin

    PubMed Central

    Chen, Yi; Xu, Chengfu; Yu, Chaohui; Li, Youming

    2017-01-01

    Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis, which may be misdiagnosed as pancreatic carcinoma. This study aims to verify new biomarkers for AIP and propose a serological pattern to differentiate AIP from pancreatic adenocarcinoma with routinely performed tests. In this study, data of serum samples were collected and compared between 25 patients with AIP and 100 patients with pancreatic carcinoma. Receiver operating characteristic analysis and logistic regression was performed to evaluate the diagnostic effect of serum parameters in differentiating AIP from pancreatic carcinoma alone or in combination. Among several serum markers observed in the two groups, carbohydrate antigen 19–9 (Ca19-9), globulin, eosinophils and hemoglobin were selected as the independent markers. Serum levels of Globulin, Eosinophil percentage in AIP group were significantly higher than in pancreatic cancer group (P<0.05), while hemoglobin and tumor marker CA19-9 levels were lower (P <0.05). The combination of these markers identified patients with AIP with 92% sensitivity and 79% specificity, which indicated relatively high diagnostic value. Elevated serum eosinophils, globulin, together with decreased hemoglobin level can be used as a preoperative indicator for AIP and can help to initiate diagnosis of AIP in time. PMID:28369140

  1. Intramuscular myxoma associated with an increased carbohydrate antigen 19.9 level in a woman: a case report

    PubMed Central

    2011-01-01

    Introduction Intramuscular myxoma is a rare benign soft tissue tumor. The lack of specific symptoms and widely used laboratory tests makes the diagnosis quite difficult. We present a case of an Intramuscular myxoma associated with an increased carbohydrate antigen 19.9 level. To the best of our knowledge, there have not been any reported cases of an association of Intramuscular myxoma with tumor markers in the literature. Case presentation A 45-year-old Caucasian woman presented to our department for resection of a mass in her left groin area, discovered incidentally on a triplex ultrasonography of her lower extremities. The diagnosis of Intramuscular myxoma was confirmed on histopathology after the complete surgical excision of the tumor. On laboratory examination, the serum level of carbohydrate antigen 19.9 was found to be elevated, but it returned to normal six months after resection of the mass. Conclusion Carbohydrate antigen 19.9 is a tumor marker that increases in a variety of malignant and benign conditions. After the exclusion of all other possible reasons for carbohydrate antigen 19.9 elevation, we assumed a possible connection of carbohydrate antigen 19.9 elevation and Intramuscular myxoma, an issue that requires needs further investigation. PMID:21569608

  2. X-15 #3 in flight (USAF Photo)

    NASA Technical Reports Server (NTRS)

    1960-01-01

    programs, and also the Space Shuttle program. The X-15s made a total of 199 flights, and were manufactured by North American Aviation. X-15-1, serial number 56-6670, is now located at the National Air and Space museum, Washington DC. North American X-15A-2, serial number 56-6671, is at the United States Air Force Museum, Wright-Patterson AFB, Ohio. Parts of the crashed X-15-3, serial number 56-6672, recovered in 1992 by Peter Merlin and Tony Moore (The X-Hunters) are on display at the Air Force Flight Test Center Museum at Edwards. The canopy from Ship #3, recovered during the original search in 1967, is displayed at the San Diego Aerospace Museum, San Diego, California.

  3. 46 CFR 63.15-3 - Fuel system.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Fuel system. 63.15-3 Section 63.15-3 Shipping COAST... General Requirements § 63.15-3 Fuel system. (a) Firing of an automatic auxiliary boiler by natural gas is prohibited unless specifically approved by the Marine Safety Center. (b) Heated heavy fuel oil may be...

  4. 46 CFR 63.15-3 - Fuel system.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Fuel system. 63.15-3 Section 63.15-3 Shipping COAST... General Requirements § 63.15-3 Fuel system. (a) Firing of an automatic auxiliary boiler by natural gas is prohibited unless specifically approved by the Marine Safety Center. (b) Heated heavy fuel oil may be...

  5. 46 CFR 111.15-3 - Battery categories.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Battery categories. 111.15-3 Section 111.15-3 Shipping... REQUIREMENTS Storage Batteries and Battery Chargers: Construction and Installation § 111.15-3 Battery categories. (a) A battery installation is classified as one of three types, based upon power output of...

  6. 46 CFR 111.15-3 - Battery categories.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Battery categories. 111.15-3 Section 111.15-3 Shipping... REQUIREMENTS Storage Batteries and Battery Chargers: Construction and Installation § 111.15-3 Battery categories. (a) A battery installation is classified as one of three types, based upon power output of...

  7. 46 CFR 111.15-3 - Battery categories.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Battery categories. 111.15-3 Section 111.15-3 Shipping... REQUIREMENTS Storage Batteries and Battery Chargers: Construction and Installation § 111.15-3 Battery categories. (a) A battery installation is classified as one of three types, based upon power output of...

  8. 46 CFR 111.15-3 - Battery categories.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Battery categories. 111.15-3 Section 111.15-3 Shipping... REQUIREMENTS Storage Batteries and Battery Chargers: Construction and Installation § 111.15-3 Battery categories. (a) A battery installation is classified as one of three types, based upon power output of...

  9. 46 CFR 111.15-3 - Battery categories.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Battery categories. 111.15-3 Section 111.15-3 Shipping... REQUIREMENTS Storage Batteries and Battery Chargers: Construction and Installation § 111.15-3 Battery categories. (a) A battery installation is classified as one of three types, based upon power output of...

  10. 15 CFR 15.3 - Acceptance of service of process.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Acceptance of service of process. 15.3... Process § 15.3 Acceptance of service of process. (a) Except as otherwise provided in this subpart, any... taken in the conduct of official business, rather than liable in an official capacity, the...

  11. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and...

  12. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and...

  13. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and...

  14. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and...

  15. 44 CFR 15.3 - Access to Mt. Weather.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and...

  16. Serum Carbohydrate Antigen 19-9 in Differential Diagnosis of Benign and Malignant Pancreatic Cystic Neoplasms: A Meta-Analysis

    PubMed Central

    Cao, Shaobo; Hu, Ya; Gao, Xiang; Liao, Quan; Zhao, Yupei

    2016-01-01

    Background Using serum carbohydrate antigen 19–9 (CA 19–9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19–9 in predicting malignant pancreatic cystic lesions. Methods Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. Results A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35–0.59), and 0.88(95% CI: 0.86–0.91), respectively, and the AUC was 0.87(95% CI, 0.84–0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. Conclusions Serum CA 19–9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods. PMID:27835676

  17. X-15 #3 with test pilot Bill Dana

    NASA Technical Reports Server (NTRS)

    1967-01-01

    NASA research pilot Bill Dana is seen here next to the X-15 #3 (56-6672) rocket-powered aircraft after a flight. William H. Dana is Chief Engineer at NASA's Dryden Flight Research Center, Edwards, California. Formerly an aerospace research pilot at Dryden, Dana flew the F-15 HIDEC research aircraft and the Advanced Fighter Technology Integration/F-16 aircraft. Dana flew the famed X-15 research airplane 16 times, reaching a top speed of 3,897 miles per hour and a peak altitude of 306,900 feet (over 58 miles high). The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow on program used the aircraft as a testbed to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. The X-15 was a rocket-powered aircraft 50 ft long with a wingspan of 22 ft. It was a missile-shaped vehicle with an unusual wedge-shaped vertical tail, thin stubby wings, and unique side fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was capable of developing 57,000 lb of thrust. North American Aviation built three X-15 aircraft for the program. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudder surfaces on the vertical stabilizers to control yaw and movable horizontal stabilizers to control pitch when moving in synchronization or roll when moved differentially. For flight in the thin air outside of the appreciable Earth's atmosphere, the X-15 used a reaction control system. Hydrogen peroxide thrust rockets located on the nose of the aircraft provided pitch and yaw control. Those on the wings provided roll control. Because of the large fuel consumption, the X-15 was air launched from a

  18. X-15 #3 being secured by ground crew after flight

    NASA Technical Reports Server (NTRS)

    1960-01-01

    The X-15-3 (56-6672) research aircraft is secured by ground crew after landing on Rogers Dry Lakebed. The work of the X-15 team did not end with the landing of the aircraft. Once it had stopped on the lakebed, the pilot had to complete an extensive post-landing checklist. This involved recording instrument readings, pressures and temperatures, positioning switches, and shutting down systems. The pilot was then assisted from the aircraft, and a small ground crew depressurized the tanks before the rest of the ground crew finished their work on the aircraft. The X-15 was a rocket-powered aircraft 50 ft long with a wingspan of 22 ft. It was a missile-shaped vehicle with an unusual wedge-shaped vertical tail, thin stubby wings, and unique fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was capable of developing 57,000 lb of rated thrust (actual thrust reportedly climbed to 60,000 lb). North American Aviation built three X-15 aircraft for the program. The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow-on program used the aircraft as a testbed to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudder surfaces on the vertical stabilizers to control yaw and canted horizontal surfaces on the tail to control pitch when moving in synchronization or roll when moved differentially. For flight in the thin air outside of the appreciable Earth's atmosphere, the X-15 used a reaction control system. Hydrogen peroxide thrust rockets located on the nose of the aircraft provided pitch and yaw control. Those on the

  19. X-15 #3 with test pilot Milt Thompson

    NASA Technical Reports Server (NTRS)

    1964-01-01

    NASA research pilot Milt Thompson stands next to the X-15 #3 ship after a research flight. Milton 0. Thompson was a research pilot, Chief Engineer and Director of Research Projects during a long career at the NASA Dryden Flight Research Center. Thompson was hired as an engineer at the Flight Research Facility on March 19, 1956, when it was still under the auspices of NACA. He became a research pilot on May 25, 1958. Thompson was one of the 12 NASA, Air Force, and Navy pilots to fly the X-15 rocket-powered research aircraft between 1959 and 1968. He began flying X-15s on October 29, 1963. He flew the aircraft 14 times during the following two years, reaching a maximum speed of 3723 mph (Mach 5.42) and a peak altitude of 214,100 feet on separate flights. Thompson concluded his active flying career in 1968, becoming Director of Research Projects. In 1975 he was appointed Chief Engineer and retained the position until his death on August 8, 1993. The X-15 was a rocket-powered aircraft 50 ft long with a wingspan of 22 ft. It was a missile-shaped vehicle with an unusual wedge-shaped vertical tail, thin stubby wings, andunique side fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was capable of developing 57,000 lb of thrust. North American Aviation built three X-15 aircraft for the program. The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow-on program used the aircraft as a testbed to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudders on the vertical stabilizers to control yaw and movable

  20. 43 CFR 15.3 - Dredging, filling, excavating and building activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating,...

  1. 43 CFR 15.3 - Dredging, filling, excavating and building activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating,...

  2. 43 CFR 15.3 - Dredging, filling, excavating and building activities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating,...

  3. 43 CFR 15.3 - Dredging, filling, excavating and building activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating,...

  4. 43 CFR 15.3 - Dredging, filling, excavating and building activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Dredging, filling, excavating and building activities. 15.3 Section 15.3 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.3 Dredging, filling, excavating and building activities. No dredging, excavating,...

  5. A new human cholangiocellular carcinoma cell line (HuCC-T1) producing carbohydrate antigen 19/9 in serum-free medium.

    PubMed

    Miyagiwa, M; Ichida, T; Tokiwa, T; Sato, J; Sasaki, H

    1989-06-01

    A human cholangiocellular carcinoma cell line, HuCC-T1, was established in vitro from the malignant cells of ascites of a 56-yr-old patient. Histologic findings of the primary liver tumor revealed a moderately differentiated adenocarcinoma. Tumor cells from the ascites have been cultured with RPMI 1640 medium containing 0.2% lactalbumin hydrolysate and the cultured cells grew as monolayers with a population doubling time of 74 h during exponential growth at Passage 25. They had an epithelial-like morphology and were positive for mucine staining. Ultrastructural studies revealed the presence of microvilli on the cell surface and poorly developed organelles in the cytoplasm. The HuCC-T1 cell was tumorigenic in nude mice. The number of chromosomes in HuCC-T1 ranged from 61 to 80. These human cholangiocellular carcinoma cells in serum-free medium secreted several tumor markers, including carbohydrate antigen 19/9, carbohydrate antigen 125, carcinoembryonic antigen, and tissue polypeptide antigen. The carbohydrate antigen 19/9 secretion level of HuCC-T1 cells cultured in RPMI 1640 medium with 1% fetal bovine serum was sixfold higher than that with 0.2% lactalbumin hydrolysate. These findings suggest that HuCC-T1 will provide useful information to clarify the mechanism of tumor marker secretion and tumor cell growth in the human cholangiocellular carcinoma.

  6. [CEA and early detection of relapse in breast cancer subtypes: Comparison with CA 15-3].

    PubMed

    Riedinger, Jean-Marc; Goussot, Vincent; Desmoulins, Isabelle; Lorgis, Véronique; Coutant, Charles; Beltjens, Françoise; Lizard, Sarab; Fumoleau, Pierre

    2016-05-01

    This retrospective study evaluates the interest of CEA measurement for early detection of breast cancer recurrences. Among 804 patients with invasive breast cancer, we selected 97 patients without recurrence (WR) for 5 years or more, 32 with a local recurrence (LR) and 131 with at least one distant metastasis (DM). Elevated CEA and CA 15-3 levels (>3.1 μg/L and >26 kU/L respectively) were found in 6 % and 22 % of patients with RL respectively and in 49 % and 69 % of patients with DM. Both CEA and CA 15-3 retained a significant value in predicting DM by univariate and multivariate analysis. Higher sensitivity of CEA and CA 15-3 were found in tumors with positive hormonal receptor status. CEA and CA 15-3 levels at DM were raised respectively in 23 and 65 % of the triple negative group, 58 and 75 % of the luminal, 56 and 78 % of the luminal-HER2 and 50 and 30 % of HER2-enriched group (P=0.0094 and 0.0252 respectively). The combination of CEA and CA 15-3 increased CA 15-3 sensitivity in especially luminal and HER2-enriched groups. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with hormonal receptor status and breast cancer subtypes. The combination of CEA and CA 15-3 appeared useful especially luminal and HER2-enriched groups.

  7. Mechanical tensile testing of titanium 15-3-3-3 and Kevlar 49 at cryogenic temperatures

    NASA Astrophysics Data System (ADS)

    James, B. L.; Martinez, R. M.; Shirron, P.; Tuttle, J.; Galassi, N. M.; McGuinness, D. S.; Puckett, D.; Francis, J. J.; Flom, Y.

    2012-06-01

    Titanium 15-3-3-3 and Kevlar 49 are highly desired materials for structural components in cryogenic applications due to their low thermal conductivity at low temperatures. Previous tests have indicated that titanium 15-3-3-3 becomes increasingly brittle as the temperature decreases. Furthermore, little is known regarding the mechanical properties of Kevlar 49 at low temperatures, most specifically its Young's modulus. This testing investigates the mechanical properties of both materials at cryogenic temperatures through cryogenic mechanical tensile testing to failure. The elongation, ultimate tensile strength, yield strength, and break strength of both materials are provided and analyzed here.

  8. 24 CFR 15.3 - What exemptions are authorized by 5 U.S.C. 552?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Housing and Urban Development PUBLIC ACCESS TO HUD RECORDS UNDER THE FREEDOM OF INFORMATION ACT AND TESTIMONY AND PRODUCTION OF INFORMATION BY HUD EMPLOYEES Purpose and Policy § 15.3 What exemptions are... by an Executive order to be kept secret in the interest of national defense or foreign policy and...

  9. 15. 3,000TON DAVYUNITED PRESS AND STEAM INTENSIFIER IN THE BLACKSMITH ...

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

    15. 3,000-TON DAVY-UNITED PRESS AND STEAM INTENSIFIER IN THE BLACKSMITH SHOP. (THIS MACHINE WAS NOT EXTANT AT THE TIME OF THE INVENTORY.) Jet Lowe, Photographer, 1989. - U.S. Steel Homestead Works, Auxiliary Buildings & Shops, Along Monongahela River, Homestead, Allegheny County, PA

  10. 46 CFR 97.15-3 - Steering gear, whistle, and means of communication.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Steering gear, whistle, and means of communication. 97... MISCELLANEOUS VESSELS OPERATIONS Tests, Drills, and Inspections § 97.15-3 Steering gear, whistle, and means of communication. (a) On all vessels making a voyage of more than 48 hours' duration, the entire steering gear,...

  11. 46 CFR 196.15-3 - Steering gear, whistle, and means of communication.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Steering gear, whistle, and means of communication. 196... RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-3 Steering gear, whistle, and means of communication. (a) On all vessels making a voyage of more than 48 hours duration, the entire steering gear,...

  12. Fatigue crack growth study of SCS6/Ti-15-3 composite

    NASA Technical Reports Server (NTRS)

    Kantzos, P.; Telesman, J.

    1990-01-01

    A study was performed to determine the fatigue crack growth (FCG) behavior and the associated fatigue damage processes in a (0)8- and (90)8-oriented SCS6/Ti-15-3 composite. Companion testing was also done on identically processed Ti-15-3 unreinforced material. The active fatigue crack growth failure processes were very similar for both composite orientations tested. For both orientations, fatigue crack growth was along the fiber direction. It was found that the composite constituent most susceptible to fatigue damage was the interface region and, in particular, the carbon coating surrounding the fiber. The failure of the interface region led to crack initiation and also strongly influenced the FCG behavior in this composite. The failure of the interface region was apparently driven by normal stresses perpendicular to the fiber direction. The FCG rates were considerably higher for the (90)8-oriented CT specimens in comparison to the unreinforced material.

  13. Heat treatment study of the SiC/Ti-15-3 composite system

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.; Gabb, Timothy P.; Mackay, Rebecca A.

    1990-01-01

    The oxidation and aging behaviors of a continuous fiber SiC/Ti-15V-3Cr-3Sn-3Al composite (SiC/Ti-15-3) were investigated. The aging characteristic of the composite were compared with those of the unreinforced Ti-15-3 matrix material, which was processed in the same manner as the composite. Various age hardened conditions of both the unreinforced matrix and the composite were evaluated by using optical microscopy, hardness measurements, and room temperature tensile tests (unreinforced matrix only). The Ti-15-3 material formed a thick surface oxide at temperature at or above 550 C when heat treated in air. The in situ composite matrix was softer than the unreinforced matrix for equivalent aging conditions. Both materials hardened to a maximum, then softened during overaging. The temperature at which peak aging occurred was approx. 450 C for both the in situ composite matrix and the unreinforced matrix. The room temperature elastic modulus and ultimate tensile strength of the unreinforced matrix varied as a function of aging treatment and paralleled the hardness behavior. The modulus and tensile strength showed little response to aging up to temperatures of 300 C; however, these properties increased after aging at 550 C. Aging at temperatures above 550 C resulted in a decrease in the modulus and tensile strength. The failure strain was a function of the precipitation state and of the amount of oxidation resulting from the heat treatment. Aging in air at the higher temperatures (greater than 550 C) caused the formation of a thick oxide layer and reduced the ductility. Aging in vacuum at these temperatures resulted in significantly higher ductilities. Long term exposures at 700 C caused the formation of a large grain boundary alpha-phase which reduced the ductility, even though the specimens were heat treated in vacuum.

  14. Matrix plasticity in SiC/Ti-15-3 composite

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.

    1991-01-01

    An experimental method is described which allows for the observation of slip bands due to matrix plasticity in the SiC/Ti-15-3 composite system. A post-test heat treatment and subsequent chemical etch is employed to reveal slip bands in the titanium matrix. Composite specimens of various laminates were examined after tensile testing at room temperature. This method definitively shows that matrix plasticity has occurred in all the laminates investigated and at load/strain levels which were insufficient to cause fiber breakage.

  15. In-phase thermomechanical fatigue mechanisms in an unidirectional SCS-6/Ti 15-3 MMC

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1995-01-01

    The objective of this investigation was to identify the inelastic deformation and damage mechanisms under in-phase (IP) thermomechanical fatigue (TMF) in a unidirectional SCS-6/Ti 15-3 metal matrix composite (MMC). Load-controlled IP TMF tests were conducted at 300-538 C at various stress ranges in high-purity argon. A major emphasis of this work was to identify damage mechanism well before final fracture of specimens, rather than to generate life diagrams, to aid development of a realistic deformation/damage and life model.

  16. Effect of heat treatment on stiffness and damping of SiC/Ti-15-3

    NASA Technical Reports Server (NTRS)

    Grady, Joseph E.; Lerch, Bradley A.

    1992-01-01

    The effect of heat treatment on material properties of SiC/Ti-15-3 was measured by vibration tests. Heat treatment changes the microstructure, which was found to stiffen the matrix and reduce its damping capacity. Test results indicate how these changes in the matrix affect the corresponding properties of the composite. Measurements show that heat treatment affects damping properties of the composite to a greater extent than stiffness properties. The extent of change in mechanical properties is shown to depend on heat treatment temperature and exposure time.

  17. Mild phenotypic manifestation of a 7p15.3p21.2 deletion.

    PubMed Central

    Wang, C; Maynard, S; Glover, T W; Biesecker, L G

    1993-01-01

    A 28 month old girl with dysmorphic features was found to have an interstitial deletion of the short arm of chromosome 7p15.3-7p21.2. The patient had ptosis, dacryostenosis, pectus excavatum, short hands, and her development was normal or mildly delayed. Craniosynostosis and growth retardation, which were present in two other patients with similar deletions, were not present. Because of the mild manifestations, this case expands the clinical spectrum of the 7p15-7p21 deletion phenotype. Images PMID:8411039

  18. Fatigue crack growth study of SCS6/Ti-15-3 composite

    NASA Technical Reports Server (NTRS)

    Kantzos, Peter; Telesman, Jack

    1989-01-01

    A study was performed to determine the fatigue crack growth (FCG) behavior and the associated fatigue damage processes in a (0)(8) and (90)(8) oriented SCS(6)/Ti-15-3 composite. Companion testing (CT) was also done on identically processed Ti-15-3 unreinforced material. The active fatigue crack growth failure processes were very similar for both composite orientations tested. For both orientations, fatigue crack growth was along the fiber direction. It was found that the composite constituent most susceptible to fatigue damage was the interface region and in particular the carbon coating surrounding the fiber. The failure of the interface region lead to crack initiation and also strongly influenced the FCG behavior in this composite. The failure of the interface region was apparently driven by normal stresses perpendicular to the fiber direction. The FCG rates were considerably higher for the (90)(8) oriented CT specimens in comparison to the unreinforced material. This is consistent with the scenario in which the interface has lower fatigue resistance than the matrix, causing lower composite fatigue resistance. The FCG rates of the (0)(8) composite could not be directly compared to the (90)(8) composite but were shown to increase with an increase in the crack length.

  19. X-15 #3 pedestal-mounted full-scale replica covered in snow

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The full scale mock-up of X-15 #3 was installed September 1995 at the NASA Dryden Flight Research Center, Edwards, California. The original X-15 #3, serial number 56-6672, was destroyed on 15 November 1967, in a crash that also fatally injured pilot Maj. Michael J. Adams. The X-15 was a rocket-powered aircraft 50 ft long with a wingspan of 22 ft. It was a missile-shaped vehicle with an unusual wedge-shaped vertical tail, thin stubby wings, and unique side fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was capable of developing 57,000 lb of thrust. North American Aviation built three X-15 aircraft for the program. The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow on program used the aircraft as a testbed to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudder surfaces on the vertical stabilizers to control yaw and movable horizontal stabilizers to control pitch when moving in synchronization or roll when moved differentially. For flight in the thin air outside of the appreciable Earth's atmosphere, the X-15 used a reaction control system. Hydrogen peroxide thrust rockets located on the nose of the aircraft provided pitch and yaw control. Those on the wings provided roll control. Because of the large fuel consumption, the X-15 was air launched from a B-52 aircraft at 45,000 ft and a speed of about 500 mph. Depending on the mission, the rocket engine provided thrust for the first 80 to 120 sec of flight. The remainder of the normal 10 to 11 min. flight was powerless and ended with a 200-mph

  20. Characterization of unnotched SCS-6/Ti-15-3 metal matrix composites at 650 C

    NASA Technical Reports Server (NTRS)

    Pollock, W. D.; Johnson, W. Steven

    1990-01-01

    Ti-15-3 reinforced with SCS-6 silicon carbide fibers, in five different layups, was tested at 650 C to determine monotonic and fatigue strengths, basic mechanical properties, and damage initiation and progression. The elevated temperature results were compared to those obtained at room temperature. Analytical predictions were made of the monotonic stress-strain response as well as cyclic stress-strain hysteresis. The fiber reinforcement was found to significantly increase the static and fatigue strengths of the laminates over that of the matrix material at elevated temperature while the increase was insignificant at room temperature. Initial damage, in either the fibers or the matrix, was partitioned as a function of the life and applied strain range in the constituents. High strains and short lives resulted in multiple fiber failure with no signs of matrix fatigue cracking. Low strains and long lives resulted in extensive matrix cracking and no fiber breaks away from the fracture surface. At 650 C the matrix was too weak to cause fiber-matrix interface failure prior to matrix yielding. Laminate fatigue lives were hypothesized to be a function of the 0 deg fiber stress. More scatter was found in the 0 deg fiber stress vs. high temperature fatigue life data than for the room temperature data. An initial unloading modulus that was greater than the initial loading modulus was observed in the elevated temperature fatigue tests.

  1. Inelastic deformation mechanisms in SCS-6/Ti 15-3 MMC lamina under compression

    NASA Technical Reports Server (NTRS)

    Newaz, Golam M.; Majumdar, Bhaskar S.

    1993-01-01

    An investigation was undertaken to study the inelastic deformation mechanisms in (0)(sub 8) and (90)(sub 8) Ti 15-3/SCS-6 lamina subjected to pure compression. Monotonic tests were conducted at room temperature (RT), 538 C and 650 C. Results indicate that mechanical response and deformation characteristics were different in monotonic tension and compression loading whereas some of those differences could be attributed to residual stress effects. There were other differences because of changes in damage and failure modes. The inelastic deformation in the (0)(sub 8) lamina under compression was controlled primarily by matrix plasticity, although some evidence of fiber-matrix debonding was observed. Failure of the specimen in compression was due to fiber buckling in a macroscopic shear zone (the failure plane). The inelastic deformation mechanisms under compression in (90)(sub 8) lamina were controlled by radial fiber fracture, matrix plasticity, and fiber-matrix debonding. The radial fiber fracture was a new damage mode observed for MMC's. Constitutive response was predicted for both the (0)(sub 8) and (90)(sub 8) laminae, using AGLPLY, METCAN, and Battelle's Unit Cell FEA model. Results from the analyses were encouraging.

  2. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... shall burn for at least 10 consecutive hours on one charge of the battery and shall give during that... percent. (d) Corrosion of contacts. Battery terminals and leads therefrom, as well as the battery...

  3. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... period a mean candlepower of light beam of not less than 1. (b) Bulb life. The average life of the bulbs shall be not less than 200 hours, and at least 92 percent of the bulbs shall have a life of 150 hours. The life of a bulb is the number of hours its main filament will burn in the cap lamp or...

  4. 22 CFR 19.9-1 - Entitlement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., 1981, becomes a former spouse of a participant (or former participant who separated from the Service after February 15, 1981) and who has not remarried prior to becoming 60 years of age, becomes...

  5. Isothermal fatigue behavior of a (90)(sub 8) SiC/Ti-15-3 composite at 426 C

    NASA Technical Reports Server (NTRS)

    Gayda, John; Gabb, Timothy P.

    1991-01-01

    The transverse fatigue behavior of a unidirectional, SiC/Ti-15-3 composite (35 v/o SiC, (90)(sub 8)) was evaluated at 426 C. The fatigue behavior of the composite along the fiber direction (0)(sub 8) and of unreinforced Ti-15-3 alloy were also studied for comparison purposes. The (90)(sub 8) composite fatigue life was much shorter then (0)(sub 8) life. Further, (90)(sub 8) fatigue life was also found to be far lower than that of the unreinforced Ti-15-3 alloys. A simple one-dimensional model for (90)(sub 8) fatigue behavior indicated that the short life of the composite in this orientation resulted, in large part, from weak fiber-matrix bond strength. This conclusion was supported by fractographic evidence showing numerous initiation sites along the fiber-matrix interfaces.

  6. Review of clinical studies of CA 27.29 in breast cancer management.

    PubMed

    Beveridge, R A

    1999-01-01

    A critical review of CA 27.29 and CA 15-3 is performed in this paper. A review of the literature is undertaken. A review of the FDA submissions for 27.29 for both early stage and monitoring metastatic breast cancer patients is reviewed.

  7. Electroreduction-based electrochemical-enzymatic redox cycling for the detection of cancer antigen 15-3 using graphene oxide-modified indium-tin oxide electrodes.

    PubMed

    Park, Seonhwa; Singh, Amardeep; Kim, Sinyoung; Yang, Haesik

    2014-02-04

    We compare herein biosensing performance of two electroreduction-based electrochemical-enzymatic (EN) redox-cycling schemes [the redox cycling combined with simultaneous enzymatic amplification (one-enzyme scheme) and the redox cycling combined with preceding enzymatic amplification (two-enzyme scheme)]. To minimize unwanted side reactions in the two-enzyme scheme, β-galactosidase (Gal) and tyrosinase (Tyr) are selected as an enzyme label and a redox enzyme, respectively, and Tyr is selected as a redox enzyme label in the one-enzyme scheme. The signal amplification in the one-enzyme scheme consists of (i) enzymatic oxidation of catechol into o-benzoquinone by Tyr and (ii) electroreduction-based EN redox cycling of o-benzoquinone. The signal amplification in the two-enzyme scheme consists of (i) enzymatic conversion of phenyl β-d-galactopyranoside into phenol by Gal, (ii) enzymatic oxidation of phenol into catechol by Tyr, and (iii) electroreduction-based EN redox cycling of o-benzoquinone including further enzymatic oxidation of catechol to o-benzoquinone by Tyr. Graphene oxide-modified indium-tin oxide (GO/ITO) electrodes, simply prepared by immersing ITO electrodes in a GO-dispersed aqueous solution, are used to obtain better electrocatalytic activities toward o-benzoquinone reduction than bare ITO electrodes. The detection limits for mouse IgG, measured with GO/ITO electrodes, are lower than when measured with bare ITO electrodes. Importantly, the detection of mouse IgG using the two-enzyme scheme allows lower detection limits than that using the one-enzyme scheme, because the former gives higher signal levels at low target concentrations although the former gives lower signal levels at high concentrations. The detection limit for cancer antigen (CA) 15-3, a biomarker of breast cancer, measured using the two-enzyme scheme and GO/ITO electrodes is ca. 0.1 U/mL, indicating that the immunosensor is highly sensitive.

  8. Ca²+ buffering at a drosophila larval synaptic terminal.

    PubMed

    He, Tao; Lnenicka, Gregory A

    2011-07-01

    A quantitative analysis of Ca²+ dynamics requires knowledge of the Ca²+-binding ratio (κ(S) ); this has not been measured at Drosophila synaptic terminals or any invertebrate synaptic terminal. We measured κ(S) at a Ib motor terminal in Drosophila larvae comparing single-AP Ca²+ transients in synaptic terminals that contained varying concentrations of the Ca²+ indicator, Oregon Green 488 BAPTA-1 (OGB-1). Using a linear single-compartment model, κ(S) was calculated based upon the effect of [OGB-1] on the time constant (τ(decay) ) for the decay of intracellular free Ca²+ concentration ([Ca²+](i)). This gave a κ(S) of 77 indicating that nearly 99% of entering Ca²+ is immediately bound by endogenous fast Ca²+ buffers. Extrapolation to zero [OGB-1] gave a τ(decay) of 46 ms and a Ca²+-removal rate constant of 1641 s⁻¹ for single APs. We calculated that a single AP produced an increase in [Ca²+](i) of 196 nM and an increase in the total intracellular [Ca²+](free + bound) of 15.3 μM for measurements made in 1.0 mM external Ca²+. The increase in [Ca²+](i) for AP trains was 185 nM/ 10 Hz; this gave a Ca²+ extrusion rate constant of 827 s⁻¹, which likely reflects the activity of the plasma membrane Ca²+ ATPase. Experiments were performed to examine the effect of altering external Ca²+ or Mg²+ on Ca²+ influx at these terminals.

  9. Cri du chat syndrome determined by the 5p15.3-->pter deletion--diagnostic problems.

    PubMed

    Laczmanska, Izabela; Stembalska, Agnieszka; Gil, Justyna; Czemarmazowicz, Halina; Sasiadek, Maria

    2006-01-01

    A cytogenetic analysis was performed on an 8-day-old girl, who was suspected of Cri du chat syndrome (CdCS) on the basis of a cat-like cry, despite her dysmorphic features not being characteristic of this syndrome. The cytogenetic analysis revealed a partial deletion of the short arm of chromosome 5, but did not allow precise specification of the break points. Fluorescence in situ hybridization (FISH) analysis, using the specific probe for CdCS, revealed two signals in all the cells analyzed. However, one of two signals was less intense than the other. Thus, telomere probes were applied for all chromosomes. Two signals from 5q and one signal from 5p were observed. The results allowed us to establish the location of the deleted fragment as 5p15.3-->5pter [46,XX,del(5)(p15.3)]. The analysis of a genotype-phenotype correlation confirmed that the cat-like cry, but not the characteristic dysmorphic features of CdCS are correlated with the deletion of 5p15.3.

  10. An overview of elevated temperature damage mechanisms and fatigue behavior of a unidirectional SCS-6/Ti-15-3 composite

    NASA Technical Reports Server (NTRS)

    Castelli, Michael G.; Gayda, John

    1993-01-01

    The fatigue behavior of a unidirectionally reinforced titanium matrix composite (TMC), SiC/Ti-15-3, was thoroughly characterized to support life prediction modeling of advanced TMC disks designed for gas turbine engine applications. The results of this coupon-level experimental investigation are reviewed. On a stress basis, the isothermal fatigue behavior of the (0 deg) TMC revealed significant improvements over the unreinforced matrix. In contrast, the (90 deg) TMC exhibited degraded properties and lives for similar comparisons. This was attributed to the weak fiber/matrix interfacial bond. Encasing the (0 deg) TMC with a Ti-15-3 case did not affect isothermal fatigue lives at higher strain levels. However, at lower strain levels, rapid initiation and propagation of large fatigue cracks in the case degraded the fatigue lives. Thermomechanical fatigue (TMF) lives were significantly reduced for the (0 deg) TMC when compared to isothermal lives. At high strains, in-phase TMF produced extremely short lives. This degradation was attributed to fiber overload failures brought about by stress relaxation in the matrix. At low strains, out-of-phase TMF conditions became life limiting. Environment-assisted surface cracking was found to accelerate fatigue failure. This produced extensive matrix damage with minimal fiber damage. For the (90 deg) TMC, TMF conditions did not promote an additional degradation in cyclic life beyond that observed under isothermal conditions.

  11. Analytical and clinical evaluation of a new tumor marker in breast cancer: CA 27.29.

    PubMed

    Correale, M; Abbate, I; Gargano, G; Catino, A; Dragone, C D; Musci, M D; Serio, G; Paradiso, A; De Lena, M

    1992-01-01

    Evaluation of a radioimmunoassay for a new tumor marker, named CA 27.29, recently proposed for use in breast cancer patients, is reported in this study. After considering the analytical performance, the clinical study was directed to a control group of 66 apparently healthy subjects (Controls), a group of 25 women with benign breast disease (BBD) and a group of 164 breast cancer patients divided into primary before any treatment (M-), in follow-up with no evidence of disease (NED) and presence of metastases (M+). When compared to CA 15.3, our results showed similar sensitivity of both markers with a slightly lower specificity for CA 27.29. In some cases, however, CA 27.29 elevation appears earlier than CA 15.3 as a sign of metastases. We thus propose their associated use.

  12. New mucin-like cancer-associated antigens (CA M 26, CA M 29 and CA 549) and a new proliferation marker (TPS) in patients with primary or advanced breast cancer.

    PubMed

    Locker, G J; Mader, R M; Braun, J; Sieder, A E; Marosi, C; Rainer, H; Jakesz, R; Steger, G G

    1995-01-01

    In patients with breast cancer no tumor markers giving satisfactory results have been found yet. The aim of our investigation was to compare the usefulness of newly developed tumor markers with the most common used carcinoembryonic antigen and cancer antigen (CA) 15-3. We evaluated the concentrations of carcinoma-associated antigen (CA) 549, carcinoma-associated mucin antigen (CA M) 26 and CA M 29, and the proliferation markers tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS) in 84 breast cancer patients with disease progression and in 69 patients with no evidence of disease after surgery for breast cancer. Using receiver-operating characteristic curves (ROC curves) we were able to demonstrate increased sensitivity and specificity of all tested tumor markers in patients with metastatic disease compared with local disease. In our investigation TPA is superior to TPS in all disease states. In local disease, none of the tested markers shows satisfying results. In metastatic disease, the new mucin markers CA M 26 and CA M 29 show slightly better results than CA 15-3 although their ROC curves are nearly congruent. CA 549 is exceeded by the other mucin markers. The best results in this investigation were obtained with CA M 29. The overall results concerning the detection of small tumor masses (i.e. local disease) were unsatisfactory.

  13. Fully Coupled Micro/Macro Deformation, Damage, and Failure Prediction for SiC/Ti-15-3 Laminates

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Arnold, Steven M.; Lerch, Brad A.

    2001-01-01

    The deformation, failure, and low cycle fatigue life of SCS-6/Ti-15-3 composites are predicted using a coupled deformation and damage approach in the context of the analytical generalized method of cells (GMC) micromechanics model. The local effects of inelastic deformation, fiber breakage, fiber-matrix interfacial debonding, and fatigue damage are included as sub-models that operate on the micro scale for the individual composite phases. For the laminate analysis, lamination theory is employed as the global or structural scale model, while GMC is embedded to operate on the meso scale to simulate the behavior of the composite material within each laminate layer. While the analysis approach is quite complex and multifaceted, it is shown, through comparison with experimental data, to be quite accurate and realistic while remaining extremely efficient.

  14. Deformation, Failure, and Fatigue Life of SiC/Ti-15-3 Laminates Accurately Predicted by MAC/GMC

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Arnold, Steven M.

    2002-01-01

    NASA Glenn Research Center's Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC) (ref.1) has been extended to enable fully coupled macro-micro deformation, failure, and fatigue life predictions for advanced metal matrix, ceramic matrix, and polymer matrix composites. Because of the multiaxial nature of the code's underlying micromechanics model, GMC--which allows the incorporation of complex local inelastic constitutive models--MAC/GMC finds its most important application in metal matrix composites, like the SiC/Ti-15-3 composite examined here. Furthermore, since GMC predicts the microscale fields within each constituent of the composite material, submodels for local effects such as fiber breakage, interfacial debonding, and matrix fatigue damage can and have been built into MAC/GMC. The present application of MAC/GMC highlights the combination of these features, which has enabled the accurate modeling of the deformation, failure, and life of titanium matrix composites.

  15. Investigation of fatigue damage mechanisms in SCS-6/Ti-15-3 metal matrix composite at elevated temperature

    NASA Astrophysics Data System (ADS)

    Mall, S.; Portner, B. D.

    A study was conducted to study the fatigue behavior of cross-ply, (0/90)2s, laminate of silicon fiber reinforced titanium matrix composite, SCS-6/Ti-15-3 at an elevated temperature of 427 C. Two sets of tests, at frequencies 0.02 and 2 Hz, were run at different stress levels which were either below or above the static first ply failure strength of laminate. Crack initiation locations and growth patterns were dependent on to specific test conditions of frequency and stress level. Also, microscopic analysis of the fatigued specimens revealed matrix failure mechanisms ranging from ductile failure to cleavage fracture. The results of this study clearly showed that temperature, frequency as well as stress levels are important design considerations for this composite in fatigue loading applications.

  16. Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE.

    PubMed

    Choi, Hoyun; Lee, Hanna; Kim, Sae Rom; Gho, Yong Song; Lee, Suk Kyeong

    2013-07-01

    Epstein-Barr Virus (EBV) generates a variety of viral microRNAs (miRNAs) by processing the BHRF1 and BamHI A rightward (BART) transcripts. BART miRNAs are expressed in all cells latently infected with EBV, but the functions of most BART miRNAs remain unknown. The results of a cell proliferation assay revealed that miR-BART15-3p inhibited cell proliferation. Fluorescence-activated cell sorting following staining with annexin V or propidium iodide showed that miR-BART15-3p promoted apoptosis. Furthermore, the inhibitor for miR-BART15-3p increased cell growth and reduced apoptosis in EBV-infected cells. Using bioinformatic analyses, we predicted that miR-BART15-3p may target the antiapoptotic B-cell lymphoma 2 (BCL2), BCL2L2, DEAD (Asp-Glu-Ala-Asp) box polypeptide 42 (DDX42), and baculovirus inhibitor of apoptosis repeat-containing ubiquitin-conjugating enzyme (BRUCE) mRNAs. The luciferase reporter assay showed that only the 3' untranslated region (UTR) of BRUCE was affected by miR-BART15-3p. Two putative seed-matched sites for miR-BART15-3p were evident on the BRUCE 3' UTR. The results of a mutation study indicated that miR-BART15-3p hybridized only with the first seed-matched site on the BRUCE 3' UTR. miR-BART15-3p downregulated the BRUCE protein in EBV-negative cells, while the inhibitor for miR-BART15-3p upregulated the BRUCE protein in EBV-infected cells without affecting the BRUCE mRNA level. miR-BART15-3p was secreted from EBV-infected gastric carcinoma cells, and the level of miR-BART15-3p was 2- to 16-fold higher in exosomes than in the corresponding cells. Our data suggest that miR-BART15-3p can induce apoptosis partially by inhibiting the translation of the apoptosis inhibitor BRUCE. Further study is warranted to understand the role of miR-BART15-3p in the EBV life cycle.

  17. Evaluation of the circulating glycoprotein CA549 in mammary cancer and other malignancies.

    PubMed

    Clocchiatti, L; De Biasi, F; Cartei, G; Sibau, A; Vigevani, E; Signor, M; Giovannoni, M; Ceschia, V; Di Chiara, F; Grandis, S

    1991-10-31

    A prospective study was carried out on a recent marker for breast cancer, CA549, a mucine-like acid glycoprotein present in the fat membranes of human milk. Fifty healthy control subjects and 91 with benign conditions, 103 mammary cancer patients and 256 patients with other types of malignancy were studied. For comparison, CEA and CA15-3 were also investigated. The CA549 cutoff was 11 U/ml. In breast cancer the marker was below the cutoff in 9 cases (92.8%); in malignancies other than breast cancer it was above the cutoff in 5 to 50% of patients. In breast cancer it was raised in 83.3% of cases (CA15-3 showed 82.9% and CEA 50%). In breast cancer after radical surgery, CA549 was normal in patients who were in TNM stage I but above the cutoff in 57.1% of those at more advanced stages. The follow-up study is ongoing among these patients. In all the study conditions, CA549 favorably compared to CA15-3 values, with sensitivity and specificity greater than CEA.

  18. CA27.29: a valuable marker for breast cancer management. A confirmatory multicentric study on 603 cases.

    PubMed

    Gion, M; Mione, R; Leon, A E; Lüftner, D; Molina, R; Possinger, K; Robertson, J F

    2001-02-01

    Recently, a fully automated method has become commercially available to measure the MUC-1-associated antigen CA27.29. The present investigation was performed in order to compare CA27.29 and CA15.3 in a wide series of patients affected with breast cancer. Overall, 603 cases with breast cancer and 194 healthy controls were investigated. Patients were enrolled in 4 institutions, while assays were performed in one laboratory. CA27.29 was measured by the ACS:180 BR assay (Bayer Diagnostics) and CA15.3 by the AxSYM (Abbott Laboratories). An excellent correlation was found between the results obtained by the two methods. The two markers showed comparable results in healthy controls, with higher levels in post-menopausal than in pre-menopausal subjects. The markers were significantly higher in primary breast cancer than in controls. The areas under the receiver operating characteristics (ROC) curves of the two tests were comparable, but CA27.29 showed better sensitivity in cases with low antigen concentrations (below the cut-off point). Accordingly, when comparing each test in different stage categories, significance levels of the differences were higher for CA27.29 than for CA15.3 for all T categories versus healthy controls, for pT1 versus pT2, for all N categories versus healthy controls and for node-negative versus N1-3 patients. From the results of the present study, that has been performed on samples taken at diagnosis and prior to any treatment from the widest series of patients with primary breast cancer reported so far, we can draw the following conclusions: CA27.29 provides comparable results to CA15.3; CA27.29 seems more sensitive than CA15.3 to limited variations of tumour extension; however, it cannot help clinicians in distinguishing stage I patients from stage II patients. However, from the point of view of clinical decision making, CA27.29 provides comparable results to CA15.3. CA27.29 is therefore suitable for routine use in the management of patients with

  19. Molecular studies of segmental aneusomy: FISHing for the atypical cry in del(5)(p15.3).

    PubMed

    Hodge, J C; Lawson-Yuen, A; Stoler, J M; Ligon, A H

    2007-01-01

    We report a newborn male with multiple congenital anomalies including growth retardation, hypotonia, dysmorphic facies, widely-spaced nipples, micropenis, cryptorchidism, optic nerve hypoplasia, heart disease, and a striking, high-pitched cry. Chromosome analysis revealed de novo partial trisomy 11q due to a der(5)t(5;11)(p15.3;q22). Fluorescence in situ hybridization (FISH) showed loss of the 5p telomere signal on the der(5) chromosome, indicating the infant has partial monosomy 5p in addition to partial trisomy 11q. Among cases involving trisomy 11q, an unusual cry has only been documented in the presence of a der(5)t(5p;11q). This apparent dependence of the abnormal cry on monosomy 5p suggested the same genetic mechanism that occurs in Cri du chat syndrome (CDCS) may be responsible for the atypical cry in der(5)t(5p;11q) individuals. Neither a commercial CDCS probe (LSI D5S23, D5S721) nor a series of BAC clones encompassing distal regions implicated in the CDCS-associated cat-cry were deleted in our patient. These results suggest a second cry-modifying locus maps telomeric to BAC RP11-94J21 in band 5p15.33. This locus may not only cause the abnormal cry in individuals with a der(5)t(5p;11q) but could also contribute to the phenotypic variability and discordant mapping studies observed for CDCS.

  20. Microstructure, In Vitro Corrosion Behavior and Cytotoxicity of Biodegradable Mg-Ca-Zn and Mg-Ca-Zn-Bi Alloys

    NASA Astrophysics Data System (ADS)

    Bakhsheshi-Rad, H. R.; Hamzah, E.; Tok, H. Y.; Kasiri-Asgarani, M.; Jabbarzare, S.; Medraj, M.

    2017-02-01

    The effects of bismuth (Bi) addition on the microstructure and corrosion behavior of the Mg-Ca-Zn-Bi alloys were evaluated using electron microscopy, electrochemical test and electrochemical impedance spectroscopy. Microstructural observations showed that Mg-1.2Ca-1Zn- xBi ( x = 0.5, 1.5, 3 wt.%) are composed of Mg2Ca, Ca2Mg6Zn3 and Mg3Bi2 phases while a new phase Mg2Bi2Ca appeared after the addition of 5 and 12 wt.% Bi to the Mg-1.2Ca-1Zn alloy. Furthermore, the additions of 0.5 wt.% Bi to the Mg-1.2Ca-1Zn alloy slightly improved the corrosion behavior of the alloy, while further increase in Bi amount from 1.5 to 12 wt.% has a deleterious effect on the corrosion behavior of the ternary Mg-1.2Ca-1Zn alloy which is driven by galvanic coupling effect. Cytotoxicity tests indicate that the Mg-1.2Ca-1Zn presents higher cell viability compared to Mg-1.2Ca-1Zn-0.5Bi alloy. In addition, the cell viability of both alloys increased with increasing incubation time while diluting the extracts to 50% and 10% improved the cell viabilities. The present results suggest that the Mg-1.2Ca-1Zn-0.5Bi can be interesting candidate for the development of degradable biomaterials and it is worthwhile for further investigation in an in vivo environment.

  1. Microstructure, In Vitro Corrosion Behavior and Cytotoxicity of Biodegradable Mg-Ca-Zn and Mg-Ca-Zn-Bi Alloys

    NASA Astrophysics Data System (ADS)

    Bakhsheshi-Rad, H. R.; Hamzah, E.; Tok, H. Y.; Kasiri-Asgarani, M.; Jabbarzare, S.; Medraj, M.

    2017-01-01

    The effects of bismuth (Bi) addition on the microstructure and corrosion behavior of the Mg-Ca-Zn-Bi alloys were evaluated using electron microscopy, electrochemical test and electrochemical impedance spectroscopy. Microstructural observations showed that Mg-1.2Ca-1Zn-xBi (x = 0.5, 1.5, 3 wt.%) are composed of Mg2Ca, Ca2Mg6Zn3 and Mg3Bi2 phases while a new phase Mg2Bi2Ca appeared after the addition of 5 and 12 wt.% Bi to the Mg-1.2Ca-1Zn alloy. Furthermore, the additions of 0.5 wt.% Bi to the Mg-1.2Ca-1Zn alloy slightly improved the corrosion behavior of the alloy, while further increase in Bi amount from 1.5 to 12 wt.% has a deleterious effect on the corrosion behavior of the ternary Mg-1.2Ca-1Zn alloy which is driven by galvanic coupling effect. Cytotoxicity tests indicate that the Mg-1.2Ca-1Zn presents higher cell viability compared to Mg-1.2Ca-1Zn-0.5Bi alloy. In addition, the cell viability of both alloys increased with increasing incubation time while diluting the extracts to 50% and 10% improved the cell viabilities. The present results suggest that the Mg-1.2Ca-1Zn-0.5Bi can be interesting candidate for the development of degradable biomaterials and it is worthwhile for further investigation in an in vivo environment.

  2. The Ca(2+)/Calmodulin/CaMKK2 Axis: Nature's Metabolic CaMshaft.

    PubMed

    Marcelo, Kathrina L; Means, Anthony R; York, Brian

    2016-10-01

    Calcium (Ca(2+)) is an essential ligand that binds its primary intracellular receptor calmodulin (CaM) to trigger a variety of downstream processes and pathways. Central to the actions of Ca(2+)/CaM is the activation of a highly conserved Ca(2+)/CaM kinase (CaMK) cascade that amplifies Ca(2+) signals through a series of subsequent phosphorylation events. Proper regulation of Ca(2+) flux is necessary for whole-body metabolism and disruption of Ca(2+) homeostasis has been linked to various metabolic diseases. Here we provide a synthesis of recent advances that highlight the roles of the Ca(2+)/CaMK axis in key metabolic tissues. An appreciation of this information is critical to understanding the mechanisms by which Ca(2+)/CaM-dependent signaling contributes to metabolic homeostasis and disease.

  3. Desulfurizing Ability of the CaOsatd.-CaCl2-CaF2 Slags

    NASA Astrophysics Data System (ADS)

    Liu, Jiazhan; Kobayashi, Yoshinao

    2017-04-01

    Desulfurizing ability of the CaO-CaCl2-CaF2 slags saturated with CaO has been investigated from the viewpoint of the sulfide capacity and CaO solubility. The CaO-CaCl2-CaF2 slags containing small amounts of Cu2O and CaS were inserted in a CaO crucible with metallic copper. The CaO crucible was sealed in a nickel holder to prevent the evaporation of CaCl2, then heated up and kept at temperatures from 1573 K (1300 °C) to 1673 K (1400 °C) for 24 hours, which enabled the system inside the CaO crucible to reach the equilibrium. As expected, the sulfide capacity derived from the data obtained as well as CaO solubility of the slag increase with an increase in temperature at a constant ratio of CaCl2/CaF2. The solubility of CaO increases by the replacement of CaF2 with CaCl2, whereas the sulfide capacity slightly decreases and the activity coefficient of CaS ( γ CaS) increases. This suggests that CaF2 has stronger interaction with CaS than CaCl2. The sulfur distribution ratio between carbon-saturated iron melts and the CaO-CaCl2 slag has been calculated to be about 10 000 at 1573 K (1300 °C) using the sulfide capacity obtained, which value is still large enough even with the replacement of CaF2 by CaCl2.

  4. Desulfurizing Ability of the CaOsatd.-CaCl2-CaF2 Slags

    NASA Astrophysics Data System (ADS)

    Liu, Jiazhan; Kobayashi, Yoshinao

    2016-12-01

    Desulfurizing ability of the CaO-CaCl2-CaF2 slags saturated with CaO has been investigated from the viewpoint of the sulfide capacity and CaO solubility. The CaO-CaCl2-CaF2 slags containing small amounts of Cu2O and CaS were inserted in a CaO crucible with metallic copper. The CaO crucible was sealed in a nickel holder to prevent the evaporation of CaCl2, then heated up and kept at temperatures from 1573 K (1300 °C) to 1673 K (1400 °C) for 24 hours, which enabled the system inside the CaO crucible to reach the equilibrium. As expected, the sulfide capacity derived from the data obtained as well as CaO solubility of the slag increase with an increase in temperature at a constant ratio of CaCl2/CaF2. The solubility of CaO increases by the replacement of CaF2 with CaCl2, whereas the sulfide capacity slightly decreases and the activity coefficient of CaS (γ CaS) increases. This suggests that CaF2 has stronger interaction with CaS than CaCl2. The sulfur distribution ratio between carbon-saturated iron melts and the CaO-CaCl2 slag has been calculated to be about 10 000 at 1573 K (1300 °C) using the sulfide capacity obtained, which value is still large enough even with the replacement of CaF2 by CaCl2.

  5. CA-125 blood test

    MedlinePlus

    ... above 35 U/mL is considered abnormal. Normal value ranges may vary slightly among different laboratories. Some ... 125 usually does not mean ovarian cancer is present. Most healthy women with an elevated CA-125 ...

  6. Ag-Al-Ca

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Ag-Al-Ca' with the content:

  7. Slide Activity along the eastern slope of the Gela Basin (offshore Sicily): First results from expedition MSM-15/3

    NASA Astrophysics Data System (ADS)

    Huhn, K.; Strasser, M.; Freudenthal, T.; Foglini, F.; Trincardi, F.; Minisini, D.; Msm15/3 Working Group

    2010-12-01

    Submarine slides occur at all sediment bearing margins worldwide (Camerlenghi et al., 2009; Masson et al., 2006). Although numerous studies have dealt with mapping and monitoring of submarine landslide as well as investigations of trigger mechanisms and sediment failure processes, many open questions persist why a given slope fails whereas adjacent remains stable. Besides large slide events, smaller scaled mid-size slides became recently of particular importance because especially these local slides enable investigation of physical and kinematical processes during failure and to test a wide range of different trigger mechanisms. Hence, during the research expedition MSM15/3 we drilled two distinct landslides in the Gela Basin offshore south of Sicily (Italy) utilizing the MARUM sea floor drill rig (MeBo). These so-called ‘Twin Slides’ have previously been identified in water depth between 200 - 800m on the basis of side-scan sonar, Chirp seismics, swath bathymetry and shallow core data. Besides, these landslides are described as multiple failures likely controlled by specific stratigraphic surfaces acting as glide planes (Minisini et al., 2007; Minisini and Trincardi, 2009). Nevertheless, failure planes are located in depth inaccessible by conventional coring and we therefore lack groundtruthing of the geophysical data. Therefore, MeBo was deployed to drill e.g. critical subsurface intervals. A systematic MeBo drilling transect from the undisturbed slope apron to the depositional area of these landslide masses recovers up to 55 meter long cores, including the failure planes and stacked mass transport deposits in the proximal and distal areas, respectively. Sedimentological, geochemical, geophysical and geotechnical analysis of these core materials will enable (1) an age dating and estimation of the recurrence rate of mid-sized slide events and (2) a sediment physical characterization to gain a deeper insight into kinematics and physical processes during failure

  8. Routes of Ca2+ Shuttling during Ca2+ Oscillations

    PubMed Central

    Pecze, László; Blum, Walter; Schwaller, Beat

    2015-01-01

    In some cell types, Ca2+ oscillations are strictly dependent on Ca2+ influx across the plasma membrane, whereas in others, oscillations also persist in the absence of Ca2+ influx. We observed that, in primary mesothelial cells, the plasmalemmal Ca2+ influx played a pivotal role. However, when the Ca2+ transport across the plasma membrane by the “lanthanum insulation method” was blocked prior to the induction of the serum-induced Ca2+ oscillations, mitochondrial Ca2+ transport was found to be able to substitute for the plasmalemmal Ca2+ exchange function, thus rendering the oscillations independent of extracellular Ca2+. However, in a physiological situation, the Ca2+-buffering capacity of mitochondria was found not to be essential for Ca2+ oscillations. Moreover, brief spontaneous Ca2+ changes were observed in the mitochondrial Ca2+ concentration without apparent changes in the cytosolic Ca2+ concentration, indicating the presence of a mitochondrial autonomous Ca2+ signaling mechanism. In the presence of calretinin, a Ca2+-buffering protein, the amplitude of cytosolic spikes during oscillations was decreased, and the amount of Ca2+ ions taken up by mitochondria was reduced. Thus, the increased calretinin expression observed in mesothelioma cells and in certain colon cancer might be correlated to the increased resistance of these tumor cells to proapoptotic/pronecrotic signals. We identified and characterized (experimentally and by modeling) three Ca2+ shuttling pathways in primary mesothelial cells during Ca2+ oscillations: Ca2+ shuttled between (i) the endoplasmic reticulum (ER) and mitochondria, (ii) the ER and the extracellular space, and (iii) the ER and cytoplasmic Ca2+ buffers. PMID:26396196

  9. Ca2+ signaling and intracellular Ca2+ binding proteins.

    PubMed

    Niki, I; Yokokura, H; Sudo, T; Kato, M; Hidaka, H

    1996-10-01

    Changes in cytosolic Ca2+ concentrations evoke a wide range of cellular responses and intracellular Ca(2+)-binding proteins are the key molecules to transduce Ca2+ signaling via enzymatic reactions or modulation of protein/protein interations (Fig.1). The EF hand proteins, like calmodulin and S100 proteins, are considered to exert Ca(2+)-dependent actions in the nucleus or the cytoplasm. The Ca2+/phospholipid binding proteins are classified into two groups, the annexins and the C2 region proteins. These proteins, distributed mainly in the cytoplasm, translocate to the plasma membrane in response to an increase in cytosolic Ca2+ and function in the vicinity of the membrane. Ca2+ storage proteins in the endoplasmic or sarcoplasmic reticulum provide the high Ca2+ capacity of the Ca2+ store sites, which regulate intracellular Ca2+ distribution. The variety and complexity of Ca2+ signaling result from the cooperative actions of specific Ca(2+)-binding proteins. This review describes biochemical properties of intracellular Ca(2+)-binding proteins and their proposed roles in mediating Ca2+ signaling.

  10. 12 CFR 19.9 - Ex parte communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... request for status of the proceeding does not constitute an ex parte communication. (b) Prohibition of ex parte communications. From the time the notice is issued by the Comptroller until the date that the... extent required for the disposition of ex parte matters as authorized by law, the administrative...

  11. Characterization of 19.9% Efficient CIGS Absorbers: Preprint

    SciTech Connect

    Repins, I.; Contreras, M.; Romero, M.; Yan, Y.; Metzger, W.; Li, J.; Johnston, S.; Egass, B.; DeHart, C.; Scharf, J.; McCandless, B. E.; Noufi, R.

    2008-05-01

    This paper documents the properties of the world-record-efficiency CIGS solar cell by a variety of characterization techniques, with an emphasis on identifying near-surface properties associated with the modified processing.

  12. 38 CFR 19.9 - Remand for further development.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Veterans Law Judge or panel of Veterans Law Judges shall remand the case to the agency of original... hearing before the Board; (2) Consideration of an appeal, in accordance with § 20.903(b) of this chapter, with respect to law not already considered by the agency of original jurisdiction. This includes,...

  13. 22 CFR 19.9-2 - Commencement and termination.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... becomes entitled to a Foreign Service annuity or on the first day of the month in which the divorce... service; (2) The date the disability annuity begins; or (3) The first of the month in which the...

  14. 22 CFR 19.9-2 - Commencement and termination.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... becomes entitled to a Foreign Service annuity or on the first day of the month in which the divorce... service; (2) The date the disability annuity begins; or (3) The first of the month in which the...

  15. 22 CFR 19.9-2 - Commencement and termination.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... becomes entitled to a Foreign Service annuity or on the first day of the month in which the divorce... service; (2) The date the disability annuity begins; or (3) The first of the month in which the...

  16. 22 CFR 19.9-2 - Commencement and termination.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... becomes entitled to a Foreign Service annuity or on the first day of the month in which the divorce... service; (2) The date the disability annuity begins; or (3) The first of the month in which the...

  17. 22 CFR 19.9-2 - Commencement and termination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... becomes entitled to a Foreign Service annuity or on the first day of the month in which the divorce... service; (2) The date the disability annuity begins; or (3) The first of the month in which the...

  18. Ca2+ current vs. Ca2+ channel cooperativity of exocytosis

    PubMed Central

    Matveev, Victor; Bertram, Richard; Sherman, Arthur

    2009-01-01

    Recently there has been significant interest and progress in the study of spatio-temporal dynamics of Ca2+ that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca2+ influx. While varying extracellular or intracellular Ca2+ concentration assesses the intrinsic biochemical Ca2+ cooperativity of neurotransmitter release, varying the number of open Ca2+ channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca2+ channels in triggering exocytosis. Despite the wide use of these Ca2+ sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca2+ sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca2+ current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca2+ current magnitude, and the underlying Ca2+ channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use 3D computational modeling of buffered Ca2+ diffusion to analyze these distinct Ca2+ cooperativity measures, and demonstrate the role of endogenous Ca2+ buffers on such measures. We show that buffers can either increase or decrease the Ca2+ current cooperativity of exocytosis, depending on their concentration and the single-channel Ca2+ current. PMID:19793978

  19. Measurement of CA1P and CA in leaves

    SciTech Connect

    Moore, B.d.; Kobza, J.; Seemann, J.R. )

    1990-05-01

    Carboxyarabinitol-1-phosphate (CA1P) and carboxyarabinitol (CA) were assayed in leaves by isotope dilution. {sup 14}C-labeled standards were synthesized from (2-{sup 14}C) CABP using acid (CA1P) or alkaline (CA) phosphatase. Either was added to boiling 80% EtOH along with liquid N{sub 2}-killed leaves. Each was largely purified by anion exchange chromatography. CA1P samples were subjected to 2D-TLE/TLC. The specific activity of the {sup 14}C-containing spot was measured using alkaline phosphatase. CA samples were run on an HPLC and the specific activity was determined using a UV monitor and a flow-through radioisotope detector. In 3 of the tested species, light/dark amount of CA1P (nmol/mg Chl) were kidney bean, 0.7/67; sugar beet, 0.8/33; and Alocasia, 0/3.4. Light/dark CA levels (nmol/mg Chl) in these respective species were 897/653, 3.2/3.5, and 5.7/4.6. These results support the hypothesis that CA is a product of CA1P metabolism in vivo under high light, but also indicate that CA is not the only intermediate involved in CA1P synthesis under low light/dark conditions.

  20. Ca isotope variations in Allende

    NASA Technical Reports Server (NTRS)

    Jungck, M. H. A.; Shimamura, T.; Lugmair, G. W.

    1984-01-01

    Ca-isotope measurements of Allende Ca-Al-rich inclusions (CAIs), together with those on an apatite-enriched fraction from Orgueil, indicate the existence of widespread excesses on the neutron-rich isotope Ca-48. Isotopic anomalies are noted in 7 out of 11 CAIs analyzed. This abundance of isotopic excesses places Ca alongside Ti and O, although no clear correlation has yet been found between Ca-48 and Ti-50, which are thought to be coproduced by neutron-rich nucleosynthetic processes within stars. It is suggested that the higher volatility of Ca, by comparison with Ti compounds, led to a variable dilution with isotopically normal Ca in vaporization and recondensation processes in stellar envelopes, the interstellar medium, and/or the solar nebula.

  1. Subplasma membrane Ca2+ signals.

    PubMed

    McCarron, John G; Chalmers, Susan; Olson, Marnie L; Girkin, John M

    2012-07-01

    Ca(2+) may selectively activate various processes in part by the cell's ability to localize changes in the concentration of the ion to specific subcellular sites. Interestingly, these Ca(2+) signals begin most often at the plasma membrane space so that understanding subplasma membrane signals is central to an appreciation of local signaling. Several experimental procedures have been developed to study Ca(2+) signals near the plasma membrane, but probably the most prevalent involve the use of fluorescent Ca(2+) indicators and fall into two general approaches. In the first, the Ca(2+) indicators themselves are specifically targeted to the subplasma membrane space to measure Ca(2+) only there. Alternatively, the indicators are allowed to be dispersed throughout the cytoplasm, but the fluorescence emanating from the Ca(2+) signals at the subplasma membrane space is selectively measured using high resolution imaging procedures. Although the targeted indicators offer an immediate appeal because of selectivity and ease of use, their limited dynamic range and slow response to changes in Ca(2+) are a shortcoming. Use of targeted indicators is also largely restricted to cultured cells. High resolution imaging applied with rapidly responding small molecule Ca(2+) indicators can be used in all cells and offers significant improvements in dynamic range and speed of response of the indicator. The approach is technically difficult, however, and realistic calibration of signals is not possible. In this review, a brief overview of local subplasma membrane Ca(2+) signals and methods for their measurement is provided.

  2. Coachella Valley, CA

    NASA Technical Reports Server (NTRS)

    2001-01-01

    These band composites, acquired on June 4, 2000, cover a 11 by 13.5 km sub-scene in the Coachella Valley, CA. The area is shown by the yellow box on the full scene in the LOWER RIGHT corner, northwest of the Salton Sea. This is a major agricultural region of California, growing fruit and produce throughout the year. Different combinations of ASTER bands help identify the different crop types. UPPER LEFT: bands 3, 2, 1 as red, green, and blue (RGB); UPPER RIGHT: bands 4, 2, 1 as RGB; LOWER LEFT: bands 4, 3, 2 as RGB. The image is centered at 33.6 degrees north latitude, 116.1 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  3. 2048 QAM (66 Gbit/s) single-carrier coherent optical transmission over 150 km with a potential SE of 15.3 bit/s/Hz.

    PubMed

    Beppu, Shohei; Kasai, Keisuke; Yoshida, Masato; Nakazawa, Masataka

    2015-02-23

    We describe a 2048 QAM single-carrier coherent optical transmission over 150 km in detail. The OSNR at the transmitter was increased by 5 dB and the phase noise at the receiver was reduced from 0.35 to 0.17 degrees compared with a previous 1024 QAM transmission. Furthermore, we employed an A/D converter with a higher ENOB (7 bit) to guarantee the SNR of the digital QAM data, and introduced a polarization-demultiplexing algorithm to fast track the polarization state transition. As a result, a 66 Gbit/s polarization-multiplexed 2048 QAM signal was successfully transmitted within an optical bandwidth of 3.6 GHz including a pilot tone, and a potential SE of 15.3 bit/s/Hz under a 20% FEC overhead was achieved.

  4. Genetic Variants at 6p21.1 and 7p15.3 Are Associated with Risk of Multiple Cancers in Han Chinese

    PubMed Central

    Jin, Guangfu; Ma, Hongxia; Wu, Chen; Dai, Juncheng; Zhang, Ruyang; Shi, Yongyong; Lu, Jiachun; Miao, Xiaoping; Wang, Meilin; Zhou, Yifeng; Chen, Jiaping; Li, Huizhang; Pan, Shandong; Chu, Minjie; Lu, Feng; Yu, Dianke; Jiang, Yue; Dong, Jing; Hu, Lingmin; Chen, Yijiang; Xu, Lin; Shu, Yongqian; Pan, Shiyang; Tan, Wen; Zhou, Baosen; Lu, Daru; Wu, Tangchun; Zhang, Zhengdong; Chen, Feng; Wang, Xinru; Hu, Zhibin; Lin, Dongxin; Shen, Hongbing

    2012-01-01

    Cancer susceptibility loci identified in reported genome-wide association studies (GWAS) are often tumor-specific; however, evidence of pleiotropy of some genes/loci has also been observed and biologically plausible. We hypothesized that there are important regions in the genome harboring genetic variants associated with risk of multiple types of cancer. In the current study, we attempted to map genetic variants that have consistent effects on risk of multiple cancers using our existing genome-wide scan data of lung cancer, noncardia gastric cancer, and esophageal squamous-cell carcinoma with overall 5,368 cases and 4,006 controls (GWAS stage), followed by a further evaluation in additional 9,001 cases with one of these cancer types and 11,436 controls (replication stage). Five variants satisfying the criteria of pleiotropy with p values from 1.10 × 10−8 to 8.96 × 10−6 for genome-wide scans of three cancer types were further evaluated in the replication stage. We found consistent associations of rs2494938 at 6p21.1 and rs2285947 at 7p15.3 with these three cancers in both GWAS and replication stages. In combined samples of GWAS and replication stages, the minor alleles of rs2494938 and rs2285947 were significantly associated with an increased risk of the cancers (odds ratio [OR] = 1.15, 95% confidence interval [CI], 1.10–1.19 and OR = 1.17, 95% CI, 1.12–1.21), with the p values being 1.20 × 10−12 and 1.26 × 10−16, respectively, which are at a genome-wide significance level. Our findings highlight the potential importance of variants at 6p21.1 and 7p15.3 in the susceptibility to multiple cancers. PMID:23103227

  5. The dynamics of mitochondrial Ca2+ fluxes.

    PubMed

    de la Fuente, Sergio; Montenegro, Pablo; Fonteriz, Rosalba I; Moreno, Alfredo; Lobatón, Carmen D; Montero, Mayte; Alvarez, Javier

    2010-10-01

    We have investigated the kinetics of mitochondrial Ca(2+) influx and efflux and their dependence on cytosolic [Ca(2+)] and [Na(+)] using low-Ca(2+)-affinity aequorin. The rate of Ca(2+) release from mitochondria increased linearly with mitochondrial [Ca(2+)] ([Ca(2+)](M)). Na(+)-dependent Ca(2+) release was predominant al low [Ca(2+)](M) but saturated at [Ca(2+)](M) around 400muM, while Na(+)-independent Ca(2+) release was very slow at [Ca(2+)](M) below 200muM, and then increased at higher [Ca(2+)](M), perhaps through the opening of a new pathway. Half-maximal activation of Na(+)-dependent Ca(2+) release occurred at 5-10mM [Na(+)], within the physiological range of cytosolic [Na(+)]. Ca(2+) entry rates were comparable in size to Ca(2+) exit rates at cytosolic [Ca(2+)] ([Ca(2+)](c)) below 7muM, but the rate of uptake was dramatically accelerated at higher [Ca(2+)](c). As a consequence, the presence of [Na(+)] considerably reduced the rate of [Ca(2+)](M) increase at [Ca(2+)](c) below 7muM, but its effect was hardly appreciable at 10muM [Ca(2+)](c). Exit rates were more dependent on the temperature than uptake rates, thus making the [Ca(2+)](M) transients to be much more prolonged at lower temperature. Our kinetic data suggest that mitochondria have little high affinity Ca(2+) buffering, and comparison of our results with data on total mitochondrial Ca(2+) fluxes indicate that the mitochondrial Ca(2+) bound/Ca(2+) free ratio is around 10- to 100-fold for most of the observed [Ca(2+)](M) range and suggest that massive phosphate precipitation can only occur when [Ca(2+)](M) reaches the millimolar range.

  6. Experimental and analytical analysis of stress-strain behavior in a (90/0 deg)2s, SiC/Ti-15-3 laminate

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.; Melis, Matthew E.; Tong, Mike

    1991-01-01

    The nonlinear stress strain behavior of 90 degree/0 degree sub 2s, SiC/Ti-15-3 composite laminate was numerically investigated with a finite element, unit cell approach. Tensile stress-strain curves from room temperature experiments depicted three distinct regions of deformation, and these regions were predicted by finite element analysis. The first region of behavior, which was linear elastic, occurred at low applied stresses. As applied stresses increased, fiber/matrix debonding in the 90 degree plies caused a break in the stress-strain curve and initiated a second linear region. In this second region, matrix plasticity in the 90 degree plies developed. The third region, which was typified by nonlinear, stress-strain behavior occr red at high stresses. In this region, the onset of matrix plasticity in the 0 degree plies stiffened the laminate in the direction transverse to the applied load. Metallographic sections confirmed the existence of matrix plasticity in specific areas of the structure. Finite element analysis also predicted these locations of matrix slip.

  7. CaPTC Biennial Meetings

    Cancer.gov

    CaPTC hosts the 'Biennial Science of Global Prostate Cancer Disparities in Black Men' conference to address the growing global public health problem of prostate cancer among Black men in industrialized and developing countries.

  8. Cathodic behavior of molten CaCl2-CaO and CaCl2-NaCl-CaO

    NASA Astrophysics Data System (ADS)

    Wang, Shu-Lan; Wang, Wei; Li, Shi-Chao; Cao, Shan-Hui

    2010-12-01

    The cathodic behavior of molten CaCl2, CaCl2-CaO and equimolar CaCl2-NaCl-CaO was studied by cyclic voltammograms and constant potential polarization at temperatures of 1123 to 1173 K on molybdenum and titanium electrodes. The diffusion coefficient of Ca2+ (CaO) in molten CaCl2-CaO was calculated from the linear relationship between the square root of scan rate and the peak current density. The deposition potentials and the potential temperature coefficient of CaO in molten CaCl2-0.5mol%CaO and CaCl2-NaCl-0.5mol%CaO were also obtained from their cyclic voltammograms. The result shows that CaO is more easily reduced than CaCl2. The addition of NaCl in molten CaCl2-CaO induces the underpotential electrodeposition of CaO.

  9. Genetic variants at 6p21.1 and 7p15.3 Identified by GWASs of multiple cancers and ovarian cancer risk: a case-control study in Han Chinese women.

    PubMed

    Li, Da-Ke; Han, Jing; Liu, Ji-Bin; Jin, Guang-Fu; Qu, Jun-Wei; Zhu, Meng; Wang, Yan-Ru; Jiang, Jie; Ma, Hong-Xia

    2014-01-01

    A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers.

  10. 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

  11. Ca2+ waves in the heart

    PubMed Central

    Izu, Leighton T.; Xie, Yuanfang; Sato, Daisuke; Bányász, Tamás; Chen-Izu, Ye

    2013-01-01

    Ca2+ waves were probably first observed in the early 1940s. Since then Ca2+ waves have captured the attention of an eclectic mixture of mathematicians, neuroscientists, muscle physiologists, developmental biologists, and clinical cardiologists. This review discusses the current state of mathematical models of Ca2+ waves, the normal physiological functions Ca2+ waves might serve in cardiac cells, as well as how the spatial arrangement of Ca2+ release channels shape Ca2+ waves, and we introduce the idea of Ca2+ phase waves that might provide a useful framework for understanding triggered arrhythmias. This article is part of a Special Issue entitled ‘Calcium Signaling in Heart’. PMID:23220129

  12. Large Ca2+-dependent facilitation of CaV2.1 channels revealed by Ca2+ photo-uncaging

    PubMed Central

    Lee, Shin-Rong; Adams, Paul J; Yue, David T

    2015-01-01

    Key points CaV2.1 channels constitute a dominant Ca2+ entry pathway into brain neurons, triggering downstream Ca2+-dependent processes such as neurotransmitter release. CaV2.1 is itself modulated by Ca2+, resulting in activity-dependent enhancement of channel opening termed Ca2+-dependent facilitation (CDF). Real-time Ca2+ imaging and Ca2+ uncaging here reveal that CDF turns out to be strikingly faster, more Ca2+ sensitive, and larger than anticipated on previous grounds. Robust resolution of the quantitative profile of CDF enables deduction of a realistic biophysical model for this process. These results suggest that CaV2.1 CDF would figure most prominently in short-term synaptic plasticity and cerebellar Purkinje cell rhythmicity. Abstract CaV2.1 (P-type) voltage-gated Ca2+ channels constitute a major source of neuronal Ca2+ current, strongly influencing rhythmicity and triggering neurotransmitter release throughout the central nervous system. Fitting with such stature among Ca2+ entry pathways, CaV2.1 is itself feedback regulated by intracellular Ca2+, acting through calmodulin to facilitate channel opening. The precise neurophysiological role of this calcium-dependent facilitation (CDF) remains uncertain, however, in large measure because the very magnitude, Ca2+ dependence and kinetics of CDF have resisted quantification by conventional means. Here, we utilize the photo-uncaging of Ca2+ with CaV2.1 channels fluxing Li+ currents, so that voltage-dependent activation of channel gating is no longer conflated with Ca2+ entry, and CDF is then driven solely by light-induced increases in Ca2+. By using this strategy, we now find that CDF can be unexpectedly large, enhancing currents by as much as twofold at physiological voltages. CDF is steeply Ca2+ dependent, with a Hill coefficient of approximately two, a half-maximal effect reached by nearly 500 nm Ca2+, and Ca2+ on/off kinetics in the order of milliseconds to tens of milliseconds. These properties were

  13. Multiple Ca2+ Binding Sites in the Extracellular Domain of Ca2+-Sensing Receptor Corresponding to Cooperative Ca2+ Response†

    PubMed Central

    Huang, Yun; Zhou, Yubin; Castiblanco, Adriana; Yang, Wei; Brown, Edward M.; Yang, Jenny J.

    2009-01-01

    A small change in the extracellular Ca2+ concentration ([Ca2+]o) integrates cell signaling responses in multiple cellular and tissue networks and functions via activation of Ca2+-sensing receptors (CaSR). Mainly through binding of Ca2+ to the large extracellular domain (ECD) of the dimeric CaSR, intracellular Ca2+ responses are highly cooperative with an apparent Hill coefficient ranging from 2 to 4. We have previously reported the identification of two continuous putative Ca2+-binding sites by grafting CaSR-derived, Ca2+-binding peptides to a scaffold protein, CD2, that does not bind Ca2+. In this paper, we predict more potential non-continuous Ca2+-binding sites in the ECD. We dissect the intact CaSR into three globular subdomains, each of which contains 2 to 3 predicted Ca2+-binding sites. This approach enables us to further understand the mechanisms underlying the binding of multiple metal ions to extended polypeptides derived from within the ECD of the CaSR, which would be anticipated to more closely mimic the structure of the native CaSR ECD. Tb3+-luminescence energy transfer, ANS fluorescence, and NMR studies show biphasic metal-binding components and Ca2+-dependent conformational changes in these subdomains. Removing the predicted Ca2+-binding ligands in site 1 and site 3 abolishes the first binding step and second binding step, respectively. Studies on these subdomains suggest the existence of multiple metal-binding sites and metal-induced conformational changes that might be responsible for switching on/off the CaSR by transition between its open inactive form and closed active form. PMID:19102677

  14. Electrocaloric Effect of Lead-Free (Ba,Ca)(Zr,Ti)O3 Ferroelectric Ceramic

    NASA Astrophysics Data System (ADS)

    Kim, You Seok; Yoo, Juhyun

    2015-08-01

    In this study, (Ba,Ca)(Zr,Ti)O3 ferroelectric ceramic was fabricated by a conventional solid-state reaction process. The electrocaloric effect was investigated using P- E hysteresis loop characteristics in a wide temperature range from room temperature to 135°C. The results showed that the temperature change Δ T could be calculated as a function of temperature using Maxwell's relation, reaching a maximum value of ~0.096°C at 110°C under an applied electric field of 15.3 kV/cm.

  15. Solar Ca II K Observations

    NASA Astrophysics Data System (ADS)

    Bertello, Luca; Pevtsov, Alexei A.; Tlatov, Andrey; Singh, Jagdev

    2016-07-01

    Some of the most important archives of past and current long-term solar synoptic observations in the resonance line of Ca II K are described here. These observations are very important for understanding the state of the solar magnetism on time scales up to several decades. The first observations of this kind began in 1904 at the Kodaikanal Observatory (India), followed by similar programs at different other locations. Regular full-disk Ca II K monitoring programs started in 1915 at the Mount Wilson Observatory (USA) and in 1917 at the National Solar Observatory of Japan. Beginning in 1919 and in 1926 regular observations were taken also at the Paris-Meudon Observatory (France) and at the "Donati solar tower telescope of the Arcetri Astrophysical Observatory in Italy, respectively. In 1926 the the Astronomical Observatory of the Coimbra University in Portugal started its own program of Ca II K observations. Although some of these programs have been terminated over the years, their data archives constitute a unique resource for studies of solar variability. In the early 1970s, the National Solar Observatory (NSO) at Sacramento Peak (USA) started a new program of daily Sun-as-a-star observations in the Ca II K line. Today the NSO is continuing these observations through its Synoptic Optical Long-term Investigations of the Sun (SOLIS) facility.

  16. Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations

    PubMed Central

    Ishii, Kiyoaki; Hirose, Kenzo; Iino, Masamitsu

    2006-01-01

    Although many cell functions are regulated by Ca2+ oscillations induced by a cyclic release of Ca2+ from intracellular Ca2+ stores, the pacemaker mechanism of Ca2+ oscillations remains to be explained. Using green fluorescent protein-based Ca2+ indicators that are targeted to intracellular Ca2+ stores, the endoplasmic reticulum (ER) and mitochondria, we found that Ca2+ shuttles between the ER and mitochondria in phase with Ca2+ oscillations. Following agonist stimulation, Ca2+ release from the ER generated the first Ca2+ oscillation and loaded mitochondria with Ca2+. Before the second Ca2+ oscillation, Ca2+ release from the mitochondria by means of the Na+/Ca2+ exchanger caused a gradual increase in cytoplasmic Ca2+ concentration, inducing a regenerative ER Ca2+ release, which generated the peak of Ca2+ oscillation and partially reloaded the mitochondria. This sequence of events was repeated until mitochondrial Ca2+ was depleted. Thus, Ca2+ shuttling between the ER and mitochondria may have a pacemaker role in the generation of Ca2+ oscillations. PMID:16415789

  17. The Banhadão Alkaline Complex, Southeastern Brazil: source and evolution of potassic SiO2-undersaturated high-Ca and low-Ca magmatic series

    NASA Astrophysics Data System (ADS)

    Ruberti, Excelso; Enrich, Gaston E. R.; Azzone, Rogério G.; Comin-Chiaramonti, Piero; de Min, Angelo; Gomes, Celso B.

    2012-01-01

    The Cretaceous Banhadão alkaline complex in southeastern Brazil presents two potassic SiO2-undersaturated series. The high-Ca magmatic series consist of initially fractionated olivine (Fo92-91) + diopside (Wo48-43En49-35Ae0-7), as evidenced by the presence of xenocrysts and xenoliths. In that sequence, diopside (Wo47-38En46-37Ae0-8) + phlogopite + apatite + perovskite (Prv>92) crystallized to form the phlogopite melteigite and led to the Ca enrichment of the magma. Diopside (Wo47-41En32-24 Ae3-14) continued to crystallize as an early mafic mineral, followed by nepheline (Ne74.8-70.1Ks26.3-21.2Qz7.6-0.9) and leucite (Lc65-56) and subsequently by melanite and potassic feldspar (Or85-99Ab1-7) to form melanite ijolites, wollastonite-melanite urtites and melanite-nepheline syenites. Melanite-pseudoleucite-nepheline syenites are interpreted to be a leucite accumulation. Melanite nephelinite dykes are believed to represent some of the magmatic differentiation steps. The low-Ca magmatic series is representative of a typical fractionation of aegirine-augite (Wo36-29En25-4Ae39-18) + alkali feldspar (Or57-96Ab3-43) + nepheline (Ne76.5-69.0Ks19.9-14.4Qz15.1-7.7) + titanite from phonolite magma. The evolution of this series from potassic nepheline syenites to sodic sodalite syenites and sodalitolites is attributed to an extensive fractionation of potassic feldspar, which led to an increase of the NaCl activity in the melt during the final stages forming sodalite-rich rocks. Phonolite dykes followed a similar evolutionary process and also registered some crustal assimilation. The mesocratic nepheline syenites showed interactions with phlogopite melteigites, such as compatible trace element enrichments and the presence of diopside xenocrysts, which were interpreted to be due to a mixing/mingling process of phonolite and nephelinite magmas. The geochemical data show higher TiO2 and P2O5 contents and lower SiO2 contents for the high-Ca series and different LILE evolution trends

  18. Decoding Ca2+ signals in plants

    NASA Technical Reports Server (NTRS)

    Sathyanarayanan, P. V.; Poovaiah, B. W.

    2004-01-01

    Different input signals create their own characteristic Ca2+ fingerprints. These fingerprints are distinguished by frequency, amplitude, duration, and number of Ca2+ oscillations. Ca(2+)-binding proteins and protein kinases decode these complex Ca2+ fingerprints through conformational coupling and covalent modifications of proteins. This decoding of signals can lead to a physiological response with or without changes in gene expression. In plants, Ca(2+)-dependent protein kinases and Ca2+/calmodulin-dependent protein kinases are involved in decoding Ca2+ signals into phosphorylation signals. This review summarizes the elements of conformational coupling and molecular mechanisms of regulation of the two groups of protein kinases by Ca2+ and Ca2+/calmodulin in plants.

  19. Ca2+ dynamics in zebrafish morphogenesis

    PubMed Central

    Tsutsui, Kenta; Ogawa, Tomohisa

    2017-01-01

    Intracellular calcium ion (Ca2+) signaling is heavily involved in development, as illustrated by the use of a number of Ca2+ indicators. However, continuous Ca2+ patterns during morphogenesis have not yet been studied using fluorescence resonance energy transfer to track the Ca2+ sensor. In the present study, we monitored Ca2+ levels during zebrafish morphogenesis and differentiation with yellow cameleon, YC2.12. Our results show not only clear changes in Ca2+ levels but also continuous Ca2+ patterns at 24 hpf and later periods for the first time. Serial Ca2+dynamics during early pharyngula period (Prim-5-20; 24–33 hpf) was successfully observed with cameleon, which have not reported anywhere yet. In fact, high Ca2+ level occurred concurrently with hindbrain development in segmentation and pharyngula periods. Ca2+ patterns in the late gastrula through segmentation periods which were obtained with cameleon, were similar to those obtained previously with other Ca2+sensor. Our results suggested that the use of various Ca2+ sensors may lead to novel findings in studies of Ca2+ dynamics. We hope that these results will prove valuable for further research in Ca2+ signaling. PMID:28133572

  20. CaFe interstellar clouds

    NASA Astrophysics Data System (ADS)

    Bondar, A.; Kozak, M.; Gnaciński, P.; Galazutdinov, G. A.; Beletsky, Y.; Krełowski, J.

    2007-07-01

    A new kind of interstellar cloud is proposed. These are rare (just a few examples among ~300 lines of sight) objects with the CaI 4227-Å, FeI 3720-Å and 3860-Å lines stronger than those of KI (near 7699 Å) and NaI (near 3302 Å). We propose the name `CaFe' for these clouds. Apparently they occupy different volumes from the well-known interstellar HI clouds where the KI and ultraviolet NaI lines are dominant features. In the CaFe clouds we have not found either detectable molecular features (CH, CN) or diffuse interstellar bands which, as commonly believed, are carried by some complex, organic molecules. We have found the CaFe clouds only along sightlines toward hot, luminous (and thus distant) objects with high rates of mass loss. In principle, the observed gas-phase interstellar abundances reflect the combined effects of the nucleosynthetic history of the material, the depletion of heavy elements into dust grains and the ionization state of these elements which may depend on irradiation by neighbouring stars. Based on data collected using the Maestro spectrograph at the Terskol 2-m telescope, Russia; and on data collected using the ESO Feros spectrograph; and on data obtained from the ESO Science Archive Facility acquired with the UVES spectrograph, Chile. E-mail: `arctur'@rambler.ru (AB); marizak@astri.uni.torun.pl (MK); pg@iftia.univ.gda.pl (PG); gala@boao.re.kr (GAG); ybialets@eso.org (YB); jacek@astri.uni.torun.pl (JK)

  1. Carcinogenesis of PIK3CA

    PubMed Central

    2013-01-01

    PIK3CA is the most frequently mutated oncogene in human cancers. PIK3CA is phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha. It controls cell growth, proliferation, motility, survival, differentiation and intracellular trafficking. In most of human cancer alteration occurred frequently in the alpha isoform of phosphatidylinositol 3 kinase. PIK3CA mutations were most frequent in endometrial, ovarian, colorectal, breast, cervical, squamous cell cancer of the head and neck, chondroma, thyroid carcinoma and in cancer family syndrome. Inhibition of PI3K signaling can diminish cell proliferation, and in some circumstances, promote cell death. Consequently, components of this pathway present attractive targets for cancer therapeutics. A number of PI3K pathway inhibitors have been developed and used. PI3K inhibitors (both pan-PI3K and isoform-specific PI3K inhibitors), dual PI3K-mTOR inhibitors that are catalytic site inhibitors of the p110 isoforms and mTOR (the kinase component of both mTORC1 and mTORC2), mTOR catalytic site inhibitors, and AKT inhibitors are the most advanced in the clinic. They are approved for the treatment of several carcinomas. PMID:23768168

  2. Calmodulin Regulates Ca2+-sensing Receptor-mediated Ca2+ Signaling and Its Cell Surface Expression*

    PubMed Central

    Huang, Yun; Zhou, Yubin; Wong, Hing-Cheung; Castiblanco, Adriana; Chen, Yanyi; Brown, Edward M.; Yang, Jenny J.

    2010-01-01

    The Ca2+-sensing receptor (CaSR) is a member of family C of the GPCRs responsible for sensing extracellular Ca2+ ([Ca2+]o) levels, maintaining extracellular Ca2+ homeostasis, and transducing Ca2+ signaling from the extracellular milieu to the intracellular environment. In the present study, we have demonstrated a Ca2+-dependent, stoichiometric interaction between CaM and a CaM-binding domain (CaMBD) located within the C terminus of CaSR (residues 871–898). Our studies suggest a wrapping around 1–14-like mode of interaction that involves global conformational changes in both lobes of CaM with concomitant formation of a helical structure in the CaMBD. More importantly, the Ca2+-dependent association between CaM and the C terminus of CaSR is critical for maintaining proper responsiveness of intracellular Ca2+ responses to changes in extracellular Ca2+ and regulating cell surface expression of the receptor. PMID:20826781

  3. Evolution of Seawater 44Ca/40Ca Through the Late Cretaceous and Cenozoic

    NASA Astrophysics Data System (ADS)

    Castillo, P. R.; Gopalan, K.; Norris, R. D.; MacIsaac, C.; Liu, X.; MacDougall, J. D.

    2009-12-01

    We analyzed the Ca concentrations and 44Ca/40Ca ratios of surface ocean planktonic (Morozovella, Acarinina, Dentoglobigerina) and benthic (Gavelinella) foraminifera of Late Cretaceous to Late Oligocene ages from DSDP and ODP sites in the Pacific, Atlantic and Indian oceans in order to fill a major gap in the Phanerozoic seawater 44Ca/40Ca curve (Farkass et al., Geochim. Cosmochim. Acta 71, 2007). Our new 44Ca/40Ca data indicate a general increase in foraminiferan-based seawater 44Ca/40Ca from ~-1.3 ‰ δ44Ca/40CaSW in Late Cretaceous to ~0.0 ‰ δ44Ca/40CaSW in Early Miocene (Heuser et al., Paleocean. 20, 2005; Sime et al., Geochim. Cosmochim. Acta 71, 2007). In detail, the 44Ca/40Ca ratio stepped abruptly from ~-1.3 ‰ δ44Ca/40CaSW to a slightly higher value of ~-1.1 ‰ δ44Ca/40CaSW across the Cretaceous-Tertiary (K/T) boundary. A slight positive excursion of ~0.2 ‰ above the background value occurred after the Paleocene Thermal Maximum (55 Ma) but otherwise, the Paleocene to Middle Eocene ratio is relatively stable at ~-1.0 ‰ δ44Ca/40CaSW. The most prominent increase in foraminiferan-based seawater 44Ca/40Ca occurred from Late Eocene to Late Oligocene, roughly coincident with the initial phase of the rapid and steady rise of marine carbonate 87Sr/86Sr ratio in the Tertiary (e.g., DePaolo and Ingram, Science 227, 1985).

  4. Cell biology of Ca2+-triggered exocytosis.

    PubMed

    Pang, Zhiping P; Südhof, Thomas C

    2010-08-01

    Ca(2+) triggers many forms of exocytosis in different types of eukaryotic cells, for example synaptic vesicle exocytosis in neurons, granule exocytosis in mast cells, and hormone exocytosis in endocrine cells. Work over the past two decades has shown that synaptotagmins function as the primary Ca(2+)-sensors for most of these forms of exocytosis, and that synaptotagmins act via Ca(2+)-dependent interactions with both the fusing phospholipid membranes and the membrane fusion machinery. However, some forms of Ca(2+)-induced exocytosis may utilize other, as yet unidentified Ca(2+)-sensors, for example, slow synaptic exocytosis mediating asynchronous neurotransmitter release. In the following overview, we will discuss the synaptotagmin-based mechanism of Ca(2+)-triggered exocytosis in neurons and neuroendocrine cells, and its potential extension to other types of Ca(2+)-stimulated exocytosis for which no synaptotagmin Ca(2+)-sensor has been identified.

  5. Fine tuning of cytosolic Ca 2+ oscillations

    PubMed Central

    Dupont, Geneviève; Combettes, Laurent

    2016-01-01

    Ca 2+ oscillations, a widespread mode of cell signaling, were reported in non-excitable cells for the first time more than 25 years ago. Their fundamental mechanism, based on the periodic Ca 2+ exchange between the endoplasmic reticulum and the cytoplasm, has been well characterized. However, how the kinetics of cytosolic Ca 2+ changes are related to the extent of a physiological response remains poorly understood. Here, we review data suggesting that the downstream targets of Ca 2+ are controlled not only by the frequency of Ca 2+ oscillations but also by the detailed characteristics of the oscillations, such as their duration, shape, or baseline level. Involvement of non-endoplasmic reticulum Ca 2+ stores, mainly mitochondria and the extracellular medium, participates in this fine tuning of Ca 2+ oscillations. The main characteristics of the Ca 2+ exchange fluxes with these compartments are also reviewed. PMID:27630768

  6. [Effect of polycarbophil Ca on IBS].

    PubMed

    Mine, Tetsuya

    2006-08-01

    In this chapter, I mentioned the effect of polycarbophil Ca on IBS. IBS is classified into 3 types; diarrhea type, constipation type and combined type. Polycarbophil Ca is effective for all types of IBS.

  7. CaMKII regulates intracellular Ca²⁺ dynamics in native endothelial cells.

    PubMed

    Toussaint, Fanny; Charbel, Chimène; Blanchette, Alexandre; Ledoux, Jonathan

    2015-09-01

    Localized endothelial Ca(2+) signalling, such as Ca(2+) pulsars, can modulate the contractile state of the underlying vascular smooth muscle cell through specific endothelial targets. In addition to K(Ca)3.1 as a target, Ca(2+) pulsars, an IP3R-dependent pulsatile Ca(2+) release from the endoplasmic reticulum (ER) could activate a frequency-sensitive Ca(2+)-dependent kinase such as CaMKII. In the absence of extracellular Ca(2+), acetylcholine increased endothelial CaMKII phosphorylation and activation, thereby suggesting CaMKII activation independently of Ca(2+) influx. Herein, a reciprocal relation where CaMKII controls endothelial Ca(2+) dynamics has been investigated in mesenteric arteries. Both CaMKIIα and β isoforms have been identified in endothelial cells and close proximity (<40 nm) suggests their association in heteromultimers. Intracellular Ca(2+) monitoring with high speed confocal microscopy then showed that inhibition of CaMKII with KN-93 significantly increased the population of Ca(2+) pulsars active sites (+89%), suggesting CaMKII as a major regulator of Ca(2+) pulsars in native endothelium. Mechanistic insights were then sought through the elucidation of the impact of CaMKII on ER Ca(2+) store. ER Ca(2+) emptying was accelerated by CaMKII inhibition and ER Ca(2+) content was assessed using ionomycin. Exposure to KN-93 strongly diminished ER Ca(2+) content (-61%) by relieving CaMKII-dependent inhibition of IP3 receptors (IP3R). Moreover, in situ proximity ligation assay suggested CaMKII-IP3R promiscuity, essential condition for a protein-protein interaction. Interestingly, segregation of IP3R within myoendothelial projection (MEP) appears to be isoform-specific. Hence, only IP3R type 1 and type 2 are detected within fenestrations of the internal elastic lamina, sites of MEP, whilst type 3 is absent from these structures. In summary, CaMKII seems to act as a Ca(2+)-sensitive switch of a negative feedback loop regulating endothelial Ca(2

  8. Mojave Toxin: A Selective Ca(++) Channel Antagonist

    DTIC Science & Technology

    1988-07-01

    other than maitotoxin, blocking 3H-nitrendipine binding to the high affinity dihydropyridine receptor associated with the Ca++ channel, as well as... dihydropyridine receptors in rat synaptic membranes suggests that this toxin may be a useful proble of the Ca++ channel complex. It is not certain whether MoTX has...increase in intracellular Ca++ resulting from the binding of the toxin to dihydropyridine receptors coupled to Ca++ channels. The resolution of this

  9. Preoperative CA125 and fibrinogen in patients with endometrial cancer: a risk model for predicting lymphovascular space invasion

    PubMed Central

    2017-01-01

    Objective The aim of this study was to build a model to predict the risk of lymphovascular space invasion (LVSI) in women with endometrial cancer (EC). Methods From December 2010 to June 2013, 211 patients with EC undergoing surgery at Shanghai First Maternity and Infant Hospital were enrolled in this retrospective study. Those patients were divided into a positive LVSI group and a negative LVSI group. The clinical and pathological characteristics were compared between the two groups; logistic regression was used to explore risk factors associated with LVSI occurrence. The threshold values of significant factors were calculated to build a risk model and predict LVSI. Results There were 190 patients who were negative for LVSI and 21 patients were positive for LVSI out of 211 patients with EC. It was found that tumor grade, depth of myometrial invasion, number of pelvic lymph nodes, and International Federation of Gynecology and Obstetrics (FIGO) stage (p<0.05) were associated with LVSI occurrence. However, cervical involvement and age (p>0.05) were not associated with LVSI. Receiver operating characteristic (ROC) curves revealed that the threshold values of the following factors were correlated with positive LVSI: 28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL of carcinoembryonic antigen (CEA) and (6.35×109)/L of white blood cell (WBC). Logistic regression analysis indicated that CA125 ≥21.2 (p=0.032) and Fn ≥2.58 mg/dL (p=0.014) were significantly associated with LVSI. Conclusion Positive LVSI could be predicted by CA125 ≥21.2 U/mL and Fn ≥2.58 mg/dL in women with EC. It could help gynecologists better adapt surgical staging and adjuvant therapies. PMID:27894164

  10. Mission CaMKIIγ: shuttle calmodulin from membrane to nucleus.

    PubMed

    Malik, Zulfiqar A; Stein, Ivar S; Navedo, Manuel F; Hell, Johannes W

    2014-10-09

    Neuronal plasticity depends on plasma membrane Ca(2+) influx, resulting in activity-dependent gene transcription. Calmodulin (CaM) activated by Ca(2+) initiates the nuclear events, but how CaM makes its way to the nucleus has remained elusive. Ma et al. now show that CaMKIIγ transports CaM from cell surface Ca(2+) channels to the nucleus.

  11. Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

    PubMed

    de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

    2016-11-01

    Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9.

  12. [Regulation of the Na/Ca exchanger].

    PubMed

    DiPolo, R; Rojas, H; Beaugé, L

    1993-01-01

    The introduction of the squid giant axon preparation to studies on Ca homeostasis has proven very useful in laying the foundations in the study of Ca regulation. In particular the Na/Ca exchange mechanism has been characterized in terms of its regulatory processes using the well define technique of intracellular dialysis and membrane potential control. The Na/Ca exchange countertransport system plays a critical role in physiological processes including cardiac contractility and photoreception. It has also been implicate in the etiology of essential hypertension, cardiac arrhythmias and cell death. The ability of the Na/Ca exchanger to regulate the intracellular ionized Ca concentration ([Ca2+i]) under physiological conditions, is determined by the direction (net Ca efflux or Ca influx), and magnitude of transport. The direction of Ca transport is decided by the chemical gradient of sodium and calcium. The magnitude of the exchange is regulated by kinetic factors. This kinetic factors are critical since they decide whether the exchanger will mediate a net Ca movement under certain conditions. Recently, a large effort has been put together to characterize the secondary modulation of the Na/Ca exchanger. In particular modulation by MgATP and intracellular Ca2+. In nerve cells we have discover that MgATP regulates the exchanger through as phosphorylation-dephosphorylation processes most probably relate to the action of a kinase-phosphatase system. The other important ligand that regulates the exchange activity is the level of [Ca2+i]. We have found the presence of a regulatory site in the cytoplasmic face of the exchanger different from the transport site and probably responsible for turning the carrier "on" or "off". In this article we will depict some of the processes involved in the metabolic and ionic regulation of the Na/Ca exchanger.

  13. Separate Ca2+ sources are buffered by distinct Ca2+ handling systems in aplysia neuroendocrine cells.

    PubMed

    Groten, Christopher J; Rebane, Jonathan T; Blohm, Gunnar; Magoski, Neil S

    2013-04-10

    Although the contribution of Ca(2+) buffering systems can vary between neuronal types and cellular compartments, it is unknown whether distinct Ca(2+) sources within a neuron have different buffers. As individual Ca(2+) sources can have separate functions, we propose that each is handled by unique systems. Using Aplysia californica bag cell neurons, which initiate reproduction through an afterdischarge involving multiple Ca(2+)-dependent processes, we investigated the role of endoplasmic reticulum (ER) and mitochondrial sequestration, as well as extrusion via the plasma membrane Ca(2+)-ATPase (PMCA) and Na(+)/Ca(2+) exchanger, to the clearance of voltage-gated Ca(2+) influx, Ca(2+)-induced Ca(2+)-release (CICR), and store-operated Ca(2+) influx. Cultured bag cell neurons were filled with the Ca(2+) indicator, fura-PE3, to image Ca(2+) under whole-cell voltage clamp. A 5 Hz, 1 min train of depolarizing voltage steps elicited voltage-gated Ca(2+) influx followed by EGTA-sensitive CICR from the mitochondria. A compartment model of Ca(2+) indicated the effect of EGTA on CICR was due to buffering of released mitochondrial Ca(2+) rather than uptake competition. Removal of voltage-gated Ca(2+) influx was dominated by the mitochondria and PMCA, with no contribution from the Na(+)/Ca(2+) exchanger or sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA). In contrast, CICR recovery was slowed by eliminating the Na(+)/Ca(2+) exchanger and PMCA. Last, store-operated influx, evoked by ER depletion, was removed by the SERCA and depended on the mitochondrial membrane potential. Our results demonstrate that distinct buffering systems are dedicated to particular Ca(2+) sources. In general, this may represent a means to differentially regulate Ca(2+)-dependent processes, and for Aplysia, influence how reproductive behavior is triggered.

  14. Ca2+ Cycling in Heart Failure

    PubMed Central

    Luo, Min; Anderson, Mark E.

    2013-01-01

    Ca2+ plays a crucial role in connecting membrane excitability with contraction in myocardium. The hallmark features of heart failure are mechanical dysfunction and arrhythmias; defective intracellular Ca2+ homeostasis is a central cause of contractile dysfunction and arrhythmias in failing myocardium. Defective Ca2+ homeostasis in heart failure can result from pathological alteration in the expression and activity of an increasingly understood collection of Ca2+ homeostatic binding proteins, ion channels and enzymes. This review focuses on the molecular mechanisms of defective Ca2+ cycling in heart failure and consider how fundamental understanding of these pathways may translate into novel and innovative therapies. PMID:23989713

  15. Distinct Roles for Dorsal CA3 and CA1 in Memory for Sequential Nonspatial Events

    ERIC Educational Resources Information Center

    Farovik, Anja; Dupont, Laura M.; Eichenbaum, Howard

    2010-01-01

    Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of…

  16. Ca2+ sensor proteins in dendritic spines: a race for Ca2+

    PubMed Central

    Raghuram, Vijeta; Sharma, Yogendra; Kreutz, Michael R.

    2012-01-01

    Dendritic spines are believed to be micro-compartments of Ca2+ regulation. In a recent study, it was suggested that the ubiquitous and evolutionarily conserved Ca2+ sensor, calmodulin (CaM), is the first to intercept Ca2+ entering the spine and might be responsible for the fast decay of Ca2+ transients in spines. Neuronal calcium sensor (NCS) and neuronal calcium-binding protein (nCaBP) families consist of Ca2+ sensors with largely unknown synaptic functions despite an increasing number of interaction partners. Particularly how these sensors operate in spines in the presence of CaM has not been discussed in detail before. The limited Ca2+ resources and the existence of common targets create a highly competitive environment where Ca2+ sensors compete with each other for Ca2+ and target binding. In this review, we take a simple numerical approach to put forth possible scenarios and their impact on signaling via Ca2+ sensors of the NCS and nCaBP families. We also discuss the ways in which spine geometry and properties of ion channels, their kinetics and distribution, alter the spatio-temporal aspects of Ca2+ transients in dendritic spines, whose interplay with Ca2+ sensors in turn influences the race for Ca2+. PMID:22586368

  17. Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients

    PubMed Central

    Zhao, Song; Mei, Yu; Wang, Yongmei; Zhu, Jiang; Zheng, Guixi; Ma, Rong

    2015-01-01

    The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations. PMID:26885008

  18. Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients.

    PubMed

    Zhao, Song; Mei, Yu; Wang, Yongmei; Zhu, Jiang; Zheng, Guixi; Ma, Rong

    2015-01-01

    The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations.

  19. Adenosine stimulates Ca2+ fluxes and increases cytosolic free Ca2+ in cultured rat mesangial cells.

    PubMed Central

    Olivera, A; López-Rivas, A; López-Novoa, J M

    1992-01-01

    Adenosine has been associated with cellular Ca2+ metabolism in some cell types. Since adenosine is able to contract glomerular mesangial cells in culture, and since Ca2+ is the main messenger mediating contractile responses, we studied the effect of adenosine on 45Ca2+ movements into and out of mesangial cells and on the cytosolic free Ca2+ concentration ([Ca2+]i). Adenosine at 0.1 mM increased 45Ca2+ uptake (basal, 9993 +/- 216; + adenosine, 14823 +/- 410 d.p.m./mg; P less than 0.01) through verapamil-sensitive Ca2+ channels. These channels seem to be of the A1-adenosine receptor subtype. Adenosine also stimulated 45Ca2+ efflux from 45Ca(2+)-loaded mesangial cells. This effect was accompanied by a net depletion of intracellular 45Ca2+ content under isotopic equilibrium conditions (basal, 24213 +/- 978; + adenosine, 18622 +/- 885 d.p.m./mg; P less than 0.05). The increase in 45Ca2+ efflux was inhibited by a Ca(2+)-free medium or in the presence of 10 microM-verapamil. However, the intracellular Ca(2+)-release blocker TMB-8 (10 microM) only partially inhibited the adenosine-stimulated 45Ca2+ efflux. In addition, adenosine induced an elevation in [Ca2+]i in mesangial cells with an initial transient peak within 15 s (basal, 113 +/- 7; adenosine, 345 +/- 46 nM), and a secondary increase which was slower (3-4 min) and of lower magnitude than the initial peak (250 +/- 21 nM). In summary, adenosine elevates [Ca2+]i and stimulates both Ca2+ uptake from the extracellular pool and Ca2+ efflux from intracellular pools in mesangial cells. The Ca2+ release from internal stores is produced by a combination of a TMB-8-inhibitable and a non-TMB-8-inhibitable mechanism, and seems to be dependent on Ca2+ influx. PMID:1554371

  20. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength.

    PubMed

    Barcomb, Kelsey; Buard, Isabelle; Coultrap, Steven J; Kulbe, Jacqueline R; O'Leary, Heather; Benke, Timothy A; Bayer, K Ulrich

    2014-08-01

    A hallmark feature of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is generation of autonomous (Ca(2+)-independent) activity by T286 autophosphorylation. Biochemical studies have shown that "autonomous" CaMKII is ∼5-fold further stimulated by Ca(2+)/CaM, but demonstration of a physiological function for such regulation within cells has remained elusive. In this study, CaMKII-induced enhancement of synaptic strength in rat hippocampal neurons required both autonomous activity and further stimulation. Synaptic strength was decreased by CaMKIIα knockdown and rescued by reexpression, but not by mutants impaired for autonomy (T286A) or binding to NMDA-type glutamate receptor subunit 2B (GluN2B; formerly NR2B; I205K). Full rescue was seen with constitutively autonomous mutants (T286D), but only if they could be further stimulated (additional T305/306A mutation), and not with two other mutations that additionally impair Ca(2+)/CaM binding. Compared to rescue with wild-type CaMKII, the CaM-binding-impaired mutants even had reduced synaptic strength. One of these mutants (T305/306D) mimicked an inhibitory autophosphorylation of CaMKII, whereas the other one (Δstim) abolished CaM binding without introducing charged residues. Inhibitory T305/306 autophosphorylation also reduced GluN2B binding, but this effect was independent of reduced Ca(2+)/CaM binding and was not mimicked by T305/306D mutation. Thus, even autonomous CaMKII activity must be further stimulated by Ca(2+)/CaM for enhancement of synaptic strength.

  1. Interplay Between Intracellular Ca2+ Oscillations and Ca2+-stimulated Mitochondrial Metabolism

    PubMed Central

    Wacquier, Benjamin; Combettes, Laurent; Van Nhieu, Guy Tran; Dupont, Geneviève

    2016-01-01

    Oscillations of cytosolic Ca2+ concentration are a widespread mode of signalling. Oscillatory spikes rely on repetitive exchanges of Ca2+ between the endoplasmic reticulum (ER) and the cytosol, due to the regulation of inositol 1,4,5-trisphosphate receptors. Mitochondria also sequester and release Ca2+, thus affecting Ca2+ signalling. Mitochondrial Ca2+ activates key enzymes involved in ATP synthesis. We propose a new integrative model for Ca2+ signalling and mitochondrial metabolism in electrically non-excitable cells. The model accounts for (1) the phase relationship of the Ca2+ changes in the cytosol, the ER and mitochondria, (2) the dynamics of mitochondrial metabolites in response to cytosolic Ca2+ changes, and (3) the impacts of cytosol/mitochondria Ca2+ exchanges and of mitochondrial metabolism on Ca2+ oscillations. Simulations predict that as expected, oscillations are slowed down by decreasing the rate of Ca2+ efflux from mitochondria, but also by decreasing the rate of Ca2+ influx through the mitochondrial Ca2+ uniporter (MCU). These predictions were experimentally validated by inhibiting MCU expression. Despite the highly non-linear character of Ca2+ dynamics and mitochondrial metabolism, bioenergetics were found to be robust with respect to changes in frequency and amplitude of Ca2+ oscillations. PMID:26776859

  2. Ca2+/Cation Antiporters (CaCA): Identification, Characterization and Expression Profiling in Bread Wheat (Triticum aestivum L.)

    PubMed Central

    Taneja, Mehak; Tyagi, Shivi; Sharma, Shailesh; Upadhyay, Santosh Kumar

    2016-01-01

    The Ca2+/cation antiporters (CaCA) superfamily proteins play vital function in Ca2+ ion homeostasis, which is an important event during development and defense response. Molecular characterization of these proteins has been performed in certain plants, but they are still not characterized in Triticum aestivum (bread wheat). Herein, we identified 34 TaCaCA superfamily proteins, which were classified into TaCAX, TaCCX, TaNCL, and TaMHX protein families based on their structural organization and evolutionary relation with earlier reported proteins. Since the T. aestivum comprises an allohexaploid genome, TaCaCA genes were derived from each A, B, and D subgenome and homeologous chromosome (HC), except chromosome-group 1. Majority of genes were derived from more than one HCs in each family that were considered as homeologous genes (HGs) due to their high similarity with each other. These HGs showed comparable gene and protein structures in terms of exon/intron organization and domain architecture. Majority of TaCaCA proteins comprised two Na_Ca_ex domains. However, TaNCLs consisted of an additional EF-hand domain with calcium binding motifs. Each TaCaCA protein family consisted of about 10 transmembrane and two α-repeat regions with specifically conserved signature motifs except TaNCL, which had single α-repeat. Variable expression of most of the TaCaCA genes during various developmental stages suggested their specified role in development. However, constitutively high expression of a few genes like TaCAX1-A and TaNCL1-B indicated their role throughout the plant growth and development. The modulated expression of certain genes during biotic (fungal infections) and abiotic stresses (heat, drought, salt) suggested their role in stress response. Majority of TaCCX and TaNCL family genes were found highly affected during various abiotic stresses. However, the role of individual gene needs to be established. The present study unfolded the opportunity for detail functional

  3. Ca isotope cycling in a forested ecosystem

    NASA Astrophysics Data System (ADS)

    Holmden, Chris; Bélanger, Nicolas

    2010-02-01

    Reports of large Ca isotope fractionations between trees and soils prompted this study of a Boreal forest ecosystem near La Ronge, Saskatchewan, to improve understanding of this phenomenon. The results on five tree species (black spruce, trembling aspen, white spruce, jack pine, balsam poplar) confirm that nutrient Ca uptake by plants favors the light isotopes, thus driving residual Ca in plant available soil pools towards enrichment in the heavy isotopes. Substantial within-tree fraction occurs in tissues formed along the transpiration stream, with low δ 44Ca values in fine roots (2 mm), intermediate values in stemwood, and high values in foliage. Separation factors between different plant tissues are similar between species, but the initial fractionation step in the tips of the fine roots is species specific, and/or sensitive to the local soil environment. Soil water δ 44Ca values appear to increase with depth to at least 35 cm below the top of the forest floor, which is close to the deepest level of fine roots. The heavy plant fractionated signature of Ca in the finely rooted upper soils filters downward where it is retained on ion exchange sites, leached into groundwater, and discharged into surface waters. The relationship between Ca uptake by tree fine roots and the pattern of δ 44Ca enrichment with soil depth was modeled for two Ca pools: the forest floor (litter) and the underlying (upper B) mineral soil. Six study plots were investigated along two hillside toposequences trending upwards from a first order stream. We used allometric equations describing the Ca distribution in boreal tree species to calculate weighted average δ 44Ca values for the stands in each plot and estimate Ca uptake rates. The δ 44Ca value of precipitation was measured, and soil weathering signatures deduced, by acid leaching of lower B mineral soils. Steady state equations were used to derive a set of model Ca fluxes and fractionation factors for each plot. The model reproduces

  4. Fortilin binds Ca2+ and blocks Ca2+-dependent apoptosis in vivo

    PubMed Central

    Graidist, Potchanapond; Yazawa, Michio; Tonganunt, Moltira; Nakatomi, Akiko; Lin, Curtis Chun-Jen; Chang, Jui-Yoa; Phongdara, Amornrat; Fujise, Ken

    2007-01-01

    Fortilin, a 172-amino-acid polypeptide present both in the cytosol and nucleus, possesses potent anti-apoptotic activity. Although fortilin is known to bind Ca2+, the biochemistry and biological significance of such an interaction remains unknown. In the present study we report that fortilin must bind Ca2+ in order to protect cells against Ca2+-dependent apoptosis. Using a standard Ca2+-overlay assay, we first validated that full-length fortilin binds Ca2+ and showed that the N-terminus (amino acids 1–72) is required for its Ca2+-binding. We then used flow dialysis and CD spectropolarimetry assays to demonstrate that fortilin binds Ca2+ with a dissociation constant (Kd) of approx. 10 μM and that the binding of fortilin to Ca2+ induces a significant change in the secondary structure of fortilin. In order to evaluate the impact of the binding of fortilin to Ca2+ in vivo, we measured intracellular Ca2+ levels upon thapsigargin challenge and found that the lack of fortilin in the cell results in the exaggerated elevation of intracellular Ca2+ in the cell. We then tested various point mutants of fortilin for their Ca2+ binding and identified fortilin(E58A/E60A) to be a double-point mutant of fortilin lacking the ability of Ca2+-binding. We then found that wild-type fortilin, but not fortilin(E58A/E60A), protected cells against thapsigargin-induced apoptosis, suggesting that the binding of fortilin to Ca2+ is required for fortilin to protect cells against Ca2+-dependent apoptosis. Together, these results suggest that fortilin is an intracellular Ca2+ scavenger, protecting cells against Ca2+-dependent apoptosis by binding and sequestering Ca2+ from the downstream Ca2+-dependent apoptotic pathways. PMID:17705784

  5. Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids.

    PubMed

    Ekinci, Derya; Karagoz, Lutfi; Ekinci, Deniz; Senturk, Murat; Supuran, Claudiu T

    2013-04-01

    A series of flavonoids, such as quercetin, catechin, apigenin, luteolin, morin, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA). The compounds were tested against four α-CA isozymes purified from human and bovine (hCA I, hCA II, bCA III, hCA IV) tissues. The four isozymes showed quite diverse inhibition profiles with these compounds. The flavonoids inhibited hCA I with K(I)-s in the range of 2.2-12.8 μM, hCA II with K(I)-s in the range of 0.74-6.2 μM, bCA III with K(I)-s in the range of 2.2-21.3 μM, and hCA IV with inhibition constants in the range of 4.4-15.7, with an esterase assay using 4-nitrophenyl acetate as substrate. Some simple phenols/sulfonamides were also investigated as standard inhibitors. The flavonoids incorporate phenol moieties which inhibit these CAs through a diverse, not yet determined inhibition mechanism, compared to classic inhibitors such as the sulfonamide/sulfamate ones.

  6. The influence of Ca²⁺ buffers on free [Ca²⁺] fluctuations and the effective volume of Ca²⁺ microdomains.

    PubMed

    Weinberg, Seth H; Smith, Gregory D

    2014-06-17

    Intracellular calcium (Ca(2+)) plays a significant role in many cell signaling pathways, some of which are localized to spatially restricted microdomains. Ca(2+) binding proteins (Ca(2+) buffers) play an important role in regulating Ca(2+) concentration ([Ca(2+)]). Buffers typically slow [Ca(2+)] temporal dynamics and increase the effective volume of Ca(2+) domains. Because fluctuations in [Ca(2+)] decrease in proportion to the square-root of a domain's physical volume, one might conjecture that buffers decrease [Ca(2+)] fluctuations and, consequently, mitigate the significance of small domain volume concerning Ca(2+) signaling. We test this hypothesis through mathematical and computational analysis of idealized buffer-containing domains and their stochastic dynamics during free Ca(2+) influx with passive exchange of both Ca(2+) and buffer with bulk concentrations. We derive Langevin equations for the fluctuating dynamics of Ca(2+) and buffer and use these stochastic differential equations to determine the magnitude of [Ca(2+)] fluctuations for different buffer parameters (e.g., dissociation constant and concentration). In marked contrast to expectations based on a naive application of the principle of effective volume as employed in deterministic models of Ca(2+) signaling, we find that mobile and rapid buffers typically increase the magnitude of domain [Ca(2+)] fluctuations during periods of Ca(2+) influx, whereas stationary (immobile) Ca(2+) buffers do not. Also contrary to expectations, we find that in the absence of Ca(2+) influx, buffers influence the temporal characteristics, but not the magnitude, of [Ca(2+)] fluctuations. We derive an analytical formula describing the influence of rapid Ca(2+) buffers on [Ca(2+)] fluctuations and, importantly, identify the stochastic analog of (deterministic) effective domain volume. Our results demonstrate that Ca(2+) buffers alter the dynamics of [Ca(2+)] fluctuations in a nonintuitive manner. The finding that Ca(2

  7. Intracellular Ca2+ oscillations generated via the extracellular Ca2+-sensing receptor (CaSR) in response to extracellular Ca2+ or L-phenylalanine: impact of the highly conservative mutation Ser170Thr

    PubMed Central

    Young, Steven H.; Rey, Osvaldo; Rozengurt, Enrique

    2015-01-01

    The extracellular Ca2+-sensing receptor (CaSR) is an allosteric protein that responds to changes in the extracellular concentration of Ca2+ ([Ca2+]e) and aromatic amino acids with the production of different patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i). An increase in [Ca2+]e stimulates sinusoidal oscillations in [Ca2+]i whereas aromatic amino acid-induced CaR activation in the presence of a threshold [Ca2+]e promotes transient oscillations in [Ca2+]i. Here, we examined spontaneous and ligand-evoked [Ca2+]i oscillations in single HEK-293 cells transfected with the wild type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T). Our analysis demonstrates that cells expressing CaSRS170T display [Ca2+]i oscillations in the presence of low concentrations of extracellular Ca2+ and respond to L-Phe with robust transient [Ca2+]i oscillations. Our results indicate that the S170T mutation induces a marked increase in CaSR sensitivity to [Ca2+]e and imply that the allosteric regulation of the CaSR by aromatic amino acids is not only mediated by an heterotropic positive effect on Ca2+ binding cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR conformation that couples to a different signaling pathway leading to transient [Ca2+]i oscillations. PMID:26431875

  8. Topographic specificity of functional connections from hippocampal CA3 to CA1

    NASA Astrophysics Data System (ADS)

    Brivanlou, Iman H.; Dantzker, Jami L. M.; Stevens, Charles F.; Callaway, Edward M.

    2004-02-01

    The hippocampus is a cortical region thought to play an important role in learning and memory. Most of our knowledge about the detailed organization of hippocampal circuitry responsible for these functions is derived from anatomical studies. These studies present an incomplete picture, however, because the functional character and importance of connections are often not revealed by anatomy. Here, we used a physiological method (photostimulation with caged glutamate) to probe the fine pattern of functional connectivity between the CA3 and CA1 subfields in the mouse hippocampal slice preparation. We recorded intracellularly from CA1 and CA3 pyramidal neurons while scanning with photostimulation across the entire CA3 subfield with high spatial resolution. Our results show that, at a given septotemporal level, nearby CA1 neurons receive synaptic inputs from neighboring CA3 neurons. Thus, the CA3 to CA1 mapping preserves neighbor relations.

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

    PubMed

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

    2009-04-01

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

  10. Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+.

    PubMed

    Mori, Masayuki X; Vander Kooi, Craig W; Leahy, Daniel J; Yue, David T

    2008-04-01

    Calmodulin (CaM) regulation of Ca(2+) channels is central to Ca(2+) signaling. Ca(V)1 versus Ca(V)2 classes of these channels exhibit divergent forms of regulation, potentially relating to customized CaM/IQ interactions among different channels. Here we report the crystal structures for the Ca(2+)/CaM IQ domains of both Ca(V)2.1 and Ca(V)2.3 channels. These highly similar structures emphasize that major CaM contacts with the IQ domain extend well upstream of traditional consensus residues. Surprisingly, upstream mutations strongly diminished Ca(V)2.1 regulation, whereas downstream perturbations had limited effects. Furthermore, our Ca(V)2 structures closely resemble published Ca(2+)/CaM-Ca(V)1.2 IQ structures, arguing against Ca(V)1/2 regulatory differences based solely on contrasting CaM/IQ conformations. Instead, alanine scanning of the Ca(V)2.1 IQ domain, combined with structure-based molecular simulation of corresponding CaM/IQ binding energy perturbations, suggests that the C lobe of CaM partially dislodges from the IQ element during channel regulation, allowing exposed IQ residues to trigger regulation via isoform-specific interactions with alternative channel regions.

  11. Dissection of local Ca(2+) signals inside cytosol by ER-targeted Ca(2+) indicator.

    PubMed

    Niwa, Fumihiro; Sakuragi, Shigeo; Kobayashi, Ayana; Takagi, Shin; Oda, Yoichi; Bannai, Hiroko; Mikoshiba, Katsuhiko

    2016-10-07

    Calcium (Ca(2+)) is a versatile intracellular second messenger that operates in various signaling pathways leading to multiple biological outputs. The diversity of spatiotemporal patterns of Ca(2+) signals, generated by the coordination of Ca(2+) influx from the extracellular space and Ca(2+) release from the intracellular Ca(2+) store the endoplasmic reticulum (ER), is considered to underlie the diversity of biological outputs caused by a single signaling molecule. However, such Ca(2+) signaling diversity has not been well described because of technical limitations. Here, we describe a new method to report Ca(2+) signals at subcellular resolution. We report that OER-GCaMP6f, a genetically encoded Ca(2+) indicator (GECI) targeted to the outer ER membrane, can monitor Ca(2+) release from the ER at higher spatiotemporal resolution than conventional GCaMP6f. OER-GCaMP6f was used for in vivo Ca(2+) imaging of C. elegans. We also found that the spontaneous Ca(2+) elevation in cultured astrocytes reported by OER-GCaMP6f showed a distinct spatiotemporal pattern from that monitored by plasma membrane-targeted GCaMP6f (Lck-GCaMP6f); less frequent Ca(2+) signal was detected by OER-GCaMP6f, in spite of the fact that Ca(2+) release from the ER plays important roles in astrocytes. These findings suggest that targeting of GECIs to the ER outer membrane enables sensitive detection of Ca(2+) release from the ER at subcellular resolution, avoiding the diffusion of GECI and Ca(2+). Our results indicate that Ca(2+) imaging with OER-GCaMP6f in combination with Lck-GCaMP6f can contribute to describing the diversity of Ca(2+) signals, by enabling dissection of Ca(2+) signals at subcellular resolution.

  12. Role of Na+/Ca2+ exchanger in Ca2+ homeostasis in rat suprachiasmatic nucleus neurons

    PubMed Central

    Wang, Yi-Chi; Chen, Ya-Shuan; Cheng, Ruo-Ciao

    2015-01-01

    Intracellular Ca2+ is critical to the central clock of the suprachiasmatic nucleus (SCN). However, the role of Na+/Ca2+ exchanger (NCX) in intracellular Ca2+ concentration ([Ca2+]i) homeostasis in the SCN is unknown. Here we show that NCX is an important mechanism for somatic Ca2+ clearance in SCN neurons. In control conditions Na+-free solution lowered [Ca2+]i by inhibiting TTX-sensitive as well as nimodipine-sensitive Ca2+ influx. With use of the Na+ ionophore monensin to raise intracellular Na+ concentration ([Na+]i), Na+-free solution provoked rapid Ca2+ uptake via reverse NCX. The peak amplitude of 0 Na+-induced [Ca2+]i increase was larger during the day than at night, with no difference between dorsal and ventral SCN neurons. Ca2+ extrusion via forward NCX was studied by determining the effect of Na+ removal on Ca2+ clearance after high-K+-induced Ca2+ loads. The clearance of Ca2+ proceeded with two exponential decay phases, with the fast decay having total signal amplitude of ∼85% and a time constant of ∼7 s. Na+-free solution slowed the fast decay rate threefold, whereas mitochondrial protonophore prolonged mostly the slow decay. In contrast, blockade of plasmalemmal and sarco(endo)plasmic reticulum Ca2+ pumps had little effect on the kinetics of Ca2+ clearance. RT-PCR indicated the expression of NCX1 and NCX2 mRNAs. Immunohistochemical staining showed the presence of NCX1 immunoreactivity in the whole SCN but restricted distribution of NCX2 immunoreactivity in the ventrolateral SCN. Together our results demonstrate an important role of NCX, most likely NCX1, as well as mitochondrial Ca2+ uptake in clearing somatic Ca2+ after depolarization-induced Ca2+ influx in SCN neurons. PMID:25568156

  13. Differential behavioral state-dependence in the burst properties of CA3 and CA1 neurons.

    PubMed

    Tropp Sneider, J; Chrobak, J J; Quirk, M C; Oler, J A; Markus, E J

    2006-09-15

    Brief bursts of fast high-frequency action potentials are a signature characteristic of CA3 and CA1 pyramidal neurons. Understanding the factors determining burst and single spiking is potentially significant for sensory representation, synaptic plasticity and epileptogenesis. A variety of models suggest distinct functional roles for burst discharge, and for specific characteristics of the burst in neural coding. However, little in vivo data demonstrate how often and under what conditions CA3 and CA1 actually exhibit burst and single spike discharges. The present study examined burst discharge and single spiking of CA3 and CA1 neurons across distinct behavioral states (awake-immobility and maze-running) in rats. In both CA3 and CA1 spike bursts accounted for less than 20% of all spike events. CA3 neurons exhibited more spikes per burst, greater spike frequency, larger amplitude spikes and more spike amplitude attenuation than CA1 neurons. A major finding of the present study is that the propensity of CA1 neurons to burst was affected by behavioral state, while the propensity of CA3 to burst was not. CA1 neurons exhibited fewer bursts during maze running compared with awake-immobility. In contrast, there were no differences in burst discharge of CA3 neurons. Neurons in both subregions exhibited smaller spike amplitude, fewer spikes per burst, longer inter-spike intervals and greater spike amplitude attenuation within a burst during awake-immobility compared with maze running. These findings demonstrate that the CA1 network is under greater behavioral state-dependent regulation than CA3. The present findings should inform both theoretic and computational models of CA3 and CA1 function.

  14. Ca isotope fractionation on the moon

    NASA Technical Reports Server (NTRS)

    Russell, W. A.; Papanastassiou, D. A.; Tombrello, T. A.; Epstein, S.

    1977-01-01

    Ca has been measured in a lunar soil in order to establish the presence of isotopically mass-fractionated components. Ca was extracted by a series of water leaches after the soils were 'activated' by brief exposures to fluorine gas. The O2 obtained by this fluorination is found to have delta (O-18) of +21 per mil and to be, therefore, significantly mass-fractionated. Ca obtained in the leaches was analyzed using the double-spike technique. Very small Ca isotope fractionation is found in the leaches of this soil of up to 1 per mil per mass unit difference. The small Ca effects are in marked contrast to the measured delta (O-18) for the same sample and to large effects observed in many soils for oxygen, silicon, sulfur, and potassium. The data on Ca provide stringent constraints on models which attempt to explain the isotope mass-fractionation effects in lunar soils.

  15. Ca2+ Channels on the Move†

    PubMed Central

    2009-01-01

    The versatility of Ca2+ as an intracellular messenger derives largely from the spatial organization of cytosolic Ca2+ signals, most of which are generated by regulated openings of Ca2+-permeable channels. Most Ca2+ channels are expressed in the plasma membrane (PM). Others, including the almost ubiquitous inositol 1,4,5-trisphosphate receptors (IP3R) and their relatives, the ryanodine receptors (RyR), are predominantly expressed in membranes of the sarcoplasmic or endoplasmic reticulum (ER). Targeting of these channels to appropriate destinations underpins their ability to generate spatially organized Ca2+ signals. All Ca2+ channels begin life in the cytosol, and the vast majority are then functionally assembled in the ER, where they may either remain or be dispatched to other membranes. Here, by means of selective examples, we review two issues related to this trafficking of Ca2+ channels via the ER. How do cells avoid wayward activity of Ca2+ channels in transit as they pass from the ER via other membranes to their final destination? How and why do some cells express small numbers of the archetypal intracellular Ca2+ channels, IP3R and RyR, in the PM? PMID:19928968

  16. 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.

  17. Supralinear dendritic Ca2+ signalling in young developing CA1 pyramidal cells

    PubMed Central

    Pohle, Jörg; Bischofberger, Josef

    2014-01-01

    Although Ca2+ is critically important in activity-dependent neuronal development, not much is known about the regulation of dendritic Ca2+ signals in developing neurons. Here, we used ratiometric Ca2+ imaging to investigate dendritic Ca2+ signalling in rat hippocampal pyramidal cells during the first 1–4 weeks of postnatal development. We show that active dendritic backpropagation of Nav channel-dependent action potentials (APs) evoked already large dendritic Ca2+ transients in animals aged 1 week with amplitudes of ∼150 nm, similar to the amplitudes of ∼160 nM seen in animals aged 4 weeks. Although the AP-evoked dendritic Ca2+ load increased about four times during the first 4 weeks, the peak amplitude of free Ca2+ concentration was balanced by a four-fold increase in Ca2+ buffer capacity κs (∼70 vs. ∼280). Furthermore, Ca2+ extrusion rates increased with postnatal development, leading to a slower decay time course (∼0.2 s vs. ∼0.1 s) and more effective temporal summation of Ca2+ signals in young cells. Most importantly, during prolonged theta-burst stimulation dendritic Ca2+ signals were up to three times larger in cells at 1 week than at 4 weeks of age and much larger than predicted by linear summation, which is attributable to an activity-dependent slow-down of Ca2+ extrusion. As Ca2+ influx is four-fold smaller in young cells, the larger Ca2+ signals are generated using four times less ATP consumption. Taken together, the data suggest that active backpropagations regulate dendritic Ca2+ signals during early postnatal development. Remarkably, during prolonged AP firing, Ca2+ signals are several times larger in young than in mature cells as a result of activity-dependent regulation of Ca2+ extrusion rates. PMID:25239458

  18. Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals.

    PubMed

    Ohkura, Masamichi; Sasaki, Takuya; Sadakari, Junko; Gengyo-Ando, Keiko; Kagawa-Nagamura, Yuko; Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Imaging the activities of individual neurons with genetically encoded Ca(2+) indicators (GECIs) is a promising method for understanding neuronal network functions. Here, we report GECIs with improved neuronal Ca(2+) signal detectability, termed G-CaMP6 and G-CaMP8. Compared to a series of existing G-CaMPs, G-CaMP6 showed fairly high sensitivity and rapid kinetics, both of which are suitable properties for detecting subtle and fast neuronal activities. G-CaMP8 showed a greater signal (F(max)/F(min) = 38) than G-CaMP6 and demonstrated kinetics similar to those of G-CaMP6. Both GECIs could detect individual spikes from pyramidal neurons of cultured hippocampal slices or acute cortical slices with 100% detection rates, demonstrating their superior performance to existing GECIs. Because G-CaMP6 showed a higher sensitivity and brighter baseline fluorescence than G-CaMP8 in a cellular environment, we applied G-CaMP6 for Ca(2+) imaging of dendritic spines, the putative postsynaptic sites. By expressing a G-CaMP6-actin fusion protein for the spines in hippocampal CA3 pyramidal neurons and electrically stimulating the granule cells of the dentate gyrus, which innervate CA3 pyramidal neurons, we found that sub-threshold stimulation triggered small Ca(2+) responses in a limited number of spines with a low response rate in active spines, whereas supra-threshold stimulation triggered large fluorescence responses in virtually all of the spines with a 100% activity rate.

  19. CaV1.1: The atypical prototypical voltage-gated Ca2+ channel

    PubMed Central

    Bannister, Roger A.; Beam, Kurt G.

    2012-01-01

    CaV1.1 is the prototype for the other nine known CaV channel isoforms, yet it has functional properties that make it truly atypical of this group. Specifically, CaV1.1 is expressed solely in skeletal muscle where it serves multiple purposes; it is the voltage sensor for excitation-contraction (EC) coupling and it is an L-type Ca2+ channel which contributes to a form of activity-dependent Ca2+ entry that has been termed Excitation-Coupled Ca2+ Entry (ECCE). The ability of CaV1.1 to serve as voltage-sensor for EC coupling appears to be unique amongst CaV channels, whereas the physiological role of its more conventional function as a Ca2+ channel has been a matter of uncertainty for nearly 50 years. In this chapter, we discuss how CaV1.1 supports EC coupling, the possible relevance of Ca2+ entry through CaV1.1 and how alterations of CaV1.1 function can have pathophysiological consequences. PMID:22982493

  20. Conservation of Ca2+/Calmodulin Regulation across Na and Ca2+ channels

    PubMed Central

    Ben-Johny, Manu; Yang, Philemon S.; Niu, Jacqueline; Yang, Wanjun; Joshi-Mukherjee, Rosy; Yue, David T.

    2014-01-01

    SUMMARY Voltage-gated Na and Ca2+channels comprise distinct ion-channel superfamilies, yet the carboxy tails of these channels exhibit high homology hinting at a long-shared and purposeful module. For different Ca2+ channels, carboxyl-tail inter actions with calmodulin do elaborate robust and similar forms of Ca2+ regulation. However, Na channels have only shown subtler Ca2+modulation that differs among reports, challenging attempts at unified understanding. Here, by rapid Ca2+photoreleaseon to Na channels, we reset this view of Na channel regulation. For cardiac muscle channels (NaV1.5), reported effects from which most mechanistic proposals derive, we observe no Ca2+modulation. Conversely, for skeletal-muscle channels (NaV1.4), we uncover fast Ca2+ regulation eerily similar to that of Ca2+ channels. Channel opathic myotonia mutations halve NaV1.4 Ca2+ regulation, and transplanting the NaV1.4 carboxy tail onto Ca2+ channels recapitulates Ca2+ regulation. Thus we argue for the persistence and physiological relevance of an ancient Ca2+ regulatory module across Na and Ca2+ channels. PMID:24949975

  1. Time Cells in Hippocampal Area CA3

    PubMed Central

    Salz, Daniel M.; Tiganj, Zoran; Khasnabish, Srijesa; Kohley, Annalyse; Sheehan, Daniel; Howard, Marc W.

    2016-01-01

    Studies on time cells in the hippocampus have so far focused on area CA1 in animals performing memory tasks. Some studies have suggested that temporal processing within the hippocampus may be exclusive to CA1 and CA2, but not CA3, and may occur only under strong demands for memory. Here we examined the temporal and spatial coding properties of CA3 and CA1 neurons in rats performing a maze task that demanded working memory and a control task with no explicit working memory demand. In the memory demanding task, CA3 cells exhibited robust temporal modulation similar to the pattern of time cell activity in CA1, and the same populations of cells also exhibited typical place coding patterns in the same task. Furthermore, the temporal and spatial coding patterns of CA1 and CA3 were equivalently robust when animals performed a simplified version of the task that made no demands on working memory. However, time and place coding did differ in that the resolution of temporal coding decreased over time within the delay interval, whereas the resolution of place coding was not systematically affected by distance along the track. These findings support the view that CA1 and CA3 both participate in encoding the temporal and spatial organization of ongoing experience. SIGNIFICANCE STATEMENT Hippocampal “time cells” that fire at specific moments in a temporally structured memory task have so far been observed only in area CA1, and some studies have suggested that temporal coding within the hippocampus is exclusive to CA1. Here we describe time cells also in CA3, and time cells in both areas are observed even without working memory demands, similar to place cells in these areas. However, unlike equivalent spatial coding along a path, temporal coding is nonlinear, with greater temporal resolution earlier than later in temporally structured experiences. These observations reveal both similarities and differences in temporal and spatial coding within the hippocampus of importance to

  2. 50 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... capacity of the species and its ecosystem, in order to ensure that utilization does not exceed those... its ecosystem. Trend means a long-term assessment of any change in the absolute or relative size of...

  3. 50 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... capacity of the species and its ecosystem, in order to ensure that utilization does not exceed those... its ecosystem. Trend means a long-term assessment of any change in the absolute or relative size of...

  4. 50 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

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    ... and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR TAKING, POSSESSION... capacity of the species and its ecosystem, in order to ensure that utilization does not exceed those... its ecosystem. Trend means a long-term assessment of any change in the absolute or relative size of...

  5. 47 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... objects within its range. (m) Harmful interference. Any emission, radiation or induction that endangers... device that intentionally generates and emits radio frequency energy by radiation or induction. (p) Kit... substation to the customer or house wiring. (u) Radio frequency (RF) energy. Electromagnetic energy at...

  6. 47 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

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    ... objects within its range. (m) Harmful interference. Any emission, radiation or induction that endangers... device that intentionally generates and emits radio frequency energy by radiation or induction. (p) Kit... substation to the customer or house wiring. (u) Radio frequency (RF) energy. Electromagnetic energy at...

  7. 47 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... objects within its range. (m) Harmful interference. Any emission, radiation or induction that endangers... device that intentionally generates and emits radio frequency energy by radiation or induction. (p) Kit... substation to the customer or house wiring. (u) Radio frequency (RF) energy. Electromagnetic energy at...

  8. 47 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... objects within its range. (m) Harmful interference. Any emission, radiation or induction that endangers... device that intentionally generates and emits radio frequency energy by radiation or induction. (p) Kit... substation to the customer or house wiring. (u) Radio frequency (RF) energy. Electromagnetic energy at...

  9. 10 CFR 15.3 - Communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... archive the submission, and process and retrieve it a single page at a time. Detailed guidance on making.... Nuclear Regulatory Commission, Washington, DC 20555-0001. The guidance discusses, among other topics,...

  10. 10 CFR 15.3 - Communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... archive the submission, and process and retrieve it a single page at a time. Detailed guidance on making.... Nuclear Regulatory Commission, Washington, DC 20555-0001. The guidance discusses, among other topics,...

  11. 10 CFR 15.3 - Communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... archive the submission, and process and retrieve it a single page at a time. Detailed guidance on making.... Nuclear Regulatory Commission, Washington, DC 20555-0001. The guidance discusses, among other topics,...

  12. 10 CFR 15.3 - Communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... archive the submission, and process and retrieve it a single page at a time. Detailed guidance on making.... Nuclear Regulatory Commission, Washington, DC 20555-0001. The guidance discusses, among other topics,...

  13. 10 CFR 15.3 - Communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... archive the submission, and process and retrieve it a single page at a time. Detailed guidance on making.... Nuclear Regulatory Commission, Washington, DC 20555-0001. The guidance discusses, among other topics,...

  14. 6 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... psychological disorder such as mental retardation, organic brain syndrome, emotional or mental illness, and... employment, an individual with a disability who satisfies the requisite skill, experience, education...

  15. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194... scientific party embarked may supervise the safety and operation of the chemical laboratory. (b)...

  16. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194... scientific party embarked may supervise the safety and operation of the chemical laboratory. (b)...

  17. 7 CFR 15.3 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... participation in the Direct Distribution Program. (ii) Discrimination in the allocation of food to eligible... children are assigned to schools on the basis of race, color, or national origin. (5) Food Stamp Program... issued food coupons. (6) Special Milk Program for Children. (i) Discrimination by a State agency in...

  18. 7 CFR 15.3 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Discrimination prohibited. (a) General. No person in the United States shall, on the ground of race, color, or... the extent set forth in paragraph (c) of this section). (vii) Deny a person the opportunity to... services, financial aid, or other benefit provided in or through a facility provided or improved in...

  19. 7 CFR 15.3 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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  20. 46 CFR 151.15-3 - Construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... construction of the types of cargo tanks defined in § 151.15-1. (a) Gravity type tanks. Gravity type cargo... society. Gravity type tanks vented at a pressure exceeding 4 but not exceeding 10 pounds per square inch gauge will be given special consideration by the Commandant. (b) Pressure vessel type tanks....

  1. 46 CFR 151.15-3 - Construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... construction of the types of cargo tanks defined in § 151.15-1. (a) Gravity type tanks. Gravity type cargo... society. Gravity type tanks vented at a pressure exceeding 4 but not exceeding 10 pounds per square inch gauge will be given special consideration by the Commandant. (b) Pressure vessel type tanks....

  2. 6 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... condition, cosmetic disfigurement, or anatomical loss affecting one or more of the following body systems...; reproductive, digestive; genitourinary; hemic and lymphatic; skin; and endocrine; or (ii) Any mental...

  3. 50 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS WILD BIRD... published results or reports from the work. Exotic bird means any live or dead member of the Class Aves that... thereof, but does not include domestic poultry, dead sport-hunted birds, dead museum specimens,...

  4. 50 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., TRANSPORTATION, SALE, PURCHASE, BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS WILD BIRD... published results or reports from the work. Exotic bird means any live or dead member of the Class Aves that... thereof, but does not include domestic poultry, dead sport-hunted birds, dead museum specimens,...

  5. X-15 #3 in flight (USAF Photo)

    NASA Technical Reports Server (NTRS)

    1960-01-01

    This U.S. Air Force photo shows the X-15 ship #3 (56-6672) in flight over the desert in the 1960s. Ship #3 made 65 flights during the program, attaining a top speed of Mach 5.65 and a maximum altitude of 354,200 feet. Only 10 of the 12 X-15 pilots flew Ship #3, and only eight of them earned their astronaut wings during the program. Robert White, Joseph Walker, Robert Rushworth, John 'Jack' McKay, Joseph Engle, William 'Pete' Knight, William Dana, and Michael Adams all earned their astronaut wings in Ship #3. Neil Armstrong and Milton Thompson also flew Ship #3. In fact, Armstrong piloted Ship #3 on its first flight, on 20 December 1961. On 15 November 1967, Ship #3 was launched over Delamar Lake, Nevada with Maj. Michael J. Adams at the controls. The vehicle soon reached a speed of Mach 5.2, and a peak altitude of 266,000 feet. During the climb, an electrical disturbance degraded the aircraft's controllability. Ship #3 began a slow drift in heading, which soon became a spin. Adams radioed that the X-15 'seems squirrelly' and then said 'I'm in a spin.' Through some combination of pilot technique and basic aerodynamic stability, Adams recovered from the spin and entered an inverted Mach 4.7 dive. As the X-15 plummeted into the increasingly thicker atmosphere, the Honeywell adaptive flight control system caused the vehicle to begin oscillating. As the pitching motion increased, aerodynamic forces finally broke the aircraft into several major pieces. Adams was killed when the forward fuselage impacted the desert. This was the only fatal accident during the entire X-15 program. The X-15 was a rocket-powered aircraft 50 ft long with a wingspan of 22 ft. It was a missile-shaped vehicle with an unusual wedge-shaped vertical tail, thin stubby wings, and unique side fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was capable of developing 57,000 lb of thrust. North American Aviation built three X-15 aircraft for the program. The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow-on program used the aircraft as a testbed to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudder surfaces on the vertical stabilizers to control yaw and movable horizontal stabilizers to control pitch when moving in synchronization or roll when moved differentially. For flight in the thin air outside of the appreciable Earth's atmosphere, the X-15 used a reaction control system. Hydrogen peroxide thrust rockets located on the nose of the aircraft provided pitch and yaw control. Those on the wings provided roll control. Because of the large fuel consumption, the X-15 was air launched from a B-52 aircraft at 45,000 ft and a speed of about 500 mph. Depending on the mission, the rocket engine provided thrust for the first 80 to 120 sec of flight. The remainder of the normal 10 to 11 min. flight was powerless and ended with a 200-mph glide landing. Generally, one of two types of X-15 flight profiles was used; a high-altitude flight plan that called for the pilot to maintain a steep rate of climb, or a speed profile that called for the pilot to push over and maintain a level altitude. The X-15 was flown over a period of nearly 10 years -- June 1959 to Oct. 1968 -- and set the world's unofficial speed and altitude records of 4,520 mph or Mach 6.7 (set by Ship #2) and 354,200 ft (set by Ship #3) in a program to investigate all aspects of manned hypersonic flight. Information gained from the highly successful X-15 program contributed to the development of the Mercury, Gemini, and Apollo manned spaceflight programs, and also the Space Shuttle program. The X-15s made a total of 199 flights, and we

  6. 6 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... sensory, manual, or speaking skills to have an equal opportunity to participate in, and enjoy the benefits... caring for one's self, performing manual tasks, walking, seeing, hearing, speaking, breathing, learning... employment, an individual with a disability who satisfies the requisite skill, experience, education...

  7. 6 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... sensory, manual, or speaking skills to have an equal opportunity to participate in, and enjoy the benefits... caring for one's self, performing manual tasks, walking, seeing, hearing, speaking, breathing, learning... employment, an individual with a disability who satisfies the requisite skill, experience, education...

  8. 6 CFR 15.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... sensory, manual, or speaking skills to have an equal opportunity to participate in, and enjoy the benefits... caring for one's self, performing manual tasks, walking, seeing, hearing, speaking, breathing, learning... employment, an individual with a disability who satisfies the requisite skill, experience, education...

  9. 7 CFR 15.3 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... training, or (3) to provide work experience which contributes to education or training. Where a primary... Extension Service of any facility, including offices, training facilities, lecture halls, or other structures or improvements; or (iii) Discrimination in training activities, admission to or participation...

  10. 46 CFR 151.15-3 - Construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... be adequately protected in areas of possible mechanical damage. (h) Fire exposure protection. Tanks which are provided with fire exposure protection of one of the following categories may be allowed a... requirements for the full head will satisfy this requirement. (d) Arrangements—(1) Collision protection....

  11. 46 CFR 151.15-3 - Construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... be adequately protected in areas of possible mechanical damage. (h) Fire exposure protection. Tanks which are provided with fire exposure protection of one of the following categories may be allowed a... requirements for the full head will satisfy this requirement. (d) Arrangements—(1) Collision protection....

  12. 46 CFR 151.15-3 - Construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... be adequately protected in areas of possible mechanical damage. (h) Fire exposure protection. Tanks which are provided with fire exposure protection of one of the following categories may be allowed a... requirements for the full head will satisfy this requirement. (d) Arrangements—(1) Collision protection....

  13. Structures of Ca(V) Ca**2+/CaM-IQ Domain Complexes Reveal Binding Modes That Underlie Calcium-Dependent Inactivation And Facilitation

    SciTech Connect

    Kim, E.Y.; Rumpf, C.H.; Fujiwara, Y.; Cooley, E.S.; Petegem, F.Van; Minor, D.L., Jr.

    2009-05-20

    Calcium influx drives two opposing voltage-activated calcium channel (Ca{sub V}) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca{sup 2+}/calmodulin (Ca{sup 2+}/CaM) lobes produce CDI and CDF through interactions with the Ca{sub V}{alpha}{sub 1} subunit IQ domain. Curiously, Ca{sup 2+}/CaM lobe modulation polarity appears inverted between Ca{sub V}1s and Ca{sub V}2s. Here, we present crystal structures of Ca{sub V}2.1, Ca{sub V}2.2, and Ca{sub V}2.3 Ca{sup 2+}/CaM-IQ domain complexes. All display binding orientations opposite to Ca{sub V}1.2 with a physical reversal of the CaM lobe positions relative to the IQ {alpha}-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to Ca{sub V}1 and Ca{sub V}2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca{sub V}2 Ca{sup 2+}/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca{sub V} feedback modulation and indicate that Ca{sub V}1 and Ca{sub V}2 IQ domains bear a dedicated CDF site that exchanges Ca{sup 2+}/CaM lobe occupants.

  14. Effect of Ca2+ efflux pathway distribution and exogenous Ca2+ buffers on intracellular Ca2+ dynamics in the rat ventricular myocyte: a simulation study.

    PubMed

    Pásek, Michal; Simurda, Jiří; Orchard, Clive H

    2014-01-01

    We have used a previously published computer model of the rat cardiac ventricular myocyte to investigate the effect of changing the distribution of Ca(2+) efflux pathways (SERCA, Na(+)/Ca(2+) exchange, and sarcolemmal Ca(2+) ATPase) between the dyad and bulk cytoplasm and the effect of adding exogenous Ca(2+) buffers (BAPTA or EGTA), which are used experimentally to differentially buffer Ca(2+) in the dyad and bulk cytoplasm, on cellular Ca(2+) cycling. Increasing the dyadic fraction of a particular Ca(2+) efflux pathway increases the amount of Ca(2+) removed by that pathway, with corresponding changes in Ca(2+) efflux from the bulk cytoplasm. The magnitude of these effects varies with the proportion of the total Ca(2+) removed from the cytoplasm by that pathway. Differences in the response to EGTA and BAPTA, including changes in Ca(2+)-dependent inactivation of the L-type Ca(2+) current, resulted from the buffers acting as slow and fast "shuttles," respectively, removing Ca(2+) from the dyadic space. The data suggest that complex changes in dyadic Ca(2+) and cellular Ca(2+) cycling occur as a result of changes in the location of Ca(2+) removal pathways or the presence of exogenous Ca(2+) buffers, although changing the distribution of Ca(2+) efflux pathways has relatively small effects on the systolic Ca(2+) transient.

  15. Literacy.CA. Issue #19, Winter 2006

    ERIC Educational Resources Information Center

    Murray, Fiona, Ed.

    2006-01-01

    The "literacy.ca" newsletter is a vehicle for literacy workers and supporters to share information, ideas, resources and research on emerging literacy issues. This issue of "literacy.ca" contains the following articles: (1) Riding The Wave: How will the federal election affect progress on a pan-Canadian literacy agenda?; (2)…

  16. Ca(2+) signalling in the Golgi apparatus.

    PubMed

    Pizzo, Paola; Lissandron, Valentina; Capitanio, Paola; Pozzan, Tullio

    2011-08-01

    The Golgi apparatus plays a central role in lipid and protein post-translational modification and sorting. Morphologically the organelle is heterogeneous and it is possible to distinguish stacks of flat cysternae (cis- and medial Golgi), tubular-reticular networks and vesicles (trans-Golgi). These morphological differences parallel a distinct functionality with a selective distribution and complementary roles of the enzymes found in the different compartments. The Golgi apparatus has been also shown to be involved in Ca(2+) signalling: it is indeed endowed with Ca(2+) pumps, Ca(2+) release channels and Ca(2+) binding proteins and is thought to participate in determining the spatio-temporal complexity of the Ca(2+) signal within the cell, though this role is still poorly understood. Recently, it has been demonstrated that the organelle is heterogeneous in terms of Ca(2+) handling and selective reduction of Ca(2+) concentration, both in vitro and in a genetic human disease, within one of its sub-compartment results in alterations of protein trafficking within the secretory pathway and of the entire Golgi morphology. In this paper we review the available information on the Ca(2+) toolkit within the Golgi, its heterogeneous distribution in the organelle sub-compartments and discuss the implications of these characteristics for the physiopathology of the Golgi apparatus.

  17. Some mineral stability relations in the system CaOMgOSiO2H2OHCl

    USGS Publications Warehouse

    Luce, R.W.; Cygan, G.L.; Hemley, J.J.; d'Angelo, W. M.

    1985-01-01

    Mineral-aqueous solution equilibria for the assemblages talc-quartz, tremolite-talc-quartz, diopside-tremolite-quartz, wollastonite-diopside-quartz and wollastonite-quartz have been studied at 2 kb total pressure, 500?? to 700??C and chloride concentrations from 0.03 to 6.0 molal. Most work was at 1 m chloride. Both buffered and unbuffered data were obtained and a recalibration of the Ag-AgCl buffer is presented. Log equilibrium quotients at 500??, 600?? and 700??C are respectively: Ta-Qz ( mMgCl2 mHCl2) 2.57, 1.71, 0.73; Tr-Ta-Qz and Di-Tr-Qz ( mCaCl2 mMgCl2mHCl2) 4.98, 3.99, 2.21 and 7.29, 5.30, 3.56; WoDi-Qz ( mCaCl2 mMgCl2) 3.30, 3.00, 2.79: Wo-Qz ( mCaCl2 mHCl2) 5.15, 3.95, 2.68. Mineral stability fields plotted in terms of these concentration data more tangibly represent the compositional character of real systems and the mass transfer capabilities of their fluids than do the analogous theoretical activity diagrams. Overall dissociation constants of MgCl2 and CaCl2 were calculated from the experimental data using the calculated ionic activity constants for the reactions and the established dissociation constants of HCl. The negative log values are respectively: 3.88. 6.63, 9.20 for CaCl2 and 4.60, 7.54, 10.37 for MgCl2 at 500??, 600?? and 700??C, 2 kb. The Ca values are about an order of magnitude more positive than the conductance-derived values by Frantz and Marshall (1982). The phase relations developed in this study have application to the genesis of talc, tremolite, and diopside-bearing assemblages in some regional metamorphic rocks, but more specifically to the calcsilicate skarn assemblages of many metasomatic aureoles. The equilibrium fluids are characterized by high concentrations of Ca relative to Mg and increasing Ca Mg ratios with decreasing temperatures. The stability fields of talc, tremolite, and quartz expand relative to those of diopside and wollastonite with decreasing temperature, hence their more common appearance as retrograde products in

  18. Role of extracellular Ca2+ in gating of CaV1.2 channels

    PubMed Central

    Babich, Olga; Isaev, Dmytro; Shirokov, Roman

    2005-01-01

    We examined changes in ionic and gating currents in CaV1.2 channels when extracellular Ca2+ was reduced from 10 mm to 0.1 μm. Saturating gating currents decreased by two-thirds (KD≈ 40 μm) and ionic currents increased 5-fold (KD≈ 0.5 μm) due to increasing Na+ conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca2+], which appeared to reflect the rapid activation of channels that were not blocked by Ca2+ and a slower reversal of Ca2+ blockade of the remaining channels. Removal of Ca2+ following inactivation of Ca2+ currents showed that Na+ currents were not affected by Ca2+-dependent inactivation. Ca2+-dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca2+ conductance and Ca2+-dependent inactivation depend on extracellular Ca2+ and are linked to changes in selectivity. PMID:15845581

  19. CaMKII in the cardiovascular system: sensing redox states.

    PubMed

    Erickson, Jeffrey R; He, B Julie; Grumbach, Isabella M; Anderson, Mark E

    2011-07-01

    The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca(2+)/CaM). Under conditions of sustained exposure to elevated Ca(2+)/CaM, CaMKII transitions into a Ca(2+)/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine-287 in the CaMKII regulatory domain "traps" CaMKII into an open configuration even after Ca(2+)/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca(2+)/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease.

  20. Localized Calcineurin Confers Ca2+-Dependent Inactivation Upon Neuronal L-Type Ca2+ Channels

    PubMed Central

    Oliveria, Seth F.; Dittmer, Philip J.; Youn, Dong-ho; Dell’Acqua, Mark L.; Sather, William A.

    2012-01-01

    Excitation-driven entry of Ca2+ through L-type voltage-gated Ca2+ channels controls gene expression in neurons and a variety of fundamental activities in other kinds of excitable cells. The probability of opening of CaV1.2 L-type channels is subject to pronounced enhancement by cAMP-dependent protein kinase (PKA), which is scaffolded to CaV1.2 channels by A-kinase anchoring proteins (AKAPs). CaV1.2 channels also undergo negative autoregulation via Ca2+-dependent inactivation (CDI), which strongly limits Ca2+ entry. An abundance of evidence indicates that CDI relies upon binding of Ca2+/calmodulin (CaM) to an IQ motif in the carboxy tail of CaV1.2 L-type channels, a molecular mechanism seemingly unrelated to phosphorylation-mediated channel enhancement. But our work reveals, in cultured hippocampal neurons and a heterologous expression system, that the Ca2+/CaM-activated phosphatase calcineurin (CaN) is scaffolded to CaV1.2 channels by the neuronal anchoring protein AKAP79/150 and that over-expression of an AKAP79/150 mutant incapable of binding CaN (ΔPIX) impedes CDI. Interventions that suppress CaN activity—mutation in its catalytic site, antagonism with cyclosporine A or FK506, or intracellular perfusion with a peptide mimicking the sequence of the phosphatase’s autoinhibitory domain—interfere with normal CDI. In cultured hippocampal neurons from a ΔPIX knock-in mouse, CDI is absent. Results of experiments with the adenylyl cyclase stimulator forskolin and with the PKA inhibitor PKI suggest that Ca2+/CaM-activated CaN promotes CDI by reversing channel enhancement effectuated by kinases such as PKA. Hence our investigation of AKAP79/150-anchored CaN reconciles the CaM-based model of CDI with an earlier, seemingly contradictory model based on dephosphorylation signaling. PMID:23115171

  1. Spontaneous and nicotine-induced Ca2+ oscillations mediated by Ca2+ influx in rat pinealocytes.

    PubMed

    Mizutani, Hiroya; Yamamura, Hisao; Muramatsu, Makoto; Kiyota, Keiko; Nishimura, Kaori; Suzuki, Yoshiaki; Ohya, Susumu; Imaizumi, Yuji

    2014-06-01

    The pineal gland regulates circadian rhythm through the synthesis and secretion of melatonin. The rise of intracellular Ca(2+) concentration ([Ca(2+)]i) following nicotinic acetylcholine receptor (nAChR) stimulation due to parasympathetic nerve activity downregulates melatonin production. Important characteristics and roles of Ca(2+) mobilization due to nAChR stimulation remain to be clarified. We report here that spontaneous Ca(2+) oscillations can be observed in ∼15% of the pinealocytes in slice preparations from rat pineal glands when this dissociation procedure is done within 6 h from a dark-to-light change. The frequency and half-life of [Ca(2+)]i rise were 0.86 min(-1) and 19 s, respectively. Similar spontaneous Ca(2+) oscillations were recorded in 17% of rat pinealocytes that were primary cultured for several days. Simultaneous measurement of [Ca(2+)]i and membrane potential revealed that spontaneous Ca(2+) oscillations were triggered by periodic membrane depolarizations. Spontaneous Ca(2+) oscillations in cultured pinealocytes were abolished by extracellular Ca(2+) removal or application of nifedipine, a blocker of voltage-dependent Ca(2+) channel (VDCC). In contrast, blockers of intracellular Ca(2+)-release channels, 2-aminoethoxydiphenylborate and ryanodine, have no effect. Our results also reveal that, in 23% quiescent pinealocytes, Ca(2+) oscillations were observed following the withdrawal of nicotine. Norepinephrine-induced melatonin secretion from whole pineal glands was significantly decreased by the coapplication of acetylcholine (ACh). This inhibitory effect of ACh was attenuated by nifedipine. In conclusion, both spontaneous and evoked Ca(2+) oscillations are due to membrane depolarization following activation of VDCCs. This consists of VDCC α1F subunit, and the associated Ca(2+) influx can strongly regulate melatonin secretion in pineal glands.

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

    PubMed

    Lytton, Jonathan

    2007-09-15

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

  3. CaMKIIδ meditates phenylephrine induced cardiomyocyte hypertrophy through store-operated Ca(2+) entry.

    PubMed

    Ji, Yawei; Guo, Xin; Zhang, Zhe; Huang, Zhuyun; Zhu, Jianghua; Chen, Qing-Hui; Gui, Le

    Evidence suggests that store-operated Ca2+ entry (SOCE) is involved in the hypertrophy of cardiomyocytes. The signaling mechanisms of SOCE contributing to cardiac hypertrophy following phenylephrine (PE) stimulation are not fully understood. Ca(2+)/calmodulin-dependent protein kinase II δ (CaMKIIδ) plays an important role in regulating intracellular Ca(2+) hemostasis and function in the cardimyocytes. This study is aimed to determine the role of CaMKIIδ in regulating the PE-induced myocardial hypertrophy and the associated molecular signaling mechanisms. We used primary cultures of neonatal cardimyocytes isolated from the left ventricle of Sprague Dawley rats to investigate the effects of CaMKIIδ on myocardial hypertrophy and intracellular Ca(2+) mobilization. We found that the expression of CaMKIIδ was enhanced in PE-induced hypertrophic cardiomyocytes. CaMKIIδ siRNA, CaMKII inhibitor KN93, and SOCE blocker BTP2 attenuated the increase in the expression of CaMKIIδ and normalized the hypertrophic markers, atrial natriuretic peptide and brain natriuretic peptide, and size of cardiomyocytes induced by PE stimulation. The protein level of stromal interaction molecule 1 and Orai1, the essential components of the SOCE, is also enhanced in hypertrophic cardiomyocytes, which were normalized by CaMKIIδ siRNA and KN93 treatment. Hypertrophic cardiomyocytes showed an increase in the peak of Ca(2+) transient following store depletion, which was inhibited by SOCE blocker BTP2, CaMKIIδ siRNA, and KN93. The Ca(2+) currents through Ca(2+) release-activated Ca(2+) channels were increased in PE-treated cardiomyocytes and were attenuated by CaMKIIδ siRNA and KN93. These data indicate that PE-induced myocardial hypertrophy requires a complex signaling pathway that involves activation of both CaMKIIδ and SOCE. In conclusion, these studies reveal that up-regulation of CaMKIIδ may contribute to the PE-induced myocardial hypertrophy through the activation of SOCE expressed in

  4. Role of sarcoplasmic reticulum Ca2+ content in Ca2+ entry of bovine airway smooth muscle cells.

    PubMed

    Bazán-Perkins, Blanca; Flores-Soto, Edgar; Barajas-López, Carlos; Montaño, Luis M

    2003-10-01

    Depletion of intracellular Ca(2+) stores induces the opening of an unknown Ca(2+ )entry pathway to the cell. We measured the intracellular free-Ca(2+) concentration ([Ca(2+)]i) at different sarcoplasmic reticulum (SR) Ca(2+) content in fura-2-loaded smooth muscle cells isolated from bovine tracheas. The absence of Ca(2+) in the extracellular medium generated a time-dependent decrement in [Ca(2+)]i which was proportional to the reduction in the SR-Ca(2+) content. This SR-Ca(2+) level was indirectly determined by measuring the amount of Ca(2+) released by caffeine. Ca(2+) restoration at different times after Ca(2+)-free incubation (2, 4, 6 and 10 min) induced an increment of [Ca(2+)]i. This increase in [Ca(2+)]i was considered as Ca(2+) entry to the cell. The rate of this entry was slow (~0.3 nM/s) when SR-Ca(2+) content was higher than 50% (2 and 4 min in Ca(2+)-free medium), and significantly ( p<0.01) accelerated (>1.0 nM/s) when SR-Ca(2+) content was lower than 50% (6 and 10 min in Ca(2+)-free medium). Thapsigargin significantly induced a higher rate of this Ca(2+) entry ( p<0.01). Variations in Ca(2+) influx after SR-Ca(2+) depletion were estimated more directly by a Mn(2+) quench approach. Ca(2+) restoration to the medium 4 min after Ca(2+) removal did not modify the Mn(2+) influx. However, when Ca(2+) was added after 10 min in Ca(2+)-free medium, an increment of Mn(2+) influx was observed, corroborating an increase in Ca(2+) entry. The fast Ca(2+) influx was Ni(2+) sensitive but was not affected by other known capacitative Ca(2+) entry blockers such as La(3+), Mg(2+), SKF 96365 and 2-APB. It was also not affected by the blockage of L-type Ca2(+) channels with methoxyverapamil or by the sustained K(+)-induced depolarisation. The slow Ca(2+) influx was only sensitive to SKF 96365. In conclusion, our results indicate that in bovine airway smooth muscle cells Ca(2+) influx after SR-Ca(2+) depletion has two rates: A) The slow Ca(2+) influx, which occurred in cells

  5. A comparison of fluorescent Ca2+ indicators for imaging local Ca2+ signals in cultured cells

    PubMed Central

    Lock, Jeffrey T.; Parker, Ian

    2015-01-01

    Localized subcellular changes in Ca2+ serve as important cellular signaling elements, regulating processes as diverse as neuronal excitability and gene expression. Studies of cellular Ca2+ signaling have been greatly facilitated by the availability of fluorescent Ca2+ indicators. The respective merits of different indicators to monitor bulk changes in cellular Ca2+ levels have been widely evaluated, but a comprehensive comparison for their use in detecting and analyzing local, subcellular Ca2+ signals is lacking. Here, we evaluated several fluorescent Ca2+ indicators in the context of local Ca2+ signals (puffs) evoked by inositol 1,4,5-trisphosphate (IP3) in cultured human neuroblastoma SH-SY5Y cells, using high-speed video-microscopy. Altogether, nine synthetic Ca2+ dyes (Fluo-4, Fluo-8, Fluo-8 high affinity, Fluo-8 low affinity, Oregon Green BAPTA-1, Cal-520, Rhod-4, Asante Calcium Red, and X-Rhod-1) and three genetically-encoded Ca2+-indicators (GCaMP6-slow, -medium and -fast variants) were tested; criteria include the magnitude, kinetics, signal-to-noise ratio and detection efficiency of local Ca2+ puffs. Among these, we conclude that Cal-520 is the optimal indicator for detecting and faithfully tracking local events; that Rhod-4 is the red-emitting indicator of choice; and that none of the GCaMP6 variants are well suited for imaging subcellular Ca2+ signals. PMID:26572560

  6. Store-Operated Ca2+ Entry Sustains the Fertilization Ca2+ Signal in Pig Eggs.

    PubMed

    Wang, Chunmin; Zhang, Lu; Jaeger, Laurie A; Machaty, Zoltan

    2015-07-01

    The role of store-operated Ca(2+) entry (SOCE) in the maintenance of sperm-induced Ca(2+) oscillations was investigated in porcine eggs. We found that 10 μM gadolinium (Gd(3+)), which is known to inhibit SOCE, blocked Ca(2+) entry that was triggered by thapsigargin-induced store depletion and also caused an abrupt cessation of the fertilization Ca(2+) signal. In a similar manner 3,5-bis(trifluoromethyl)pyrazole 2 (20 μM), and tetrapandin-2 (10 μM), potent SOCE inhibitors, also blocked thapsigargin-stimulated Ca(2+) entry and disrupted the Ca(2+) oscillations after sperm-egg fusion. The downregulation of Stim1 or Orai1 in the eggs did not alter the Ca(2+) content of the intracellular stores, whereas co-overexpression of these proteins led to the generation of irregular Ca(2+) transients after fertilization that stopped prematurely. We also found that thapsigargin completely emptied the endoplasmic reticulum, and that the series of Ca(2+) transients stopped abruptly after the addition of thapsigargin to the fertilized eggs, indicating that the proper reloading of the intracellular stores is a prerequisite for the maintenance of the Ca(2+) oscillations. These data strengthen our previous findings that in porcine eggs SOCE is a major signaling cascade that is responsible for sustaining the repetitive Ca(2+) signal at fertilization.

  7. Combining Ca2+ imaging with -glutamate photorelease

    PubMed Central

    Canepari, Marco; De Waard, Michel; Ogden, David

    2013-01-01

    We describe simple configurations and methods to measure optical Ca2+ signals in response to photorelease of L-glutamate. This photostimulation allows activation of postsynaptic glutamate receptors without activation of voltage-gated Ca2+ channels permitting the separation and the analysis of different Ca2+ components. We give details of basic microscopy configurations and of tools to efficiently illuminate the preparation while preserving the healthy conditions of the tissues. We also suggest methodological procedures and we discuss protocols of linear optics to achieve simultaneous imaging and uncaging in relation to protocols using two photon illumination. PMID:24298028

  8. Thermoluminescence properties of Mn-doped CaYAl3O7 phosphor irradiated with ultra-violet, mega-voltage and gamma radiation

    NASA Astrophysics Data System (ADS)

    Pathak, Pushpraj; Selot, Anupam; Kurchania, Rajnish

    2014-06-01

    Low temperature combustion synthesis was employed for the preparation of CaYAl3O7(Mn2+) phosphor. X-Ray diffraction (XRD) patterns were recorded to confirm the phase formation. Estimated particle size was found to be ~19.9 nm by using the Debye Scherrer's formula. FTIR study confirms the formation of CaYAl3O7 compound, escape of nitrates and other organic products. Thermoluminescence (TL) glow curves of the prepared phosphor were recorded after exposing the sample with Ultra-violet (UV), 6-Mega-voltage (MV), 16-MV and Co-60(Cobalt-60, 1.25-MeV average gamma energy) radiation. Trapping parameters namely activation energy (E), order of kinetics (b) and frequency factor(s) of main peak, centered around 186 °C in the sample irradiated with UV source for 20 min, were determined using glow curve shape (Chen's) method. It has been observed that the TL peak intensity increases with increasing the exposure from UV source. Also with increases the energy of incident radiation a decrease in TL peak intensity were observed. This could be due to higher penetration power and less absorbance of incident beam in the phosphor material. Analysis suggests that possibility of utilizing this phosphor in futuristic low and high energy dosimetric applications as well as in solid state lighting devices.

  9. Ontogeny of Ca2+-induced Ca2+ release in rabbit ventricular myocytes.

    PubMed

    Huang, Jingbo; Hove-Madsen, Leif; Tibbits, Glen F

    2008-02-01

    It is commonly accepted that L-type Ca(2+) channel-mediated Ca(2+)-induced Ca(2+) release (CICR) is the dominant mode of excitation-contraction (E-C) coupling in the adult mammalian heart and that there is no appreciable CICR in neonates. However, we have observed that cell contraction in the neonatal heart was significantly decreased after sarcoplasmic reticulum (SR) Ca(2+) depletion with caffeine. Therefore, the present study investigated the developmental changes of CICR in rabbit ventricular myocytes at 3, 10, 20, and 56 days of age. We found that the inhibitory effect of the L-type Ca(2+) current (I(Ca)) inhibitor nifedipine (Nif; 15 microM) caused an increasingly larger reduction of Ca(2+) transients on depolarization in older age groups [from approximately 15% in 3-day-old (3d) myocytes to approximately 90% in 56-day-old (56d) myocytes]. The remaining Ca(2+) transient in the presence of Nif in younger age groups was eliminated by the inhibition of Na(+)/Ca(2+) exchanger (NCX) with the subsequent addition of 10 microM KB-R7943 (KB-R). Furthermore, Ca(2+) transients were significantly reduced in magnitude after the depletion of SR Ca(2+) with caffeine in all age groups, although the effect was significantly greater in the older age groups (from approximately 40% in 3d myocytes up to approximately 70% in 56d myocytes). This SR Ca(2+)-sensitive Ca(2+) transient in the earliest developmental stage was insensitive to Nif but was sensitive to the subsequent addition of KB-R, indicating the presence of NCX-mediated CICR that decreased significantly with age (from approximately 37% in 3d myocytes to approximately 0.5% in 56d myocytes). In contrast, the I(Ca)-mediated CICR increased significantly with age (from approximately 10% in 3d myocytes to approximately 70% in 56d myocytes). The CICR gain as estimated by the integral of the CICR Ca(2+) transient divided by the integral of its Ca(2+) transient trigger was smaller when mediated by NCX ( approximately 1.0 for 3d

  10. Regulated release of Ca2+ from respiring mitochondria by Ca2+/2H+ antiport.

    PubMed

    Fiskum, G; Lehninger, A L

    1979-07-25

    Simultaneous measurements of oxygen consumption and transmembrane transport of Ca2+, H+, and phosphate show that the efflux of Ca2+ from respiring tightly coupled rat liver mitochondria takes place by an electroneutral Ca2+/2H+ antiport process that is ruthenium red-insensitive and that is regulated by the oxidation-reduction state of the mitochondrial pyridine nucleotides. When mitochondrial pyridine nucleotides are kept in a reduced steady state, the efflux of Ca2+ is inhibited; when they are in an oxidized state, Ca2+ efflux is activated. These processes were demonstrated by allowing phosphate-depleted mitochondria respiring on succinate in the presence of rotenone to take up Ca2+ from the medium. Upon subsequent addition of ruthenium red to block Ca2+ transport via the electrophoretic influx pathway, and acetoacetate, to bring mitochondrial pyridine nucleotides into the oxidized state, Ca2+ efflux and H+ influx ensued. The observed H+ influx/Ca2+ efflux ratio was close to the value 2.0 predicted for the operation of an electrically neutral Ca2+/2H+ antiport process.

  11. Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals.

    PubMed

    Jin, Xin; Shah, Sihab; Du, Xiaona; Zhang, Hailin; Gamper, Nikita

    2016-01-01

    Ca(2+)-activated chloride channels (CaCCs) regulate numerous physiological processes including epithelial transport, smooth muscle contraction and sensory processing. Anoctamin-1 (ANO1, TMEM16A) is a principal CaCC subunit in many cell types, yet our understanding of the mechanisms of ANO1 activation and regulation are only beginning to emerge. Ca(2+) sensitivity of ANO1 is rather low and at negative membrane potentials the channel requires several micromoles of intracellular Ca(2+) for activation. However, global Ca(2+) levels in cells rarely reach such levels and, therefore, there must be mechanisms that focus intracellular Ca(2+) transients towards the ANO1 channels. Recent findings indeed indicate that ANO1 channels often co-localize with sources of intracellular Ca(2+) signals. Interestingly, it appears that in many cell types ANO1 is particularly tightly coupled to the Ca(2+) release sites of the intracellular Ca(2+) stores. Such preferential coupling may represent a general mechanism of ANO1 activation in native tissues.

  12. Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling

    PubMed Central

    Baumgart, Joel P.; Zhou, Zhen-Yu; Hara, Masato; Cook, Daniel C.; Hoppa, Michael B.; Ryan, Timothy A.; Hemmings, Hugh C.

    2015-01-01

    Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in Ca2+ entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca2+ entry without significant direct effects on Ca2+-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca2+ influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID:26351670

  13. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling

    PubMed Central

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-01-01

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca2+ signals, which are confined in their spatiotemporal extent by endogenous Ca2+ buffers. However, it remains elusive how rapid and reliable Ca2+ signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca2+ imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca2+-binding ratio (∼15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca2+ from the active zone during repetitive firing. Measuring Ca2+ signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca2+ buffering enables fast active zone Ca2+ signaling, suggesting that the strength of endogenous Ca2+ buffering limits the rate of synchronous synaptic transmission. PMID:26015575

  14. 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

  15. 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.

  16. Endogenous Ca2+ buffer concentration and Ca2+ microdomains in hippocampal neurons.

    PubMed

    Müller, Andreas; Kukley, Maria; Stausberg, Pia; Beck, Heinz; Müller, Wolfgang; Dietrich, Dirk

    2005-01-19

    Ca2+-binding proteins are ubiquitously expressed throughout the CNS and serve as valuable immunohistochemical markers for certain types of neurons. However, the functional role of most Ca2+-binding proteins has to date remained obscure because their concentration in central neurons is not known. In this study, we investigate the intracellular concentration of the widely expressed Ca2+-binding protein calbindin-D28k in adult hippocampal slices using patch-clamp recordings and immunohistochemistry. First, we show that calbindin-D28k freely exchanges between patch pipette and cytoplasm during whole cell patch-clamp recordings with a time constant of approximately 10 min. Substituting known concentrations of recombinant calbindin-D28k in patch pipettes enabled us to determine the endogenous calbindin-D28k concentration by postrecording immunohistochemistry. Using this calibration procedure, we find that mature granule cells (doublecortin-) contain approximately 40 microm, and newborn granule cells (doublecortin+) contain 0-20 microm calbindin-D28k. CA3 stratum radiatum interneurons and CA1 pyramidal cells enclose approximately 47 and approximately 45 microm calbindin-D28k, respectively. Numerical simulations showed that 40 microm calbindin-D28k is capable of tuning Ca2+ microdomains associated with action potentials at the mouth of single or clustered Ca2+ channels: calbindin-D28k reduces the increment in free Ca2+ at a distance of 100 and 200 nm by 20 and 35%, respectively, and strongly accelerates the collapse of the Ca2+ gradient after cessation of Ca2+ influx. These data suggest that calbindin-D28k equips hippocampal neurons with approximately 160 microm mobile, high-affinity Ca2+-binding sites (kappa(S) approximately 200) that slow and reduce global Ca2+ signals while they enhance the spatiotemporal fidelity of submicroscopic Ca2+ signals.

  17. Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload-induced triggered arrhythmias

    PubMed Central

    Nagy, Norbert; Kormos, Anita; Kohajda, Zsófia; Szebeni, Áron; Szepesi, Judit; Pollesello, Piero; Levijoki, Jouko; Acsai, Károly; Virág, László; Nánási, Péter P; Papp, Julius Gy; Varró, András; Tóth, András

    2014-01-01

    Background and Purpose Augmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti-arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump. Experimental Approach Action potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole-cell patch clamp technique. Ca2+i transients (CaTs) were monitored with a Ca2+-sensitive fluorescent dye, Fluo-4. Key Results Enhanced INaL increased the Ca2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX-II)-induced [Ca2+]i rise without influencing APD, CaT or cell shortening, or affecting the ATX-II-induced increased APD. ORM10103 significantly decreased the number of strophanthidin-induced spontaneous diastolic Ca2+ release events; however, SEA0400 failed to restrict the veratridine-induced augmentation in Purkinje-ventricle APD dispersion. Conclusions and Implications Selective NCX inhibition – presumably by blocking revINCX (reverse mode NCX current) – is effective against arrhythmogenesis caused by [Na+]i-induced [Ca2+]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca2+i handling, should be considered as a promising anti-arrhythmic therapeutic strategy. PMID:25073832

  18. Calcium transport in bovine rumen epithelium as affected by luminal Ca concentrations and Ca sources

    PubMed Central

    Schröder, Bernd; Wilkens, Mirja R; Ricken, Gundula E; Leonhard-Marek, Sabine; Fraser, David R; Breves, Gerhard

    2015-01-01

    The quantitative role of different segments of the gastrointestinal tract for Ca absorption, the respective mechanisms, and their regulation are not fully identified for ruminants, that is, cattle. In different in vitro experiments the forestomach wall has been demonstrated to be a major site for active Ca absorption in sheep and goats. In order to further clarify the role of the bovine rumen for Ca transport with special attention to luminal Ca concentrations, its ionic form, and pH, electrophysiological and unidirectional flux rate measurements were performed with isolated bovine rumen epithelial tissues. For Ca flux studies (Jms, Jsm) in vitro Ussing chamber technique was applied. Standard RT-PCR method was used to characterize TRPV6 and PMCA1 as potential contributors to transepithelial active Ca transport. At Ca concentrations of 1.2 mmol L−1 on both sides of the tissues, Jms were higher than Jsm resulting under some conditions in significant Ca net flux rates (Jnet), indicating the presence of active Ca transport. In the absence of an electrical gradient, Jnet could significantly be stimulated in the presence of luminal short-chain fatty acids (SCFAs). Increasing the luminal Ca concentrations up to 11.2 mmol L−1 resulted in significant increases in Jms without influencing Jsm. Providing Ca in its form as respective chloride, formate, or propionate salts there was no significant effect on Jms. No transcripts specific for Ca channel TRPV6 could be demonstrated. Our results indicate different mechanisms for Ca absorption in bovine rumen as compared with those usually described for the small intestines. PMID:26564067

  19. Pituitary Ca/sup 2 +/ channels: blockade by conventional and novel Ca/sup 2 +/ antagonists

    SciTech Connect

    Enyeart, J.J.; Sheu, S.S.; Hinkle, P.M.

    1987-07-01

    The authors have identified several new agents that block Ca/sup 2 +/ channels in the rat pituitary GH/sub 4/C/sub 1/ cell line. These drugs, which include the diphenylbutylpiperidine antipsychotic pimozide, the calmodulin antagonist calmidazolium, and the steroidal Na/sup +/ channel toxin veratridine, were compared with several conventional Ca/sup 2 +/ antagonists in /sup 45/Ca/sup 2 +/ uptake, prolactin secretion, and whole cell patch voltage-clamp experiments. Pimozide, the most potent of these novel Ca/sup 2 +/ antagonists, inhibited depolarization-dependent /sup 45/Ca/sup 2 +/ uptake and prolactin secretion half maximally at a concentration of 100 nM, whereas calmidazolium and veratridine produced 50% inhibition at concentrations of 500 nM and 1 ..mu..M. In comparison, the three organic Ca/sup 2 +/ antagonists nitrendipine, verapamil, and diltiazem blocked /sup 45/Ca/sup 2 +/ uptake half maximally at concentrations of 2.5 nM, 1 ..mu..M, and 2.5 ..mu..M, respectively. All of the antagonists inhibited Ca/sup 2 +/ uptake and prolactin secretion stimulated by the dihydropyridine Ca/sup 2 +/ agonist BAY-K 8644 less potently than KCl-stimulated responses. In patch-clamp experiments, pimozide, veratridine, and nitrendipine blocked Ca/sup 2 +/ current through the slowly inactivating Ca/sup 2 +/ channels of GH/sub 4/C/sub 1/ cells. These results demonstrate that Ca/sup 2 +/ channels in an endocrine cell line can be blocked by a variety of molecules including sodium channel toxins and calmodulin antagonists. The data extend the pharmacological similarity between Ca/sup 2 +/ channels in pituitary and other excitable cells and suggest a structural similarity among several cellular proteins.

  20. Ca Isotope Fractionation in the Hawaiian Ecosystem

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

    Investigations of the nutrient budgets in Hawaiian soils show the sources of major cations to be weathering of volcanic rock, marine aerosols, and Asian dust inputs. Especially at deeply weathered sites older than 150 ka, soils show strong depletion of the macronutrient calcium. Most of the calcium supply in these soils is of atmospheric origin (marine aerosols and continental dust). In contrast, younger soils are mainly supplied by calcium from weathering of volcanic bedrock. Based on the results of previous studies using strontium isotopic signatures and Sr/Ca ratios (e.g. Kennedy et al. 1998, Chadwick et al. 1999, Whipkey et al. 2000, Stewart et al. 2001) we have conducted research focusing on the isotope composition of calcium as a new tool for the investigation of sources of calcium and biogeochemical processes effecting Ca isotope fractionation in the plant-soil system. The study combines δ 44Ca with 87Sr/86Sr and Sr/Ca data of soils (bulk compositions and extractable Ca and Sr from soil exchange sites) and different plant species including native Ohia trees (Metrosideros polymorpha) from a soil chronosequence along the Hawaiian Island chain. The study sites differ in age of the underlying substrate from 0.3 ka to 4,100 ka, but show similar recent climate (mean annual temperature of 16 ° C) and amount of precipitation (about 2,500 mm/y). 44Ca/40Ca ratios were measured on a MAT262 at Stanford University, using a 42Ca-48Ca double spike, and are reported as δ 44Ca values relative to seawater (δ 44Ca = 0 ‰ ). Results of the extractable, plant available calcium from six soil sites show δ 44Ca values in the range of +1.2 ‰ to -1.3 ‰ with generally more negative values related to younger soil sites where calcium is mainly derived from weathering of volcanic rocks. Bulk soil samples, however, show δ 44Ca values between -0.1 ‰ and -2.5 ‰ , indicating differences in composition as a result of contributions from volcanic minerals, continental dust, and

  1. Motion of the Ca2+-pump captured.

    PubMed

    Yokokawa, Masatoshi; Takeyasu, Kunio

    2011-09-01

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

  2. 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.

  3. 17beta-Estradiol potentiates field excitatory postsynaptic potentials within each subfield of the hippocampus with greatest potentiation of the associational/commissural afferents of CA3.

    PubMed

    Kim, M T; Soussou, W; Gholmieh, G; Ahuja, A; Tanguay, A; Berger, T W; Brinton, R D

    2006-08-11

    We sought to determine the impact of 17beta-estradiol throughout the hippocampal trisynaptic pathway and to investigate the afferent fiber systems within CA1 and CA3 in detail. To achieve this objective, we utilized multielectrode arrays to simultaneously record the field excitatory postsynaptic potentials from the CA1, dentate gyrus, and CA3 of rat hippocampal slices in the presence or absence of 100 pM 17beta-estradiol. We confirmed our earlier findings in CA1, where 17beta-estradiol significantly increased field excitatory postsynaptic potentials amplitude (20%+/-3%) and slope (22%+/-7%). 17beta-Estradiol significantly potentiated the field excitatory postsynaptic potentials in dentate gyrus, amplitude (15%+/-4%) and slope (17%+/-5), and in CA3, amplitude (15%+/-4%) and slope (19%+/-5%). Using a high-density multielectrode array, we sought to determine the source of potentiation in CA1 and CA3 by determining the impact of 17beta-estradiol on the apical afferents and the basal afferents within CA1 and on the mossy fibers and the associational/commissural fibers within CA3. In CA1, 17beta-estradiol induced a modest increase in the amplitude (7%+/-2%) and slope (9%+/-3%) following apical stimulation with similar magnitude of increase following basal stimulation amplitude (10%+/-2%) and slope (12%+/-3%). In CA3, 17beta-estradiol augmented the mossy fiber amplitude (15%+/-3%) and slope (18%+/-6%) and the associational/commissural fiber amplitude (31%+/-13%) and slope (40%+/-15%). These results indicate that 17beta-estradiol potentiated synaptic transmission in each subfield of the hippocampal slice, with the greatest magnitude of potentiation at the associational/commissural fibers in CA3. 17beta-Estradiol regulation of CA3 responses provides a novel site of 17beta-estradiol action that corresponds to the density of estrogen receptors within the hippocampus. The implications of 17beta-estradiol potentiation of the field potential in each of the hippocampal subfields

  4. 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.

  5. Ca2+ transients in cardiac myocytes measured with high and low affinity Ca2+ indicators.

    PubMed Central

    Berlin, J R; Konishi, M

    1993-01-01

    Intracellular calcium ion ([Ca2+]i) transients were measured in voltage-clamped rat cardiac myocytes with fura-2 or furaptra to quantitate rapid changes in [Ca2+]i. Patch electrode solutions contained the K+ salt of fura-2 (50 microM) or furaptra (300 microM). With identical experimental conditions, peak amplitude of stimulated [Ca2+]i transients in furaptra-loaded myocytes was 4- to 6-fold greater than that in fura-2-loaded cells. To determine the reason for this discrepancy, intracellular fura-2 Ca2+ buffering, kinetics of Ca2+ binding, and optical properties were examined. Decreasing cellular fura-2 concentration by lowering electrode fura-2 concentration 5-fold, decreased the difference between the amplitudes of [Ca2+]i transients in fura-2 and furaptra-loaded myocytes by twofold. Thus, fura-2 buffers [Ca2+]i under these conditions; however, Ca2+ buffering is not the only factor that explains the different amplitudes of the [Ca2+]i transients measured with these indicators. From the temporal comparison of the [Ca2+]i transients measured with fura-2 and furaptra, the apparent reverse rate constant for Ca2+ binding of fura-2 was at least 65s-1, much faster than previously reported in skeletal muscle fibers. These binding kinetics do not explain the difference in the size of the [Ca2+]i transients reported by fura-2 and furaptra. Parameters for fura-2 calibration, Rmin, Rmax, and beta, were obtained in salt solutions (in vitro) and in myocytes exposed to the Ca2+ ionophore, 4-Br A23187, in EGTA-buffered solutions (in situ). Calibration of fura-2 fluorescence signals with these in situ parameters yielded [Ca2+]i transients whose peak amplitude was 50-100% larger than those calculated with in vitro parameters. Thus, in vitro calibration of fura-2 fluorescence significantly underestimates the amplitude of the [Ca2+]i transient. These data suggest that the difference in amplitude of [Ca2+]i transients in fura-2 and furaptra-loaded myocytes is due, in part, to Ca2

  6. Identification of the neighborhood and CA rules from spatio-temporal CA patterns.

    PubMed

    Billings, S A; Yang, Yingxu

    2003-01-01

    Extracting the rules from spatio-temporal patterns generated by the evolution of cellular automata (CA) usually produces a CA rule table without providing a clear understanding of the structure of the neighborhood or the CA rule. In this paper, a new identification method based on using a modified orthogonal least squares or CA-OLS algorithm to detect the neighborhood structure and the underlying polynomial form of the CA rules is proposed. The Quine-McCluskey method is then applied to extract minimum Boolean expressions from the polynomials. Spatio-temporal patterns produced by the evolution of 1D, 2D, and higher dimensional binary CAs are used to illustrate the new algorithm, and simulation results show that the CA-OLS algorithm can quickly select both the correct neighborhood structure and the corresponding rule.

  7. X-Ray Data on Extraterrestrial CA Dialuminate (CaAl4O7)

    NASA Astrophysics Data System (ADS)

    Weber, D.; Ross, C. R., II; Bischoff, A.

    1993-07-01

    After the first discovery of Ca-dialuminate (CaAl4O7) in Allende [1], in recent years this phase has been found in several carbonaceous chondrites. Ca- dialuminate is a major phase in Ca,Al-rich inclusions from ALH85085 (e.g., [2]) and a dominating phase in CAIs from Acfer 182 ([3,4]). X-ray data on Ca-dialuminate are known from synthetic (e.g., [5-8]; cell constants) and terrestrial CaAl4O7 ([9]; only d-spacings), but are not available from extraterrestrial Ca-dialuminate. We report here the results of the first X-ray study of extraterrestrial Ca- dialuminate. The data (Table 1) were obtained by microdiffraction using a Rigaku PSPC microdiffractometer at the Bayerisches Geoinstitut. Ni-filtered Cr radiation was used with a direct beam diameter of about 50 micrometers. This powder diffraction method allows in situ measurement of polycrystalline Ca- dialuminate in a thin section. The CaAl4O7-rich inclusion 022/9 described in [4], consisting of a ~200-micrometer-sized core of Ca-dialuminate surrounded by layers of melilite and Ca-pyroxene, was chosen for analysis. The polycrystalline core contains only a small number of tiny inclusions (especially perovskite) and is therefore an excellent candidate for an X-ray study. For determination of the d-spacings of Ca-dialuminate an external standard (Ag6Ge10P12) was used for detector calibration. A large number of reflections could be indexed based upon comparison with the X-ray pattern of synthetic CaAl4O7 available in the JCPDS compilation [7]. The comparison was simplified because of the high purity of CaAl4O7 in inclusion 022/9 [4], and suggests the same structure for synthetic and extraterrestrial Ca-dialuminate. For determination of lattice parameters (cell constants, cell volume) refinement calculations were made based on 14 reflections (Table 1). The data for extraterrestrial CaAl4O7 shown in Table 1 indicate a close similarity to those obtained for synthetic CaAl4O7. The cell constants a, b, and therefore the cell

  8. Autophosphorylation-based Calcium (Ca2+) Sensitivity Priming and Ca2+/Calmodulin Inhibition of Arabidopsis thaliana Ca2+-dependent Protein Kinase 28 (CPK28)*♦

    PubMed Central

    Blackburn, R. Kevin; Monaghan, Jacqueline; Derbyshire, Paul; Menke, Frank L. H.; Zipfel, Cyril; Goshe, Michael B.; Zielinski, Raymond E.; Huber, Steven C.

    2017-01-01

    Plant calcium (Ca2+)-dependent protein kinases (CPKs) represent the primary Ca2+-dependent protein kinase activities in plant systems. CPKs are composed of a dual specificity (Ser/Thr and Tyr) kinase domain tethered to a calmodulin-like domain (CLD) via an autoinhibitory junction (J). Although regulation of CPKs by Ca2+ has been extensively studied, the contribution of autophosphorylation in controlling CPK activity is less well understood. Furthermore, whether calmodulin (CaM) contributes to CPK regulation, as is the case for Ca2+/CaM-dependent protein kinases outside the plant lineage, remains an open question. We therefore screened a subset of plant CPKs for CaM binding and found that CPK28 is a high affinity Ca2+/CaM-binding protein. Using synthetic peptides and native gel electrophoresis, we coarsely mapped the CaM-binding domain to a site within the CPK28 J domain that overlaps with the known site of intramolecular interaction between the J domain and the CLD. Peptide kinase activity of fully dephosphorylated CPK28 was Ca2+-responsive and was inhibited by Ca2+/CaM. Using in situ autophosphorylated protein, we expand on the known set of CPK28 autophosphorylation sites, and we demonstrate that, unexpectedly, autophosphorylated CPK28 had enhanced kinase activity at physiological concentrations of Ca2+ compared with the dephosphorylated protein, suggesting that autophosphorylation functions to prime CPK28 for Ca2+ activation and might also allow CPK28 to remain active when Ca2+ levels are low. Furthermore, CPK28 autophosphorylation substantially reduced sensitivity of the kinase to Ca2+/CaM inhibition. Overall, our analyses uncover new complexities in the control of CPK28 and provide mechanistic support for Ca2+ signaling specificity through Ca2+ sensor priming. PMID:28154194

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

    PubMed

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

    2016-08-01

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

  10. Functional properties of a sarcoplasmic reticulum Ca(2+)-ATPase with an altered Ca(2+)-binding mechanism.

    PubMed Central

    Martinez-Azorin, F; Soler, F; Gomez-Fernandez, J C; Fernandez-Belda, F

    1995-01-01

    Treatment of sarcoplasmic reticulum vesicles with diethylpyrocarbonate in the presence of a large excess of reagent, at pH 6.2 and at room temperature, reveals both a fast- and a slow-reacting population of protein residues. The loss of the Ca(2+)-ATPase activity is mainly associated with the fast-reacting population being partially sensitive to hydroxylamine. There is also an effect on the Ca(2+)-binding mechanism. Shorter derivatization times (5 min) produce a loss of the positive cooperativity of Ca2+ binding. When the treatment was prolonged for 30 min there was an additional decrease in the overall Ca2+ affinity. Curve-fitting procedures applied to the non-cooperative binding isotherms provide the equilibrium constants for the two Ca2+ sites, although they cannot discriminate between interacting and independent site mechanisms. Prestationary kinetics assays show 2 Ca2+:1 ATP ratios, at any extent of Ca2+ saturation, indicating that the Ca2+ sites are not independent. The Ca2+ dissociation profile after derivatization shows a decrease in the dissociation constant for the release of the second Ca2+, which is consistent with interacting sites. Isotopic exchange experiments show fast and slow components of equal amplitude even at subsaturating Ca2+ concentrations, which is incompatible with independent binding sites. The experimental data suggest a modification of the equilibrium binding constants making them more similar, but keeping the interacting character. The structural position of the external (cytoplasmic) and the internal (lumenal) Ca2+ sites remains unaltered in the absence of positive cooperativity. PMID:7626012

  11. Modulation of Ca(2+) release and Ca(2+) oscillations in HeLa cells and fibroblasts by mitochondrial Ca(2+) uniporter stimulation.

    PubMed

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

    2007-04-01

    The recent availability of activators of the mitochondrial Ca(2+) uniporter allows direct testing of the influence of mitochondrial Ca(2+) uptake on the overall Ca(2+) homeostasis of the cell. We show here that activation of mitochondrial Ca(2+) uptake by 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca(2+) release from the endoplasmic reticulum (ER) and that this effect is enhanced if the mitochondrial Na(+)-Ca(2+) exchanger is simultaneously inhibited with CGP37157. This suggests that both Ca(2+) uptake and release from mitochondria control the ability of local Ca(2+) microdomains to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP(3)Rs). In addition, the ability of mitochondria to control Ca(2+) release from the ER allows them to modulate cytosolic Ca(2+) oscillations. In histamine stimulated HeLa cells and human fibroblasts, both PPT and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually induced a more prolonged period of stimulation. Both compounds were also able to induce the generation of Ca(2+) oscillations in previously silent fibroblasts. Our data suggest that cytosolic Ca(2+) oscillations are exquisitely sensitive to the rates of mitochondrial Ca(2+) uptake and release, which precisely control the size of the local Ca(2+) microdomains around InsP(3)Rs and thus the ability to produce feedback activation or inhibition of Ca(2+) release.

  12. Modulation of Ca2+ release and Ca2+ oscillations in HeLa cells and fibroblasts by mitochondrial Ca2+ uniporter stimulation

    PubMed Central

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

    2007-01-01

    The recent availability of activators of the mitochondrial Ca2+ uniporter allows direct testing of the influence of mitochondrial Ca2+ uptake on the overall Ca2+ homeostasis of the cell. We show here that activation of mitochondrial Ca2+ uptake by 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca2+ release from the endoplasmic reticulum (ER) and that this effect is enhanced if the mitochondrial Na+–Ca2+ exchanger is simultaneously inhibited with CGP37157. This suggests that both Ca2+ uptake and release from mitochondria control the ability of local Ca2+ microdomains to produce feedback inhibition of inositol 1,4,5-trisphosphate receptors (InsP3Rs). In addition, the ability of mitochondria to control Ca2+ release from the ER allows them to modulate cytosolic Ca2+ oscillations. In histamine stimulated HeLa cells and human fibroblasts, both PPT and kaempferol initially stimulated and later inhibited oscillations, although kaempferol usually induced a more prolonged period of stimulation. Both compounds were also able to induce the generation of Ca2+ oscillations in previously silent fibroblasts. Our data suggest that cytosolic Ca2+ oscillations are exquisitely sensitive to the rates of mitochondrial Ca2+ uptake and release, which precisely control the size of the local Ca2+ microdomains around InsP3Rs and thus the ability to produce feedback activation or inhibition of Ca2+ release. PMID:17234694

  13. Role of [Ca2+]i in "Ca2+ stores depletion-Ca2+ entry coupling' in fibroblasts expressing the rat neurotensin receptor.

    PubMed Central

    Gailly, P; Hermans, E; Gillis, J M

    1996-01-01

    1. Transfected Chinese hamster ovary fibroblasts expressing the rat neurotensin receptor were used to study the 'Ca2+ stores depletion-Ca2+ entry coupling' which follows stimulation with neurotensin and liberation of InsP3. 2. This coupling could be dissociated in time. Firstly, stores depletion was produced by neurotensin or thapsigargin which caused a first [Ca2+]i transient in a Ca(2+)-free external medium. Secondly, readmission of external Ca2+ produced an influx of Ca2+ and a second [Ca2+]i transient. 3. Various concentrations of thapsigargin (20 nM to 1 microM) were used to produce complete stores depletion with small or large first peaks of [Ca2+]i. Upon return to external Ca2+, small or large second [Ca2+]i peaks were observed. The amplitudes of both peaks were positively correlated. 4. The Ca2+ entry which followed stores depletion could occur at very low basal values of [Ca2+]i, was accelerated by okadaic acid and inhibited by staurosporine and the calmodulin antagonist W-7. 5. It is concluded that the rise in [Ca2+]i during Ca2+ stores depletion is an essential parameter which determines the size of the subsequent Ca2+ entry. PMID:8815199

  14. Physical conditions in CaFe interstellar clouds

    NASA Astrophysics Data System (ADS)

    Gnaciński, P.; Krogulec, M.

    2008-01-01

    Interstellar clouds that exhibit strong Ca I and Fe I lines are called CaFe clouds. Ionisation equilibrium equations were used to model the column densities of Ca II, Ca I, K I, Na I, Fe I and Ti II in CaFe clouds. We find that the chemical composition of CaFe clouds is solar and that there is no depletion into dust grains. CaFe clouds have high electron densities, n_e≈1 cm-3, that lead to high column densities of neutral Ca and Fe.

  15. Regulation of RYR1 activity by Ca(2+) and calmodulin

    NASA Technical Reports Server (NTRS)

    Rodney, G. G.; Williams, B. Y.; Strasburg, G. M.; Beckingham, K.; Hamilton, S. L.

    2000-01-01

    The skeletal muscle calcium release channel (RYR1) is a Ca(2+)-binding protein that is regulated by another Ca(2+)-binding protein, calmodulin. The functional consequences of calmodulin's interaction with RYR1 are dependent on Ca(2+) concentration. At nanomolar Ca(2+) concentrations, calmodulin is an activator, but at micromolar Ca(2+) concentrations, calmodulin is an inhibitor of RYR1. This raises the question of whether the Ca(2+)-dependent effects of calmodulin on RYR1 function are due to Ca(2+) binding to calmodulin, RYR1, or both. To distinguish the effects of Ca(2+) binding to calmodulin from those of Ca(2+) binding to RYR1, a mutant calmodulin that cannot bind Ca(2+) was used to evaluate the effects of Ca(2+)-free calmodulin on Ca(2+)-bound RYR1. We demonstrate that Ca(2+)-free calmodulin enhances the affinity of RYR1 for Ca(2+) while Ca(2+) binding to calmodulin converts calmodulin from an activator to an inhibitor. Furthermore, Ca(2+) binding to RYR1 enhances its affinity for both Ca(2+)-free and Ca(2+)-bound calmodulin.

  16. Negative feedback from CaSR signaling to aquaporin-2 sensitizes vasopressin to extracellular Ca2.

    PubMed

    Ranieri, Marianna; Tamma, Grazia; Di Mise, Annarita; Russo, Annamaria; Centrone, Mariangela; Svelto, Maria; Calamita, Giuseppe; Valenti, Giovanna

    2015-07-01

    We previously described that high luminal Ca(2+) in the renal collecting duct attenuates short-term vasopressin-induced aquaporin-2 (AQP2) trafficking through activation of the Ca(2+)-sensing receptor (CaSR). Here, we evaluated AQP2 phosphorylation and permeability, in both renal HEK-293 cells and in the dissected inner medullary collecting duct, in response to specific activation of CaSR with NPS-R568. In CaSR-transfected cells, CaSR activation drastically reduced the basal levels of AQP2 phosphorylation at S256 (AQP2-pS256), thus having an opposite effect to vasopressin action. When forskolin stimulation was performed in the presence of NPS-R568, the increase in AQP2-pS256 and in the osmotic water permeability were prevented. In the freshly isolated inner mouse medullar collecting duct, stimulation with forskolin in the presence of NPS-R568 prevented the increase in AQP2-pS256 and osmotic water permeability. Our data demonstrate that the activation of CaSR in the collecting duct prevents the cAMP-dependent increase in AQP2-pS256 and water permeability, counteracting the short-term vasopressin response. By extension, our results suggest the attractive concept that CaSR expressed in distinct nephron segments exerts a negative feedback on hormones acting through cAMP, conferring high sensitivity of hormone to extracellular Ca(2+).

  17. Spatial Ca(2+) profiling: decrypting the universal cytosolic Ca(2+) oscillation.

    PubMed

    Samanta, Krishna; Parekh, Anant B

    2016-11-17

    Stimulation of cell-surface receptors that couple to phospholipase C to generate the second messenger inositol trisphosphate often evokes repetitive oscillations in cytosolic Ca(2+) . Signalling information is encoded in both the amplitude and frequency of the Ca(2+) spikes. Recent studies have revealed that the spatial profile of the oscillation also imparts signalling power; Ca(2+) microdomains near store-operated CRAC channels in the plasma membrane and inositol trisphosphate-gated channels in the endoplasmic reticulum both signal to distinct downstream targets. Spatial profiling therefore increases the transduction power of the universal oscillatory cytosolic Ca(2+) signal.

  18. Radioisotope tracer studies of inorganic carbon and Ca in microbially derived CaCO3

    USGS Publications Warehouse

    Yates, Kimberly K.; Robbins, Lisa L.

    1999-01-01

    Microbial calcification significantly impacts the cycling and deposition of inorganic carbon. This research employs 45Ca and 14C techniques as radioisotopic tracers to examine the role of cellular cycling of Ca2+ and inorganic carbon in CaCO3 precipitation by the unicellular green alga Nannochloris atomus. Implications of the effects of these physiological aspects on CaCO3 precipitation and the effects of microbial calcification on CaCO3 δ13C ratios are discussed. Results from pulse/chase experiments indicate that intracellular Ca2+ is incorporated into extracellular CaCO3. Intracellular inorganic carbon leaks from cells within 10 to 12 s after injection of unlabelled NaHCO3, providing a source of inorganic carbon for extracellular CaCO3. Cellular expulsion of calcium plays a key role in increasing the CaCO3 saturation state at the site of calcification. The δ13C ratios of microbial carbonates may vary depending on the amount of photorespiratory CO2 incorporated.

  19. Mg/Ca of Continental Ostracode Shells

    NASA Astrophysics Data System (ADS)

    Ito, E.; Forester, R. M.; Marco-Barba, J.; Mezquita, F.

    2007-12-01

    Marine ionic chemistry is thought to remain constant. This, together with the belief that marine calcifiers partition Mg/Ca in a systematic manner as functions of temperature (and Mg/Ca) of water forms the basis of the Mg/Ca thermometer. In continental settings both of these assumptions are usually not true. Continental waters contain a wide variety of solutes in absolute and relative ion concentrations. Hence, waters with identical Mg/Ca may have very different concentrations of Mg and Ca and very different anions. Here we use two examples to focus on the effects of ion chemistry on Mg/Ca partitioning in continental ostracode shells and we ignore the complexities of solute evolution, which can change Mg/Ca over timescales of minutes to millennia. Palacios-Fest and Dettman (2001) conducted a monthly study of ,Cypridopsis vidua at El Yeso Lake in Sonora, Mexico. They established a relation between temperature and average shell Mg/Ca using regression analyses on averaged data. When their Mg/Ca-temperature relation is applied to monthly ,C. vidua data from Page Pond near Cleveland, Ohio, water temperatures of -8 to -1°C are obtained. The observed Mg/Ca ranges for El Yeso Lake (0.31 to 0.46) and Page Pond (0.33 to 0.46) are similar, as are their specific conductivities (700 to 850μS for El Yeso Lake; 400 to 600μS for Page Pond). However, [Ca] is 140-260 mg/L for El Yeso, but only 70-90 mg/L for Page Pond. Page Pond data, in fact, shows a good temperature shell Mg/Ca relation for .C. vidua, but the relation is different from that at El Yeso. Hence, shell Mg/Ca is a multi-valued, family of curves function of temperature and Mg/Ca of water that depends on the [Mg] and [Ca] values in water and perhaps other factors. Our second example comes from sites near Valencia, Spain and involves shell data for ,Cyprideis torosa, an estuarine ostracode that is tolerant of a wide range of salinity and can live in continental waters as long as the carbonate alkalinity to Ca ratio is

  20. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... warehouse as prescribed by § 19.12. (c) Release of merchandise. Merchandise in general order may be released... presentation to the warehouse proprietor of an approved copy of Customs Form 5251 (Order to Transfer... 19 Customs Duties 1 2010-04-01 2010-04-01 false General order, abandoned, and seized...

  1. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Customs-authorized permit to transfer or in-bond entry) is responsible for preparing a Customs Form (CF... and condition of the goods and that reported on CF 6043, or other similar Customs document...

  2. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Customs-authorized permit to transfer or in-bond entry) is responsible for preparing a Customs Form (CF... and condition of the goods and that reported on CF 6043, or other similar Customs document...

  3. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Customs-authorized permit to transfer or in-bond entry) is responsible for preparing a Customs Form (CF... and condition of the goods and that reported on CF 6043, or other similar Customs document...

  4. Dual PI3K/mTOR Inhibition in Colorectal Cancers with APC and PIK3CA Mutations.

    PubMed

    Foley, Tyler M; Payne, Susan N; Pasch, Cheri A; Yueh, Alex E; Van De Hey, Dana R; Korkos, Demetra P; Clipson, Linda; Maher, Molly E; Matkowskyj, Kristina A; Newton, Michael A; Deming, Dustin A

    2017-02-09

    Therapeutic targeting of the PI3K pathway is an active area of research in multiple cancer types, including breast and endometrial cancers. This pathway is commonly altered in cancer and plays an integral role in numerous vital cellular functions. Mutations in the PIK3CA gene, resulting in a constitutively active form of PI3K, often occur in colorectal cancer, though the population of patients who would benefit from targeting this pathway has yet to be identified. In human colorectal cancers, PIK3CA mutations most commonly occur concomitantly with loss of adenomatous polyposis coli (APC). Here, treatment strategies are investigated that target the PI3K pathway in colon cancers with mutations in APC and PIK3CA Colorectal cancer spheroids with Apc and Pik3ca mutations were generated and characterized confirming that these cultures represent the tumors from which they were derived. Pan and alpha isomer-specific PI3K inhibitors did not induce a significant treatment response, whereas the dual PI3K/mTOR inhibitors BEZ235 and LY3023414 induced a dramatic treatment response through decreased cellular proliferation and increased differentiation. The significant treatment responses were confirmed in mice with Apc and Pik3ca-mutant colon cancers as measured using endoscopy with a reduction in median lumen occlusion of 53% with BEZ235 and a 24% reduction with LY3023414 compared with an increase of 53% in controls (P < 0.001 and P = 0.03, respectively). This response was also confirmed with (18)F-FDG microPET/CT imaging.Implications: Spheroid models and transgenic mice suggest that dual PI3K/mTOR inhibition is a potential treatment strategy for APC and PIK3CA-mutant colorectal cancers. Thus, further clinical studies of dual PI3K/mTOR inhibitors are warranted in colorectal cancers with these mutations. Mol Cancer Res; 15(3); 1-11. ©2016 AACR.

  5. The Phosphatase-Resistant Isoform of CaMKI, Ca²⁺/Calmodulin-Dependent Protein Kinase Iδ (CaMKIδ), Remains in Its "Primed" Form without Ca²⁺ Stimulation.

    PubMed

    Senga, Yukako; Ishida, Atsuhiko; Shigeri, Yasushi; Kameshita, Isamu; Sueyoshi, Noriyuki

    2015-06-16

    Ca²⁺/calmodulin-dependent protein kinase I (CaMKI) is known to play pivotal roles in Ca²⁺ signaling pathways. Four isoforms of CaMKI (α, β, γ, and δ) have been reported so far. CaMKI is activated through phosphorylation by the upstream kinase, CaMK kinase (CaMKK), and phosphorylates downstream targets. When CaMKI was transiently expressed in 293T cells, CaMKIα was not phosphorylated at all under low-Ca²⁺ conditions in the cells. In contrast, we found that CaMKIδ was significantly phosphorylated and activated to phosphorylate cAMP response element-binding protein (CREB) under the same conditions. Herein, we report that the sustained activation of CaMKIδ is ascribed to its phosphatase resistance resulting from the structure of its N-terminal region. First, we examined whether CaMKIδ is more readily phosphorylated by CaMKK than CaMKIα, but no significant difference was observed. Next, to compare the phosphatase resistance between CaMKIα and CaMKIδ, we assessed the dephosphorylation of the phosphorylated CaMKIs by CaMK phosphatase (CaMKP/PPM1F). Surprisingly, CaMKIδ was hardly dephosphorylated by CaMKP, whereas CaMKIα was significantly dephosphorylated under the same conditions. To date, there have been no detailed reports concerning dephosphorylation of CaMKI. Through extensive analysis of CaMKP-catalyzed dephosphorylation of various chimeric and point mutants of CaMKIδ and CaMKIα, we identified the amino acid residues responsible for the phosphatase resistance of CaMKIδ (Pro-57, Lys-62, Ser-66, Ile-68, and Arg-76). These results also indicate that the phosphatase resistance of CaMKI is largely affected by only several amino acids in its N-terminal region. The phosphatase-resistant CaMKI isoform may play a physiological role under low-Ca²⁺ conditions in the cells.

  6. Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.

    PubMed

    Sag, Can M; Wolff, Hendrik A; Neumann, Kay; Opiela, Marie-Kristin; Zhang, Juqian; Steuer, Felicia; Sowa, Thomas; Gupta, Shamindra; Schirmer, Markus; Hünlich, Mark; Rave-Fränk, Margret; Hess, Clemens F; Anderson, Mark E; Shah, Ajay M; Christiansen, Hans; Maier, Lars S

    2013-11-01

    Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative

  7. Ultrastructural and immunohistochemical localization of plasma membrane Ca2+-ATPase 4 in Ca2+-transporting epithelia.

    PubMed

    Alexander, R Todd; Beggs, Megan R; Zamani, Reza; Marcussen, Niels; Frische, Sebastian; Dimke, Henrik

    2015-10-01

    Plasma membrane Ca(2+)-ATPases (PMCAs) participate in epithelial Ca(2+) transport and intracellular Ca(2+) signaling. The Pmca4 isoform is enriched in distal nephron isolates and decreased in mice lacking the epithelial transient receptor potential vanilloid 5 Ca(2+) channel. We therefore hypothesized that Pmca4 plays a significant role in transcellular Ca(2+) flux and investigated the localization and regulation of Pmca4 in Ca(2+)-transporting epithelia. Using antibodies directed specifically against Pmca4, we found it expressed only in the smooth muscle layer of mouse and human intestines, whereas pan-specific Pmca antibodies detected Pmca1 in lateral membranes of enterocytes. In the kidney, Pmca4 showed broad localization to the distal nephron. In the mouse, expression was most abundant in segments coexpressing the epithelial ransient receptor potential vanilloid 5 Ca(2+) channel. Significant, albeit lower, expression was also evident in the region encompassing the cortical thick ascending limbs, macula densa, and early distal tubules as well as smooth muscle layers surrounding renal vessels. In the human kidney, a similar pattern of distribution was observed, with the highest PMCA4 expression in Na(+)-Cl(-) cotransporter-positive tubules. Electron microscopy demonstrated Pmca4 localization in distal nephron cells at both the basolateral membrane and intracellular perinuclear compartments but not submembranous vesicles, suggesting rapid trafficking to the plasma membrane is unlikely to occur in vivo. Pmca4 expression was not altered by perturbations in Ca(2+) balance, pointing to a housekeeping function of the pump in Ca(2+)-transporting epithelia. In conclusion, Pmca4 shows a divergent expression pattern in Ca(2+)-transporting epithelia, inferring diverse roles for this isoform not limited to transepithelial Ca(2+) transport.

  8. CaF2:Yb laser ceramics

    NASA Astrophysics Data System (ADS)

    Akchurin, M. Sh.; Basiev, T. T.; Demidenko, A. A.; Doroshenko, M. E.; Fedorov, P. P.; Garibin, E. A.; Gusev, P. E.; Kuznetsov, S. V.; Krutov, M. A.; Mironov, I. A.; Osiko, V. V.; Popov, P. A.

    2013-01-01

    CaF2:Yb fluoride laser ceramics, prepared by hot-forming, exhibit the same optical properties as starting single crystals. Slope efficiency of the Сa0.95Yb0.05F2.05 is equal to 35% in the pulsed mode of laser operation. Decrease of ytterbium concentration in CaF2:Yb samples down to 3 mol.% resulted in the essential improvement of Сa0.97Yb0.03F2.03 thermal conductivity from 3.5 to 4.5 W/m K, but slightly decreased (down to 30%) slope efficiency of the samples under both pulsed and CW mode of operation. Alternative hot-pressing synthesis of CaF2:Yb fluoride laser ceramics provided materials with superior mechanical properties (microhardness Н = 3.2 GPa and fracture toughness К1С = 0.65 МPа m1/2) in comparison with hot-formed and/or single crystal CaF2:Yb specimens. For the first time, lasing has been observed for the novel aforementioned hot-pressed CaF2:Yb ceramics.

  9. Analysing force-pCa curves.

    PubMed

    Walker, John S; Li, Xiaotao; Buttrick, Peter M

    2010-07-01

    We investigated three forms of the Hill equation used to fit force-calcium data from skinned muscle experiments; Two hyperbolic forms that relate force to calcium concentration directly, and a sigmoid form that relates force to the -log(10) of the calcium concentration (pCa). The equations were fit to force-calcium data from 39 cardiac myocytes (up to five myocytes from each of nine mice) and the Hill coefficient and the calcium required for half maximal activation, expressed as a concentration (EC(50)) and as a pCa value (pCa(50)) were obtained. The pCa(50) values were normally distributed and the EC(50) values were found to approximate a log-normal distribution. Monte Carlo simulations confirmed that these distributions were intrinsic to the Hill equation. Statistical tests such as the t-test are robust to moderate levels of departure from normality as seen here, and either EC(50) or pCa(50) may be used to test for significant differences so long as it is kept in mind that ΔEC₅₀ is an additive measure of change and that ΔpCa₅₀ is a ratiometric measure of change. The Hill coefficient was found to be sufficiently log-normally distributed that log-transformed values should be used to test for statistically significant differences.

  10. Diffusion of Ca and Mg in Calcite

    SciTech Connect

    Cygan, R.T.; Fisler, D.K.

    1999-02-10

    The self-diffusion of Ca and the tracer diffusion of Mg in calcite have been experimentally measured using isotopic tracers of {sup 25}Mg and {sup 44}Ca. Natural single crystals of calcite were coated with a thermally-sputtered oxide thin film and then annealed in a CO{sub 2} gas at one atmosphere total pressure and temperatures from 550 to 800 C. Diffusion coefficient values were derived from the depth profiles obtained by ion microprobe analysis. The resultant activation energies for Mg tracer diffusion and Ca self-diffusion are respectively: E{sub a}(Mg) = 284 {+-} 74 kJ/mol and E{sub a}(Ca) = 271 {+-} 80 kJ/mol. For the temperature ranges in these experiments, the diffusion of Mg is faster than Ca. The results are generally consistent in magnitude with divalent cation diffusion rates obtained in previous studies and provide a means of interpreting the thermal histories of carbonate minerals, the mechanism of dolomitization, and other diffusion-controlled processes. The results indicate that cation diffusion in calcite is relatively slow and cations are the rate-limiting diffusing species for the deformation of calcite and carbonate rocks. Application of the calcite-dolomite geothermometer to metamorphic assemblages will be constrained by cation diffusion and cooling rates. The direct measurement of Mg tracer diffusion in calcite indicates that dolomitization is unlikely to be accomplished by Mg diffusion in the solid state but by a recrystallization process.

  11. Modeling the contributions of Ca2+ flows to spontaneous Ca2+ oscillations and cortical spreading depression-triggered Ca2+ waves in astrocyte networks.

    PubMed

    Li, Bing; Chen, Shangbin; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

    2012-01-01

    Astrocytes participate in brain functions through Ca(2+) signals, including Ca(2+) waves and Ca(2+) oscillations. Currently the mechanisms of Ca(2+) signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca(2+) flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca(2+) oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca(2+) waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca(2+) released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca(2+) influx. It predicts that voltage-gated Ca(2+) influx is able to generate Ca(2+) waves during the process of CSD even after depleting internal Ca(2+) stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca(2+) signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca(2+) signals might help to understand the ways by which astrocytes participate in information processing in brain functions.

  12. Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

    PubMed

    Gao, Ya-dong; Hanley, Peter J; Rinné, Susanne; Zuzarte, Marylou; Daut, Jurgen

    2010-07-01

    STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes. We have previously shown that human macrophages express K(Ca)3.1, and here we used the whole-cell patch-clamp technique to investigate the activity of these channels during Ca(2+) store depletion and store-operated Ca(2+) influx. Using RT-PCR, we found that macrophages express the elementary CRAC channel components Orai1 and STIM1, as well as Orai2, Orai3 and STIM2, but not the putatively STIM1-activated channels TRPC1, TRPC3-7 or TRPV6. In whole-cell configuration, a robust Ca(2+)-induced outwardly rectifying K(+) current inhibited by clotrimazole and augmented by DC-EBIO could be detected, consistent with K(Ca)3.1 channel current (also known as intermediate-conductance IK1). Introduction of extracellular Ca(2+) following Ca(2+) store depletion via P2Y(2) receptors induced a robust charybdotoxin (CTX)- and 2-APB-sensitive outward K(+) current and hyperpolarization. We also found that SOC entry induced by thapsigargin treatment induced CTX-sensitive K(+) current in HEK293 cells transiently expressing K(Ca)3.1. Our data suggest that SOC and K(Ca)3.1 channels are tightly coupled, such that a small Ca(2+) influx current induces a much large K(Ca)3.1 channel current and hyperpolarization, providing the necessary electrochemical driving force for prolonged Ca(2+) signaling and store repletion.

  13. [Tumor markers in the diagnosis of pancreatic cancer].

    PubMed

    Cappelli, G; Paladini, S; D'Agata, A

    1999-01-01

    The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The gangliosides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a "triplet" of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an "integrated" use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of radiochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.

  14. Excitotoxicity through Ca2+-permeable AMPA receptors requires Ca2+-dependent JNK activation

    PubMed Central

    Vieira, M.; Fernandes, J.; Burgeiro, A.; Thomas, G.M.; Huganir, R.L.; Duarte, C.B.; Carvalho, A.L.; Santos, A.E.

    2010-01-01

    The GluA4-containing Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors (Ca-AMPARs) were previously shown to mediate excitotoxicity through mechanisms involving the activator protein-1 (AP-1), a c-Jun N-terminal kinase (JNK) substrate. To further investigate JNK involvement in excitotoxic pathways coupled to Ca-AMPARs we used HEK293 cells expressing GluA4-containing Ca-AMPARs (HEK-GluA4). Cell death induced by overstimulation of Ca-AMPARs was mediated, at least in part, by JNK. Importantly, JNK activation downstream of these receptors was dependent on the extracellular Ca2+ concentration. In our quest for a molecular link between Ca-AMPARs and the JNK pathway we found that the JNK interacting protein-1 (JIP-1) interacts with the GluA4 subunit of AMPARs through the N-terminal domain. In vivo, the excitotoxin kainate promoted the association between GluA4 and JIP-1 in the rat hippocampus. Taken together, our results show that the JNK pathway is activated by Ca-AMPARs upon excitotoxic stimulation and suggest that JIP-1 may contribute to the propagation of the excitotoxic signal. PMID:20708684

  15. Cultivation of 'Candidatus Liberibacter asiaticus', 'Ca. L. africanus', and 'Ca. L. americanus' associated with huanglongbing.

    PubMed

    Sechler, A; Schuenzel, E L; Cooke, P; Donnua, S; Thaveechai, N; Postnikova, E; Stone, A L; Schneider, W L; Damsteegt, V D; Schaad, N W

    2009-05-01

    A new medium designated Liber A has been designed and used to successfully cultivate all three 'Candidatus Liberibacter spp.,' the suspect causative agents of huanglongbing (HLB) in citrus. The medium containing citrus vein extract and a growth factor sustained growth of 'Ca. Liberibacter spp.' for four or five single-colony transfers before viability declined. Colonies, positive for 'Ca. L. asiaticus' by a 16s-based rDNA real-time polymerase chain reaction (RT-PCR) assay and sequencing, were irregular-shaped, convex, and 0.1 to 0.3 mm after 3 to 4 days. Suspect 'Ca. L. asiaticus' and 'Ca. L. americanus' cells were observed in infected tissue and on agar culture by scanning electron microscopy. The cells were ovoid to rod shaped, 0.3 to 0.4 by 0.5 to 2.0 microm, often with fimbriae-like appendages. Two strains of 'Ca. L. asiaticus' and one of 'Ca. L. americanus' grown on Liber A medium were pathogenic on citrus and could be isolated from noninoculated tissues of inoculated trees and seedlings 9 and 2 months later, respectively. The identity was confirmed by RT-PCR and 16s rDNA sequencing. This is the first report of the cultivation and pathogenicity of 'Ca. L. asiaticus' and 'Ca. L. americanus' associated with symptoms of HLB.

  16. Intercellular Ca2+ Waves: Mechanisms and Function

    PubMed Central

    Sanderson, Michael J.

    2012-01-01

    Intercellular calcium (Ca2+) waves (ICWs) represent the propagation of increases in intracellular Ca2+ through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent studies focus on ICWs in vivo. ICWs are triggered by a variety of stimuli and involve the release of Ca2+ from internal stores. The propagation of ICWs predominately involves cell communication with internal messengers moving via gap junctions or extracellular messengers mediating paracrine signaling. ICWs appear to be important in both normal physiology as well as pathophysiological processes in a variety of organs and tissues including brain, liver, retina, cochlea, and vascular tissue. We review here the mechanisms of initiation and propagation of ICWs, the key intra- and extracellular messengers (inositol 1,4,5-trisphosphate and ATP) mediating ICWs, and the proposed physiological functions of ICWs. PMID:22811430

  17. Differential NMDA receptor-dependent calcium loading and mitochondrial dysfunction in CA1 vs. CA3 hippocampal neurons

    PubMed Central

    Stanika, Ruslan I.; Winters, Christine A.; Pivovarova, Natalia B.; Andrews, S. Brian

    2009-01-01

    Hippocampal CA1 pyramidal neurons are selectively vulnerable to ischemia, while adjacent CA3 neurons are relatively resistant. Although glutamate receptor-mediated mitochondrial Ca2+ overload and dysfunction is a major component of ischemia-induced neuronal death, no direct relationship between selective neuronal vulnerability and mitochondrial dysfunction has been demonstrated in intact brain preparations. Here, we show that in organotypic slice cultures NMDA induces much larger Ca2+ elevations in vulnerable CA1 neurons than in resistant CA3. Consequently, CA1 mitochondria exhibit stronger calcium accumulation, more extensive swelling and damage, stronger depolarization of their membrane potential, and a significant increase in ROS generation. NMDA-induced Ca2+ and ROS elevations were abolished in Ca2+-free medium or by NMDAR antagonists, but not by zinc chelation. We conclude that Ca2+-overload-dependent mitochondrial dysfunction is a determining factor in the selective vulnerability of CA1 neurons. PMID:19879359

  18. Characterizing CA{sub 2} and CA{sub 6} using ELNES

    SciTech Connect

    Altay, A.; Carter, C.B.; Rulis, P.; Ching, W.-Y.; Arslan, I.; Guelguen, M.A.

    2010-08-15

    Calcium aluminates, compounds in the CaO-Al{sub 2}O{sub 3} phase system, are used in high-temperature cements and refractory oxides and have wide range of potential technological applications due to their interesting optical, electrical, thermal, and mechanical properties. They are used in both crystalline and glassy form; the glass is an isotropic material while the crystalline materials may be highly anisotropic. This paper will consider two particular crystalline materials, CA{sub 2} and CA{sub 6}, but the results should be applicable to all calcium aluminates. Although CA{sub 2} and CA{sub 6} crystals contain the same chemical species, Ca, Al, and O, the coordination and local environments of these species are different in the two structures and hence they show very different energy-loss near-edge structures (ELNES) when examined by electron energy-loss spectroscopy (EELS) in the TEM. The data obtained using ELNES can effectively provide a fingerprint for each compound and a map for their electronic structure. Once such fingerprints are obtained, they can be used to identify nano-sized particles/grains or material at interfaces and grain boundaries. In the present study, the local symmetry fingerprints for CA{sub 2} and CA{sub 6} structures are reported combining experimental spectra with electronic-structure calculations that allow the different features in the spectra to be interpreted. Al-L{sub 2,3} and O-K edge core-loss spectra from CA{sub 2} and CA{sub 6} were measured experimentally using electron energy-loss spectroscopy in a monochromated scanning transmission electron microscope. The near-edge structures were calculated for the different phases using the orthogonalized linear combination of atomic-orbitals method, and took account of core-hole interactions. It is shown that CA{sub 2} and CA{sub 6} structures exhibit distinctive experimental ELNES fingerprints so that these two phases can be separately identified even when present in small volumes

  19. IP3R, store-operated Ca2+ entry and neuronal Ca2+ homoeostasis in Drosophila.

    PubMed

    Chakraborty, Sumita; Hasan, Gaiti

    2012-02-01

    The IP3R (inositol 1,4,5-trisphosphate receptor) releases Ca2+ from the ER (endoplasmic reticulum) store upon binding to its ligand InsP3, which is thought to be generated by activation of certain membrane-bound G-protein-coupled receptors in Drosophila. Depletion of Ca2+ in the ER store also activates SOCE (store-operated Ca2+ entry) from the extracellular milieu across the plasma membrane, leading to a second rise in cytosolic Ca2+, which is then pumped back into the ER. The role of the IP3R and SOCE in mediating Ca2+ homoeostasis in neurons, their requirement in neuronal function and effect on neuronal physiology and as a consequence behaviour, are reviewed in the present article.

  20. Growth rate effects on Mg/Ca and Sr/Ca ratios constrained by belemnite calcite

    NASA Astrophysics Data System (ADS)

    Vinzenz Ullmann, Clemens

    2016-04-01

    Multiple temperature proxies from single species are important to achieve robust palaeotemperature estimates. Besides the commonly employed oxygen isotope thermometer, also Mg/Ca and Sr/Ca ratios perform well as proxies for calcification temperature in the shells of some species. While salinity changes affect the ratios of earth alkaline elements much less than the δ18O thermometer, metabolic effects may exert a strong control on the expression of element ratios. Such effects are hard to study because biomineralization experiments have to overcome large intraspecific variability and can hardly ever isolate the controls of a single parameter on shell geochemistry. The unique geometry of the belemnite rostrum constitutes an exception to this rule. Its shape, large size, and the visibility of growth increments as bands enable the analysis of multiple, correlatable, high resolution geochemical profiles in a single fossil. The effects of the growth rate variability amongst these profiles on Mg/Ca and Sr/Ca ratios has been tested here. Within a specimen of Passaloteuthis bisulcata (Early Toarcian, Cleveland Basin, UK), Mg/Ca and Sr/Ca data were obtained from four profiles. With respect to growth rate in the first profile, which was taken as a reference, the relative growth rates in the remaining three profiles varied by a factor of 0.9 to 2.7. Results suggest that relative growth rate is linearly correlated with Mg/Ca and Sr/Ca, with a decrease of Mg/Ca by 8 % and increase of Sr/Ca by 6 % per 100 % increase in relative growth rate. The observed trends are consistent with abiogenic precipitation experiments and suggest that crystal precipitation rate exerts a significant, predictable control on the element distribution in biogenic calcite.

  1. Novel antimigraineur dotarizine releases Ca2+ from caffeine-sensitive Ca2+ stores of chromaffin cells

    PubMed Central

    Novalbos, Jesús; Abad-Santos, Francisco; Zapater, Pedro; Alvarez, Javier; Alonso, María Teresa; Montero, Mayte; García, Antonio G

    1999-01-01

    The novel antimigraineur, dotarizine (30 μM), increased cytosolic Ca2+ concentration, [Ca2+]c, in fura-2-loaded bovine adrenal chromaffin cells. This increase was transient, reached a peak in about 2–5 min (0.53±0.07 μM; n=19) and then declined to basal levels over a further 5 min period.This transient rise of [Ca2+]c was mimicked by 1 μM thapsigargin and by 30 μM cyclopiazonic acid (CPA), but not by 30 μM flunarizine. Both thapsigargin and CPA occluded the effects of dotarizine and vice versa.All three compounds suppressed the transient [Ca2+]c rises induced by caffeine (10 mM, 10 s); blockade induced by thapsigargin was irreversible and that induced by CPA and dotarizine was reversible.Of the three compounds, only dotarizine blocked reversibly the [Ca2+]c spikes induced by short pulses of high K+ (70 mM, 5 s), suggesting that dotarizine blocks voltage-dependent Ca2+ channels but CPA and thapsigargin do not.Dotarizine caused a gradual and reversible depletion of endoplasmic reticulum (ER) Ca2+ in chromaffin cells transfected with ER-targeted aequorin. CPA had a similar effect.These data show that dotarizine shares with thapsigargin and CPA the ability to deplete Ca2+ in the ER; this novel action of dotarizine could be relevant to its prophylactic effects in migraine. Unlike thapsigargin and CPA, however, dotarizine additionally and reversibly blocks Ca2+ entry through voltage-dependent Ca2+ channels. PMID:10516641

  2. Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.

    PubMed

    Zhou, Jingsong; Dhakal, Kamal; Yi, Jianxun

    2016-08-01

    Muscle uses Ca(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca(2+) from their surroundings, a process called mitochondrial Ca(2+) uptake. Under physiological conditions, Ca(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca(2+) uptake could shape spatio-temporal patterns of intracellular Ca(2+) signaling. Malfunction of mitochondrial Ca(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca(2+) levels. Besides the sudden elevation of Ca(2+) level induced by action potentials, Ca(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca(2+) uptake is fast and big enough to shape intracellular Ca(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca(2+) uptake in skeletal muscle and its role in muscle physiology and diseases.

  3. Electrochemical formation of Mg-Li-Ca alloys by codeposition of Mg, Li and Ca from LiCl-KCl-MgCl2-CaCl2 melts.

    PubMed

    Yan, Yong De; Zhang, Mi Lin; Xue, Yun; Han, Wei; Cao, Dian Xue; Jing, Xiao Yan; He, Li Yi; Yuan, Yi

    2009-08-07

    This work presents electrochemical formation of Mg-Li-Ca alloys via codeposition of Mg, Li and Ca on a molybdenum electrode in KCl-LiCl-MgCl(2)-CaCl(2) melts at 943 K. Cyclic voltammograms (CVs) showed that the underpotential deposition (UPD) of calcium on pre-deposited magnesium leads to the formation of a liquid Mg-Ca alloy, and the succeeding underpotential deposition of lithium on pre-deposited Mg-Ca alloy leads to the formation of a liquid Mg-Li-Ca solution. Chronopotentiometric measurements indicated that the codepositon of Mg, Li and Ca occurs at current densities more negative than -0.31 A cm(-2) in LiCl-KCl-MgCl(2) (5 wt%) melts containing 1 wt% CaCl(2). Chronoamperograms demonstrated that the onset potential for the codeposition of Mg, Li and Ca is -2.200 V, and the codeposition of Mg, Li and Ca is formed when the applied potentials are more negative than -2.200 V. X-Ray diffraction (XRD) indicated that Mg-Li-Ca alloys with different phases were formed via galvanostatic electrolysis. The microstructures of typical alpha and beta phases of Mg-Li-Ca alloys were characterized by optical microscope (OM) and scanning electron microscopy (SEM). The analysis of energy dispersive spectrometry (EDS) showed that the element Ca mainly distributes along grain boundary in Mg-Li-Ca alloys. The results of inductively coupled plasma analysis determined that the chemical compositions of Mg-Li-Ca alloys correspond with the phase structures of XRD patterns, and the lithium and calcium contents of Mg-Li-Ca alloys depend on the concentrations of MgCl(2) and CaCl(2).

  4. Single-Channel Monitoring of Reversible L-Type Ca2+ Channel CaVα1-CaVβ Subunit Interaction

    PubMed Central

    Jangsangthong, Wanchana; Kuzmenkina, Elza; Böhnke, Ann Kristin; Herzig, Stefan

    2011-01-01

    Voltage-dependent Ca2+ channels are heteromultimers of CaVα1 (pore), CaVβ- and CaVα2δ-subunits. The stoichiometry of this complex, and whether it is dynamically regulated in intact cells, remains controversial. Fortunately, CaVβ-isoforms affect gating differentially, and we chose two extremes (CaVβ1a and CaVβ2b) regarding single-channel open probability to address this question. HEK293α1C cells expressing the CaV1.2 subunit were transiently transfected with CaVα2δ1 alone or with CaVβ1a, CaVβ2b, or (2:1 or 1:1 plasmid ratio) combinations. Both CaVβ-subunits increased whole-cell current and shifted the voltage dependence of activation and inactivation to hyperpolarization. Time-dependent inactivation was accelerated by CaVβ1a-subunits but not by CaVβ2b-subunits. Mixtures induced intermediate phenotypes. Single channels sometimes switched between periods of low and high open probability. To validate such slow gating behavior, data were segmented in clusters of statistically similar open probability. With CaVβ1a-subunits alone, channels mostly stayed in clusters (or regimes of alike clusters) of low open probability. Increasing CaVβ2b-subunits (co-)expressed (1:2, 1:1 ratio or alone) progressively enhanced the frequency and total duration of high open probability clusters and regimes. Our analysis was validated by the inactivation behavior of segmented ensemble averages. Hence, a phenotype consistent with mutually exclusive and dynamically competing binding of different CaVβ-subunits is demonstrated in intact cells. PMID:22261054

  5. Inhibitors of the Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase family (CaMKP and CaMKP-N)

    SciTech Connect

    Sueyoshi, Noriyuki; Takao, Toshihiko; Nimura, Takaki; Sugiyama, Yasunori; Numano, Takamasa; Shigeri, Yasushi; Taniguchi, Takanobu; Kameshita, Isamu Ishida, Atsuhiko

    2007-11-23

    Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP) and its nuclear isoform CaMKP-N are unique Ser/Thr protein phosphatases that negatively regulate the Ca{sup 2+}/calmodulin-dependent protein kinase (CaMK) cascade by dephosphorylating multifunctional CaMKI, II, and IV. However, the lack of specific inhibitors of these phosphatases has hampered studies on these enzymes in vivo. In an attempt to obtain specific inhibitors, we searched inhibitory compounds and found that Evans Blue and Chicago Sky Blue 6B served as effective inhibitors for CaMKP. These compounds also inhibited CaMKP-N, but inhibited neither protein phosphatase 2C, another member of PPM family phosphatase, nor calcineurin, a typical PPP family phosphatase. The minimum structure required for the inhibition was 1-amino-8-naphthol-4-sulfonic acid. When Neuro2a cells cotransfected with CaMKIV and CaMKP-N were treated with these compounds, the dephosphorylation of CaMKIV was strongly suppressed, suggesting that these compounds could be used as potent inhibitors of CaMKP and CaMKP-N in vivo as well as in vitro.

  6. Ca²⁺ waves in the heart.

    PubMed

    Izu, Leighton T; Xie, Yuanfang; Sato, Daisuke; Bányász, Tamás; Chen-Izu, Ye

    2013-05-01

    Ca(2+) waves were probably first observed in the early 1940s. Since then Ca(2+) waves have captured the attention of an eclectic mixture of mathematicians, neuroscientists, muscle physiologists, developmental biologists, and clinical cardiologists. This review discusses the current state of mathematical models of Ca(2+) waves, the normal physiological functions Ca(2+) waves might serve in cardiac cells, as well as how the spatial arrangement of Ca(2+) release channels shape Ca(2+) waves, and we introduce the idea of Ca(2+) phase waves that might provide a useful framework for understanding triggered arrhythmias.

  7. Ca2+-induced Ca2+ Release Phenomena in Mammalian Sympathetic Neurons Are Critically Dependent on the Rate of Rise of Trigger Ca2+

    PubMed Central

    Hernández-Cruz, Arturo; Escobar, Ariel L.; Jiménez, Nicolás

    1997-01-01

    The role of ryanodine-sensitive intracellular Ca2+ stores present in nonmuscular cells is not yet completely understood. Here we examine the physiological parameters determining the dynamics of caffeine-induced Ca2+ release in individual fura-2–loaded sympathetic neurons. Two ryanodine-sensitive release components were distinguished: an early, transient release (TR) and a delayed, persistent release (PR). The TR component shows refractoriness, depends on the filling status of the store, and requires caffeine concentrations ≥10 mM. Furthermore, it is selectively suppressed by tetracaine and intracellular BAPTA, which interfere with Ca2+-mediated feedback loops, suggesting that it constitutes a Ca2+-induced Ca2+-release phenomenon. The dynamics of release is markedly affected when Sr2+ substitutes for Ca2+, indicating that Sr2+ release may operate with lower feedback gain than Ca2+ release. Our data indicate that when the initial release occurs at an adequately fast rate, Ca2+ triggers further release, producing a regenerative response, which is interrupted by depletion of releasable Ca2+ and Ca2+-dependent inactivation. A compartmentalized linear diffusion model can reproduce caffeine responses: When the Ca2+ reservoir is full, the rapid initial Ca2+ rise determines a faster occupation of the ryanodine receptor Ca2+ activation site giving rise to a regenerative release. With the store only partially loaded, the slower initial Ca2+ rise allows the inactivating site of the release channel to become occupied nearly as quickly as the activating site, thereby suppressing the initial fast release. The PR component is less dependent on the store's Ca2+ content. This study suggests that transmembrane Ca2+ influx in rat sympathetic neurons does not evoke widespread amplification by CICR because of its inability to raise [Ca2+] near the Ca2+ release channels sufficiently fast to overcome their Ca2+-dependent inactivation. Conversely, caffeine-induced Ca2+ release can

  8. Prenatal morphine exposure reduces pyramidal neurons in CA1, CA2 and CA3 subfields of mice hippocampus

    PubMed Central

    Ghafari, Soraya; Golalipour, Mohammad Jafar

    2014-01-01

    Objective(s): This study was carried out to evaluate the effect of maternal morphine exposure during gestational and lactation period on pyramidal neurons of hippocampus in 18 and 32 day mice offspring. Materials and Methods: Thirty female mice were randomly allocated into cases and controls. In case group, animals received morphine sulfate 10 mg/kg.body weight intraperitoneally during 7 days before mating, gestational period (GD 0-21), 18 and 32 days after delivery in the experimental groups. The control animals received an equivalent volume of normal saline. Cerebrum of six offsprings in each group was removed and stained with cresyl violet and a monoclonal antibody NeuN for immunohistochemical detection of surviving pyramidal neurons. Quantitative computer-assisted morphometric study was done on hippocampus. Results: The number of pyramidal neurons in CA1, CA2 and CA3 in treated groups was significantly reduced in postnatal day 18 and 32 (P18, P32) compared to control groups (P<0.05). The mean thickness of the stratum pyramidal layer was decreased in the treated groups in comparison with controls (P<0.05), whereas the mean thickness of the stratum oriens, stratum radiatum and stratum lacunosum-moleculare in CA1 field and stratum oriens, stratum lucidum, stratum radiatum and stratum lacunosum-moleculare in CA3 were significantly increased in morphine treated group in comparison with controls (P<0.05). Conclusion: Morphine administration before and during pregnancy and during lactation period causes pyramidal neurons loss in 18 and 32 days old infant mice. PMID:24847417

  9. Neurotransmitter release evoked by nerve impulses without Ca2+ entry through Ca2+ channels in frog motor nerve endings.

    PubMed Central

    Silinsky, E M; Watanabe, M; Redman, R S; Qiu, R; Hirsh, J K; Hunt, J M; Solsona, C S; Alford, S; MacDonald, R C

    1995-01-01

    1. The requirement for extracellular Ca2+ in the process of evoked acetylcholine (ACh) release by nerve impulses was tested at endplates in frog skeletal muscle. Ca(2+)-containing lipid vesicles (Ca2+ liposomes) were used to elevate cytoplasmic Ca2+ concentrations under conditions in which Ca2+ entry from the extracellular fluid was prevented. 2. In an extracellular solution containing no added Ca2+ and 1 mM Mg2+ ('Ca(2+)-free' solution), Ca2+ liposomes promoted the synchronous release of ACh quanta, reflected electrophysiologically as endplate potentials (EPPs), in response to temporally isolated nerve impulses. 3. Motor nerve stimulation generated EPPs during superfusion with Ca2+ liposomes in Ca(2+)-free solutions containing the Ca2+ channel blocker Co2+ (1 mM), and the Ca2+ chelator EGTA (2 mM). As a physiological control for Ca2+ leakage from the liposomes to the extracellular fluid, the effect of Ca2+ liposomes on asynchronous evoked ACh release mediated by Ba2+ was examined. In contrast to the effects of 0.2-0.3 mM extracellular Ca2+, which generated EPPs but antagonized Ba(2+)-mediated asynchronous ACh release, Ca2+ liposomes generated EPPs but did not reduce asynchronous release mediated by Ba2+. The effects of Ca2+ liposomes were thus not due to leakage of Ca2+ from the liposome to the extracellular fluid. 4. Morphological studies using fluorescently labelled liposomes in conjunction with a confocal microscope demonstrate that lipid is transferred from the liposomes to nerve endings and liposomal contents are delivered to the nerve terminal cytoplasm. 5. The results suggest that when intracellular Ca2+ is elevated using liposomes as a vehicle, evoked ACh release can occur in the absence of Ca2+ entry via Ca2+ channels. Images Figure 5 Figure 6 PMID:7738845

  10. Na-Ca exchange and the trigger for sarcoplasmic reticulum Ca release: studies in adult rabbit ventricular myocytes.

    PubMed Central

    Litwin, S E; Li, J; Bridge, J H

    1998-01-01

    The importance of Na-Ca exchange as a trigger for sarcoplasmic reticulum (SR) Ca release remains controversial. Therefore, we measured whole-cell Ca currents (ICa), Na-Ca exchange currents (INaCa), cellular contractions, and intracellular Ca transients in adult rabbit cardiac myocytes. We found that changing pipette Na concentration markedly affected the relationship between cell shortening (or Ca transients) and voltage, but did not affect the Ca current-voltage relationship. We then inhibited Na-Ca exchange and varied SR content (by changing the number of conditioning pulses before each test pulse). Regardless of SR Ca content, the relationship between contraction and voltage was bell-shaped in the absence of Na-Ca exchange. Next, we rapidly and completely blocked ICa by applying nifedipine to cells. Cellular shortening was variably reduced in the presence of nifedipine. The component of shortening blocked by nifedipine had a bell-shaped relationship with voltage, whereas the "nifedipine-insensitive" component of contraction increased with voltage. With the SR disabled (ryanodine and thapsigargin pretreatment), ICa could initiate late-peaking contractions that were approximately 70% of control amplitude. In contrast, nifedipine-insensitive contractions could not be elicited in the presence of ryanodine and thapsigargin. Finally, we recorded reverse Na-Ca exchange currents that were activated by membrane depolarization. The estimated sarcolemmal Ca flux occurring by Na-Ca exchange (during voltage clamp steps to +30 mV) was approximately 10-fold less than that occurring by ICa. Therefore, Na-Ca exchange alone is unlikely to raise cytosolic Ca concentration enough to directly activate the myofilaments. We conclude that reverse Na-Ca exchange can trigger SR Ca release. Because of the sigmoidal relationship between the open probability of the SR Ca release channel and pCa, the effects of ICa and INaCa may not sum in a linear fashion. Rather, the two triggers may act

  11. Regulation of Ca2+ and electrical alternans in cardiac myocytes: Role of CaMKII and repolarizing currents

    PubMed Central

    Livshitz, Leonid M.; Rudy, Yoram

    2007-01-01

    Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca2+ transient (CaT). Because of experimental difficulty in independently controlling the Ca2+ and electrical subsystems, mathematical modelling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1. (I) CaT alternans results from refractoriness of the SR Ca2+ release system; alternation of the L-type calcium current (ICa(L)) has a negligible effect; (II) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger (INaCa) and underlies APD alternans; (III) Increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; (IV). Increase of the rapid delayed rectifier current (IKr) also suppresses APD alternans, but without suppressing CaT alternans. Thus, CaMKII inhibition eliminates APD alternans by eliminating its cause (CaT alternans), while IKr enhancement does so by weakening CaT-APD coupling. The simulations identify combined CaMKII inhibition and IKr enhancement as a possible antiar-rhythmic intervention. PMID:17277017

  12. Hippocampal CA1 Ripples as Inhibitory Transients

    PubMed Central

    Krishnan, Giri P; Fellous, Jean-Marc; Bazhenov, Maxim

    2016-01-01

    Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network. PMID:27093059

  13. literacy.ca EXPRESS. April 2010

    ERIC Educational Resources Information Center

    Movement for Canadian Literacy, 2010

    2010-01-01

    This issue of "literacy.ca EXPRESS" focuses on poverty. The articles included in this issue are: (1) Poverty Overview; (2) Tony's Story; (3) LAN (Learner Advisory Network) Member's Story (Dianne Smith); (4) Linking Adult Literacy to Poverty Reduction; (5) MCL (Movement for Canadian Literacy) Update; (6) Highlights from the LAN; (7) Good…

  14. 76 FR 24555 - California Disaster #CA-00171

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-02

    ... ADMINISTRATION California Disaster CA-00171 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of CALIFORNIA dated 04/26...: California: Monterey, San Benito, San Mateo, Santa Clara. The Interest Rates are: Percent For Physical...

  15. 75 FR 22872 - California Disaster # CA-00154

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... ADMINISTRATION California Disaster CA-00154 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 04/21/2010. Incident: Northern Baja California Earthquake. Incident Period: 04/04/2010 and...

  16. 76 FR 38263 - California Disaster #CA-00172

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... From the Federal Register Online via the Government Publishing Office Small Business Administration California Disaster CA-00172 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of California (FEMA- 1968-DR), dated 06/20/2011. Incident: Tsunami Waves. Incident Period:...

  17. 77 FR 61815 - California Disaster #CA-00190

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ... ADMINISTRATION California Disaster CA-00190 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of the Administrative declaration of a disaster for the State of California...'s disaster declaration for the State of California, dated 09/14/2012 I hereby amended to...

  18. 75 FR 17792 - California Disaster # CA-00150

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-07

    ... ADMINISTRATION California Disaster CA-00150 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of the Administrative declaration of disaster for the State of California.... SUPPLEMENTARY INFORMATION: The notice of the Administrative disaster declaration for the State of...

  19. 76 FR 80446 - California Disaster #CA-00182

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ...] California Disaster CA-00182 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 12/19/2011... adversely affected by the disaster: Primary Counties: Los Angeles. Contiguous Counties: California:...

  20. 75 FR 27846 - California Disaster # CA-00155

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... [Federal Register Volume 75, Number 95 (Tuesday, May 18, 2010)] [Notices] [Page 27846] [FR Doc No: 2010-11746] SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12166 and 12167] California Disaster CA... Presidential declaration of a major disaster for Public Assistance Only for the State of California (FEMA-...

  1. 75 FR 13144 - California Disaster #CA-00151

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-18

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION California Disaster CA-00151 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of California (FEMA- 1884-DR), dated 03/08/2010. Incident: Severe Winter Storms, Flooding,...

  2. 76 FR 11307 - California Disaster #CA-00162

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-01

    ... ADMINISTRATION California Disaster CA-00162 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of the Administrative declaration of a disaster for the State of California... California, dated 02/02/2011 is hereby amended to include the following areas as adversely affected by...

  3. 75 FR 8414 - California Disaster # CA-00150

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... ADMINISTRATION California Disaster CA-00150 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 02/16... disaster: Primary Counties: Los Angeles. Contiguous Counties: California: Kern, Orange San...

  4. 76 FR 18614 - California Disaster #CA-00167

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-04

    ... ADMINISTRATION California Disaster CA-00167 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 03/29... the disaster: Primary Counties: Del Norte. Contiguous Counties: California: Humboldt, Siskiyou....

  5. 76 FR 7622 - California Disaster #CA-00162

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    ... ADMINISTRATION California Disaster CA-00162 AGENCY: U.S. Small Business Administration. ] ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 02/02... Bernardino, San Luis Obispo. Contiguous Counties: California: Inyo, Kern, Kings, Los Angeles,...

  6. CA125 — EDRN Public Portal

    Cancer.gov

    MUC16 (CA125) is a highly glycosylated sialomucin that is expressed on epithelial cell surface, especially on ovarian cancer cells. MUC16 is anchored to the epithelium by a transmembrane domain and is released into the extracellular space by enzymatic cleavage. It is thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.

  7. 77 FR 1971 - California Disaster #CA-00183

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-12

    ... ADMINISTRATION California Disaster CA-00183 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 01/05/2012. Incident: 1502 Golden Gate Fire. Incident Period: 12/22/2011. Effective Date:...

  8. 76 FR 62132 - California Disaster #CA-00176

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-06

    ... ADMINISTRATION California Disaster CA-00176 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 09/29/2011. Incident: Canyon Fire. Incident Period: 09/04/2011 through 09/11/2011. Effective Date:...

  9. 75 FR 69733 - California Disaster #CA-00161

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... Doc No: 2010-28587] SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12373 and 12374] California Disaster CA-00161 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 11/05/2010....

  10. 78 FR 55771 - California Disaster #CA-00207

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... ADMINISTRATION California Disaster CA-00207 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of CALIFORNIA dated 08/26/2013. Incident: Silver Fire. Incident Period: 08/07/2013 through 08/14/2013. Effective Date:...

  11. 76 FR 16029 - CALIFORNIA Disaster #CA-00165

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... ADMINISTRATION CALIFORNIA Disaster CA-00165 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of CALIFORNIA dated 03/16/2011. Incident: Garden Breeze Apartment Complex Fire. Incident Period: 02/20/2011. DATES:...

  12. 76 FR 20433 - California Disaster #CA-00169

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-12

    ... ADMINISTRATION California Disaster CA-00169 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 04/05/2011. Incident: Center Fire. Incident Period: 03/18/2011 through 03/20/2011. Effective Date:...

  13. 78 FR 77195 - California Disaster #CA-00214

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... ADMINISTRATION California Disaster CA-00214 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice of the Presidential declaration of a major disaster for Public Assistance Only for the State of California (FEMA- 4158-DR), dated 12/13/2013. Incident: Rim Fire. Incident Period:...

  14. 78 FR 39821 - California Disaster #CA-00202

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... ADMINISTRATION California Disaster CA-00202 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 06/25/2013. Incident: Powerhouse Fire. Incident Period: 05/30/2013 through 06/11/2013. Effective Date:...

  15. 76 FR 79751 - California Disaster #CA-00181

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-22

    ... ADMINISTRATION California Disaster CA-00181 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of California dated 12/14/2011. Incident: Sequoia Apartment Complex Fire. Incident Period: 11/18/2011. Effective Date:...

  16. SNL/CA Cultural Resources Management Plan.

    SciTech Connect

    Larsen, Barbara L.

    2005-11-01

    The SNL/CA Cultural Resources Management Plan satisfies the site's Environmental Management System requirement to promote long-term stewardship of cultural resources. The plan summarizes the cultural and historical setting of the site, identifies existing procedures and processes that support protection and preservation of resources, and outlines actions that would be initiated if cultural resources were discovered onsite in the future.3

  17. Inositol Trisphosphate Receptor Ca2+ Release Channels

    PubMed Central

    FOSKETT, J. KEVIN; WHITE, CARL; CHEUNG, KING-HO; MAK, DON-ON DANIEL

    2010-01-01

    The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R. PMID:17429043

  18. 78 FR 60366 - California Disaster #CA-00212

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION California Disaster CA-00212 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY...: 06/24/2014. ADDRESSES: Submit completed loan applications to: U.S. Small Business...

  19. Hippocampal CA1 Ripples as Inhibitory Transients.

    PubMed

    Malerba, Paola; Krishnan, Giri P; Fellous, Jean-Marc; Bazhenov, Maxim

    2016-04-01

    Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.

  20. Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR.

    PubMed

    Riccardi, Daniela; Finney, Brenda A; Wilkinson, William J; Kemp, Paul J

    2009-10-01

    The capacity to sense and adapt to changes in environmental cues is of paramount importance for every living organism. From yeast to man, cells must be able to match cellular activities to growth environment and nutrient availability. Key to this process is the development of membrane-bound systems that can detect modifications in the extracellular environment and to translate these into biological responses. Evidence gathered over the last 15 years has demonstrated that many of these cell surface "sensors" belong to the G protein-coupled receptor superfamily. Crucial to our understanding of nutrient sensing in mammalian species has been the identification of the extracellular Ca(2+)/cation-sensing receptor, CaR. CaR was the first ion-sensing molecule identified in man and genetic studies in humans have revealed the importance of the CaR in mineral ion metabolism. Latter, it has become apparent that the CaR also plays an important role outside the Ca(2+) homeostatic system, as an integrator of multiple environmental signals for the regulation of many vital cellular processes, from cell-to-cell communication to secretion and cell survival/cell death. Recently, novel aspects of receptor function reveal an unexpected role for the CaR in the regulation of growth and development in utero.

  1. Mg-Ca Alloys Produced by Reduction of CaO: Understanding of ECO-Mg Alloy Production

    NASA Astrophysics Data System (ADS)

    Jung, In-Ho; Lee, Jin Kyu; Kim, Shae K.

    2017-04-01

    There have been long debates about the environment conscious (ECO) Mg technology which utilizes CaO to produce Ca-containing Mg alloys. Two key process technologies of the ECO-Mg process are the chemical reduction of CaO by liquid Mg and the maintenance of melt cleanliness during the alloying of Ca. Thermodynamic calculations using FactSage software were performed to explain these two key issues. In addition, an experimental study was performed to compare the melt cleanliness of the Ca-containing Mg alloys produced by the conventional route with metallic Ca and the ECO-Mg route with CaO.

  2. Mg-Ca Alloys Produced by Reduction of CaO: Understanding of ECO-Mg Alloy Production

    NASA Astrophysics Data System (ADS)

    Jung, In-Ho; Lee, Jin Kyu; Kim, Shae K.

    2016-12-01

    There have been long debates about the environment conscious (ECO) Mg technology which utilizes CaO to produce Ca-containing Mg alloys. Two key process technologies of the ECO-Mg process are the chemical reduction of CaO by liquid Mg and the maintenance of melt cleanliness during the alloying of Ca. Thermodynamic calculations using FactSage software were performed to explain these two key issues. In addition, an experimental study was performed to compare the melt cleanliness of the Ca-containing Mg alloys produced by the conventional route with metallic Ca and the ECO-Mg route with CaO.

  3. DA-6034 Induces [Ca(2+)]i Increase in Epithelial Cells.

    PubMed

    Yang, Yu-Mi; Park, Soonhong; Ji, Hyewon; Kim, Tae-Im; Kim, Eung Kweon; Kang, Kyung Koo; Shin, Dong Min

    2014-04-01

    DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces Ca(2+) signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in Ca(2+) signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated Ca(2+)-activated Cl(-) channels (CaCCs) and increased intracellular calcium concentrations ([Ca(2+)]i) in primary cultured human conjunctival cells. DA-6034 also increased [Ca(2+)]i in mouse salivary gland cells and human corneal epithelial cells. [Ca(2+)]i increase of DA-6034 was dependent on the Ca(2+) entry from extracellular and Ca(2+) release from internal Ca(2+) stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate (IP3) pathway and lysosomal Ca(2+) stores. These results suggest that DA-6034 induces Ca(2+) signaling via extracellular Ca(2+) entry and RyRs-sensitive Ca(2+) release from internal Ca(2+) stores in epithelial cells.

  4. Ca2+-permeable AMPA receptors in mouse olfactory bulb astrocytes

    PubMed Central

    Droste, Damian; Seifert, Gerald; Seddar, Laura; Jädtke, Oliver; Steinhäuser, Christian; Lohr, Christian

    2017-01-01

    Ca2+ signaling in astrocytes is considered to be mainly mediated by metabotropic receptors linked to intracellular Ca2+ release. However, recent studies demonstrate a significant contribution of Ca2+ influx to spontaneous and evoked Ca2+ signaling in astrocytes, suggesting that Ca2+ influx might account for astrocytic Ca2+ signaling to a greater extent than previously thought. Here, we investigated AMPA-evoked Ca2+ influx into olfactory bulb astrocytes in mouse brain slices using Fluo-4 and GCaMP6s, respectively. Bath application of AMPA evoked Ca2+ transients in periglomerular astrocytes that persisted after neuronal transmitter release was inhibited by tetrodotoxin and bafilomycin A1. Withdrawal of external Ca2+ suppressed AMPA-evoked Ca2+ transients, whereas depletion of Ca2+ stores had no effect. Both Ca2+ transients and inward currents induced by AMPA receptor activation were partly reduced by Naspm, a blocker of Ca2+-permeable AMPA receptors lacking the GluA2 subunit. Antibody staining revealed a strong expression of GluA1 and GluA4 and a weak expression of GluA2 in periglomerular astrocytes. Our results indicate that Naspm-sensitive, Ca2+-permeable AMPA receptors contribute to Ca2+ signaling in periglomerular astrocytes in the olfactory bulb. PMID:28322255

  5. Calculated and measured [Ca(2+)] in buffers used to calibrate Ca(2+) macroelectrodes.

    PubMed

    McGuigan, John A S; Stumpff, Friederike

    2013-05-01

    The ionized concentration of calcium in physiological buffers ([Ca(2+)]) is normally calculated using either tabulated constants or software programs. To investigate the accuracy of such calculations, the [Ca(2+)] in EGTA [ethylene glycol-bis(β-aminoethylether)-N,N,N|,N|-tetraacetic acid], BAPTA [1,2-bis(o-aminophenoxy) ethane-N,N,N|,N|-tetraacetic acid], HEDTA [N-(2-hydroxyethyl)-ethylenediamine-N,N|,N|-triacetic acid], and NTA [N,N-bis(carboxymethyl)glycine] buffers was estimated using the ligand optimization method, and these measured values were compared with calculated values. All measurements overlapped in the pCa range of 3.51 (NTA) to 8.12 (EGTA). In all four buffer solutions, there was no correlation between measured and calculated values; the calculated values differed among themselves by factors varying from 1.3 (NTA) to 6.9 (EGTA). Independent measurements of EGTA purity and the apparent dissociation constants for HEDTA and NTA were not significantly different from the values estimated by the ligand optimization method, further substantiating the method. Using two calibration solutions of pCa 2.0 and 3.01 and seven buffers in the pCa range of 4.0-7.5, calibration of a Ca(2+) electrode over the pCa range of 2.0-7.5 became a routine procedure. It is proposed that such Ca(2+) calibration/buffer solutions be internationally defined and made commercially available to allow the precise measurement of [Ca(2+)] in biology.

  6. Voltage-gated Ca2+ influx and mitochondrial Ca2+ initiate secretion from Aplysia neuroendocrine cells.

    PubMed

    Hickey, C M; Groten, C J; Sham, L; Carter, C J; Magoski, N S

    2013-10-10

    Neuroendocrine secretion often requires prolonged voltage-gated Ca(2+) entry; however, the ability of Ca(2+) from intracellular stores, such as endoplasmic reticulum or mitochondria, to elicit secretion is less clear. We examined this using the bag cell neurons, which trigger ovulation in Aplysia by releasing egg-laying hormone (ELH) peptide. Secretion from cultured bag cell neurons was observed as an increase in plasma membrane capacitance following Ca(2+) influx evoked by a 5-Hz, 1-min train of depolarizing steps under voltage-clamp. The response was similar for step durations of ≥ 50 ms, but fell off sharply with shorter stimuli. The capacitance change was attenuated by replacing external Ca(2+) with Ba(2+), blocking Ca(2+) channels, buffering intracellular Ca(2+) with EGTA, disrupting synaptic protein recycling, or genetic knock-down of ELH. Regarding intracellular stores, liberating mitochondrial Ca(2+) with the protonophore, carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP), brought about an EGTA-sensitive elevation of capacitance. Conversely, no change was observed to Ca(2+) released from the endoplasmic reticulum or acidic stores. Prior exposure to FCCP lessened the train-induced capacitance increase, suggesting overlap in the pool of releasable vesicles. Employing GTP-γ-S to interfere with endocytosis delayed recovery (presumed membrane retrieval) of the capacitance change following FCCP, but not the train. Finally, secretion was correlated with reproductive behavior, in that neurons isolated from animals engaged in egg-laying presented a greater train-induced capacitance elevation vs quiescent animals. The bag cell neuron capacitance increase is consistent with peptide secretion requiring high Ca(2+), either from influx or stores, and may reflect the all-or-none nature of reproduction.

  7. ASteCA: Automated Stellar Cluster Analysis

    NASA Astrophysics Data System (ADS)

    Perren, G. I.; Vázquez, R. A.; Piatti, A. E.

    2015-04-01

    We present the Automated Stellar Cluster Analysis package (ASteCA), a suit of tools designed to fully automate the standard tests applied on stellar clusters to determine their basic parameters. The set of functions included in the code make use of positional and photometric data to obtain precise and objective values for a given cluster's center coordinates, radius, luminosity function and integrated color magnitude, as well as characterizing through a statistical estimator its probability of being a true physical cluster rather than a random overdensity of field stars. ASteCA incorporates a Bayesian field star decontamination algorithm capable of assigning membership probabilities using photometric data alone. An isochrone fitting process based on the generation of synthetic clusters from theoretical isochrones and selection of the best fit through a genetic algorithm is also present, which allows ASteCA to provide accurate estimates for a cluster's metallicity, age, extinction and distance values along with its uncertainties. To validate the code we applied it on a large set of over 400 synthetic MASSCLEAN clusters with varying degrees of field star contamination as well as a smaller set of 20 observed Milky Way open clusters (Berkeley 7, Bochum 11, Czernik 26, Czernik 30, Haffner 11, Haffner 19, NGC 133, NGC 2236, NGC 2264, NGC 2324, NGC 2421, NGC 2627, NGC 6231, NGC 6383, NGC 6705, Ruprecht 1, Tombaugh 1, Trumpler 1, Trumpler 5 and Trumpler 14) studied in the literature. The results show that ASteCA is able to recover cluster parameters with an acceptable precision even for those clusters affected by substantial field star contamination. ASteCA is written in Python and is made available as an open source code which can be downloaded ready to be used from its official site.

  8. Cenozoic seawater Sr/Ca evolution

    NASA Astrophysics Data System (ADS)

    Sosdian, Sindia M.; Lear, Caroline H.; Tao, Kai; Grossman, Ethan L.; O'Dea, Aaron; Rosenthal, Yair

    2012-10-01

    Records of seawater chemistry help constrain temporal variations in geochemical processes that impact the global carbon cycle and climate through Earth's history. Here we reconstruct Cenozoic seawater Sr/Ca (Sr/Casw) using fossil Conus and turritellid gastropod Sr/Ca. Combined with an oxygen isotope paleotemperature record from the same samples, the gastropod record suggests that Sr/Caswwas slightly higher in the Eocene (˜11.4 ± 3 mmol/mol) than today (˜8.54 mmol/mol) and remained relatively stable from the mid- to late Cenozoic. We compare our gastropod Cenozoic Sr/Casw record with a published turritellid gastropod Sr/Casw record and other published biogenic (benthic foraminifera, fossil fish teeth) and inorganic precipitate (calcite veins) Sr/Caswrecords. Once the uncertainties with our gastropod-derived Sr/Casw are taken into account the Sr/Casw record agrees reasonably well with biogenic Sr/Caswrecords. Assuming a seawater [Ca] history derived from marine evaporite inclusions, all biogenic-based Sr/Casw reconstructions imply decreasing seawater [Sr] through the Cenozoic, whereas the calcite vein Sr/Casw reconstruction implies increasing [Sr] through the Cenozoic. We apply a simple geochemical model to examine the implications of divergence among these seawater [Sr] reconstructions and suggest that the interpretation and uncertainties associated with the gastropod and calcite vein proxies need to be revisited. Used in conjunction with records of carbonate depositional fluxes, our favored seawater Sr/Ca scenarios point to a significant increase in the proportion of aragonite versus calcite deposition in shelf sediments from the Middle Miocene, coincident with the proliferation of coral reefs. We propose that this occurred at least 10 million years after the seawater Mg/Ca threshold was passed, and was instead aided by declining levels of atmospheric carbon dioxide.

  9. Ca2+ currents in cerebral artery smooth muscle cells of rat at physiological Ca2+ concentrations

    PubMed Central

    1996-01-01

    Single Ca2+ channel and whole cell currents were measured in smooth muscle cells dissociated from resistance-sized (100-microns diameter) rat cerebral arteries. We sought to quantify the magnitude of Ca2+ channel currents and activity under the putative physiological conditions of these cells: 2 mM [Ca2+]o, steady depolarizations to potentials between -50 and -20 mV, and (where possible) without extrinsic channel agonists. Single Ca2+ channel conductance was measured over a broad range of Ca2+ concentrations (0.5-80 mM). The saturating conductance ranged from 1.5 pS at 0.5 mM to 7.8 pS at 80 mM, with a value of 3.5 pS at 2 mM Ca (unitary currents of 0.18 pA at -40 mV). Both single channel and whole cell Ca2+ currents were measured during pulses and at steady holding potentials. Ca2+ channel open probability and the lower limit for the total number of channels per cell were estimated by dividing the whole-cell Ca2+ currents by the single channel current. We estimate that an average cell has at least 5,000 functional channels with open probabilities of 3.4 x 10(-4) and 2 x 10(-3) at -40 and -20 mV, respectively. An average of 1-10 (-40 mV and -20 mV, respectively) Ca2+ channels are thus open at physiological potentials, carrying approximately 0.5 pA steady Ca2+ current at -30 mV. We also observed a very slow reduction in open probability during steady test potentials when compared with peak pulse responses. This 4- 10-fold reduction in activity could not be accounted for by the channel's normal inactivation at our recording potentials between -50 and -20 mV, implying that an additional slow inactivation process may be important in regulating Ca2+ channel activity during steady depolarization. PMID:8722560

  10. The Electronic Spectra of CaN2(+) and Ca(N2)2(+)

    NASA Technical Reports Server (NTRS)

    Rodriguez-Santiago, Luis; Bauschlicher, Charles W., Jr.; Arnold, James (Technical Monitor)

    1998-01-01

    The ground and low-lying electronic states of CaN2(+) are studied at several levels of theory. The results for the X(sup 2)Sigma(+) state and the excited (2)(sup 2)Pi state, arising from occupying the Ca 4p orbital, are in good agreement with experiment. The analogous states of Ca(N2)2(+) are studied using the same theoretical approaches, and predictions are made as to the changes caused by the addition of the second N2 ligand.

  11. Simultaneous measurement of Ca2+ in muscle with Ca electrodes and aequorin. Diffusible cytoplasmic constituent reduces Ca(2+)-independent luminescence of aequorin

    PubMed Central

    1991-01-01

    Estimates of cytoplasmic Ca2+ concentration ([Ca2+]i) were made essentially simultaneously in the same intact frog skeletal muscle fibers with aequorin and with Ca-selective microelectrodes. In healthy fibers under truly resting conditions [Ca2+]i was too low to be measured reliably with either technique. The calibration curves for both indicators were essentially flat in this range of [Ca2+], and the aequorin light signal was uniformly below the level to be expected in the total absence of Ca2+. When [Ca2+]i had been raised to a stable level below the threshold for contracture by increasing [K+]o to 12.5 mM, [Ca2+]i was 38 nM according to aequorin and 59 nM according to the Ca-selective microelectrodes. These values are not significantly different. Our estimates of [Ca2+]i are lower than most others obtained with microelectrodes, probably because the presence of aequorin in the cells allowed us to detect damaging microelectrode impalements that otherwise we would have had no reason to reject. The observation that the light emission from aequorin-injected fibers in normal Ringer solution was below the level expected from the Ca(2+)-independent luminescence of aequorin in vitro was investigated further, with the conclusion that the myoplasm contains a diffusible macromolecule (between 10 and 30 kD) that interacts with aequorin to reduce light emission in the absence of Ca2+. PMID:1783896

  12. Feedforward inhibition underlies the propagation of cholinergically induced gamma oscillations from hippocampal CA3 to CA1.

    PubMed

    Zemankovics, Rita; Veres, Judit M; Oren, Iris; Hájos, Norbert

    2013-07-24

    Gamma frequency (30-80 Hz) oscillations are implicated in memory processing. Such rhythmic activity can be generated intrinsically in the CA3 region of the hippocampus from where it can propagate to the CA1 area. To uncover the synaptic mechanisms underlying the intrahippocampal spread of gamma oscillations, we recorded local field potentials, as well as action potentials and synaptic currents in anatomically identified CA1 and CA3 neurons during carbachol-induced gamma oscillations in mouse hippocampal slices. The firing of the vast majority of CA1 neurons and all CA3 neurons was phase-coupled to the oscillations recorded in the stratum pyramidale of the CA1 region. The predominant synaptic input to CA1 interneurons was excitatory, and their discharge followed the firing of CA3 pyramidal cells at a latency indicative of monosynaptic connections. Correlation analysis of the input-output characteristics of the neurons and local pharmacological block of inhibition both agree with a model in which glutamatergic CA3 input controls the firing of CA1 interneurons, with local pyramidal cell activity having a minimal role. The firing of phase-coupled CA1 pyramidal cells was controlled principally by their inhibitory inputs, which dominated over excitation. Our results indicate that the synchronous firing of CA3 pyramidal cells rhythmically recruits CA1 interneurons and that this feedforward inhibition generates the oscillatory activity in CA1. These findings identify distinct synaptic mechanisms underlying the generation of gamma frequency oscillations in neighboring hippocampal subregions.

  13. Modeling Ca(2+) currents and buffered diffusion of Ca(2+) in human β-cells during voltage clamp experiments.

    PubMed

    Félix-Martínez, Gerardo J; Godínez-Fernández, J Rafael

    2015-12-01

    Macroscopic Ca(2+) currents of the human β-cells were characterized using the Hodgkin-Huxley formalism. Expressions describing the Ca(2+)-dependent inactivation process of the L-type Ca(2+) channels in terms of the concentration of Ca(2+) were obtained. By coupling the modeled Ca(2+) currents to a three-dimensional model of buffered diffusion of Ca(2+), we simulated the Ca(2+) transients formed in the immediate vicinity of the cell membrane during voltage clamp experiments performed in high buffering conditions. Our modeling approach allowed us to consider the distribution of the Ca(2+) sources over the cell membrane. The effect of exogenous (EGTA) and endogenous Ca(2+) buffers on the temporal course of the Ca(2+) transients was evaluated. We show that despite the high Ca(2+) buffering capacity, nanodomains are formed in the submembrane space, where a peak Ca(2+) concentration between ∼76 and 143 µM was estimated from our simulations. In addition, the contribution of each Ca(2+) current to the formation of the Ca(2+) nanodomains was also addressed. Here we provide a general framework to incorporate the spatial aspects to the models of the pancreatic β-cell, such as a more detailed and realistic description of Ca(2+) dynamics in response to electrical activity in physiological conditions can be provided by future models.

  14. Two families with isolated cat cry without the cri-du-chat syndrome phenotype have an inherited 5p15.3 deletion: Delineation of the larynx malformation region

    SciTech Connect

    Gersh, M.; Overhauser, J.; Pasztor, L.M.

    1994-09-01

    The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p). Patients present with a cat-like cry at birth that is usually considered diagnostic of this syndrome. Additional features of the syndrome include failure to thrive, microcephaly, hypertelorism, epicanthal folds, hypotonia, and severe mental retardation. We report on two families in which the patients with 5p deletions have only the characteristic cat-like cry with normal to mildly delayed development. One family has three children with varying levels of developmental delay and a deletion of 5p15.3 that was inherited from the father. The second family has a mother and daughter both presenting with a cat-like cry and normal intelligence. A de novo deletion in a patient with isolated cat cry and mild developmental delay was also identified. The precise locations of the deletions in each family were determined by fluorescent in situ hybridization using lambda phage, cosmids, and YAC clones. Cryptic translocations and mosaicism were not detected in the parents transmitting the deletion. All of the deletion breakpoints map distal to the previously defined cri-du-chat critical region. A YAC contig has been constructed for the chromosomal region implicated in the larynx malformation. DNA clones mapping in this region will be useful diagnostic tools for delineating 5p deletions that result in the typical features of cri-du-chat syndrome with deletions that result in the isolated cat-like cry feature which is associated with a better prognosis.

  15. The alterations of Ca2+/calmodulin/CaMKII/CaV1.2 signaling in experimental models of Alzheimer's disease and vascular dementia.

    PubMed

    Min, Dongyu; Guo, Feng; Zhu, Shu; Xu, Xiaoxue; Mao, Xiaoyuan; Cao, Yonggang; Lv, Xintong; Gao, Qinghua; Wang, Lei; Chen, Tianbao; Shaw, Chris; Hao, Liying; Cai, Jiqun

    2013-03-22

    The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca(2+)/calmodulin/CaMKII/CaV1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/CaV1.2 by double-labeling immunofluorescence in the hippocampus of APP/PS1 mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with Aβ1-42. The expression of CaV1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PS1 mice; the expression of calmodulin protein was increased in APP/PS1 mice and VD gerbils; levels of p-CaMKII, p-CREB and BDNF proteins were decreased in AD and VD models. The number of neurons in which p-CaMKII and CaV1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with Aβ1-42. Collectively, our results suggest that the alterations in CaV1.2, calmodulin, p-CaMKII, p-CREB and BDNF can be reflective of an involvement in the impairment in memory and cognition in AD and VD models.

  16. Plasma membrane Ca2+ release-activated Ca2+ channels with a high selectivity for Ca2+ identified by patch-clamp recording in rat liver cells.

    PubMed

    Rychkov, G; Brereton, H M; Harland, M L; Barritt, G J

    2001-04-01

    Repetitive waves of increased cytoplasmic Ca2+ concentration play a central role in the process by which hormones regulate liver function. Maintenance of these Ca2+ waves requires Ca2+ inflow through store-operated Ca2+ channels. The properties and mechanism(s) of activation of these channels are not well understood. Store-operated Ca2+ channels (SOCs) in the H4-IIE rat liver cell line were studied by whole-cell patch clamping. Depletion of Ca2+ in intracellular stores by intracellular perfusion with either inositol 1,4,5-trisphosphate (InsP(3)) or thapsigargin in the presence of 10 mmol/L ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid (EGTA), or with 10 mmol/L EGTA alone, activated an inward current that reversed at a membrane potential above +40 mV. In physiologic extracellular medium, this inward current was carried exclusively by Ca2+ and was blocked by a variety of di- and trivalent cations. In the absence of extracellular Ca2+ and Mg2+, the inward current was carried by monovalent cations. This current was 10 to 30 times larger than that observed in the presence of extracellular Ca2+, and permitted the detection of single-channel events that corresponded to a single-channel conductance of about 40 pS. Both the Ca2+ and Na+ inward currents were blocked by the calmodulin antagonist, N-(6-amino hexyl)-5-chloro-1-naphthalenesulphonamide (W7), but not by calmidazolium or calmodulin-dependent protein kinase II fragment 290-309. It is concluded that liver cells possess plasma membrane Ca2+ channels that have a high selectivity for Ca2+, are activated by a decrease in the concentration of Ca2+ in intracellular stores through a mechanism that is unlikely to involve calmodulin, and are involved in re-filling intracellular Ca2+ stores during Ca2+ signaling.

  17. Phosphorylation and activation of nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) by Ca{sup 2+}/calmodulin-dependent protein kinase I (CaMKI)

    SciTech Connect

    Onouchi, Takashi; Sueyoshi, Noriyuki; Ishida, Atsuhiko; Kameshita, Isamu

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer CaMKP-N/PPM1E underwent proteolytic processing and translocated to cytosol. Black-Right-Pointing-Pointer The proteolysis was effectively inhibited by the proteasome inhibitors. Black-Right-Pointing-Pointer Ser-480 of zebrafish CaMKP-N was phosphorylated by cytosolic CaMKI. Black-Right-Pointing-Pointer Phosphorylation-mimic mutants of CaMKP-N showed enhanced activity. Black-Right-Pointing-Pointer These results suggest that CaMKP-N is regulated by CaMKI. -- Abstract: Nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) is an enzyme that dephosphorylates and downregulates multifunctional Ca{sup 2+}/calmodulin-dependent protein kinases (CaMKs) as well as AMP-dependent protein kinase. In our previous study, we found that zebrafish CaMKP-N (zCaMKP-N) underwent proteolytic processing and translocated to cytosol in a proteasome inhibitor-sensitive manner. In the present study, we found that zCaMKP-N is regulated by phosphorylation at Ser-480. When zCaMKP-N was incubated with the activated CaMKI, time-dependent phosphorylation of the enzyme was observed. This phosphorylation was significantly reduced when Ser-480 was replaced by Ala, suggesting that CaMKI phosphorylates Ser-480 of zCaMKP-N. Phosphorylation-mimic mutants, S480D and S480E, showed higher phosphatase activities than those of wild type and S480A mutant in solution-based phosphatase assay using various substrates. Furthermore, autophosphorylation of CaMKII after ionomycin treatment was more severely attenuated in Neuro2a cells when CaMKII was cotransfected with the phosphorylation-mimic mutant of zCaMKP-N than with the wild-type or non-phosphorylatable zCaMKP-N. These results strongly suggest that phosphorylation of zCaMKP-N at Ser-480 by CaMKI activates CaMKP-N catalytic activity and thereby downregulates multifunctional CaMKs in the cytosol.

  18. Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.

    PubMed

    Zhou, Hong; Kim, Seong-Ah; Kirk, Elizabeth A; Tippens, Alyssa L; Sun, Hong; Haeseleer, Françoise; Lee, Amy

    2004-05-12

    Ca2+-binding protein-1 (CaBP1) is a Ca2+-binding protein that is closely related to calmodulin (CaM) and localized in somatodendritic regions of principal neurons throughout the brain, but how CaBP1 participates in postsynaptic Ca2+ signaling is not known. Here, we describe a novel role for CaBP1 in the regulation of Ca2+ influx through Ca(v)1.2 (L-type) Ca2+ channels. CaBP1 interacts directly with the alpha1 subunit of Ca(v)1.2 at sites that also bind CaM. CaBP1 binding to one of these sites, the IQ domain, is Ca2+ dependent and competitive with CaM binding. The physiological significance of this interaction is supported by the association of Ca(v)1.2 and CaBP1 in postsynaptic density fractions purified from rat brain. Moreover, in double-label immunofluorescence experiments, CaBP1 and Ca(v)1.2 colocalize in numerous cell bodies and dendrites of neurons, particularly in pyramidal cells in the CA3 region of the hippocampus and in the dorsal cortex. In electrophysiological recordings of cells transfected with Ca(v)1.2, CaBP1 greatly prolonged Ca2+ currents, prevented Ca2+-dependent inactivation, and caused Ca2+-dependent facilitation of currents evoked by step depolarizations and repetitive stimuli. These effects contrast with those of CaM, which promoted strong Ca2+-dependent inactivation of Ca(v)1.2 with these same voltage protocols. Our findings reveal how Ca2+-binding proteins, such as CaM and CaBP1, differentially adjust Ca2+ influx through Ca(v)1.2 channels, which may specify diverse modes of Ca2+ signaling in neurons.

  19. Normalization of Ca2+ signals by small oblique dendrites of CA1 pyramidal neurons.

    PubMed

    Frick, Andreas; Magee, Jeffrey; Koester, Helmut J; Migliore, Michele; Johnston, Daniel

    2003-04-15

    Oblique dendrites of CA1 pyramidal neurons predominate in stratum radiatum and receive approximately 80% of the synaptic input from Schaffer collaterals. Despite this fact, most of our understanding of dendritic signal processing in these neurons comes from studies of the main apical dendrite. Using a combination of Ca2+ imaging and whole-cell recording techniques in rat hippocampal slices, we found that the properties of the oblique dendrites differ markedly from those of the main dendrites. These different properties tend to equalize the Ca2+ rise from single action potentials as they backpropagate into the oblique dendrites from the main trunk. Evidence suggests that this normalization of Ca2+ signals results from a higher density of a transient, A-type K+ current [I(K(A))] in the oblique versus the main dendrites. The higher density of I(K(A)) may have important implications for our understanding of synaptic integration and plasticity in these structures.

  20. Deep inelastic separated response functions from 40Ca and 48Ca

    NASA Astrophysics Data System (ADS)

    Deady, M.; Williamson, C. F.; Zimmerman, P. D.; Altemus, R.; Whitney, R. R.

    1986-06-01

    Deep inelastic scattering cross sections have been measured for 40Ca and 48Ca at electron energies between 100 and 375 MeV at scattering angles of 90° and 140°. Longitudinal and transverse response functions at three-momentum transfers between 250 and 410 MeV/c have been extracted using a Rosenbluth separation. The response functions are compared to calculations modeling the nucleus as a noninteracting relativistic Fermi gas. The model is found to agree with the observed transverse response function in the region of expected quasi-free nucleon knockout, but the model overestimates the observed longitudinal response. Comparisons of the response functions of the two isotopes are made, and differences between 40Ca and 48Ca are seen.

  1. Human carcinoma-associated and salivary mucins detected by anti-bovine submaxillary mucin antibodies.

    PubMed

    Golubović, S J; Bojić-Trbojević, Z T

    2006-01-01

    Polyclonal rabbit anti-bovine submaxillary mucin antibodies, anti-BSM IgG, were analyzed by autoradiography and densitometry (after SDS electrophoresis and blotting), ELISA, and IRMA assays for reactivity against native antigen BSM, deglycosylated and desialylated BSM, and human salivary and carcinoma-associated mucins. Known human tumor marker CA19-9 antigen reacted with rabbit anti-BSM IgG under different conditions, either soluble or immobilized. As soluble antigen, in IRMA it reacted with anti-BSM antibodies used both as a catcher and a tracer, as well as in combination with monoclonal anti-CA19-9 antibodies as a catcher. MUC1 mucin is a carrier of this carbohydrate antigen, CA19-9, or sialyl-Lewis(a), as well as of CA15-3 antigen, a known breast tumor marker. Autoradiography and densitometry demonstrated binding of anti-BSM IgG to intact MUC1 in a sample of commercial standard preparation of CA19-9 antigen. The same method and analysis demonstrated binding of anti-BSM IgG to MUC1 and to smaller antigens of 85-120 kD in samples containing CA15-3 antigen: commercial standard preparation, human breast tissue, and human milk. In a sample of whole human saliva, reactions of both isoforms of MUC7 were detected by autoradiography, as bands of 85 and 115 kD, and densitogram analysis also demonstrated reaction with MUC5B. Chemical modifications performed as periodate oxidation and desialylation of the BSM demonstrated carbohydrate (i.e., sialic acid) epitope sensitivity for anti-BSM IgG. The results presented in this work indicate that polyclonal anti-BSM antibodies are specific for sialylated carbohydrate structure on mucins and could serve as a tool for investigation of human carcinoma-associated and salivary mucins.

  2. Microdomain [Ca(2+)] Fluctuations Alter Temporal Dynamics in Models of Ca(2+)-Dependent Signaling Cascades and Synaptic Vesicle Release.

    PubMed

    Weinberg, Seth H

    2016-03-01

    Ca(2+)-dependent signaling is often localized in spatially restricted microdomains and may involve only 1 to 100 Ca(2+) ions. Fluctuations in the microdomain Ca(2+) concentration (Ca(2+)) can arise from a wide range of elementary processes, including diffusion, Ca(2+) influx, and association/dissociation with Ca(2+) binding proteins or buffers. However, it is unclear to what extent these fluctuations alter Ca(2+)-dependent signaling. We construct Markov models of a general Ca(2+)-dependent signaling cascade and Ca(2+)-triggered synaptic vesicle release. We compare the hitting (release) time distribution and statistics for models that account for [Ca(2+)] fluctuations with the corresponding models that neglect these fluctuations. In general, when Ca(2+) fluctuations are much faster than the characteristic time for the signaling event, the hitting time distributions and statistics for the models with and without Ca(2+) fluctuation are similar. However, when the timescale of Ca(2+) fluctuations is on the same order as the signaling cascade or slower, the hitting time mean and variability are typically increased, in particular when the average number of microdomain Ca(2+) ions is small, a consequence of a long-tailed hitting time distribution. In a model of Ca(2+)-triggered synaptic vesicle release, we demonstrate the conditions for which [Ca(2+)] fluctuations do and do not alter the distribution, mean, and variability of release timing. We find that both the release time mean and variability can be increased, demonstrating that Ca(2+) fluctuations are an important aspect of microdomain Ca(2+) signaling and further suggesting that Ca(2+) fluctuations in the presynaptic terminal may contribute to variability in synaptic vesicle release and thus variability in neuronal spiking.

  3. Maitotoxin converts the plasmalemmal Ca(2+) pump into a Ca(2+)-permeable nonselective cation channel.

    PubMed

    Sinkins, William G; Estacion, Mark; Prasad, Vikram; Goel, Monu; Shull, Gary E; Kunze, Diana L; Schilling, William P

    2009-12-01

    Maitotoxin (MTX) activates Ca(2+)-permeable nonselective cation channels and causes a dramatic increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in every cell examined to date, but the molecular identity of the channels involved remains unknown. A clue came from studies of a structurally related marine toxin called palytoxin (PTX). PTX binds to the plasmalemmal Na(+)-K(+)-ATPase (NKA) and converts the Na(+) pump into a nonselective cation channel. Given the high permeability of the MTX channel for Ca(2+), we considered the possibility that MTX may bind to the plasmalemmal Ca(2+)-ATPase (PMCA) pump, and like PTX, convert the pump into a channel. To test this hypothesis, the PMCA was overexpressed in Spodoptera frugiperda (Sf9) insect cells and in human embryonic kidneys (HEK) 293 cells. In both cell types, enhanced expression of the PMCA was associated with a significant increase in MTX-induced whole cell membrane currents. The effect of MTX on whole cell currents in both wild-type and PMCA overexpressing HEK cells was sensitive to pump ligands including Ca(2+) and ATP. MTX-induced currents were significantly reduced by knockdown of PMCA1 in HEK cells using small interfering RNA or in mouse embryonic fibroblasts from genetically modified mice with the PMCA1(+/-) PMCA4(-/-) genotype. Finally, PMCA catalytic activity (i.e., Ca(2+)-ATPase) in isolated membranes, or in purified PMCA preparations, was inhibited by MTX. Together, these results suggest that MTX binds to and converts the PMCA pump into a Ca(2+)-permeable nonselective cation channel.

  4. Maitotoxin converts the plasmalemmal Ca2+ pump into a Ca2+-permeable nonselective cation channel

    PubMed Central

    Sinkins, William G.; Estacion, Mark; Prasad, Vikram; Goel, Monu; Shull, Gary E.; Kunze, Diana L.

    2009-01-01

    Maitotoxin (MTX) activates Ca2+-permeable nonselective cation channels and causes a dramatic increase in cytosolic free Ca2+ concentration ([Ca2+]i) in every cell examined to date, but the molecular identity of the channels involved remains unknown. A clue came from studies of a structurally related marine toxin called palytoxin (PTX). PTX binds to the plasmalemmal Na+-K+-ATPase (NKA) and converts the Na+ pump into a nonselective cation channel. Given the high permeability of the MTX channel for Ca2+, we considered the possibility that MTX may bind to the plasmalemmal Ca2+-ATPase (PMCA) pump, and like PTX, convert the pump into a channel. To test this hypothesis, the PMCA was overexpressed in Spodoptera frugiperda (Sf9) insect cells and in human embryonic kidneys (HEK) 293 cells. In both cell types, enhanced expression of the PMCA was associated with a significant increase in MTX-induced whole cell membrane currents. The effect of MTX on whole cell currents in both wild-type and PMCA overexpressing HEK cells was sensitive to pump ligands including Ca2+ and ATP. MTX-induced currents were significantly reduced by knockdown of PMCA1 in HEK cells using small interfering RNA or in mouse embryonic fibroblasts from genetically modified mice with the PMCA1(+/−) PMCA4(−/−) genotype. Finally, PMCA catalytic activity (i.e., Ca2+-ATPase) in isolated membranes, or in purified PMCA preparations, was inhibited by MTX. Together, these results suggest that MTX binds to and converts the PMCA pump into a Ca2+-permeable nonselective cation channel. PMID:19794142

  5. Transverse response functions in deep inelastic electron scattering for 40Ca, 48Ca, and 56Fe

    NASA Astrophysics Data System (ADS)

    Meziani, Z. E.; Barreau, P.; Bernheim, M.; Morgenstern, J.; Turck-Chieze, S.; Altemus, R.; McCarthy, J.; Orphanos, L. J.; Whitney, R. R.; Capitani, G. P.; de Sanctis, E.; Frullani, S.; Garibaldi, F.

    1985-03-01

    Deep-inelastic inclusive electron-scattering cross sections from 40Ca, 48Ca, and 56Fe have been measured at 60°, 90°, and 140° and at energy transfers including the Δ(3,3) region. The transverse response function in the momentum interval 300 MeV/c<||q-->||<600 MeV/c was extracted by the Rosenbluth prescription. Different theoretical approaches to the quasielastic region are compared to the data. A mass-number scaling is observed.

  6. Progressive alterations of hippocampal CA3-CA1 synapses in an animal model of depression.

    PubMed

    Qiao, Hui; An, Shu-Cheng; Ren, Wei; Ma, Xin-Ming

    2014-12-15

    Major depressive disorder is the most prevalent psychiatric condition, but the cellular and molecular mechanisms underlying this disorder are largely unknown, although multiple hypotheses have been proposed. The aim of this study was to characterize the progressive alteration of neuronal plasticity in the male rat hippocampus during depression induced by chronic unpredictable mild stress (CUMS), an established animal model of depression. The data in the hippocampus were collected on days 7, 14 and 21 after the onset of three-week CUMS. When analyzed on day 21, three-week CUMS induced typically depressive-like behaviors, impaired LTP induction, and decreased basal synaptic transmission at hippocampal CA3-CA1 synapses recorded in vivo, which was accompanied by decreased density of dendritic spines in CA1 and CA3 pyramidal neurons. The levels of both Kalirin-7 and brain-derived neurotrophic factor (BDNF) in the hippocampus were decreased at the same time. On day 14 (middle phase), some depressive-like behaviors were observed, which was accompanied by depressed basal synaptic transmission and enhanced LTP induction at the CA3-CA1 synapses. However, BDNF expression was decreased without alteration of Kalirin7 expression in comparison with no-stress control. Depressed basal synaptic transmission occurred in the middle phase of CUMS may contribute to decreased expression of BDNF. On day 7, depressive-like behaviors were not observed, and LTP induction, spine density, Kalirin-7 and BDNF expression were not altered by CUMS in comparison with no-stress control. These results showed that the functional changes at CA3-CA1synapses occurred earlier than the structural alteration during three-week CUMS as a strategy of neural adaptation, and rats required three weeks to develop depressive-like behaviors during CUMS. Our results suggest an important role of Kalirin-7 in CUMS-mediated alterations in spine density, synaptic function and overall depressive-like behaviors on day 21.

  7. Dual Effect of Phosphate Transport on Mitochondrial Ca2+ Dynamics*

    PubMed Central

    Wei, An-Chi; Liu, Ting; O'Rourke, Brian

    2015-01-01

    The large inner membrane electrochemical driving force and restricted volume of the matrix confer unique constraints on mitochondrial ion transport. Cation uptake along with anion and water movement induces swelling if not compensated by other processes. For mitochondrial Ca2+ uptake, these include activation of countertransporters (Na+/Ca2+ exchanger and Na+/H+ exchanger) coupled to the proton gradient, ultimately maintained by the proton pumps of the respiratory chain, and Ca2+ binding to matrix buffers. Inorganic phosphate (Pi) is known to affect both the Ca2+ uptake rate and the buffering reaction, but the role of anion transport in determining mitochondrial Ca2+ dynamics is poorly understood. Here we simultaneously monitor extra- and intra-mitochondrial Ca2+ and mitochondrial membrane potential (ΔΨm) to examine the effects of anion transport on mitochondrial Ca2+ flux and buffering in Pi-depleted guinea pig cardiac mitochondria. Mitochondrial Ca2+ uptake proceeded slowly in the absence of Pi but matrix free Ca2+ ([Ca2+]mito) still rose to ∼50 μm. Pi (0.001–1 mm) accelerated Ca2+ uptake but decreased [Ca2+]mito by almost 50% while restoring ΔΨm. Pi-dependent effects on Ca2+ were blocked by inhibiting the phosphate carrier. Mitochondrial Ca2+ uptake rate was also increased by vanadate (Vi), acetate, ATP, or a non-hydrolyzable ATP analog (AMP-PNP), with differential effects on matrix Ca2+ buffering and ΔΨm recovery. Interestingly, ATP or AMP-PNP prevented the effects of Pi on Ca2+ uptake. The results show that anion transport imposes an upper limit on mitochondrial Ca2+ uptake and modifies the [Ca2+]mito response in a complex manner. PMID:25963147

  8. Ionic Mechanisms Underlying Spontaneous CA1 Neuronal Firing in Ca2+-Free Solution

    PubMed Central

    Shuai, Jianwei; Bikson, Marom; Hahn, Philip J.; Lian, Jun; Durand, Dominique M.

    2003-01-01

    Hippocampal CA1 neurons exposed to zero-[Ca2+] solutions can generate periodic spontaneous synchronized activity in the absence of synaptic function. Experiments using hippocampal slices showed that, after exposure to zero-[Ca2+]0 solution, CA1 pyramidal cells depolarized 5–10 mV and started firing spontaneous action potentials. Spontaneous single neuron activity appeared in singlets or was grouped into bursts of two or three action potentials. A 16-compartment, 23-variable cable model of a CA1 pyramidal neuron was developed to study mechanisms of spontaneous neuronal bursting in a calcium-free extracellular solution. In the model, five active currents (a fast sodium current, a persistent sodium current, an A-type transient potassium current, a delayed rectifier potassium current, and a muscarinic potassium current) are included in the somatic compartment. The model simulates the spontaneous bursting behavior of neurons in calcium-free solutions. The mechanisms underlying several aspects of bursting are studied, including the generation of triplet bursts, spike duration, burst termination, after-depolarization behavior, and the prolonged inactive period between bursts. We show that the small persistent sodium current can play a key role in spontaneous CA1 activity in zero-calcium solutions. In particular, it is necessary for the generation of an after-depolarizing potential and prolongs both individual bursts and the interburst interval. PMID:12609911

  9. Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep

    PubMed Central

    Jeong, Kyunghwa; Lee, Soyoung; Seo, Haengsoo; Oh, Yangkyun; Jang, Donghoon; Choe, Joonho; Kim, Daesoo; Lee, Jung-Ha; Jones, Walton D.

    2015-01-01

    Mammalian T-type Ca2+ channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). These channels are reported to be sleep stabilizers important in the generation of the delta rhythms of deep sleep, but controversy remains. The identification of precise physiological functions for the T-type channels has been hindered, at least in part, by the potential for compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene, but its functions are even less well-studied. We cloned Ca-α1T, the only Cav3 channel gene in Drosophila melanogaster, expressed it in Xenopus oocytes and HEK-293 cells, and confirmed it passes typical T-type currents. Voltage-clamp analysis revealed the biophysical properties of Ca-α1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found Ca-α1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-α1T show an abnormal increase in sleep duration most pronounced during subjective day under continuous dark conditions despite normal oscillations of the circadian clock. Thus, our study suggests invertebrate T-type Ca2+ channels promote wakefulness rather than stabilizing sleep. PMID:26647714

  10. Rediscovering area CA2: unique properties and functions

    PubMed Central

    Dudek, Serena M.; Alexander, Georgia M.; Farris, Shannon

    2016-01-01

    Hippocampal area CA2 has several features that distinguish it from CA1 and CA3, including a unique gene expression profile, failure to display long-term potentiation and relative resistance to cell death. A recent increase in interest in the CA2 region, combined with the development of new methods to define and manipulate its neurons, has led to some exciting new discoveries on the properties of CA2 neurons and their role in behaviour. Here, we review these findings and call attention to the idea that the definition of area CA2 ought to be revised in light of gene expression data. PMID:26806628

  11. Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx

    PubMed Central

    Kilpatrick, Bethan S.; Yates, Elizabeth; Grimm, Christian; Schapira, Anthony H.

    2016-01-01

    ABSTRACT Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endo-lysosomal ion channels crucial for membrane trafficking. Several lines of evidence suggest that TRPMLs mediate localised Ca2+ release but their role in Ca2+ signalling is not clear. Here, we show that activation of endogenous and recombinant TRPMLs with synthetic agonists evoked global Ca2+ signals in human cells. These signals were blocked by a dominant-negative TRPML1 construct and a TRPML antagonist. We further show that, despite a predominant lysosomal localisation, TRPML1 supports both Ca2+ release and Ca2+ entry. Ca2+ release required lysosomal and ER Ca2+ stores suggesting that TRPMLs, like other endo-lysosomal Ca2+ channels, are capable of ‘chatter’ with ER Ca2+ channels. Our data identify new modalities for TRPML1 action. PMID:27577094

  12. Kinetics and stoichiometry of coupled Na efflux and Ca influx (Na/Ca exchange) in barnacle muscle cells

    PubMed Central

    1989-01-01

    Coupled Na+ exit/Ca2+ entry (Na/Ca exchange operating in the Ca2+ influx mode) was studied in giant barnacle muscle cells by measuring 22Na+ efflux and 45Ca2+ influx in internally perfused, ATP-fueled cells in which the Na+ pump was poisoned by 0.1 mM ouabain. Internal free Ca2+, [Ca2+]i, was controlled with a Ca-EGTA buffering system containing 8 mM EGTA and varying amounts of Ca2+. Ca2+ sequestration in internal stores was inhibited with caffeine and a mitochondrial uncoupler (FCCP). To maximize conditions for Ca2+ influx mode Na/Ca exchange, and to eliminate tracer Na/Na exchange, all of the external Na+ in the standard Na+ sea water (NaSW) was replaced by Tris or Li+ (Tris-SW or LiSW, respectively). In both Na-free solutions an external Ca2+ (Cao)-dependent Na+ efflux was observed when [Ca2+]i was increased above 10(-8) M; this efflux was half-maximally activated by [Ca2+]i = 0.3 microM (LiSW) to 0.7 microM (Tris-SW). The Cao-dependent Na+ efflux was half-maximally activated by [Ca2+]o = 2.0 mM in LiSW and 7.2 mM in Tris-SW; at saturating [Ca2+]o, [Ca2+]i, and [Na+]i the maximal (calculated) Cao-dependent Na+ efflux was approximately 75 pmol#cm2.s. This efflux was inhibited by external Na+ and La3+ with IC50's of approximately 125 and 0.4 mM, respectively. A Nai-dependent Ca2+ influx was also observed in Tris-SW. This Ca2+ influx also required [Ca2+]i greater than 10(-8) M. Internal Ca2+ activated a Nai-independent Ca2+ influx from LiSW (tracer Ca/Ca exchange), but in Tris-SW virtually all of the Cai-activated Ca2+ influx was Nai-dependent (Na/Ca exchange). Half-maximal activation was observed with [Na+]i = 30 mM. The fact that internal Ca2+ activates both a Cao-dependent Na+ efflux and a Nai- dependent Ca2+ influx in Tris-SW implies that these two fluxes are coupled; the activating (intracellular) Ca2+ does not appear to be transported by the exchanger. The maximal (calculated) Nai-dependent Ca2+ influx was -25 pmol/cm2.s. At various [Na+]i between 6 and 106 m

  13. Neuronal Ca(2+) dyshomeostasis in Huntington disease.

    PubMed

    Giacomello, Marta; Oliveros, Juan C; Naranjo, Jose R; Carafoli, Ernesto

    2013-01-01

    The expansion of the N-terminal poly-glutamine tract of the huntingtin (Htt) protein is responsible for Huntington disease (HD). A large number of studies have explored the neuronal phenotype of HD, but the molecular aethiology of the disease is still very poorly understood. This has hampered the development of an appropriate therapeutical strategy to at least alleviate its symptoms. In this short review, we have focused our attention on the alteration of a specific cellular mechanism common to all HD models, either genetic or induced by treatment with 3-NPA, i.e. the cellular dyshomeostasis of Ca(2+). We have highlighted the direct and indirect (i.e. transcriptionally mediated) effects of mutated Htt on the maintenance of the intracellular Ca(2+) balance, the correct modulation of which is fundamental to cell survival and the disturbance of which plays a key role in the death of the cell.

  14. Plant mechanosensing and Ca2+ transport.

    PubMed

    Kurusu, Takamitsu; Kuchitsu, Kazuyuki; Nakano, Masataka; Nakayama, Yoshitaka; Iida, Hidetoshi

    2013-04-01

    Mechanical stimuli generate Ca(2+) signals and influence growth and development in plants. Recently, candidates for Ca(2+)-permeable mechanosensitive (MS) channels have been identified. These channels are thought to be responsible for sensing osmotic shock, touch, and gravity. One candidate is the MscS-like (MSL) protein family, a homolog of the typical bacterial MS channels. Some of the MSL proteins are localized to plastids to maintain their shape and size. Another candidate is the mid1-complementing activity (MCA) protein family, which is structurally unique to the plant kingdom. MCA proteins are localized in the plasma membrane and are suggested to be involved in mechanosensing and to be functionally related to reactive oxygen species (ROS) signaling. Here, we review their structural features and role in planta.

  15. Importance of extracellular Ca2+ and intracellular Ca2+ release in ethanol-induced contraction of cerebral arterial smooth muscle.

    PubMed

    Yang, Z; Wang, J; Zheng, T; Altura, B T; Altura, B M

    2001-07-01

    The present study was designed to investigate the roles of extracellular Ca2+ ([Ca2+]0) influx and intracellular free Ca2+ ([Ca2+]i) release in ethanol-induced contractions of isolated canine cerebral arteries and primary cultured, cerebral vascular smooth muscle cells. Ethanol (20-200 mM) produced significant contractions in isolated canine basilar arterial rings in a concentration-dependent manner. Removal of [Ca2+]0 and pretreatment of canine basilar arterial rings with verapamil (an antagonist of voltage-gated Ca2+ channels), thapsigargin (a selective antagonist of the sarcoplasmic reticulum Ca2+ pump), caffeine plus ryanodine (a specific antagonist of ryanodine-sensitive Ca2+ release), or heparin (an inositol 1,4,5,-trisphosphate [InsP3]-mediated Ca2+ release antagonist) markedly attenuated (approximately 50%-80%) ethanol-induced contractions. The absence of [Ca2+]0 and preincubation of primary single smooth muscle cells obtained from canine basilar arteries with verapamil, thapsigargin, heparin, or caffeine plus ryanodine markedly attenuated (approximately 50%-80%) the transient and sustained elevations in [Ca2+]i induced by ethanol. Results of the present study suggest to us that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores (both InsP3 sensitive and ryanodine sensitive) are required for ethanol-induced contractions of isolated canine basilar arteries.

  16. Honeybee locomotion is impaired by Am-CaV3 low voltage-activated Ca2+ channel antagonist

    PubMed Central

    Rousset, M.; Collet, C.; Cens, T.; Bastin, F.; Raymond, V.; Massou, I.; Menard, C.; Thibaud, J.-B.; Charreton, M.; Vignes, M.; Chahine, M.; Sandoz, J. C.; Charnet, P.

    2017-01-01

    Voltage‐gated Ca2+ channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca2+ channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca2+ channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type CaV3 Ca2+ channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca2+ currents recorded in bee neurons and myocytes with Ca2+ currents recorded in Xenopus oocytes expressing the honeybee CaV3 gene suggests native expression in bee muscle cells only. High‐voltage activated Ca2+ channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a CaV3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of CaV3 suggest a role in honeybee muscle function. PMID:28145504

  17. Phosphorylation of the Ca2+-Binding Protein CaBP4 by Protein Kinase C ζ in Photoreceptors

    PubMed Central

    Lee, Amy; Jimenez, Amber; Cui, Guiying; Haeseleer, Françoise

    2009-01-01

    CaBP4 is a calmodulin-like neuronal calcium-binding protein that is crucial for the development and/or maintenance of the cone and rod photoreceptor synapse. Previously, we showed that CaBP4 directly regulates Cav1 L-type Ca2+ channels, which are essential for normal photoreceptor synaptic transmission. Here, we show that the function of CaBP4 is regulated by phosphorylation. CaBP4 is phosphorylated by protein kinase C ζ (PKCζ) at serine 37 both in vitro and in the retina and colocalizes with PKCζ in photoreceptors. CaBP4 phosphorylation is greater in light-adapted than dark-adapted mouse retinas. In electrophysiological recordings of cells transfected with Cav1.3 and CaBP4, mutation of the serine 37 to alanine abolished the effect of CaBP4 in prolonging the Ca2+ current through Cav1.3 channel, whereas inactivating mutations in the CaBP4 Ca2+-binding sites strengthened Cav1.3 modulation. These findings demonstrate how light-stimulated changes in CaBP4 phosphorylation and Ca2+ binding may regulate presynaptic Ca2+ signals in photoreceptors. PMID:18003854

  18. Honeybee locomotion is impaired by Am-CaV3 low voltage-activated Ca(2+) channel antagonist.

    PubMed

    Rousset, M; Collet, C; Cens, T; Bastin, F; Raymond, V; Massou, I; Menard, C; Thibaud, J-B; Charreton, M; Vignes, M; Chahine, M; Sandoz, J C; Charnet, P

    2017-02-01

    Voltage-gated Ca(2+) channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca(2+) channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca(2+) channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type CaV3 Ca(2+) channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca(2+) currents recorded in bee neurons and myocytes with Ca(2+) currents recorded in Xenopus oocytes expressing the honeybee CaV3 gene suggests native expression in bee muscle cells only. High-voltage activated Ca(2+) channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a CaV3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of CaV3 suggest a role in honeybee muscle function.

  19. Effect of CaTiO(3)-CaCO(3) prepared by alkoxide method on cell response.

    PubMed

    Rodriguez, Andrea P; Inoue, Miho; Tanaka, Toshiyuki; Miyake, Michihiro; Sfer, Ana M; Kishimoto, Etsuo; Tsujigiwa, Hidetsugu; Rivera, Rosario S; Nagatsuka, Hitoshi

    2010-04-01

    In recent years, calcium titanate (CaTiO(3)) and carbon-containing materials have gained much attention in a number of biomedical material researches. To maximize the advantages of both materials, we developed a novel alkoxide method to get "calcium titanate with calcium carbonate" (CaTiO(3)-CaCO(3)). The objective was to evaluate the crystallinity and elemental composition of CaTiO(3)-CaCO(3) prepared by alkoxide method, CaTiO(3)-aC elaborated by modified thermal decomposition method, commercially-prepared CaTiO(3), and the effect of these materials on the bone marrow stromal cell. Hydroxyapatite was used as positive control material. We examined the cellular proliferation, osteoblastic differentiation, and mineralization of KUSA/A1 cells cultured with the materials. The results showed that CaTiO(3)-CaCO(3) and CaTiO(3)-aC contained evidence of calcium carbonate enhancing cell proliferation, osteoblastic differentiation, and mineralization. On the contrary, the commercially-prepared CaTiO(3) revealed absence of calcium carbonate with lower cell response than the other groups. The results indicated that calcium carbonate could play a key role in the cell response of CaTiO(3) material. In conclusion, our findings suggest that CaTiO(3)-CaCO(3) could be considered an important candidate as a biomaterial for medical and dental applications.

  20. Superconductivity in Ca-doped graphene laminates

    PubMed Central

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-01-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp. PMID:26979564

  1. Superconductivity in Ca-doped graphene laminates.

    PubMed

    Chapman, J; Su, Y; Howard, C A; Kundys, D; Grigorenko, A N; Guinea, F; Geim, A K; Grigorieva, I V; Nair, R R

    2016-03-16

    Despite graphene's long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc's strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp.

  2. Ca sup + emission in the sunlit ionosphere

    SciTech Connect

    Torr, M.R. ); Torr, D.G.; Bhatt, P.; Swift, W.; Dougani, H. )

    1990-03-01

    In the course of a program of twilight airglow observations from the McDonald Observatory in southwest Texas, the resonance fluorescence emissions from calcium ions were measured. In particular, twilight sequences were obtained during the period of December 19-22, 1987, which coincided with the Ursids meteorite shower. During this meteorite event the intensities of the Ca{sup +} emission lines at 3,934 {angstrom} increased to the point that the surface brightness profiles could be inverted to volume emission rate profiles. These profiles show evidence for strong spatial redistribution of the Ca{sup +} over the course of three days. Prior to the onset of the meteorite activity, emissions from the Ca{sup +} originate from below 100 km, on the occasions when the emissions are visible. By the evening of December 19 a peak is measurable at 108 km. On the morning of December 22, a high-altitude peak was observed above 250 km, with a larger peak down at approximately 85 km. By the evening of December 22, the emission had substantially intensified, with the peak of the layer being at 80 km or below, but with emission being produced all the way up to at least 160 km. Observations of these emissions during meteor shower periods could provide a valuable tracer for the processes responsible for the transport of ions in the D, E, and F region, allowing the full altitude and latitude extent of the distribution to be determined.

  3. Superconductivity in CaBi2.

    PubMed

    Winiarski, M J; Wiendlocha, B; Gołąb, S; Kushwaha, S K; Wiśniewski, P; Kaczorowski, D; Thompson, J D; Cava, R J; Klimczuk, T

    2016-08-03

    Superconductivity is observed with critical temperature Tc = 2.0 K in self-flux-grown single crystals of CaBi2. This material adopts the ZrSi2 structure type with lattice parameters a = 4.696(1) Å, b = 17.081(2) Å and c = 4.611(1) Å. The crystals of CaBi2 were studied by means of magnetic susceptibility, specific heat and electrical resistivity measurements. The heat capacity jump at Tc is ΔC/γTc = 1.41, confirming bulk superconductivity; the Sommerfeld coefficient γ = 4.1 mJ mol(-1) K(-2) and the Debye temperature ΘD = 157 K. The electron-phonon coupling strength is λel-ph = 0.59, and the thermodynamic critical field Hc is low, between 111 and 124 Oe CaBi2 is a moderate coupling type-I superconductor. Results of electronic structure calculations are reported and charge densities, electronic bands, densities of states and Fermi surfaces are discussed, focusing on the effects of spin-orbit coupling and electronic property anisotropy. We find a mixed quasi-2D + 3D character in the electronic structure, which reflects the layered crystal structure of the material.

  4. Toward Laser Cooling of CaF

    NASA Astrophysics Data System (ADS)

    Hemmerling, Boerge; Drayna, Garrett; Chae, Eunmi; Ravi, Aakash; Lu, Hsin-I.; Yeo, Mark; Hummon, Matthew; Collopy, Alejandra; Stuhl, Benjamin; Ye, Jun; Doyle, John

    2013-05-01

    The prospects of novel physics employing polar cold molecules encompass quantum computing and simulations, controlled ultra-cold chemistry and precision measurements. However, a method liable to bring a general class of chemically diverse molecules to the ultracold regime still needs to be developed. We report on the progress of experiments to laser cool CaF molecules, including the implementation of a magneto-optical trap (MOT). We use a 2-stage buffer-gas cooled beam source to produce a cold and slow beam of particles. In this experiment, we plan to load the trap from this buffer-gas source. As a precursor to working with CaF, we successfully implemented the first buffer-gas loaded MOT of Yb, without the use of a Zeeman slower, but using only a non-chirped slowing laser. The lifetime of the MOT was measured to be > 100 ms, with the distance between the source and the MOT ~ 30 cm. We describe a scheme for the laser cooling and magneto-optical confinement of CaF molecules, following an approach similar to those used in the cooling of SrF and YO.

  5. Superconductivity in Ca-doped graphene laminates

    NASA Astrophysics Data System (ADS)

    Chapman, J.; Su, Y.; Howard, C. A.; Kundys, D.; Grigorenko, A. N.; Guinea, F.; Geim, A. K.; Grigorieva, I. V.; Nair, R. R.

    2016-03-01

    Despite graphene’s long list of exceptional electronic properties and many theoretical predictions regarding the possibility of superconductivity in graphene, its direct and unambiguous experimental observation has not been achieved. We searched for superconductivity in weakly interacting, metal decorated graphene crystals assembled into so-called graphene laminates, consisting of well separated and electronically decoupled graphene crystallites. We report robust superconductivity in all Ca-doped graphene laminates. They become superconducting at temperatures (Tc) between ≈4 and ≈6 K, with Tc’s strongly dependent on the confinement of the Ca layer and the induced charge carrier concentration in graphene. We find that Ca is the only dopant that induces superconductivity in graphene laminates above 1.8 K among several dopants used in our experiments, such as potassium, caesium and lithium. By revealing the tunability of the superconducting response through doping and confinement of the metal layer, our work shows that achieving superconductivity in free-standing, metal decorated monolayer graphene is conditional on an optimum confinement of the metal layer and sufficient doping, thereby bringing its experimental realization within grasp.

  6. Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice.

    PubMed

    Wang, Kang; Kelley, Melissa H; Wu, Wendy W; Adelman, John P; Maylie, James

    2015-01-01

    SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R-type Ca2+ channels. Recent studies have challenged the functional coupling between NMDARs and SK2-containing channels, suggesting that synaptic SK2-containing channels are instead activated by Ca2+ entry through R-type Ca2+ channels. Furthermore, SNX has been implicated to have off target affects, which would challenge the proposed coupling between R-type Ca2+ channels and KV4.2-containing K+ channels. To reconcile these conflicting results, we evaluated the effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3 null mice. The results show that in the absence of CaV2.3 channels, apamin application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers on EPSPs observed in neurons from wild type mice was not observed in neurons from CaV2.3 null mice. These data are consistent with a model in which SK2-containing channels are functionally coupled to NMDARs and KV4.2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons.

  7. Dissociation of Ca-bearing Molecules as a Source of Mercury's Ca Exosphere

    NASA Astrophysics Data System (ADS)

    Burger, Matthew H.; Killen, Rosemary M.

    2015-11-01

    Observations of Mercury's calcium exosphere by MESSENGER have revealed three key features: (1) The Ca is extremely energetic, with a temperature ~70,000 K if the source is thermal, (2) the source region is located in the dawn hemisphere, and (3) there is a strong annual variation in the Ca source rate (Burger et al. 2014). Killen and Hahn (2015) have shown that the source rate is consistent with impact vaporization by interplanetary dust and the intersection of Mercury with a cometary dust stream (likely associated with Comet Encke, Christou et al., submitted).Killen et al. (2005) suggested that energetic calcium could be produced by the dissociation of Ca-bearing molecules produced in impact vaporization plumes. We test this hypothesis with a Monte Carlo model that follows the evolution of atomic and molecular calcium produced in impact plumes. Ca-bearing molecules such as CaO, CaOH, and Ca(OH)2 are more likely to be are produced in vapor plumes than atomic Ca (Berezhnoy and Klumov 2008); these molecules quickly break apart either through vibrational dissociation or photodissociation. The excess energy associated with dissociation gives the atomic Ca an extra energy boost above the temperature of the impact plumes (~5000 K). We determine impact vaporization rates and excess energies required by the dissociation process to reproduce the scale height and spatial morphology of the Ca exosphere as observed by the MESSENGER Ultraviolet and Visible Spectrometer (UVVS).ReferencesBerezhnoy, A.A. and Klumov, B.A., Impacts as sources of the exosphere on Mercury, Icarus, 195, 511-522, 2008, doi:10.1016/j.icarus.2008.01.005.Burger, M.H., et al., Seasonal variations in Mercury's dayside calcium exosphere, Icarus, 238, 51-58, 2014, doi:10.1016/j.icarus.2014.04.049.Killen, R.M., et al., The calcium exosphere of Mercury, Icarus, 173, 300-311, 2005, doi:10.1016/j.icarus.2004.08.022.Killen, R.M. and Hahn, J.M., Impact vaporization as a possible source ofMercury's calcium exosphere

  8. Predicting Ca2+-binding Sites Using Refined Carbon Clusters

    PubMed Central

    Zhao, Kun; Wang, Xue; Wong, Hing C.; Wohlhueter, Robert; Kirberger, Michael P.; Chen, Guantao; Yang, Jenny J.

    2012-01-01

    Identifying Ca2+-binding sites in proteins is the first step towards understanding the molecular basis of diseases related to Ca2+-binding proteins. Currently, these sites are identified in structures either through X-ray crystallography or NMR analysis. However, Ca2+-binding sites are not always visible in X-ray structures due to flexibility in the binding region or low occupancy in a Ca2+-binding site. Similarly, both Ca2+ and its ligand oxygens are not directly observed in NMR structures. To improve our ability to predict Ca2+-binding sites in both X-ray and NMR structures, we report a new graph theory algorithm (MUGC) to predict Ca2+-binding sites. Using carbon atoms covalently bonded to the chelating oxygen atoms, and without explicit reference to side-chain oxygen ligand coordinates, MUGC is able to achieve 94% sensitivity with 76% selectivity on a dataset of X-ray structures comprised of 43 Ca2+-binding proteins. Additionally, prediction of Ca2+-binding sites in NMR structures were obtained by MUGC using a different set of parameters determined by analysis of both Ca2+-constrained and unconstrained Ca2+-loaded structures derived from NMR data. MUGC identified 20 out of 21 Ca2+-binding sites in NMR structures inferred without the use of Ca2+ constraints. MUGC predictions are also highly-selective for Ca2+-binding sites as analyses of binding sites for Mg2+, Zn2+, and Pb2+ were not identified as Ca2+-binding sites. These results indicate that the geometric arrangement of the second-shell carbon cluster is sufficient for both accurate identification of Ca2+-binding sites in NMR and X-ray structures, and for selective differentiation between Ca2+ and other relevant divalent cations. PMID:22821762

  9. Conserved properties of individual Ca2+-binding sites in calmodulin

    PubMed Central

    Halling, D. Brent; Liebeskind, Benjamin J.; Hall, Amelia W.; Aldrich, Richard W.

    2016-01-01

    Calmodulin (CaM) is a Ca2+-sensing protein that is highly conserved and ubiquitous in eukaryotes. In humans it is a locus of life-threatening cardiomyopathies. The primary function of CaM is to transduce Ca2+ concentration into cellular signals by binding to a wide range of target proteins in a Ca2+-dependent manner. We do not fully understand how CaM performs its role as a high-fidelity signal transducer for more than 300 target proteins, but diversity among its four Ca2+-binding sites, called EF-hands, may contribute to CaM’s functional versatility. We therefore looked at the conservation of CaM sequences over deep evolutionary time, focusing primarily on the four EF-hand motifs. Expanding on previous work, we found that CaM evolves slowly but that its evolutionary rate is substantially faster in fungi. We also found that the four EF-hands have distinguishing biophysical and structural properties that span eukaryotes. These results suggest that all eukaryotes require CaM to decode Ca2+ signals using four specialized EF-hands, each with specific, conserved traits. In addition, we provide an extensive map of sites associated with target proteins and with human disease and correlate these with evolutionary sequence diversity. Our comprehensive evolutionary analysis provides a basis for understanding the sequence space associated with CaM function and should help guide future work on the relationship between structure, function, and disease. PMID:26884197

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

    NASA Astrophysics Data System (ADS)

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

    2005-06-01

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

  11. Quantitative proteomics analysis of CaMKII phosphorylation and the CaMKII interactome in the mouse forebrain

    PubMed Central

    Shonesy, Brian C.; Rose, Kristie L.

    2015-01-01

    Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) autophosphorylation at Thr286 and Thr305/Thr306 regulates kinase activity, modulates subcellular targeting, and is critical for normal synaptic plasticity and learning and memory. Here, a mass spectrometry-based approach was used to identify Ca2+-dependent and -independent in vitro autophosphorylation sites in recombinant CaMKIIα and CaMKIIβ. CaMKII holoenzymes were then immunoprecipitated from subcellular fractions of forebrains isolated from either wildtype (WT) mice or mice with a Thr286 to Ala knock-in mutation of CaMKIIα (T286A-KI mice) and analyzed using the same approach in order to characterize in vivo phosphorylation sites in both CaMKII isoforms and identify CaMKII associated proteins (CaMKAPs). A total of 6 and 7 autophosphorylation sites in CaMKIIα and CaMKIIβ, respectively, were detected in WT mice. Thr286-phosphorylated CaMKIIα and Thr287-phosphorylated CaMKIIβ were selectively enriched in WT Triton-insoluble (synaptic) fractions compared to Triton-soluble (membrane) and cytosolic fractions. In contrast, Thr306-phosphorylated CaMKIIα and Ser315- and Thr320/Thr321-phosphorylated CaMKIIβ were selectively enriched in WT cytosolic fractions. The T286A-KI mutation significantly reduced levels of phosphorylation of CaMKIIα at Ser275 across all subcellular fractions, and of cytosolic CaMKIIβ at Ser315 and Thr320/Thr321. Significantly more CaMKAPs co-precipitated with WT CaMKII holoenzymes in the synaptic fraction compared to the membrane fraction, with functions including scaffolding, microtubule organization, actin organization, ribosomal function, vesicle trafficking, and others. The T286A-KI mutation altered the interactions of multiple CaMKAPs with CaMKII, including several proteins linked to autism spectrum disorders. These data identify CaMKII isoform phosphorylation sites and a network of synaptic protein interactions that are sensitive to the abrogation of Thr286 autophosphorylation

  12. Ca2+ influx in resting rat sensory neurones that regulates and is regulated by ryanodine-sensitive Ca2+ stores

    PubMed Central

    Usachev, Yuriy M; Thayer, Stanley A

    1999-01-01

    Store-operated, voltage-independent Ca2+ channels are activated by depletion of intracellular Ca2+ stores and mediate Ca2+ influx into non-excitable cells at resting membrane potential. We used microfluorimetry, patch-clamp and Mn2+-quench techniques to explore the possibility that a similar mechanism exists in rat dorsal root ganglion (DRG) neurones in primary culture. Following caffeine-induced depletion, ryanodine-sensitive Ca2+ stores refilled with Ca2+ at resting membrane potential. The refilling process required extracellular Ca2+, was blocked by 2 mM Ni2+, and was facilitated by membrane hyperpolarization from −55 to −80 mV, indicating a key role for Ca2+ influx. This influx of Ca2+ was not affected by the voltage-operated Ca2+ channel (VOCC) antagonists nicardipine (10 μM), nimodipine (10 μm) or ω-grammotoxin SIA (1 μm). When ryanodine-sensitive Ca2+ stores were depleted in Ca2+-free media, a return to 2 mM external Ca2+ resulted in a pronounced [Ca2+]i overshoot, indicating an increased permeability to Ca2+. Depletion of Ca2+ stores also produced a 2-fold increase in the rate of Mn2+ influx. The [Ca2+]i overshoot and Mn2+ entry were both inhibited by Ni2+, but not by VOCC antagonists. Caffeine induced periodic Ca2+ release from, and reuptake into, ryanodine-sensitive stores. The [Ca2+]i oscillations were arrested by removal of extracellular Ca2+ or by addition of Ni2+, but they were not affected by VOCC antagonists. Hyperpolarization increased the frequency of this rhythmic activity. These data suggest the presence of a Ca2+ entry pathway in mammalian sensory neurones that is distinct from VOCCs and is regulated by ryanodine-sensitive Ca2+ stores. This pathway participates in refilling intracellular Ca2+ stores and maintaining [Ca2+]i oscillations and thus controls the balance between intra- and extracellular Ca2+ reservoirs in resting DRG neurones. PMID:10432343

  13. Blood oxygenation level-dependent (BOLD) total and extravascular signal changes and ΔR2* in human visual cortex at 1.5, 3.0 and 7.0 T.

    PubMed

    Donahue, Manus J; Hoogduin, Hans; van Zijl, Peter C M; Jezzard, Peter; Luijten, Peter R; Hendrikse, Jeroen

    2011-01-01

    The characterisation of the extravascular (EV) contribution to the blood oxygenation level-dependent (BOLD) effect is important for understanding the spatial specificity of BOLD contrast and for modelling approaches that aim to extract quantitative metabolic parameters from the BOLD signal. Using bipolar crusher gradients, total (b = 0 s/mm(2) ) and predominantly EV (b = 100 s/mm(2) ) gradient echo BOLD ΔR(2)* and signal changes (ΔS/S) in response to visual stimulation (flashing checkerboard; f = 8 Hz) were investigated sequentially (within < 3 h) at 1.5, 3.0 and 7.0 T in the same subgroup of healthy volunteers (n = 7) and at identical spatial resolutions (3.5 × 3.5 × 3.5 mm(3)). Total ΔR(2)* (z-score analysis) values were -0.61 ± 0.10 s(-1) (1.5 T), -0.74 ± 0.05 s(-1) (3.0 T) and -1.37 ± 0.12 s(-1) (7.0 T), whereas EV ΔR(2)* values were -0.28 ± 0.07 s(-1) (1.5 T), -0.52 ± 0.07 s(-1) (3.0 T) and -1.25 ± 0.11 s(-1) (7.0 T). Although EV ΔR(2)* increased linearly with field, as expected, it was found that EV ΔS/S increased less than linearly with field in a manner that varied with TE choice. Furthermore, unlike ΔR(2)*, total and EV ΔS/S did not converge at 7.0 T. These trends were similar whether a z-score analysis or occipital lobe-based region-of-interest approach was used for voxel selection. These findings suggest that calibrated BOLD approaches may benefit from an EV ΔR(2)* measurement as opposed to a ΔS/S measurement at a single TE.

  14. Differential time-course of slow afterhyperpolarizations and associated Ca2+ transients in rat CA1 pyramidal neurons: further dissociation by Ca2+ buffer.

    PubMed

    Jahromi, B S; Zhang, L; Carlen, P L; Pennefather, P

    1999-01-01

    Hippocampal neurons exhibit a slow afterhyperpolarization following membrane depolarization; this is thought to reflect an underlying Ca2+-dependent K+ current. This current is potentiated by intermediate concentrations (0.1-1.0 mM) of exogenous Ca2+ buffer [Schwindt P. C. et al. (1992) Neuroscience 47, 571-578; Zhang L. et al. (1995) J. Neurophysiol. 74, 2225-2241]. The relationship between the slow afterhyperpolarization and associated Ca2+ transients was investigated in the presence and absence of added exogenous Ca2+ buffer. Slow afterhyperpolarizations and underlying K+ currents were measured using whole-cell patch-clamp recordings from hippocampal CA1 neurons in acute rat brain slices. Inclusion of fluorescent Ca2+ indicators in the patch pipette solution allowed simultaneous measurement of the evoked subcellular Ca2+ transients using a confocal microscope. The peak Ca2+ signal exhibited an incremental increase with each action potential. This increase eventually reached a plateau with increasing numbers of action potentials, suggesting dye saturation with peak Ca2+ concentrations. As the K(D) for Ca2+ of the indicator dyes used was between 200 and 300 nM, it is predicted that saturation will occur when the peak Ca2+ signal exceeds 1 microM. This occurred with fewer action potentials in dendritic vs somatic compartments. Neither compartment exhibited averaged Ca2+ transients matching the slow afterhyperpolarization time-course, dendritic Ca2+ transients being most divergent. Intracellular accumulation of exogenous Ca2+ buffer, either by inclusion in the patch pipette or by incubation of the brain slice with its membrane-permeable form, caused a prolongation of the slow afterhyperpolarization but not of the somatic Ca2+ transient. The initial rate of decline of the dendritic Ca2+ transient was diminished, but remained faster than that of the slow afterhyperpolarization. We conclude that neither dendritic nor somatic Ca2+ signals match the slow

  15. 1. Photocopy of book illustration, undated ca. 1898; LIGHTHOUSE CONSTRUCTED ...

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

    1. Photocopy of book illustration, undated ca. 1898; LIGHTHOUSE CONSTRUCTED CA. 1876, DESTROYED 1898 - Castillo de San Felipe del Morro Lighthouse, Summit of Castillo de San Felipe del Morro, San Juan Antiguo (subdivision), San Juan Municipio, PR

  16. The emerging role of CaMKII in cancer.

    PubMed

    Wang, Yan-yang; Zhao, Ren; Zhe, Hong

    2015-05-20

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinases best known for its critical role in learning and memory. Recent studies suggested that high levels of CaMKII also expressed in variety of malignant diseases. In this review, we focus on the structure and biology properties of CaMKII, including the role of CaMKII in the regulation of cancer progression and therapy response. We also describe the role of CaMKII in the diagnosis of different kinds of cancer and recent progress in the development of CaMKII inhibitors. These data establishes CaMKII as a novel target whose modulation presents new opportunities for cancer diagnosis and treatment.

  17. Pressure-induced structural transformation of CaC2.

    PubMed

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-21

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2.

  18. Pressure-induced structural transformation of CaC2

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Huang, Xiaoli; Li, Da; Huang, Yanping; Bao, Kuo; Li, Fangfei; Wu, Gang; Liu, Bingbing; Cui, Tian

    2016-05-01

    The high pressure structural changes of calcium carbide CaC2 have been investigated with Raman spectroscopy and synchrotron X-ray diffraction (XRD) techniques in a diamond anvil cell at room temperature. At ambient conditions, two forms of CaC2 co-exist. Above 4.9 GPa, monoclinic CaC2-ii diminished indicating the structural phase transition from CaC2-ii to CaC2-i. At about 7.0 GPa, both XRD patterns and Raman spectra confirmed that CaC2-i transforms into a metallic Cmcm structure which contains polymeric carbon chains. Along with the phase transition, the isolated C2 dumbbells are polymerized into zigzag chains resulting in a large volume collapse with 22.4%. Above 30.0 GPa, the XRD patterns of CaC2 become featureless and remain featureless upon decompression, suggesting an irreversible amorphization of CaC2.

  19. Capacitative Ca2+ Entry Is Closely Linked to the Filling State of Internal Ca2+ Stores: A Study Using Simultaneous Measurements of ICRAC and Intraluminal [Ca2+

    PubMed Central

    Hofer, Aldebaran M.; Fasolato, Cristina; Pozzan, Tullio

    1998-01-01

    ICRAC (the best characterized Ca2+ current activated by store depletion) was monitored concurrently for the first time with [Ca2+] changes in internal stores. To establish the quantitative and kinetic relationship between these two parameters, we have developed a novel means to clamp [Ca2+] within stores of intact cells at any level. The advantage of this approach, which is based on the membrane-permeant low-affinity Ca2+ chelator N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylene diamine (TPEN), is that [Ca2+] within the ER can be lowered and restored to its original level within 10–15 s without modifications of Ca2+ pumps or release channels. Using these new tools, we demonstrate here that Ca2+ release–activated Ca2+ current (ICRAC) is activated (a) solely by reduction of free [Ca2+] within the ER and (b) by any measurable decrease in [Ca2+]ER. We also demonstrate that the intrinsic kinetics of inactivation are relatively slow and possibly dependent on soluble factors that are lost during the whole-cell recording. PMID:9442108

  20. Inhibition by Ca2+ of inositol trisphosphate-mediated Ca2+ liberation: a possible mechanism for oscillatory release of Ca2+.

    PubMed Central

    Parker, I; Ivorra, I

    1990-01-01

    Light-flash photolysis of caged inositol 1,4,5-trisphosphate (InsP3) was used to generate reproducible transients of free InsP3 in Xenopus oocytes, and the resulting liberation of Ca2+ from intracellular stores was monitored by recording Ca2+-activated membrane currents and by use of the fluorescent Ca2+ indicator fluo-3. InsP3-mediated Ca2+ release was inhibited by elevating the intracellular free Ca2+ level, either by microinjecting Ca2+ into the cell or by applying conditioning light flashes to liberate Ca2+. This inhibition followed a slow time course, being maximal after about 2 s and subsequently declining over several seconds. Negative feedback of Ca2+ ions on InsP3-mediated Ca2+ liberation may explain the oscillatory release of Ca2+ seen during activation of inositol phospholipid signaling in the oocyte, and the time course of the inhibition is consistent with the period of the oscillations. PMID:2296584

  1. Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP.

    PubMed

    Tang, Wannan; Szokol, Karolina; Jensen, Vidar; Enger, Rune; Trivedi, Chintan A; Hvalby, Øivind; Helm, P Johannes; Looger, Loren L; Sprengel, Rolf; Nagelhus, Erlend A

    2015-02-18

    To date, it has been difficult to reveal physiological Ca(2+) events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca(2+) signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca(2+) indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca(2+) signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca(2+) signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca(2+) transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca(2+) signals in processes and failed to affect the somatic Ca(2+) response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca(2+) signals that mimicked the stimulation-evoked astrocytic Ca(2+) responses. We conclude that stimulation-evoked Ca(2+) signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP.

  2. A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic β cells

    PubMed Central

    Kang, Guoxin; Chepurny, Oleg G; Rindler, Michael J; Collis, Leon; Chepurny, Zina; Li, Wen-hong; Harbeck, Mark; Roe, Michael W; Holz, George G

    2005-01-01

    The blood glucose-lowering hormone glucagon-like peptide-1 (GLP-1) stimulates cAMP production, promotes Ca2+ influx, and mobilizes an intracellular source of Ca2+ in pancreatic β cells. Here we provide evidence that these actions of GLP-1 are functionally related: they reflect a process of Ca2+-induced Ca2+ release (CICR) that requires activation of protein kinase A (PKA) and the Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). In rat insulin-secreting INS-1 cells or mouse β cells loaded with caged Ca2+ (NP-EGTA), a GLP-1 receptor agonist (exendin-4) is demonstrated to sensitize intracellular Ca2+ release channels to stimulatory effects of cytosolic Ca2+, thereby allowing CICR to be generated by the uncaging of Ca2+ (UV flash photolysis). This sensitizing action of exendin-4 is diminished by an inhibitor of PKA (H-89) or by overexpression of dominant negative Epac. It is reproduced by cell-permeant cAMP analogues that activate PKA (6-Bnz-cAMP) or Epac (8-pCPT-2′-O-Me-cAMP) selectively. Depletion of Ca2+ stores with thapsigargin abolishes CICR, while inhibitors of Ca2+ release channels (ryanodine and heparin) attenuate CICR in an additive manner. Because the uncaging of Ca2+ fails to stimulate CICR in the absence of cAMP-elevating agents, it is concluded that there exists in β cells a process of second messenger coincidence detection, whereby intracellular Ca2+ release channels (ryanodine receptors, inositol 1,4,5-trisphosphate (IP3) receptors) monitor a simultaneous increase of cAMP and Ca2+ concentrations. We propose that second messenger coincidence detection of this type may explain how GLP-1 interacts with β cell glucose metabolism to stimulate insulin secretion. PMID:15860526

  3. Stimulation-Evoked Ca2+ Signals in Astrocytic Processes at Hippocampal CA3–CA1 Synapses of Adult Mice Are Modulated by Glutamate and ATP

    PubMed Central

    Szokol, Karolina; Jensen, Vidar; Enger, Rune; Trivedi, Chintan A.; Hvalby, Øivind; Helm, P. Johannes; Looger, Loren L.; Sprengel, Rolf

    2015-01-01

    To date, it has been difficult to reveal physiological Ca2+ events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca2+ signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca2+ indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca2+ signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca2+ signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca2+ transients by 30–40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca2+ signals in processes and failed to affect the somatic Ca2+ response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca2+ signals that mimicked the stimulation-evoked astrocytic Ca2+ responses. We conclude that stimulation-evoked Ca2+ signals in astrocytic processes at CA3–CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP. PMID:25698739

  4. Measurement of mitochondrial Ca2+ transport mediated by three transport proteins: VDAC1, the Na+/Ca2+ exchanger, and the Ca2+ uniporter.

    PubMed

    Ben-Hail, Danya; Palty, Raz; Shoshan-Barmatz, Varda

    2014-02-01

    Ca(2+) is a ubiquitous cellular signal, with changes in intracellular Ca(2+) concentration not only stimulating a number of intercellular events but also triggering cell death pathways, including apoptosis. Mitochondrial Ca(2+) uptake and release play pivotal roles in cellular physiology by regulating intracellular Ca(2+) signaling, energy metabolism and cell death. Ca(2+) transport across the inner and outer mitochondrial membranes is mediated by several proteins, including channels, antiporters, and a uniporter. In this article, we present the background to several methods now established for assaying mitochondrial Ca(2+) transport activity across both mitochondrial membranes. The first of these is Ca(2+) transport mediated by the outer mitochondrial protein, the voltage-dependent anion-selective channel protein 1 (VDAC1, also known as porin 1), both as a purified protein reconstituted into a planar lipid bilayer (PLB) or into liposomes and as a mitochondrial membrane-embedded protein. The second method involves isolated mitochondria for assaying the activity of an inner mitochondrial membrane transport protein, the mitochondrial Ca(2+) uniporter (MCU) that transports Ca(2+) and is powered by the steep mitochondrial membrane potential. In the event of Ca(2+) overload, this leads to opening of the mitochondrial permeability transition pore (MPTP) and cell death. The third method describes how Na(+)-dependent mitochondrial Ca(2+) efflux mediated by mitochondrial NCLX, a member of the Na(+)/Ca(2+) exchanger superfamily, can be assayed in digitonin-permeabilized HEK-293 cells. The Ca(2+)-transport assays can be performed under various conditions and in combination with inhibitors, allowing detailed characterization of the transport activity of interest.

  5. Application of Ca stable isotopes to long-term changes in the Ca cycle of a Northern Hardwood forest

    NASA Astrophysics Data System (ADS)

    Kurtz, A. C.; Takagi, K.; Bailey, S. W.; Bullen, T. D.

    2015-12-01

    The Hubbard Brook Ecosystem Study (New Hampshire, USA) presents an unusual opportunity for the application of innovative isotope methods in forest biogeochemistry. Changes in biogeochemical cycling resulting from decades of acid deposition, subsequent reductions in acid deposition, and a series of experimental treatments (harvesting, Ca amendment) have been studied continuously for 60 years at this site. Importantly, researchers have archived soil, water, and vegetation samples for much of the site's history. Our work seeks to complement earlier mass balance studies of Ca cycling by measuring Ca isotope ratios on archived samples. In the first component of our study, we examined the Ca isotopic response to an experimental clearcut in the early 1980's. Earlier work showed that the clearcut promoted dramatic loss of Ca from the watershed, indicated by a 5-fold increase in streamwater Ca concentrations. The mechanism for this loss was unclear as no resolvable changes in soil Ca pools were observed. Our work shows that streamwater dissolved Ca becomes isotopically lighter as Ca concentrations increase. These data are best accounted for by an increase in Ca loss from the soil cation exchange complex. Soil exchangeable δ44Ca itself evolves towards lighter values in the years following the experimental harvest. We interpret this as replenishment of the soil exchange complex by release of isotopically light Ca from root biomass. In the second component of our study, we examine decadal-scale changes in streamwater and soil Ca in an un-manipulated biogeochemical reference watershed. Historical data from Hubbard Brook show that streamwater Ca concentrations began decreasing sharply in the early 1970's, attributed to decreased deposition of both acidity and Ca with the passage of the Clean Air Act. Preliminary data indicate no resolvable change in the average δ44Ca of streamwater, with variability mostly attributable to discharge (flowpath control). Preliminary data

  6. Sr/Ca and Ba/Ca variations in environmental and biological sources: A survey of marine and terrestrial systems

    NASA Astrophysics Data System (ADS)

    Peek, Stephanie; Clementz, Mark T.

    2012-10-01

    The relative concentrations of strontium to calcium (Sr/Ca) and barium to calcium (Ba/Ca) in mammalian bioapatite are common biogeochemical indicators for trophic level and/or dietary preferences in terrestrial foodwebs; however, similar research in marine foodwebs is lacking. This study combined environmental and biological Sr/Ca and Ba/Ca data from both terrestrial and marine settings from 62 published books, reports, and studies along with original data collected from 149 marine mammals (30 species) and 83 prey items (18 species) and found that variations in Sr/Ca and Ba/Ca ratios of biological and environmental samples are appreciably different in terrestrial and marine systems. In terrestrial systems, environmental sources account for most of the variations in Sr/Ca and Ba/Ca ratios. In contrast, environmental sources in marine systems (i.e., seawater) are comparatively invariant, meaning most of the variations in Sr/Ca and Ba/Ca ratios originate from biological processes. Marine consumers, particularly non-mammalian and mammalian vertebrates, show evidence of biopurification of Ca relative to Sr and Ba, similar to what is observed in terrestrial systems; however, unlike terrestrial systems, variations in Sr/Ca and Ba/Ca ratios of environmental sources are overprinted by bioaccumulation of Sr and Ba at the base of marine foodwebs. This demonstrates that in marine systems, spatial or temporal differences may have little to no effect on Sr/Ca and Ba/Ca ratios of marine vertebrates, making Sr/Ca, and to a lesser extent Ba/Ca, potentially useful global proxies for trophic level and dietary preferences of marine vertebrates.

  7. MicroRNA-145 suppresses ROS-induced Ca{sup 2+} overload of cardiomyocytes by targeting CaMKIIδ

    SciTech Connect

    Cha, Min-Ji; Jang, Jin-Kyung; Ham, Onju; Song, Byeong-Wook; Lee, Se-Yeon; Lee, Chang Yeon; Park, Jun-Hee; Lee, Jiyun; Seo, Hyang-Hee; Choi, Eunhyun; Jeon, Woo-min; Hwang, Hye Jin; Shin, Hyun-Taek; and others

    2013-06-14

    Highlights: •CaMKIIδ mediates H{sub 2}O{sub 2}-induced Ca{sup 2+} overload in cardiomyocytes. •miR-145 can inhibit Ca{sup 2+} overload. •A luciferase assay confirms that miR-145 functions as a CaMKIIδ-targeting miRNA. •Overexpression of miR-145 regulates CaMKIIδ-related genes and ameliorates apoptosis. -- Abstract: A change in intracellular free calcium (Ca{sup 2+}) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca{sup 2+} signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca{sup 2+}-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H{sub 2}O{sub 2}-mediated Ca{sup 2+} overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca{sup 2+} overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca{sup 2+}-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca{sup 2+} overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.

  8. Termination of cAMP signals by Ca2+ and Gαi via extracellular Ca2+ sensors

    PubMed Central

    Gerbino, Andrea; Ruder, Warren C.; Curci, Silvana; Pozzan, Tullio; Zaccolo, Manuela; Hofer, Aldebaran M.

    2005-01-01

    Termination of cyclic adenosine monophosphate (cAMP) signaling via the extracellular Ca2+-sensing receptor (CaR) was visualized in single CaR-expressing human embryonic kidney (HEK) 293 cells using ratiometric fluorescence resonance energy transfer–dependent cAMP sensors based on protein kinase A and Epac. Stimulation of CaR rapidly reversed or prevented agonist-stimulated elevation of cAMP through a dual mechanism involving pertussis toxin–sensitive Gαi and the CaR-stimulated increase in intracellular [Ca2+]. In parallel measurements with fura-2, CaR activation elicited robust Ca2+ oscillations that increased in frequency in the presence of cAMP, eventually fusing into a sustained plateau. Considering the Ca2+ sensitivity of cAMP accumulation in these cells, lack of oscillations in [cAMP] during the initial phases of CaR stimulation was puzzling. Additional experiments showed that low-frequency, long-duration Ca2+ oscillations generated a dynamic staircase pattern in [cAMP], whereas higher frequency spiking had no effect. Our data suggest that the cAMP machinery in HEK cells acts as a low-pass filter disregarding the relatively rapid Ca2+ spiking stimulated by Ca2+-mobilizing agonists under physiological conditions. PMID:16247029

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

    PubMed

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

    2015-09-01

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

  10. The EF-Hand Ca2+ Binding Protein MICU Choreographs Mitochondrial Ca2+ Dynamics in Arabidopsis[OPEN

    PubMed Central

    Carraretto, Luca; Teardo, Enrico; Cendron, Laura; Füßl, Magdalena; Doccula, Fabrizio G.; Szabò, Ildikò

    2015-01-01

    Plant organelle function must constantly adjust to environmental conditions, which requires dynamic coordination. Ca2+ signaling may play a central role in this process. Free Ca2+ dynamics are tightly regulated and differ markedly between the cytosol, plastid stroma, and mitochondrial matrix. The mechanistic basis of compartment-specific Ca2+ dynamics is poorly understood. Here, we studied the function of At-MICU, an EF-hand protein of Arabidopsis thaliana with homology to constituents of the mitochondrial Ca2+ uniporter machinery in mammals. MICU binds Ca2+ and localizes to the mitochondria in Arabidopsis. In vivo imaging of roots expressing a genetically encoded Ca2+ sensor in the mitochondrial matrix revealed that lack of MICU increased resting concentrations of free Ca2+ in the matrix. Furthermore, Ca2+ elevations triggered by auxin and extracellular ATP occurred more rapidly and reached higher maximal concentrations in the mitochondria of micu mutants, whereas cytosolic Ca2+ signatures remained unchanged. These findings support the idea that a conserved uniporter system, with composition and regulation distinct from the mammalian machinery, mediates mitochondrial Ca2+ uptake in plants under in vivo conditions. They further suggest that MICU acts as a throttle that controls Ca2+ uptake by moderating influx, thereby shaping Ca2+ signatures in the matrix and preserving mitochondrial homeostasis. Our results open the door to genetic dissection of mitochondrial Ca2+ signaling in plants. PMID:26530087

  11. Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

    PubMed Central

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca2+ to calmodulin (CaM) and proceed through Ca2+/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca2+]i decreases, but persists longer than the current that evoked it, providing evidence for ‘molecular memory’. Our findings suggest a model for CaV1.2 channel gating and Ca2+-influx amplification that unifies diverse observations about Ca2+ signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. DOI: http://dx.doi.org/10.7554/eLife.05608.001 PMID:25714924

  12. Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels.

    PubMed Central

    Peterson, B Z; Lee, J S; Mulle, J G; Wang, Y; de Leon, M; Yue, D T

    2000-01-01

    L-type (alpha(1C)) calcium channels inactivate rapidly in response to localized elevation of intracellular Ca(2+), providing negative Ca(2+) feedback in a diverse array of biological contexts. The dominant Ca(2+) sensor for such Ca(2+)-dependent inactivation has recently been identified as calmodulin, which appears to be constitutively tethered to the channel complex. This Ca(2+) sensor induces channel inactivation by Ca(2+)-dependent CaM binding to an IQ-like motif situated on the carboxyl tail of alpha(1C). Apart from the IQ region, another crucial site for Ca(2+) inactivation appears to be a consensus Ca(2+)-binding, EF-hand motif, located approximately 100 amino acids upstream on the carboxyl terminus. However, the importance of this EF-hand motif for channel inactivation has become controversial since the original report from our lab implicating a critical role for this domain. Here, we demonstrate not only that the consensus EF hand is essential for Ca(2+) inactivation, but that a four-amino acid cluster (VVTL) within the F helix of the EF-hand motif is itself essential for Ca(2+) inactivation. Mutating these amino acids to their counterparts in non-inactivating alpha(1E) calcium channels (MYEM) almost completely ablates Ca(2+) inactivation. In fact, only a single amino acid change of the second valine within this cluster to tyrosine (V1548Y) supports much of the functional knockout. However, mutations of presumed Ca(2+)-coordinating residues in the consensus EF hand reduce Ca(2+) inactivation by only approximately 2-fold, fitting poorly with the EF hand serving as a contributory inactivation Ca(2+) sensor, in which Ca(2+) binds according to a classic mechanism. We therefore suggest that while CaM serves as Ca(2+) sensor for inactivation, the EF-hand motif of alpha(1C) may support the transduction of Ca(2+)-CaM binding into channel inactivation. The proposed transduction role for the consensus EF hand is compatible with the detailed Ca(2+)-inactivation

  13. Ca2+ dynamics along identified synaptic terminals in Drosophila larvae.

    PubMed

    Lnenicka, Gregory A; Grizzaffi, Jeffrey; Lee, Bomi; Rumpal, Nidhi

    2006-11-22

    Changes in intracellular Ca2+ concentration ([Ca2+]i) play an important role in the function and plasticity of synapses. We characterized the changes in [Ca2+]i produced by action potentials (APs) along two identified motor terminals found on separate muscle fibers in Drosophila larvae and examined factors that influence the amplitude and duration of the residual Ca2+ signal. We were able to measure Ca2+ transients produced along terminals by both single APs and AP trains using Oregon Green 488 BAPTA-1 and streaming images at 20-50 Hz. The decay of [Ca2+]i after single APs or AP trains was well fit by a single exponential. For single APs, the Ca2+ transient amplitude and decay rate were similar at boutons and bottleneck regions and much smaller at the axon. Also, the amplitude of single-AP Ca2+ transients was inversely correlated with bouton width. During AP trains, the increase in [Ca2+]i became more uniform: the difference in boutons and axons was reduced, and the increase in [Ca2+]i was not correlated with bouton width. The [Ca2+]i decay tau was directly correlated with bouton width for both single APs and AP trains. For one terminal, distal boutons had larger single-AP Ca2+ transients than proximal ones, probably attributable to greater Ca2+ influx for distal boutons. Pharmacological studies showed that Ca2+ clearance from these synaptic terminals after single APs and AP trains was primarily attributable to Ca2+ extrusion by the plasma membrane Ca2+ ATPase (PMCA). Immunostaining of larval muscle fibers showed high levels of the PMCA at the neuromuscular junction.

  14. Ca++ induced hypothermia in a hibernator /Citellus beechyi/

    NASA Technical Reports Server (NTRS)

    Hanegan, J. L.; Williams, B. A.

    1975-01-01

    Results of perfusion of excess Ca++ and Na+ into the hypothalamus of the hibernating ground squirrel Citellus beechyi are presented. The significant finding is that perfused excess Ca++ causes a reduction in core temperature when ambient temperature is low (12 C). Ca++ also causes a rise in rectal temperature at high ambient temperature (33 C). Thus hypothalamic Ca++ perfusion apparently causes a nonspecific depression of thermoregulatory control.

  15. High precision calcium isotope analysis using 42Ca-48Ca double-spike TIMS technique

    NASA Astrophysics Data System (ADS)

    Feng, L.; Zhou, L.; Gao, S.; Tong, S. Y.; Zhou, M. L.

    2014-12-01

    Double spike techniques are widely used for determining calcium isotopic compositions of natural samples. The most important factor controlling precision of the double spike technique is the choice of appropriate spike isotope pair, the composition of double spikes and the ratio of spike to sample(CSp/CN). We propose an optimal 42Ca-48Ca double spike protocol which yields the best internal precision for calcium isotopic composition determinations among all kinds of spike pairs and various spike compositions and ratios of spike to sample, as predicted by linear error propagation method. It is suggested to use spike composition of 42Ca/(42Ca+48Ca) = 0.44 mol/mol and CSp/(CN+ CSp)= 0.12mol/mol because it takes both advantages of the largest mass dispersion between 42Ca and 48Ca (14%) and lowest spike cost. Spiked samples were purified by pass through homemade micro-column filled with Ca special resin. K, Ti and other interference elements were completely separated, while 100% calcium was recovered with negligible blank. Data collection includes integration time, idle time, focus and peakcenter frequency, which were all carefully designed for the highest internal precision and lowest analysis time. All beams were automatically measured in a sequence by Triton TIMS so as to eliminate difference of analytical conditions between samples and standards, and also to increase the analytical throughputs. The typical internal precision of 100 duty cycles for one beam is 0.012‒0.015 ‰ (2δSEM), which agrees well with the predicted internal precision of 0.0124 ‰ (2δSEM). Our methods improve internal precisions by a factor of 2‒10 compared to previous methods of determination of calcium isotopic compositions by double spike TIMS. We analyzed NIST SRM 915a, NIST SRM 915b and Pacific Seawater as well as interspersed geological samples during two months. The obtained average δ44/40Ca (all relative to NIST SRM 915a) is 0.02 ± 0.02 ‰ (n=28), 0.72±0.04 ‰ (n=10) and 1

  16. Registration of CA0469C025C chickpea germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chickpea (Cicer arientinum L.) germplasm CA0469C025C (Reg. No. XXX; PI XXX), was released by the USDA-ARS in 2010. CA0469C025C was released based on its improved yield and reaction to Ascochyta blight relative to the popular commercial cultivars ‘Dwelley’, ‘Sierra’, and ‘Sawyer’. CA0490C025C is deri...

  17. Integrated mechanisms of CaMKII-dependent ventricular remodeling

    PubMed Central

    Kreusser, Michael M.; Backs, Johannes

    2014-01-01

    CaMKII has been shown to be activated during different cardiac pathological processes, and CaMKII-dependent mechanisms contribute to pathological cardiac remodeling, cardiac arrhythmias, and contractile dysfunction during heart failure. Activation of CaMKII during cardiac stress results in a broad number of biological effects such as, on the one hand, acute effects due to phosphorylation of distinct cellular proteins as ion channels and calcium handling proteins and, on the other hand, integrative mechanisms by changing gene expression. This review focuses on transcriptional and epigenetic effects of CaMKII activation during chronic cardiac remodeling. Multiple mechanisms have been described how CaMKII mediates changes in cardiac gene expression. CaMKII has been shown to directly phosphorylate components of the cardiac gene regulation machinery. CaMKII phosphorylates several transcription factors such as CREB that induces the activation of specific gene programs. CaMKII activates transcriptional regulators also indirectly by phosphorylating histone deacetylases, especially HDAC4, which in turn inhibits transcription factors that drive cardiac hypertrophy, fibrosis, and dysfunction. Recent studies demonstrate that CaMKII also phosphorylate directly histones, which may contribute to changes in gene expression. These findings of CaMKII-dependent gene regulation during cardiac remodeling processes suggest novel strategies for CaMKII-dependent “transcriptional or epigenetic therapies” to control cardiac gene expression and function. Manipulation of CaMKII-dependent signaling pathways in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach. PMID:24659967

  18. 78 FR 36655 - Drawbridge Operation Regulation; Carquinez Strait, Martinez, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-19

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Carquinez Strait, Martinez, CA AGENCY... Drawbridge across the Carquinez Strait, mile 7.0 at Martinez, CA. The deviation is necessary to perform a..., at Martinez, CA. The drawbridge navigation span provides 135 feet vertical clearance above Mean...

  19. Electronic structure of Ca, Sr, and Ba under pressure.

    NASA Technical Reports Server (NTRS)

    Animalu, A. O. E.; Heine, V.; Vasvari, B.

    1967-01-01

    Electronic band structure calculations phase of Ca, Sr and Ba over wide range of atomic volumes under pressure electronic band structure calculations for fcc phase of Ca, Sr and Ba over wide range of atomic volumes under pressure electronic band structure calculations for fcc phase of Ca, Sr and Ba over wide range of atomic volumes under pressure

  20. Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis.

    PubMed

    Rasola, Andrea; Bernardi, Paolo

    2011-09-01

    A variety of stimuli utilize an increase of cytosolic free Ca(2+) concentration as a second messenger to transmit signals, through Ca(2+) release from the endoplasmic reticulum or opening of plasma membrane Ca(2+) channels. Mitochondria contribute to the tight spatiotemporal control of this process by accumulating Ca(2+), thus shaping the return of cytosolic Ca(2+) to resting levels. The rise of mitochondrial matrix free Ca(2+) concentration stimulates oxidative metabolism; yet, in the presence of a variety of sensitizing factors of pathophysiological relevance, the matrix Ca(2+) increase can also lead to opening of the permeability transition pore (PTP), a high conductance inner membrane channel. While transient openings may serve the purpose of providing a fast Ca(2+) release mechanism, persistent PTP opening is followed by deregulated release of matrix Ca(2+), termination of oxidative phosphorylation, matrix swelling with inner membrane unfolding and eventually outer membrane rupture with release of apoptogenic proteins and cell death. Thus, a rise in mitochondrial Ca(2+) can convey both apoptotic and necrotic death signals by inducing opening of the PTP. Understanding the signalling networks that govern changes in mitochondrial free Ca(2+) concentration, their interplay with Ca(2+) signalling in other subcellular compartments, and regulation of PTP has important implications in the fine comprehension of the main biological routines of the cell and in disease pathogenesis.

  1. Theoretical analysis of the Ca2+ spark amplitude distribution.

    PubMed Central

    Izu, L T; Wier, W G; Balke, C W

    1998-01-01

    A difficulty of using confocal microscopy to study Ca2+ sparks is the uncertainty of the linescan position with respect to the source of Ca2+ release. Random placement of the linescan is expected to result in a broad distribution of measured Ca2+ spark amplitudes (a) even if all Ca2+ sparks were generated identically. Thus variations in Ca2+ spark amplitude due to positional differences between confocal linescans and Ca2+ release site are intertwined with variations due to intrinsic differences in Ca2+ release properties. To separate these two sources of variations on the Ca2+ spark amplitude, we determined the effect changes of channel current or channel open time--collectively called the source strength, alpha--had on the measured Ca2+ spark amplitude histogram, N(a). This was done by 1) simulating Ca2+ release, Ca2+ and fluo-3 diffusion, and Ca2+ binding reactions; 2) simulation of image formation of the Ca2+ spark by a confocal microscope; and 3) using a novel automatic Ca2+ spark detector. From these results we derived an integral equation relating the probability density function of source strengths, f alpha (alpha), to N(a), which takes into account random positional variations between the source and linescan. In the special, but important, case that the spatial distribution of Ca(2+)-bound fluo-3 is Gaussian, we show the following: 1) variations of Ca2+ spark amplitude due to positional or intrinsic differences can be separated, and 2) f alpha (alpha) can, in principle, be calculated from the Ca2+ spark amplitude histogram since N(a) is the sum of shifted hyperbolas, where the magnitudes of the shifts and weights depend on f alpha (alpha). In particular, if all Ca2+ sparks were generated identically, then the plot of 1/N(a) against a will be a straight line. Multiple populations of channels carrying distinct currents are revealed by discontinuities in the 1/N(a) plot. 3) Although the inverse relationship between Ca2+ spark amplitude and decay time might be

  2. 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

  3. Using Ca isotopes to constrain source of streamwater Ca following clear-cutting of a New England watershed

    NASA Astrophysics Data System (ADS)

    Takagi, K.; Kurtz, A. C.; Bailey, S. W.

    2011-12-01

    Stable Ca isotopes have been used in applications ranging from use as a paleooceanographic temperature proxy to tracing continental weathering fluxes to the oceans. One of the most important applications has been in understanding Ca cycling in terrestrial ecosystems. Major land use disturbance such as forest harvesting results in increased hydrologic export of cations but the mechanisms that lead to increased Ca export and the sources of streamwater Ca following disturbance remain uncertain. Ca isotope ratios may allow us to determine the internal Ca pools that contribute to increased export. We measured stable Ca isotopes on archived streamwater samples from Hubbard Brook Watershed 5 before and after a 1983 whole-watershed harvest experiment to test the following hypothesis: following harvest, the Ca isotopic value of streamwater will shift towards an isotopically light composition reflecting loss of biologically cycled Ca from soil pools. Ca concentrations measured on archived samples correspond exactly to values measured at the time of collection indicating adequate sample preservation over several decades of storage. Preliminary stable Ca isotopic results on these streamwater samples indicate a robust shift in δ40Ca from a pre-harvest value of -0.95% (vs. seawater) to a post-harvest value of -1.45%. We developed a box model of Ca cycling in forested ecosystems that includes Ca isotopes as tracer in order to model the δ40Ca of the various soil and vegetation pools. Steady-state model results indicate that vegetation is isotopically light relative to the B-horizon and forest floor soil pools and the forest floor soil pool is isotopically light relative to the B-horizon soil pool. We used modeled δ40Ca values of B-horizon and forest floor soil pools in a two end-member mixing analysis to evaluate changes in streamwater δ40Ca following harvesting. Our mixing analysis indicates that the observed decrease in the δ40Ca of streamwater following harvest requires an

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

    PubMed Central

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

    2000-01-01

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

  5. Modulation of histamine-induced Ca2+ release by protein kinase C. Effects on cytosolic and mitochondrial [Ca2+] peaks.

    PubMed

    Montero, Mayte; Lobatón, Carmen D; Gutierrez-Fernández, Silvia; Moreno, Alfredo; Alvarez, Javier

    2003-12-12

    In HeLa cells, histamine induces production of inositol 1,4,5-trisphosphate (InsP3) and release of Ca2+ from the endoplasmic reticulum (ER). Ca2+ release is typically biphasic, with a fast and brief initial phase, followed by a much slower and prolonged one. In the presence of inhibitors of protein kinase C (PKC), including staurosporine and the specific inhibitors GF109203X and Ro-31-8220, the fast phase continued until the ER became fully empty. On the contrary, treatment with phorbol 12,13-dibutyrate inhibited Ca2+ release. Staurosporine had no effect on InsP3-induced Ca2+ release in permeabilized cells and did not modify either histamine-induced InsP3 production. These data suggest that histamine induces Ca2+ release and with a short lag activates PKC to down-regulate it. Consistently, Ca2+ oscillations induced by histamine were increased in amplitude and decreased in frequency in the presence of PKC inhibitors. We show also that mitochondrial [Ca2+] was much more sensitive to changes in ER-Ca2+ release induced by PKC modulation than cytosolic [Ca2+]. PKC inhibitors increased the histamine-induced mitochondrial [Ca2+] peak by 4-fold but increased the cytosolic [Ca2+] peak only by 20%. On the contrary, PKC activation inhibited the mitochondrial [Ca2+] peak by 90% and the cytosolic one by only 50%. Similarly, the combination of PKC inhibitors with the mitochondrial Ca2+ uniporter activator SB202190 led to dramatic increases in mitochondrial [Ca2+] peaks, with little effect on cytosolic ones. This suggests that activation of ER-Ca2+ release by PKC inhibitors could be involved in apoptosis induced by staurosporine. In addition, these mechanisms allow flexible and independent regulation of cytosolic and mitochondrial [Ca2+] during cell stimulation.

  6. Reorientable dipolar CuCa antisite and anomalous screening in CaCu3Ti4O12

    NASA Astrophysics Data System (ADS)

    Delugas, Pietro; Alippi, Paola; Fiorentini, Vincenzo; Raineri, Vito

    2010-02-01

    Based on first-principles calculations, we show that the abundant CuCa antisite defect contributes sizably to dielectric screening in single-crystal CaCu3Ti4O12 . CuCa has a multi-minimum off-center equilibrium configuration, whereby it possesses a large and easily reorientable dipole moment. The low-temperature and frequency cut-off behavior of CuCa -induced response is consistent with experiment.

  7. LFA-1-dependent Ca2+ entry following suboptimal T cell receptor triggering proceeds without mobilization of intracellular Ca2+.

    PubMed

    Kim, Kwangmi; Wang, Lin; Hwang, Inkyu

    2009-08-14

    A surge in cytosolic calcium ion concentration by entry of extracellular Ca2+ is a hallmark of T cell activation. According to store-operated Ca2+ entry mechanism, the Ca2+ entry is preceded by activation of phospholipase C-gamma1 (PLC-gamma1) and the consequent mobilization of intracellular Ca2+. Using membrane vesicles expressing the mouse class I major histocompatibility complex, i.e. Ld plus costimulatory ligands, i.e. B7-1 and intercellular adhesion molecule-1 along with 2C T cell receptor transgenic T cells, we investigated the roles of CD28 and LFA-1 (lymphocyte function-associated antigen-1) in the activation of PLC-gamma1 and Ca2+ signaling. Both CD28 and LFA-1 made significant and comparable contributions to the activation of PLC-gamma1 as gauged by the level of its phosphorylation at tyrosine 783. In contrast, their roles in Ca2+ signaling were quite distinct so that LFA-1/intercellular adhesion molecule-1 interaction exerted a determining role, whereas CD28/B7-1 interaction played only a minimal role. In particular, when the T cells were activated by suboptimal T cell receptor stimulation, LFA-1 played an indispensable role in the Ca2+ signaling. Further experiments using Ca2+-free medium demonstrated that the entry of extracellular Ca2+ was not always accompanied by mobilization of intracellular Ca2+. Thus, intracellular Ca2+ mobilization was hardly detected under the condition that LFA-1 played the indispensable role in the entry of extracellular Ca2+, while a distinct level of intracellular Ca2+ mobilization was readily detected under the condition that LFA-1 played only the supporting role. These results ensure the unique role of LFA-1 in T cell Ca2+ signaling and reveal that LFA-1-dependent Ca2+ entry proceeds via a mechanism separate from store-operated Ca2+ entry.

  8. An ID-like current that is downregulated by Ca2+ modulates information coding at CA3-CA3 synapses in the rat hippocampus.

    PubMed

    Saviane, Chiara; Mohajerani, Majid H; Cherubini, Enrico

    2003-10-15

    Voltage-gated K+ channels localised on presynaptic nerve terminals control information coding by modulating presynaptic firing and synaptic efficacy in target neurones. We found that at CA3-CA3 connections in hippocampal slice cultures, a fast-activating, slowly inactivating K+ conductance similar to the so-called delay current (ID) is responsible for the delayed appearance of the first spike upon membrane depolarisation, for action potential repolarisation and for modulation of transmitter release. The ID-like current was downregulated by intracellular Ca2+, as indicated by the increased delay in the appearance of the first action potential following either the block of Ca2+ flux through voltage-dependent Ca2+ channels with Cd2+ or replacement of the bathing solution with one devoid of Ca2+. In both cases, this effect was reversed by blocking this conductance with a low concentration of 4-aminopyridine (4-AP, 10-50 muM). Application of 4-AP shortened the delay to the first spike generation, prevented the effect of Cd2+ and increased the spike duration. The earlier appearance of the first action potential was also observed in the presence of dendrotoxin-1 (100 nM). In voltage-clamp experiments larger currents were recorded in the absence of extracellular Ca2+, thus confirming the downregulation of the ID-like current by Ca2+ due to the positive shift of its inactivation. Spike broadening was associated with an enhancement of synaptic efficacy in target neurones, as assessed by the increase in EPSC amplitude and in the percentage of successes. Moreover, in the presence of 4-AP, EPSCs appeared with a longer latency and were more scattered. This conductance is therefore crucial for setting the timing and strength of synaptic transmission at CA3-CA3 connections. It is conceivable that switching off ID by increasing intracellular Ca2+ following activity-dependent processes may facilitate network synchronisation and crosstalk between CA3 pyramidal cells, leading to

  9. Mechanics of Old Faithful Geyser, Calistoga, CA

    USGS Publications Warehouse

    Rudolph, M.L.; Manga, M.; Hurwitz, Shaul; Johnston, Malcolm J.; Karlstrom, L.; Wang, Chun-Yong

    2012-01-01

    In order to probe the subsurface dynamics associated with geyser eruptions, we measured ground deformation at Old Faithful Geyser of Calistoga, CA. We present a physical model in which recharge during the period preceding an eruption is driven by pressure differences relative to the aquifer supplying the geyser. The model predicts that pressure and ground deformation are characterized by an exponential function of time, consistent with our observations. The geyser's conduit is connected to a reservoir at a depth of at least 42 m, and pressure changes in the reservoir can produce the observed ground deformations through either a poroelastic or elastic mechanical model.

  10. Isoscalar giant resonances in {sup 48}Ca

    SciTech Connect

    Lui, Y.-W.; Youngblood, D. H.; Shlomo, S.; Chen, X.; Tokimoto, Y.; Krishichayan,; Anders, M.; Button, J.

    2011-04-15

    The giant resonance region from 9.5 MeV < E{sub x} < 40 MeV in {sup 48}Ca has been studied with inelastic scattering of 240-MeV {alpha} particles at small angles, including 0 deg. 95{sub -15}{sup +11}% of E0 energy-weighted sum rule (EWSR), 83{sub -16}{sup +10}% of E2 EWSR, and 137 {+-} 20% of E1 EWSR were located below E{sub x}=40 MeV. A comparison of the experimental data with calculated results for the isoscalar giant monopole resonance, obtained within the mean-field-based random-phase approximation, is also given.

  11. Gulf of Alaska and California bamboo corals: Ba/Ca and Sr/Ca records

    NASA Astrophysics Data System (ADS)

    Sauthoff, W.; LaVigne, M.; Hill, T. M.; Roark, E.; Dunbar, R. B.; Guilderson, T. P.; Spero, H. J.

    2012-12-01

    Deep-sea bamboo coral communities form on seamounts and along continental margins with near global distribution. Bamboo [Isididae] corals record surrounding ocean geochemistry presenting reliable proxy records of changes in seawater conditions, including productivity and nutrient content. Here we investigate bamboo coral specimens from the California margin and Gulf of Alaska (634-1288 m water depth; ~37oN-48oN), to provide insight into latitudinal and temporal differences in eastern Pacific Ocean climate processes. Past oceanic conditions were reconstructed in this investigation by trace element analyses (Ba/Ca, Sr/Ca) using laser ablation ICP-MS, using a 85 μm spot size at 10 μm/s, 4.45 J/cm2 fluence, and 10 Hz repetition rate. Two California specimens show differences in mean Ba/Ca content: 13.73 compared to 18.55 μmol/mol, which we attribute to differences in collection depth (T1104 A10: 833 m and T1100 A04: 1288 m, respectively). Gulf of Alaska corals show a more subdued nutrient signal with lower mean Ba/Ca values of 10.56 and 10.05 μmol/mol across a narrower depth range (ALV3803 #3: 720 m; ALV3803 #5: 634 m, respectively). This trend of increasing Ba/Ca with depth is in consensus with eastern Pacific dissolved barium and California margin bamboo coral depth transects. Sr/Ca content was uniform between four coral specimens with values ranging from 3.01 to 3.06 mmol/mol. Coral chronologies were compared against indices of climate oscillations, including El Niño Southern Oscillation and Pacific Decadal Oscillation, using time series based upon radiocarbon dating. The corals investigated here show a limited connection with El Niño Southern Oscillation; longer-term changes related Pacific Decadal Oscillation may be evidenced in this climate archive.

  12. Encoding, consolidation, and retrieval of contextual memory: Differential involvement of dorsal CA3 and CA1 hippocampal subregions

    PubMed Central

    Daumas, Stéphanie; Halley, Hélène; Francés, Bernard; Lassalle, Jean-Michel

    2005-01-01

    Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3- and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition. PMID:16027176

  13. Relationship between Ca2+-affinity and shielding of bulk water in the Ca2+-pump from molecular dynamics simulations.

    PubMed

    Sugita, Yuji; Ikeguchi, Mitsunori; Toyoshima, Chikashi

    2010-12-14

    The sarcoplasmic reticulum Ca(2+)-ATPase transports two Ca(2+) per ATP hydrolyzed from the cytoplasm to the lumen against a large concentration gradient. During transport, the pump alters the affinity and accessibility for Ca(2+) by rearrangements of transmembrane helices. In this study, all-atom molecular dynamics simulations were performed for wild-type Ca(2+)-ATPase in the Ca(2+)-bound form and the Gln mutants of Glu771 and Glu908. Both of them contribute only one carboxyl oxygen to site I Ca(2+), but only Glu771Gln completely looses the Ca(2+)-binding ability. The simulations show that: (i) For Glu771Gln, but not Glu908Gln, coordination of Ca(2+) was critically disrupted. (ii) Coordination broke at site II first, although Glu771 and Glu908 only contribute to site I. (iii) A water molecule bound to site I Ca(2+) and hydrogen bonded to Glu771 in wild-type, drastically changed the coordination of Ca(2+) in the mutant. (iv) Water molecules flooded the binding sites from the lumenal side. (v) The side chain conformation of Ile775, located at the head of a hydrophobic cluster near the lumenal surface, appears critical for keeping out bulk water. Thus the simulations highlight the importance of the water molecule bound to site I Ca(2+) and point to a strong relationship between Ca(2+)-coordination and shielding of bulk water, providing insights into the mechanism of gating of ion pathways in cation pumps.

  14. Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

    PubMed Central

    Moreno, Claudia M; Dixon, Rose E; Tajada, Sendoa; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Santana, Luis F

    2016-01-01

    CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca2+ influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca2+ signaling and electrical activity. DOI: http://dx.doi.org/10.7554/eLife.15744.001 PMID:27187148

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

    PubMed

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

    2006-07-01

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

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

    PubMed

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

    2015-08-01

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

  17. Increased Myofilament Ca2+-Sensitivity and Arrhythmia Susceptibility

    PubMed Central

    Huke, Sabine; Knollmann, Bjorn C.

    2010-01-01

    Increased myofilament Ca2+ sensitivity, a common attribute of inherited and acquired cardiomyopathies, is often associated with cardiac arrhythmias. Accumulating evidence supports that increased myofilament Ca2+ sensitivity is an independent risk factor for arrhythmias, but the underlying molecular mechanism remains unclear. This review focuses on potential mechanisms how myofilament Ca2+ sensitivity may affect cardiac excitation and leads to the generation of arrhythmias. We discuss in detail the downstream effects of increased myofilament Ca2+ sensitivity, i.e. altered Ca2+ buffering/handling, impaired energy metabolism and increased mechanical stretch, and how they may contribute to the proarrhythmic effect. PMID:20097204

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

    PubMed Central

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

    2013-01-01

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

  19. An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.

    PubMed

    Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A; Uhlén, Per; Hill, Joseph A; Lavandero, Sergio

    2014-10-01

    In cardiomyocytes, Ca(2+) plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca(2+) within subcellular microdomains: transcription is regulated by Ca(2+) release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca(2+). Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca(2+) signals. However, signaling pathways coupling surface receptor activation to nuclear Ca(2+) release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca(2+) signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca(2+) release from perinuclear Ca(2+) stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca(2+) release. In this review, we discuss mechanisms for the selective control of nuclear Ca(2+) signals with special focus on emerging models of agonist receptor activation.

  20. An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling

    PubMed Central

    Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A.; Uhlén, Per; Hill, Joseph A.; Lavandero, Sergio

    2015-01-01

    In cardiomyocytes, Ca2+ plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca2+ within subcellular microdomains: transcription is regulated by Ca2+ release within nuclear microdomains, and excitation–contraction coupling is regulated by cytosolic Ca2+. Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca2+ signals. However, signaling pathways coupling surface receptor activation to nuclear Ca2+ release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca2+ signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca2+ release from perinuclear Ca2+ stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca2+ release. In this review, we discuss mechanisms for the selective control of nuclear Ca2+ signals with special focus on emerging models of agonist receptor activation. PMID:24997440

  1. Accretion rate of extraterrestrial 41Ca in Antarctic snow samples

    NASA Astrophysics Data System (ADS)

    Gómez-Guzmán, J. M.; Bishop, S.; Faestermann, T.; Famulok, N.; Fimiani, L.; Hain, K.; Jahn, S.; Korschinek, G.; Ludwig, P.; Rodrigues, D.

    2015-10-01

    Interplanetary Dust Particles (IDPs) are small grains, generally less than a few hundred micrometers in size. Their main source is the Asteroid Belt, located at 3 AU from the Sun, between Mars and Jupiter. During their flight from the Asteroid Belt to the Earth they are irradiated by galactic and solar cosmic rays (GCR and SCR), thus radionuclides are formed, like 41Ca and 53Mn. Therefore, 41Ca (T1/2 = 1.03 × 105 yr) can be used as a key tracer to determine the accretion rate of IDPs onto the Earth because there are no significant terrestrial sources for this radionuclide. The first step of this study consisted to calculate the production rate of 41Ca in IDPs accreted by the Earth during their travel from the Asteroid Belt. This production rate, used in accordance with the 41Ca/40Ca ratios that will be measured in snow samples from the Antarctica will be used to calculate the amount of extraterrestrial material accreted by the Earth per year. There challenges for this project are, at first, the much longer time for the flight needed by the IDPs to travel from the Asteroid Belt to the Earth in comparison with the 41Ca half-life yields an early saturation for the 41Ca/40Ca ratio, and second, the importance of selecting the correct sampling site to avoid a high influx of natural 40Ca, preventing dilution of the 41Ca/40Ca ratio, the quantity measured by AMS.

  2. Ca2+ signaling, genes and the cell cycle

    PubMed Central

    Machaca, Khaled

    2013-01-01

    Changes in the concentration and spatial distribution of Ca2+ ions in the cytoplasm constitute a ubiquitous intracellular signaling module in cellular physiology. With the advent of Ca2+ dyes that allow direct visualization of Ca2+ transients, combined with powerful experimental tools such as electrophysiological recordings, intracellular Ca2+ transients have been implicated in practically every aspect of cellular physiology, including cellular proliferation. Ca2+ signals are associated with different phases of the cell cycle and interfering with Ca2+ signaling or downstream pathways often disrupts progression of the cell cycle. Although there exists a dependence between Ca2+ signals and the cell cycle the mechanisms involved are not well defined and given the cross-talk between Ca2+ and other signaling modules, it is difficult to assess the exact role of Ca2+ signals in cell cycle progression. Two exceptions however, include fertilization and T-cell activation, where well-defined roles for Ca2+ signals in mediating progression through specific stages of the cell cycle have been clearly established. In the case of T-cell activation Ca2+ regulates entry into the cell cycle through the induction of gene transcription. PMID:21084120

  3. Ca handling during Excitation-Contraction Coupling in Heart Failure

    PubMed Central

    Zima, Aleksey V.; Bovo, Elisa; Mazurek, Stefan R.; Rochira, Jennifer A.; Li, Weiyan; Terentyev, Dmitry

    2017-01-01

    In the heart, coupling between excitation of the surface membrane and activation of contractile apparatus is mediated by Ca released from the sarcoplasmic reticulum (SR). Several components of Ca machinery are perfectly arranged within the SR network and the T-tubular system to generate a regular Ca cycling and thereby rhythmic beating activity of the heart. Among these components, ryanodine receptor (RyR) and SR Ca ATPase (SERCA) complexes play a particularly important role and their dysfunction largely underlies abnormal Ca homeostasis in diseased hearts such as in heart failure. The abnormalities in Ca regulation occur at practically all main steps of Ca cycling in the failing heart, including activation and termination of SR Ca release, diastolic SR Ca leak, and SR Ca uptake. The contributions of these different mechanisms to depressed contractile function and enhanced arrhythmogenesis may vary in different HF models. This brief review will therefore focus on modifications in RyR and SERCA structure that occur in the failing heart and how these molecular modifications affect SR Ca regulation and excitation-contraction coupling. PMID:24515294

  4. The hippocampal CA2 region is essential for social memory.

    PubMed

    Hitti, Frederick L; Siegelbaum, Steven A

    2014-04-03

    The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where and when. Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus to CA3 and then to CA1, the main hippocampal output. Genetic lesions of EC (ref. 3) and hippocampal dentate gyrus (ref. 4), CA3 (ref. 5) and CA1 (ref. 6) regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output. Here we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioural role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory--the ability of an animal to remember a conspecific--with no change in sociability or several other hippocampus-dependent behaviours, including spatial and contextual memory. These behavioural and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.

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

    PubMed Central

    Weisleder, Noah; Ma, Jianjie

    2008-01-01

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

  6. Effects of the removal of extracellular Ca2+ on [Ca2+]i responses to FCCP and acetate in carotid body glomus cells of adult rabbits.

    PubMed

    Sato, M

    1997-09-12

    The effects of the removal of extracellular Ca2+ on the responses of cytosolic concentrations of Ca2+ ([Ca2+]i) to acidic stimuli, a protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and an organic acid acetate, were examined in clusters of cultured carotid body glomus cells of adult rabbits using fura-2 microfluorometry. Application of FCCP (1 microM) induced an increase in [Ca2+]i (mean +/- S.E.M., 108 +/- 14%). After withdrawal of the protonophore the increased [Ca2+]i returned slowly to a resting level. The [Ca2+]i response was attenuated by an inorganic Ca2+ channel antagonist Ni2+ (2 mM) by 81 +/- 4%, and by an L-type voltage-gated Ca2+ channel antagonist D600 (10 microM) by 53 +/- 13%. The removal of extracellular Ca2+ eliminated the [Ca2+]i response in 71% of the tested cells (n = 17), and depressed it by 68 +/- 6% in the rest. Recovery following stimulation with FCCP in the absence of Ca2+ reversibly produced a rapid and large rise in [Ca2+]i, referred to as a [Ca2+]i rise after Ca2+-free/FCCP. The magnitude of a [Ca2+]i rise after Ca2+-free/FCCP (285 +/- 28%, P < 0.05) was larger than that of an increase in [Ca2+]i induced by FCCP in the presence of Ca2+ and had a correlation with the intensity of the suppression of the [Ca2+]i response by Ca2+ removal. A [Ca2+]i rise after Ca2+-free/FCCP was inhibited mostly by D600. Similarly, recovery following exposure to acetate in the absence of Ca2+ caused a rise in [Ca2+]i, referred to as a [Ca2+]i rise after Ca2+-free/acetate which was sensitive to D600. The magnitude of the [Ca2+]i rise was larger than that of a change in [Ca2+]i caused by acetate in the presence of Ca2+. These results suggest that FCCP-induced increase in [Ca2+]i was, in most cells, due to Ca2+ influx via L-type voltage-gated Ca2+ channels and, in some cells, due to both Ca2+ influx and Ca2+ release from internal Ca2+ pool. The removal of extracellular Ca2+ might modify [Ca2+]i responses to acidic stimuli, causing [Ca2+]i

  7. Inhibitory Gating of Input Comparison in the CA1 Microcircuit.

    PubMed

    Milstein, Aaron D; Bloss, Erik B; Apostolides, Pierre F; Vaidya, Sachin P; Dilly, Geoffrey A; Zemelman, Boris V; Magee, Jeffrey C

    2015-09-23

    Spatial and temporal features of synaptic inputs engage integration mechanisms on multiple scales, including presynaptic release sites, postsynaptic dendrites, and networks of inhibitory interneurons. Here we investigate how these mechanisms cooperate to filter synaptic input in hippocampal area CA1. Dendritic recordings from CA1 pyramidal neurons reveal that proximal inputs from CA3 as well as distal inputs from entorhinal cortex layer III (ECIII) sum sublinearly or linearly at low firing rates due to feedforward inhibition, but sum supralinearly at high firing rates due to synaptic facilitation, producing a high-pass filter. However, during ECIII and CA3 input comparison, supralinear dendritic integration is dynamically balanced by feedforward and feedback inhibition, resulting in suppression of dendritic complex spiking. We find that a particular subpopulation of CA1 interneurons expressing neuropeptide Y (NPY) contributes prominently to this dynamic filter by integrating both ECIII and CA3 input pathways and potently inhibiting CA1 pyramidal neuron dendrites.

  8. The molecular identity of the mitochondrial Ca2+ sequestration system

    PubMed Central

    Starkov, Anatoly A.

    2013-01-01

    There is ample evidence to suggest that a dramatic decrease in mitochondrial Ca2+ retention may contribute to the cell death associated with stroke, excitotoxicity, ischemia and reperfusion, and neurodegenerative diseases. Mitochondria from all studied tissues can accumulate and store Ca2+, but the maximum Ca2+ storage capacity varies widely and exhibits striking tissue specificity. There is currently no explanation for this fact. Precipitation of Ca2+ and phosphate in the mitochondrial matrix has been suggested to be the major form of storage of accumulated Ca2+ in mitochondria. How this precipitate is formed is not known. The molecular identity of almost all proteins involved in Ca2+ transport, storage and formation of the permeability transition pore is also unknown. This review summarizes studies aimed at identifying these proteins, and describes the properties of a known mitochondrial protein that may be involved in Ca2+ transport and the structure of the permeability transition pore. PMID:20659159

  9. Spectroscopy of neutron-deficient nuclei around 36Ca

    SciTech Connect

    Buerger, A.; Azaiez, F.; Bourgeois, Ch.; Franchoo, S.; Ibrahim, F.; Verney, D.; Dombradi, Zs.; Algora, A.; Fueloep, Zs.; Sohler, D.; Al-Khatib, A.; Bringel, P.; Engelhardt, C.; Huebel, H.; Bastin, B.; Benzoni, G.; Borcea, R.; Rotaru, F.; Sorlin, O.

    2006-04-26

    An experiment was performed to extend the knowledge of excited states in neutron-deficient Ca isotopes. In particular, excited states in 36Ca were searched for to allow for a comparison with its stable mirror nucleus, 36S. Secondary beams of 37Ca and 36Ca were produced by fragmentation of a primary 40Ca beam with an energy of 95 {center_dot} A MeV on the SISSI target at GANIL. A variety of nuclei around 36Ca has been produced in a secondary Be target by neutron and proton-removal at beam energies around 61 {center_dot} A MeV. The produced nuclei were identified using the spectrometer SPEG, and prompt {gamma} rays were measured with the Chateau de Cristal. A preliminary value for the energy of the first 2+ state of 36Ca has been determined.

  10. The Ca2+-Transport ATPase of Plant Plasma Membrane Catalyzes a nH+/Ca2+ Exchange 1

    PubMed Central

    Rasi-Caldogno, Franca; Pugliarello, Maria C.; De Michelis, Maria I.

    1987-01-01

    Microsomal vesicles from 24-hour-old radish (Raphanus sativus L.) seedlings accumulate Ca2+ upon addition of MgATP. MgATP-dependent Ca2+ uptake co-migrates with the plasma membrane H+-ATPase on a sucrose gradient. Ca2+ uptake is insensitive to oligomycin, inhibited by vanadate (IC50 40 micromolar) and erythrosin B (IC50 0.2 micromolar) and displays a pH optimum between pH 6.6 and 6.9. MgATP-dependent Ca2+ uptake is insensitive to protonophores. These results indicate that Ca2+ transport in these microsomal vesicles is catalyzed by a Mg2+-dependent ATPase localized on the plasma membrane. Ca2+ strongly reduces ΔpH generation by the plasma membrane H+-ATPase and increases MgATP-dependent membrane potential difference (Δψ) generation. These effects of Ca2+ on ΔpH and Δψ generation are drastically reduced by micromolar erythrosin B, indicating that they are primarily a consequence of Ca2+ uptake into plasma membrane vesicles. The Ca2+-induced increase of Δψ is collapsed by permeant anions, which do not affect Ca2+-induced decrease of ΔpH generation by the plasma membrane H+-ATPase. The rate of decay of MgATP-dependent ΔpH, upon inhibition of the plasma membrane H+-ATPase, is accelerated by MgATP-dependent Ca2+ uptake, indicating that the decrease of ΔpH generation induced by Ca2+ reflects the efflux of H+ coupled to Ca2+ uptake into plasma membrane vesicles. It is therefore proposed that Ca2+ transport at the plasma membrane is mediated by a Mg2+-dependent ATPase which catalyzes a nH+/Ca2+ exchange. PMID:16665378

  11. Interpreting the Ca isotope record of marine biogenic carbonates

    NASA Astrophysics Data System (ADS)

    Sime, Neil G.; De La Rocha, Christina L.; Tipper, Edward T.; Tripati, Aradhna; Galy, Albert; Bickle, Michael J.

    2007-08-01

    An 18 million year record of the Ca isotopic composition (δ 44/42Ca) of planktonic foraminiferans from ODP site 925, in the Atlantic, on the Ceara Rise, provides the opportunity for critical analysis of Ca isotope-based reconstructions of the Ca cycle. δ 44/42Ca in this record averages +0.37 ± 0.05 (1 σ SD) and ranges from +0.21‰ to +0.52‰. The record is a good match to previously published Neogene Ca isotope records based on foraminiferans, but is not similar to the record based on bulk carbonates, which has values that are as much as 0.25‰ lower. Bulk carbonate and planktonic foraminiferans from core tops differ slightly in their δ 44/42Ca (i.e., by 0.06 ± 0.06‰ ( n = 5)), while the difference between bulk carbonate and foraminiferan values further back in time is markedly larger, leaving open the question of the cause of the difference. Modeling the global Ca cycle from downcore variations in δ 44/42Ca by assuming fixed values for the isotopic composition of weathering inputs (δ 44/42Ca w) and for isotope fractionation associated with the production of carbonate sediments (Δ sed) results in unrealistically large variations in the total mass of Ca 2+ in the oceans over the Neogene. Alternatively, variations of ±0.05‰ in the Ca isotope composition of weathering inputs or in the extent of fractionation of Ca isotopes during calcareous sediment formation could entirely account for variations in the Ca isotopic composition of marine carbonates. Ca isotope fractionation during continental weathering, such as has been recently observed, could easily result in variations in δ 44/42Ca w of a few tenths of permil. Likewise a difference in the fractionation factors associated with aragonite versus calcite formation could drive shifts in Δ sed of tenths of permil with shifts in the relative output of calcite and aragonite from the ocean. Until better constraints on variations in δ 44/42Ca w and Δ sed have been established, modeling the Ca 2+ content

  12. Effect of Ca doping on microstructural and superconducting properties of DyBa2Cu3O7-delta/Caz (0 leq z leq 0.2) ceramics

    NASA Astrophysics Data System (ADS)

    Y Laval, J.; Orlova, T. S.

    2003-10-01

    Using bright-field and energy selective x-ray analysis techniques in transmission electron microscopy, we have studied the effect of Ca doping on the microstructural and superconducting properties in DyBa2Cu3Oy/Caz (z = 0, 0.05, 0.1 and 0.2) ceramics, i.e. for the case when Ca was added in excess to the stoichiometric 123 composition. It was found that in this case approximately half of the added Ca amount entered the 123-lattice. Thus, in the composition with nominal z = 0.1 (0.77 at%) average Ca concentration in the grains was about 0.4 at%. On the basis of measured atomic concentrations and 123 stoichiometry of grains, it was concluded that Ca predominantly substituted Dy in the bulk for all levels of doping (0 leq z leq 0.2), although for z = 0.2 the rate of substitution for Ba also became pronounced. This substitution of Dy3+ by Ca2+ seems to explain the observed decrease in Tc from 92 K in an undoped sample to 74 77 K for compositions with z = 0.1 0.2. Ca segregated in grain boundaries (GBs). The concentration of Ca in most 'clean' (secondary-phase-free) GBs was 1.5 3.5 times higher than in the adjacent grains. Ca segregated in a narrow region (d leq 5 nm) around the GB. In the majority of GBs, Ca substitution for Dy was favoured, although with increasing the doping level from z = 0.1 to z = 0.2 the rate of the substitution for Ba increased. This substitution for Dy most probably explains the obtained dramatic increase of Jc at T leq 0.8 Tc in the Ca-doped samples. Ca segregation in GBs is the most probable reason for the superconductor normal-metal superconductor (SNS) behaviour of the GB network in Ca-doped samples. Ca doping led to a higher proportion of clean GBs, in the sample with z = 0.1, that could be responsible for a slower decrease of Jc with magnetic field in this sample.

  13. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury.

    PubMed

    Norris, Christopher M; Sompol, Pradoldej; Roberts, Kelly N; Ansari, Mubeen; Scheff, Stephen W

    2016-02-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague-Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10 mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma.

  14. Pycnogenol protects CA3-CA1 synaptic function in a rat model of traumatic brain injury

    PubMed Central

    Sompol, Pradoldej; Roberts, Kelly N.; Ansari, Mubeen

    2015-01-01

    Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. Previously, we showed that PYC administration to rats within hours after a controlled cortical impact (CCI) injury significantly protects against the loss of several synaptic proteins in the hippocampus. Here, we investigated the effects of PYC on CA3-CA1 synaptic function following CCI. Adult Sprague Dawley rats received an ipsilateral CCI injury followed 15 min later by intravenous injection of saline vehicle or PYC (10mg/kg). Hippocampal slices from the injured (ipsilateral) and uninjured (contralateral) hemispheres were prepared at seven and fourteen days post-CCI for electrophysiological analyses of CA3-CA1 synaptic function and induction of long-term depression (LTD). Basal synaptic strength was impaired in slices from the ipsilateral, relative to the contralateral, hemisphere at seven days post-CCI and susceptibility to LTD was enhanced in the ipsilateral hemisphere at both post-injury timepoints. No interhemispheric differences in basal synaptic strength or LTD induction were observed in rats treated with PYC. The results show that PYC preserves synaptic function after CCI and provides further rationale for investigating the use of PYC as a therapeutic in humans suffering from neurotrauma. PMID:26607913

  15. Design and application of a class of sensors to monitor Ca2+ dynamics in high Ca2+ concentration cellular compartments

    PubMed Central

    Tang, Shen; Wong, Hing-Cheung; Wang, Zhong-Min; Huang, Yun; Zou, Jin; Zhuo, You; Pennati, Andrea; Gadda, Giovanni; Delbono, Osvaldo; Yang, Jenny J.

    2011-01-01

    Quantitative analysis of Ca2+ fluctuations in the endoplasmic/sarcoplasmic reticulum (ER/SR) is essential to defining the mechanisms of Ca2+-dependent signaling under physiological and pathological conditions. Here, we developed a unique class of genetically encoded indicators by designing a Ca2+ binding site in the EGFP. One of them, calcium sensor for detecting high concentration in the ER, exhibits unprecedented Ca2+ release kinetics with an off-rate estimated at around 700 s−1 and appropriate Ca2+ binding affinity, likely attributable to local Ca2+-induced conformational changes around the designed Ca2+ binding site and reduced chemical exchange between two chromophore states. Calcium sensor for detecting high concentration in the ER reported considerable differences in ER Ca2+ dynamics and concentration among human epithelial carcinoma cells (HeLa), human embryonic kidney 293 cells (HEK-293), and mouse myoblast cells (C2C12), enabling us to monitor SR luminal Ca2+ in flexor digitorum brevis muscle fibers to determine the mechanism of diminished SR Ca2+ release in aging mice. This sensor will be invaluable in examining pathogenesis characterized by alterations in Ca2+ homeostasis. PMID:21914846

  16. Synthesis of Ca P nanoparticles and fabrication of Ca P/PHBV nanocomposite microspheres for bone tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Duan, B.; Wang, M.; Zhou, W. Y.; Cheung, W. L.

    2008-11-01

    As the first step in producing totally bioresorbable osteoconductive composite scaffolds for bone tissue engineering using the selective laser sintering technology, bioresorbable nanoparticles of calcium phosphate (Ca-P) similar in composition to β-tricalcium phosphate were synthesized and Ca-P nanoparticle filled poly(hydroxybutyrate- co-hydroxyvalerate) (PHBV) microspheres were fabricated. The pH of the chemical reaction for Ca-P particle synthesis was found to have significant effects on the morphology and chemical composition of Ca-P precipitated. Ca-P particles produced at the pH of 10.0-11.0 were amorphous, had a Ca:P molar ratio of about 1.5, were spherical in shape and had sizes in the range of 10-30 nm. The Ca-P particles were used to form Ca-P nanocomposite microspheres through a solid-in-oil-in-water (S/O/W) emulsion solvent evaporation process. Ca-P nanoparticles were mostly encapsulated inside the microspheres and some Ca-P nanoparticles were superficially embedded on the microspheres. The Ca-P/PHBV microspheres had an average diameter of about 48 μm which is suitable for selective laser sintering for constructing osteoconductive composite scaffolds.

  17. Distinct Ca2+ sources in dendritic spines of hippocampal CA1 neurons couple to SK and Kv4 channels

    PubMed Central

    Wang, Kang; Lin, Mike T.; Adelman, John P.; Maylie, James

    2013-01-01

    SUMMARY Ca2+-activated SK channels and voltage-gated A-type Kv4 channels shape dendritic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1 pyramidal neurons. Synaptically evoked Ca2+ influx through N-methyl-D-aspartate receptors (NMDARs) activates spine SK channels, reducing EPSPs and the associated spine head Ca2+ transient. However, results using glutamate uncaging implicated Ca2+ influx through SNX-482 (SNX) sensitive Cav2.3 (R-type) Ca2+ channels as the Ca2+ source for SK channel activation. The present findings show that using Schaffer collateral stimulation the effects of SNX and apamin are not mutually exclusive and SNX increases EPSPs independent of SK channel activity. Dialysis with 1,2-bis(o-aminophenoxy)ethane-N’N’N’-tetraacetic acid (BAPTA), application of 4-Aminopyridine (4-AP), expression of a Kv4.2 dominant negative subunit, and dialysis with a KChIPs antibody occluded the SNX-induced increase of EPSPs. The results suggest two distinct Ca2+ signaling pathways within dendritic spines, that links Ca2+ influx through NMDARs to SK channels and Ca2+ influx through R-type Ca2+ channels to Kv4.2-containing channels. PMID:24462100

  18. Aluminian Low-Ca Pyroxene in a Ca-Al-rich Chondrule from the Semarkona Meteorite

    NASA Technical Reports Server (NTRS)

    Rubin, Alan E.

    2006-01-01

    A Ca-AI-rich chondrule (labeled G7) from the Semarkona LL3.0 ordinary chondrite (OC) consists of 73 vol% glassy mesostasis, 22 vol% skeletal forsterite. 3 vol% fassaite (i.e., Al-Ti diopside), and 2 vol% Al-rich, low-Ca pyroxene. The latter phase, which contains up to 16.3 wt% A1203, is among the most AI-rich, low-Ca pyroxene grains ever reported. It is inferred that 20% of the tetrahedral sites and 13% of the octahedral sites in this grain are occupied by Al. Approximately parallel optical extinction implies that the Al-rich, low-Ca pyroxene grains are probably orthorhombic, consistent with literature data that show that A1203 stabilizes the orthoenstatite structure relative to protoenstatite at low pressure. The order of crystallization in the chondrule was forsterite, AI-rich low-Ca pyroxene, and fassaite; the residual liquid vitrified during chondrule quenching. Phase relationships indicate that, for a G7-composition liquid at equilibrium, spinel and anorthite should crystallize early and orthopyroxene should not crystallize at all. The presence of AI-rich orthopyroxene in G7 is due mainly to the kinetic failure of anorthite to crystallize; this failure was caused by quenching of the G7 precursor droplet. Aluminum preferentially enters the relatively large B tetrahedra of orthopyroxene; because only one tetrahedral size occurs in fassaite, this phase contains higher mean concentrations of Al2O3 than the Al-rich orthopyroxene (17.8 and 14.7 wt%, respectively). Chondrule G7 may have formed by remelting an amoeboid olivine inclusion that entered the OC region of the solar nebula during an episode of chondrule formation.

  19. Characterization of hydromedusan Ca(2+)-regulated photoproteins as a tool for measurement of Ca(2+)concentration.

    PubMed

    Malikova, Natalia P; Burakova, Ludmila P; Markova, Svetlana V; Vysotski, Eugene S

    2014-09-01

    Calcium ion is a ubiquitous intracellular messenger, performing this function in many eukaryotic cells. To understand calcium regulation mechanisms and how disturbances of these mechanisms are associated with disease states, it is necessary to measure calcium inside cells. Ca(2+)-regulated photoproteins have been successfully used for this purpose for many years. Here we report the results of comparative studies on the properties of recombinant aequorin from Aequorea victoria, recombinant obelins from Obelia geniculata and Obelia longissima, recombinant mitrocomin from Mitrocoma cellularia, and recombinant clytin from Clytia gregaria as intracellular calcium indicators in a set of identical in vitro and in vivo experiments. Although photoproteins reveal a high degree of identity of amino acid sequences and spatial structures, and, apparently, have a common mechanism for the bioluminescence reaction, they were found to differ in the Ca(2+) concentration detection limit, the sensitivity of bioluminescence to Mg(2+), and the rates of the rise of the luminescence signal with a sudden change of Ca(2+) concentration. In addition, the bioluminescence activities of Chinese hamster ovary cells expressing wild-type photoproteins also differed. The light signals of cells expressing mitrocomin, for example, slightly exceeded the background, suggesting that mitrocomin may be hardly used to detect intracellular Ca(2+) without modifications improving its properties. On the basis of experiments on the activation of endogenous P2Y2 receptor in Chinese hamster ovary cells by ATP, we suggest that wild-type aequorin and obelin from O. longissima are more suitable for calcium detection in cytoplasm, whereas clytin and obelin from O. geniculata can be used for calcium measurement in cell compartments with high Ca(2+) concentration.

  20. Impact of Genetic Variation on Human CaMKK2 Regulation by Ca2+-Calmodulin and Multisite Phosphorylation

    PubMed Central

    O’Brien, Matthew T.; Oakhill, Jonathan S.; Ling, Naomi X. Y.; Langendorf, Christopher G.; Hoque, Ashfaqul; Dite, Toby A.; Means, Anthony R.; Kemp, Bruce E.; Scott, John W.

    2017-01-01

    The Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2. Four mutations (G87R, R139W, R142W and E268K) cause a marked decrease in Ca2+-independent autonomous activity, however S137L and P138S mutants displayed increased autonomous and Ca2+-CaM stimulated activities. Furthermore, the G87R mutant is defective in Thr85-autophosphorylation dependent autonomous activity, whereas the A329T mutation rendered CaMKK2 virtually insensitive to Ca2+-CaM stimulation. The G87R and R139W mutants behave as dominant-negative inhibitors of CaMKK2 signaling in cells as they block phosphorylation of the downstream substrate AMP-activated protein kinase (AMPK) in response to ionomycin. Our study provides insight into functionally disruptive, rare-variant mutations in human CaMKK2, which have the potential to influence risk and burden of disease associated with aberrant CaMKK2 activity in human populations carrying these variants. PMID:28230171

  1. Ca2+ accumulation into acidic organelles mediated by Ca2+- and vacuolar H+-ATPases in human platelets

    PubMed Central

    2005-01-01

    Most physiological agonists increase cytosolic free [Ca2+]c (cytosolic free Ca2+ concentration) to regulate a variety of cellular processes. How different stimuli evoke distinct spatiotemporal Ca2+ responses remains unclear, and the presence of separate intracellular Ca2+ stores might be of great functional relevance. Ca2+ accumulation into intracellular compartments mainly depends on the activity of Ca2+- and H+-ATPases. Platelets present two separate Ca2+ stores differentiated by the distinct sensitivity to thapsigargin and TBHQ [2,5-di-(t-butyl)-1,4-hydroquinone]. Although one store has long been identified as the dense tubular system, the nature of the TBHQ-sensitive store remains uncertain. Treatment of platelets with GPN (glycylphenylalanine-2-naphthylamide) impaired Ca2+ release by TBHQ and reduced that evoked by thrombin. In contrast, GPN did not modify Ca2+ mobilization stimulated by ADP or AVP ([arginine]vasopressin). Treatment with nigericin, a proton carrier, and bafilomycin A1, an inhibitor of the vacuolar H+-ATPase, to dissipate the proton gradient into acidic organelles induces a transient increase in [Ca2+]c that was abolished by previous treatment with the SERCA (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase) 3 inhibitor TBHQ. Depleted acidic stores after nigericin or bafilomycin A1 were refilled by SERCA 3. Thrombin, but not ADP or AVP, reduces the rise in [Ca2+]c evoked by nigericin and bafilomycin A1. Our results indicate that the TBHQ-sensitive store in human platelets is an acidic organelle whose Ca2+ accumulation is regulated by both Ca2+- and vacuolar H+-ATPases. PMID:15847604

  2. Induction of CaSR expression circumvents the molecular features of malignant CaSR null colon cancer cells.

    PubMed

    Singh, Navneet; Chakrabarty, Subhas

    2013-11-15

    We recently reported on the isolation and characterization of calcium sensing receptor (CaSR) null human colon cancer cells (Singh et al., Int J Cancer 2013; 132: 1996-2005). CaSR null cells possess a myriad of molecular features that are linked to a highly malignant and drug resistant phenotype of colon cancer. The CaSR null phenotype can be maintained in defined human embryonic stem cell culture medium. We now show that the CaSR null cells can be induced to differentiate in conventional culture medium, regained the expression of CaSR with a concurrent reversal of the cellular and molecular features associated with the null phenotype. These features include cellular morphology, expression of colon cancer stem cell markers, expression of survivin and thymidylate synthase and sensitivity to fluorouracil. Other features include the expression of epithelial mesenchymal transition linked molecules and transcription factors, oncogenic miRNAs and tumor suppressive molecule and miRNA. With the exception of cancer stem cell markers, the reversal of molecular features, upon the induction of CaSR expression, is directly linked to the expression and function of CaSR because blocking CaSR induction by shRNA circumvented such reversal. We further report that methylation and demethylation of the CaSR gene promoter underlie CaSR expression. Due to the malignant nature of the CaSR null cells, inclusion of the CaSR null phenotype in disease management may improve on the mortality of this disease. Because CaSR is a robust promoter of differentiation and mediates its action through diverse mechanisms and pathways, inactivation of CaSR may serve as a new paradigm in colon carcinogenesis.

  3. Foeniculum vulgare Mill. increases cytosolic Ca(2+) concentration and inhibits store-operated Ca(2+) entry in vascular endothelial cells.

    PubMed

    Han, A Young; Lee, Hui Su; Seol, Geun Hee

    2016-12-01

    This study assessed the effects of essential oil of Foeniculum vulgare Mill. (fennel oil) and of trans-anethole, the main component of fennel oil, on extracellular Ca(2+)-induced store-operated Ca(2+) entry (SOCE) into vascular endothelial (EA) cells and their mechanisms of action. Components of fennel oil were analyzed by gas chromatography-mass spectrometry. Cytosolic Ca(2+) concentration ([Ca(2+)]c) in EA cells was determined using Fura-2 fluorescence. In the presence of extracellular Ca(2+), fennel oil significantly increased [Ca(2+)]c in EA cells; this increase was significantly inhibited by the Ca(2+) channel blockers La(3+) and nifedipine. In contrast, fennel oil induced [Ca(2+)]c was significantly lower in Ca(2+)-free solution, suggesting that fennel oil increases [Ca(2+)]c mainly by enhancing Ca(2+) influx into EA cells. [Ca(2+)]c mobilization by trans-anethole was similar to that of fennel oil. Moreover, SOCE was suppressed by fennel oil and trans-anethole. SOCE was also attenuated by lanthanum (La(3+)), a non-selective cation channel (NSC) blocker; 2-aminoethoxydiphenyl borane (2-APB), an inositol 1,4,5-triphosphate (IP3) receptor inhibitor and SOCE blocker; and U73122, an inhibitor of phospholipase C (PLC). Further, SOCE was more strongly inhibited by La(3+) plus fennel oil or trans-anethole than by La(3+) alone. These findings suggest that fennel oil and trans-anethole significantly inhibit SOCE-induced [Ca(2+)]c increase in vascular endothelial cells and that these reactions may be mediated by NSC, IP3-dependent Ca(2+) mobilization, and PLC activation.

  4. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    SciTech Connect

    Chen, Min; Wang, Yanru; Qu, Aijuan

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that my