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Sample records for clara cell secretory

  1. Ultrastructural immunohistochemical localization of Clara cell secretory protein in pulmonary epithelium of rabbits.

    OpenAIRE

    Patton, S E; Gupta, R. P.; Nishio, S.; Eddy, E M; Jetten, A. M.; Plopper, C. G.; Nettesheim, P; Hook, G E

    1991-01-01

    Highly purified Clara cells (93 +/- 3%) isolated from the lungs of rabbits were used to produce an antiserum against Clara cell secretory proteins. This antiserum was used to identify and study the biosynthesis and secretion of [35S]methionine-labeled proteins from isolated Clara cells. The antiserum recognized one major secretory protein with apparent molecular weight of 6 kDa and reacted weakly with a higher molecular weight protein of about 180 kDa. Biosynthesis and secretion of these prot...

  2. Novel method for isolation of murine clara cell secretory protein-expressing cells with traces of stemness.

    Directory of Open Access Journals (Sweden)

    Xiao-Yang Wang

    Full Text Available Clara cells are non-ciliated, secretory bronchiolar epithelial cells that serve to detoxify harmful inhaled substances. Clara cells also function as stem/progenitor cells for repair in the bronchioles. Clara cell secretory protein (CCSP is specifically expressed in pulmonary Clara cells and is widely used as a Clara cell marker. In addition CCSP promoter is commonly used to direct gene expression into the lung in transgenic models. The discovery of CCSP immunoreactivity in plasma membranes of airway lining cells prompted us to explore the possibility of enriching Clara cells by flow cytometry. We established a novel and simple method for the isolation of CCSP-expressing cell Clara cells using a combination of mechanical and enzymatic dissociation followed by flow cytometry sorting technology. We showed that ∼25% of dissociated cells from whole lung expressed CCSP. In the resulting preparation, up to 98% of cells expressed CCSP. Notably, we found that several common stem cell markers including CD44, CD133, Sca-1 and Sox2 were expressed in CCSP(+ cells. Moreover, CCSP(+ cells were able to form spheroid colonies in vitro with 0.97‰ efficiency. Parallel studies in vivo confirmed that a small population of CCSP(-expressing cells in mouse airways also demonstrates stem cell-like properties such as label retention and harboring rare bronchioalveolar stem cells (BASCs in terminal bronchioles (TBs. We conclude that CCSP(+ cells exhibit a number of stem cell-like features including stem cell marker expression, bronchosphere colony formation and self-renewal ability. Clara cell isolation by flow cytometry sorting is a useful method for investigating the function of primary Clara cells in stem cell research and mouse models.

  3. Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice.

    Science.gov (United States)

    Johnston, C J; Mango, G W; Finkelstein, J N; Stripp, B R

    1997-08-01

    Clara cell secretory protein (CCSP) is an abundant component of the extracellular lining fluid of airways. Even though the in vivo function of CCSP is unknown, in vitro studies support a potential role of CCSP in the control of inflammatory responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in vivo function of this protein (13). In this study, we used hyperoxia exposure as a model to investigate phenotypic consequences of CCSP deficiency following acute lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery of the lung, include inflammatory cell infiltrate and edema. Continuous exposure to > 95% O2 was associated with significantly reduced survival time among CCSP -/- mice as compared with strain-, age-, and sex-matched wild-type control mice. Differences in survival were associated with early onset of lung edema in CCSP -/- mice as compared with wild-type controls. To further investigate these differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung RNA was characterized for changes in the abundance of cytokine messenger RNA (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia, interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher, respectively, in CCSP -/- mice than in similarly exposed wild-type control mice. Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was localized principally within the lung parenchyma, suggesting that the effects of CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP deficiency results in increased sensitivity to hyperoxia-induced lung injury as measured by increased mortality, early onset of lung edema, and induction of proinflammatory cytokine mRNAs.

  4. Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein.

    Science.gov (United States)

    Plopper, C G; Mango, G W; Hatch, G E; Wong, V J; Toskala, E; Reynolds, S D; Tarkington, B K; Stripp, B R

    2006-05-15

    Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O3). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice homozygous for a null allele of the CCSP gene (CCSP-/-) and wild type (CCSP+/+) littermates were exposed to ozone (0.2 ppm, 8 h; 1 ppm, 8 h) or filtered air. Injury was evaluated by light and scanning electron microscopy, and the abundance of necrotic, ciliated, and nonciliated cells was estimated by morphometry. Proximal and midlevel intrapulmonary airways and terminal bronchioles were evaluated. There was no difference in airway epithelial composition between CCSP+/+ and CCSP-/- mice exposed to filtered air, and exposure to 0.2 ppm ozone caused little injury to the epithelium of both CCSP+/+ and CCSP-/- mice. After exposure to 1.0 ppm ozone, CCSP-/- mice suffered from a greater degree of epithelial injury throughout the airways compared to CCSP+/+ mice. CCSP-/- mice had both ciliated and nonciliated cell injury. Furthermore, lack of CCSP was associated with a shift in airway injury to include proximal airway generations. Therefore, we conclude that CCSP modulates the susceptibility of the epithelium to oxidant-induced injury. Whether this is due to the presence of CCSP on the acellular lining layer surface and/or its intracellular distribution in the secretory cell population needs to be defined.

  5. Regulation on the expression of Clara cell secretory protein in the lungs of the rats with acute lung injury by growth hormone

    Institute of Scientific and Technical Information of China (English)

    MIN Jia; LUO Fo-quan; ZHAO Wei-lu

    2012-01-01

    Background Clara cell secretory protein (CC16) is an important lung derived protective factor and may play an important role on the pathogenesis of acute lung injury (ALl) induced by endotoxemia.Growth hormone (GH) is an important anabolism hormone secreted by GH cells of the hypophysis.Pravious research showed that GH would significantly exacerbate ALl induced by endotoxemia,but the mechanism is not very clear yet.Whether the effects are related to CC16 or not is undetermined.Methods One hundred and twelve male Sprague-Dawley rats were randomly divided into an ALl group and a GH group.The rats in the two groups were subdivided into seven subgroups,according to injection with lipopolysaccharides (LPS) or not,then according to different intervals of time after LPS injection; 0 hour (pre-injection of LPS,acted as control group),0.5 hour,1 hour,2 hours,4 hours,6 hours and 24 hours for subgroups.Pulmonary alveolar septa area density (PASAD) and ploymorphonuclear cells (PMN) in the lungs were analyzed morphometrically.The levels of tumor necrosis factor (TNF) and interleukin 6 (1L-6) were determined by radioimmunoassay.To analyze the expression and activation of nuclear factor kappa B (NF-kB),the numbers of NF-kB positive cells in lungs were counted after immunofluorescence staining.and the levels of NF-KB inhibitory protein-α (1KB-α) in lung homogenates of rats were detected by Western blotting.The expression levels of CC16 mRNA in lungs of the rats with ALl were determined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).The levels of CC16 protein in lung homogenates were detected by Western blotting.Results Half an hour after LPS injury both the PASAD and PMN numbers in lungs of the rats with ALl began to increase significantly and peaked at 6-hour post-injury.They then began to recover and reached normal levels at 24-hour post-injury.Both the PASAD and PMN numbers in the GH group increased more significantly than those in the ALl group

  6. The lung enriched transcription factor TTF-1 and the ubiquitously expressed proteins Sp1 and Sp3 interact with elements located in the minimal promoter of the rat Clara cell secretory protein gene.

    Science.gov (United States)

    Toonen, R F; Gowan, S; Bingle, C D

    1996-01-01

    The mechanisms that direct expression of the Clara cell secretory protein (CCSP) gene to the bronchiolar epithelial cells of the lung remain to be elucidated. Previous studies have identified a number of proteins which bind to a functionally important region (Region 1) located -132 to -76 bp from the transcription start site in the rat CCSP gene. Subsequently we have shown that while Region 1 is an important positive regulator of CCSP gene expression, sequences 3' of this region (-75 to +38) are sufficient to confer tissue-specific expression of a reporter gene. In the present study we have used transient transfections with a deletion series of CCSP-CAT reporter plasmids (where CAT is chloramphenicol acetyltransferase) and gel mobility shift assays with a series of overlapping oligonucleotides covering the whole minimal promoter region to study protein-DNA interactions within this region. These studies have identified a conserved functional binding site for the lung and thyroid enriched homeodomain transcription factor TTF-1, located between positions -51 and -42 from the transcription start site. CCSP-CAT chimaeric reporters containing this region are specifically activated by TTF-1 in co-transfection assays, and nuclear extracts from cells which express TTF-1 bind to this region, as does in vitro translated rat TTF-1. Three additional conserved regions were identified, and in further gel mobility shift studies with an oligonucleotide spanning the conserved region immediately 5' to the TTF-1 site we identified a binding site for the ubiquitously expressed zinc-finger-containing proteins Sp1 and Sp3. These studies suggest that cell-type-restricted and ubiquitous nuclear proteins may play a combined role in the regulation of the CCSP gene within the bronchiolar epithelium by interacting with the minimal promoter region. PMID:8687389

  7. Effects of ultrafine particles-induced oxidative stress on Clara cells in allergic lung inflammation

    Science.gov (United States)

    2010-01-01

    Background Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation. Methods Ovalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 μg/m3 for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-α mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations. Results In non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-α relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells. Conclusion Our findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation. PMID:20420656

  8. Effects of ultrafine particles-induced oxidative stress on Clara cells in allergic lung inflammation.

    Science.gov (United States)

    Alessandrini, Francesca; Weichenmeier, Ingrid; van Miert, Erik; Takenaka, Shinji; Karg, Erwin; Blume, Cornelia; Mempel, Martin; Schulz, Holger; Bernard, Alfred; Behrendt, Heidrun

    2010-04-26

    Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation. Ovalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 microg/m(3) for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-alpha mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations. In non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-alpha relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells. Our findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation.

  9. Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells.

    Science.gov (United States)

    Reynolds, S D; Hong, K U; Giangreco, A; Mango, G W; Guron, C; Morimoto, Y; Stripp, B R

    2000-06-01

    The neuroepithelial body (NEB) is a highly dynamic structure that responds to chronic airway injury through hyperplasia of associated pulmonary neuroendocrine (PNE) cells. Although NEB dysplasia is correlated with preneoplastic conditions and PNE cells are thought to serve as a precursor for development of small cell lung carcinoma, mechanisms regulating expansion of the PNE cell population are not well understood. Based on studies performed in animal models, it has been suggested that NEB-associated progenitor cells that are phenotypically distinct from PNE cells contribute to PNE cell hyperplasia. We have previously used a Clara cell-specific toxicant, naphthalene, to induce airway injury in mice and have demonstrated that naphthalene-resistant Clara cells, characterized by their expression of Clara cell secretory protein (CCSP), and PNE cells contribute to airway repair and associated hyperplasia of NEBs. This study was conducted to define the contribution of NEB-associated CCSP-expressing progenitor cells to PNE cell hyperplasia after Clara cell ablation. Transgenic (CCtk) mice were generated in which herpes simplex virus thymidine kinase was expressed within all CCSP-expressing cells of the conducting airway epithelium through the use of transcriptional regulatory elements from the mouse CCSP promoter. Chronic administration of ganciclovir (GCV) to CCtk transgenic mice resulted in selective ablation of CCSP-expressing cells within conducting airways. Proliferation and hyperplasia of PNE cells occurred in the absence of detectable proliferation among any other residual airway epithelial cell populations. These results demonstrate that PNE cells function as a self-renewing progenitor population and that NEB-associated Clara cells are not necessary for PNE cell hyperplasia.

  10. Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis.

    Science.gov (United States)

    Tomita, T; Sakurai, Y; Ishibashi, S; Maru, Y

    2011-08-04

    We have previously shown that tumor necrosis factor (TNF)α produced from primary tumor-induced expression of two endogenous Toll-like receptor 4 (TLR4) ligands, S100A8 and serum amyloid A3 (SAA3), in pre-metastatic lungs. However, mechanistic details of the signaling network and relevance to pulmonary physiology are poorly understood. Here, we identify Clara cells as a control tower of the network. Clara cell ablation by naphthalene suppressed pulmonary recruitment of CD11b+TLR4+ cells and spontaneous lung metastasis. Clara cells turned out to express TLR4 through which SAA3 was auto-amplified. Reciprocal bone marrow transplantation between wild-type and TLR4 knockout mice demonstrated that pulmonary TLR4+ Clara cells could be derived from bone marrow. SAA3-induced TNFα expression in both alveolar type II cells and macrophages. Primary co-cultures of alveolar type II cells and Clara cells revealed that the induction of TNFα in alveolar type II cells was dependent on the Clara cell-mediated amplification of SAA3. SAA3 induction by bacterial endotoxin also required both Clara cells and TLR4. Thus, pulmonary metastatic soil may feature deregulation of homeostatic inflammatory responses to constant assaults of microbes with endotoxin.

  11. Rab18 inhibits secretory activity in neuroendocrine cells by interacting with secretory granules.

    Science.gov (United States)

    Vazquez-Martinez, Rafael; Cruz-Garcia, David; Duran-Prado, Mario; Peinado, Juan R; Castaño, Justo P; Malagon, Maria M

    2007-07-01

    Rab proteins comprise a complex family of small GTPases involved in the regulation of intracellular membrane trafficking and reorganization. In this study, we identified Rab18 as a new inhibitory player of the secretory pathway in neuroendocrine cells. In adrenal chromaffin PC12 cells and pituitary AtT20 cells, Rab18 is located at the cytosol but associates with a subpopulation of secretory granules after stimulation of the regulated secretory pathway, strongly suggesting that induction of secretion provokes Rab18 activation and recruitment to these organelles. In support of this, a dominant-inactive Rab18 mutant was found to distribute diffusely in the cytosol, whereas a dominant-active Rab18 mutant was predominantly associated to secretory granules. Furthermore, interaction of Rab18 with secretory granules was associated to an inhibition in the secretory activity of PC12 and AtT20 cells in response to stimulatory challenges. Association of Rab18 with secretory granules was also observed by immunoelectron microscopy in normal, non-tumoral endocrine cells (pituitary melanotropes), wherein Rab18 protein content is inversely correlated to the level of secretory activity of cells. Taken together, these findings suggest that, in neuroendocrine cells, Rab18 acts as a negative regulator of secretory activity, likely by impairing secretory granule transport.

  12. Tracheobronchial epithelium of the sheep: IV. Lectin histochemical characterization of secretory epithelial cells.

    Science.gov (United States)

    Mariassy, A T; Plopper, C G; St George, J A; Wilson, D W

    1988-09-01

    Conventional histochemical characterization of the mucus secretory apparatus is often difficult to reconcile with the biochemical analysis of respiratory secretions. This study was designed to examine the secretory glycoconjugates in airways using lectins with biochemically defined affinities for main sugar residues of mucus. We used five biotinylated lectins--DBA (Dolichos biflorus) and SBA (Glycine max) for N-acetyl galactosamine (galNAc), BSA I (Bandeiraea simplicifolia) and PNA (Arachis hypogea) for galactose (gal), and UEA I (Ulex europeus)--for detection of fucose (fuc) in HgCl2-fixed, paraffin-embedded, serially sectioned trachea, lobar and segmental bronchi and bronchioles of nine sheep. Lectins selectively localized the carbohydrate residues in luminal secretions, on epithelial cell surfaces, and in secretory cells. In proximal airways, the major carbohydrate residues in luminal secretions, cell surfaces, goblet cells, and glands were fuc and gal-NAc. PNA reacted mainly with apical granules of less than 10% of goblet cells, and gal residues were only detected in some of the mucous cells and on basolateral cell surfaces. Distal airways contained sparse secretion in the lumen, mucous cells contained weakly reactive fuc and gal-NAc, and the epithelial surfaces of Clara cells contained gal. Sugars abundant in the airway secretions were also the major component of cells in glands. We conclude that there is a correlation between specific sugar residues in secretory cells, glycocalyx, and luminal secretions in proximal and distal airways. This suggests that lectins may be used to obtain information about airway secretory cell composition from respiratory secretions.

  13. 急性肺损伤/急性呼吸窘迫综合征新生儿血清Clara细胞分泌蛋白、肺表面活性蛋白A变化的意义%Significance of changes of serum Clara cell secretory protein 16, pulmonary surfactant protein A in newborn infants with acute lung injury/acute respiratory distress syndrome

    Institute of Scientific and Technical Information of China (English)

    刘改英; 林广; 刘颖; 王艳芳; 张成; 刘芳; 马海燕; 郭锐

    2013-01-01

    Objective To investigate the effect of serum Clara cell secretory protein 16 (CC16),pulmonary surfactant protein A(SP-A) in diagnosis of acute lung injury (ALI)/acute respiratory distress syndrome(ARDS) in newborn infants.Methods Fifty ALI/ARDS newborn infants in Zhuhai People's Hospital between 2011 Sep.and Dec.2012 were selected as treatment group (ALI group including 35 cases,ARDS group including 15 cases),50 healthy newborns were selected as healthy control group.The changes of serum CC16,SP-A were detected by enzyme-linked immuno sorbent assay and were compared in the 3 groups.Results 1.Serum CC16 in ALI group and ARDS group were (34.19 ± 1.09) mg/L,(55.28 ± 0.82) mg/L,respectively,which were significantly higher than that in healthy control group [(12.67 ± 1.10) mg/L] (all P < 0.05),and there was significant difference between ALI group and ARDS group(P <0.05).2.Serum SP-A in ALI group and ARDS group were(56.78 ± 3.48) mg/L,(70.23 ± 5.14) mg/L respectively,which were significantly higher than that in healthy control group [(22.10 ± 3.32) mg/L] (all P < 0.05),and there was significant difference between ALI group and ARDS group (P < 0.05).Conclusion Serum CC16,SP-A can be effective parameter for early monitoring ALI/ARDS in newborn infants.%目的 探讨血清Clara细胞分泌蛋白(CC16)、肺表面活性蛋白A(SP-A)在新生儿急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)诊断中的作用.方法 选取2011年9月至2012年12月珠海市人民医院收治的50例ALI/ARDS新生儿作为观察组,其中ALI组35例,ARDS组15例;将同期健康体检的50例新生儿作为健康对照组.采用ELISA法检测3组患儿血清CC16及SP-A水平,比较3组患儿血清CC16、SP-A水平的变化.结果 1.血清CC 16:ALI组[(34.19 ±1.09) mg/L]、ARDS组[(55.28 ±0.82) mg/L]明显高于健康对照组[(12.67±1.10)mg/L](P均<0.05),且ALI组与ARDS组比较差异亦有统计学意义(P<0.05).2.血清SP-A:ALI组[(56.78±3.48) mg

  14. Power conversion and quality of the Santa Clara 2 MW direct carbonate fuel cell demonstration plant

    Energy Technology Data Exchange (ETDEWEB)

    Skok, A.J. [Fuel Cell Engineering Corp., Danbury, CT (United States); Abueg, R.Z. [Basic Measuring Instruments, Santa Clara, CA (United States); Schwartz, P. [Fluor Daniel, Inc., Irvine, CA (United States)] [and others

    1996-12-31

    The Santa Clara Demonstration Project (SCDP) is the first application of a commercial-scale carbonate fuel cell power plant on a US electric utility system. It is also the largest fuel cell power plant ever operated in the United States. The 2MW plant, located in Santa Clara, California, utilizes carbonate fuel cell technology developed by Energy Research Corporation (ERC) of Danbury, Connecticut. The ultimate goal of a fuel cell power plant is to deliver usable power into an electrical distribution system. The power conversion sub-system does this for the Santa Clara Demonstration Plant. A description of this sub-system and its capabilities follows. The sub-system has demonstrated the capability to deliver real power, reactive power and to absorb reactive power on a utility grid. The sub-system can be operated in the same manner as a conventional rotating generator except with enhanced capabilities for reactive power. Measurements demonstrated the power quality from the plant in various operating modes was high quality utility grade power.

  15. Mouse bronchiolar cell carcinogenesis. Histologic characterization and expression of Clara cell antigen in lesions induced by N-nitrosobis-(2-chloroethyl) ureas.

    Science.gov (United States)

    Rehm, S.; Lijinsky, W.; Singh, G.; Katyal, S. L.

    1991-01-01

    Female Swiss mice (Cr:NIH(S)) developed bronchiolar cell hyperplasia, dysplasia, metaplasia, and various morphologic types of bronchiolar cell tumors after topical (skin) application of N-nitroso-methyl-bis-chloroethylurea (NMBCU) or N-nitroso-tris-chloroethylurea (NTCU). These compounds are the first found to induce systemically bronchiolar cell tumors in mice in high incidence. Twice a week, with a 3-day interval, a 25-microliter drop of 0.04 mol/l (molar) NMBCU or NTCU in acetone was applied to the shaved interscapular integument for a maximum of 35 to 40 weeks. The earliest lung neoplasms were seen in mice that died after 23 weeks of treatment and affected 11 of 19 with NMBCU and 14 of 19 with NTCU treatment. Tumor growth pattern was nodular or the neoplastic tissue was frequently disseminated throughout the parenchyma, starting from multicentric peribronchiolar foci. The most common tumor types were squamous cell carcinomas and adenosquamous carcinomas, followed by adenocarcinomas with or without secretory cells, and a single ciliated-cell tumor. Histochemical and immunohistochemical studies were carried out on paraffin-embedded lungs using the avidin-biotin immunoperoxidase complex procedure and antisera against keratin, Clara cell antigen, surfactant apoprotein, neuron-specific enolase, bombesin, and chromogranin A. In several mice from both groups, hyperplasias and tumors were composed of cells expressing Clara cell antigen. No tumor cells were found expressing alveolar type II or neuroendocrine cell markers. It appeared that bronchiolar cells, in particular Clara cells, had migrated from terminal bronchioles or invaded bronchiolar walls to extend into the alveolar parenchyma. Squamous cell metaplasia with keratin expression was seen within airways or associated with glandular tumors, especially at the periphery. A unique cell type, with large eosinophilic globules and associated eosinophilic crystals, was seen lining airways or forming hyperplastic and

  16. Effects of N-acetylcysteine on Clara cells in rats with cigarette smoke exposure

    Institute of Scientific and Technical Information of China (English)

    LIAO Ji-ping; CHI Chun-hua; LI Hai-chao; TANG Xiu-ying

    2010-01-01

    Background The number of Clare cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.Methods Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS+NAC group) oral intake of NAC 80 mg·kg~(-1)·d~(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The Mrna expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.Results Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3±14.7 vs. 53.7±11.5, P 0.05). No significant difference was found in the expression of CC16 Mrna among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r=-0.592, P<0.05), but not with GSH level.Conclusions One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16.

  17. Remodeling of bovine oviductal epithelium by mitosis of secretory cells.

    Science.gov (United States)

    Ito, Sayaka; Kobayashi, Yoshihiko; Yamamoto, Yuki; Kimura, Koji; Okuda, Kiyoshi

    2016-11-01

    Two types of oviductal epithelial cells, secretory and ciliated, play crucial roles in the first days after fertilization in mammals. Secretory cells produce various molecules promoting embryo development, while ciliated cells facilitate transport of oocytes and zygotes by ciliary beating. The proportions of the two cell types change during the estrous cycle. The proportion of ciliated cells on the oviductal luminal surface is abundant at the follicular phase, whereas the proportion of secretory cells gradually increases with the formation of the corpus luteum. In the present study, we hypothesize that the proportions of ciliated and secretory epithelial cells are regulated by mitosis. The proportion of the cells being positive for FOXJ1 (a ciliated cell marker) or Ki67 (a mitosis marker) in epithelial cells during the estrous cycle were immunohistochemically examined. Ki67 and FOXJ1 or PAX8 (a secretory cell marker), were double-stained to clarify which types of epithelial cells undergo mitosis. In the ampulla, the percentage of FOXJ1-positive cells was highest at the day of ovulation (Day 0) and decreased by about 50 % by Days 8-12, while in the isthmus it did not change during the estrous cycle. The proportion of Ki67-positive cells was highest at around the time of ovulation in both the ampulla and isthmus. All the Ki67-positive cells were PAX8-positive and FOXJ1-negative in both the ampulla and isthmus. These findings suggest that epithelial remodeling, which is regulated by differentiation and/or proliferation of secretory cells of the oviduct, provides the optimal environment for gamete transport, fertilization and embryonic development.

  18. Characterization of mast cell secretory granules and their cell biology.

    Science.gov (United States)

    Azouz, Nurit Pereg; Hammel, Ilan; Sagi-Eisenberg, Ronit

    2014-10-01

    Exocytosis and secretion of secretory granule (SG) contained inflammatory mediators is the primary mechanism by which mast cells exert their protective immune responses in host defense, as well as their pathological functions in allergic reactions and anaphylaxis. Despite their central role in mast cell function, the molecular mechanisms underlying the biogenesis and secretion of mast cell SGs remain largely unresolved. Early studies have established the lysosomal nature of the mast cell SGs and implicated SG homotypic fusion as an important step occurring during both their biogenesis and compound secretion. However, the molecular mechanisms that account for key features of this process largely remain to be defined. A novel high-resolution imaging based methodology allowed us to screen Rab GTPases for their phenotypic and functional impact and identify Rab networks that regulate mast cell secretion. This screen has identified Rab5 as a novel regulator of homotypic fusion of the mast cell SGs that thereby regulates their size and cargo composition.

  19. Startup, testing, and operation of the Santa Clara 2MW direct carbonate fuel cell demonstration plant

    Energy Technology Data Exchange (ETDEWEB)

    Skok, A.J.; Leo, A.J. [Fuel Cell Engineering Corp., Danbury, CT (United States); O`Shea, T.P. [Santa Clara Demonstration Project, CA (United States)

    1996-12-31

    The Santa Clara Demonstration Project (SCDP) is a collaboration between several utility organizations, Fuel Cell Engineering Corporation (FCE), and the U.S. Dept. Of Energy aimed at the demonstration of Energy Research Corporation`s (ERC) direct carbonate fuel cell (DFC) technology. ERC has been pursuing the development of the DFC for commercialization near the end of this decade, and this project is an integral part of the ERC commercialization effort. The objective of the Santa Clara Demonstration Project is to provide the first full, commercial scale demonstration of this technology. The approach ERC has taken in the commercialization of the DFC is described in detail elsewhere. An aggressive core technology development program is in place which is focused by ongoing interaction with customers and vendors to optimize the design of the commercial power plant. ERC has selected a 2.85 MW power plant unit for initial market entry. Two ERC subsidiaries are supporting the commercialization effort: the Fuel Cell Manufacturing Corporation (FCMC) and the Fuel Cell Engineering Corporation (FCE). FCMC manufactures carbonate stacks and multi-stack modules, currently from its production facility in Torrington, CT. FCE is responsible for power plant design, integration of all subsystems, sales/marketing, and client services. FCE is serving as the prime contractor for the design, construction, and testing of the SCDP Plant. FCMC has manufactured the multi-stack submodules used in the DC power section of the plant. Fluor Daniel Inc. (FDI) served as the architect-engineer subcontractor for the design and construction of the plant and provided support to the design of the multi-stack submodules. FDI is also assisting the ERC companies in commercial power plant design.

  20. Unremitting Cell Proliferation in the Secretory Phase of Eutopic Endometriosis

    Science.gov (United States)

    Franco-Murillo, Yanira; Miranda-Rodríguez, José Antonio; Rendón-Huerta, Erika; Montaño, Luis F.; Cornejo, Gerardo Velázquez; Gómez, Lucila Poblano; Valdez-Morales, Francisco Javier; Gonzalez-Sanchez, Ignacio

    2014-01-01

    Objective: Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium. Design: Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle. Results: Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis. Conclusion: Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways. PMID:25194152

  1. Calcium dynamics in the secretory granules of neuroendocrine cells.

    Science.gov (United States)

    Alvarez, Javier

    2012-01-01

    Cellular Ca(2+)signaling results from a complex interplay among a variety of Ca(2+) fluxes going across the plasma membrane and across the membranes of several organelles, together with the buffering effect of large numbers of Ca(2+)-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic reticulum, mitochondria and even nucleus have all been involved in cellular Ca(2+) signaling, and the mechanisms for Ca(2+) uptake and release from these organelles are well known. In neuroendocrine cells, the secretory granules also constitute a very important Ca(2+)-storing organelle, and the possible role of the stored Ca(2+) as a trigger for secretion has attracted considerable attention. However, this possibility is frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the main questions related with granular Ca(2+) dynamics, e.g., the free granular [Ca(2+)], the physical state of the stored Ca(2+) or the mechanisms for Ca(2+) accumulation and release from the granules. This review will give a critical overview of the present state of knowledge and the main conflicting points on secretory granule Ca(2+) homeostasis in neuroendocrine cells.

  2. Tissue-specific expression, hormonal regulation and 5'-flanking gene region of the rat Clara cell 10 kDa protein: comparison to rabbit uteroglobin.

    Science.gov (United States)

    Hagen, G; Wolf, M; Katyal, S L; Singh, G; Beato, M; Suske, G

    1990-01-01

    The amino acid sequence of rat Clara Cell 10 kDa secretory protein (CC10) shows 55% identity to rabbit uteroglobin. In order to define the relationship between rat CC10 and rabbit uteroglobin in detail, the tissue-specific expression and hormonal regulation of rat CC10 mRNA was analyzed. We report that like rabbit uteroglobin, rat CC10 mRNA is expressed in lung and esophagus, as well as in uteri of estrogen- and progesterone-treated females. Expression of CC10 mRNA in lung is regulated by glucocorticoids. The similarity in expression pattern of rat CC10 mRNA and rabbit uteroglobin mRNA is reflected by a striking similarity in the 5'-flanking regions of the two genes. Despite this overall similarity, two regions of 0.3 kb and 2.1 kb are absent in the rat CC10 upstream gene region. The larger region includes a cluster of hormone receptor binding sites, believed to be responsible for differential regulation of rabbit uteroglobin by glucocorticoids and progesterone. Thus, while the sequence identities in the coding and 5'-flanking regions point towards a common ancestor for the uteroglobin and CC10 gene, later events (deletions/insertions) might have caused species-specific differences in their regulation. Images PMID:2349092

  3. Epithelial Cell Culture from Human Adenoids: A Functional Study Model for Ciliated and Secretory Cells

    Directory of Open Access Journals (Sweden)

    Claudia González

    2013-01-01

    Full Text Available Background. Mucociliary transport (MCT is a defense mechanism of the airway. To study the underlying mechanisms of MCT, we have both developed an experimental model of cultures, from human adenoid tissue of ciliated and secretory cells, and characterized the response to local chemical signals that control ciliary activity and the secretion of respiratory mucins in vitro. Materials and Methods. In ciliated cell cultures, ciliary beat frequency (CBF and intracellular Ca2+ levels were measured in response to ATP, UTP, and adenosine. In secretory cultures, mucin synthesis and secretion were identified by using immunodetection. Mucin content was taken from conditioned medium and analyzed in the presence or absence of UTP. Results. Enriched ciliated cell monolayers and secretory cells were obtained. Ciliated cells showed a basal CBF of 10.7 Hz that increased significantly after exposure to ATP, UTP, or adenosine. Mature secretory cells showed active secretion of granules containing different glycoproteins, including MUC5AC. Conclusion. Culture of ciliated and secretory cells grown from adenoid epithelium is a reproducible and feasible experimental model, in which it is possible to observe ciliary and secretory activities, with a potential use as a model to understand mucociliary transport control mechanisms.

  4. Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers.

    Science.gov (United States)

    Romberg, Kerstin; Bjermer, Leif; Tufvesson, Ellen

    2011-01-01

    Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11β-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11β-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11β-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11β-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge. Copyright © 2010 Elsevier Ltd. All rights reserved.

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  7. Partitioning and Exocytosis of Secretory Granules during Division of PC12 Cells

    Directory of Open Access Journals (Sweden)

    Nickolay Vassilev Bukoreshtliev

    2012-01-01

    Full Text Available The biogenesis, maturation, and exocytosis of secretory granules in interphase cells have been well documented, whereas the distribution and exocytosis of these hormone-storing organelles during cell division have received little attention. By combining ultrastructural analyses and time-lapse microscopy, we here show that, in dividing PC12 cells, the prominent peripheral localization of secretory granules is retained during prophase but clearly reduced during prometaphase, ending up with only few peripherally localized secretory granules in metaphase cells. During anaphase and telophase, secretory granules exhibited a pronounced movement towards the cell midzone and, evidently, their tracks colocalized with spindle microtubules. During cytokinesis, secretory granules were excluded from the midbody and accumulated at the bases of the intercellular bridge. Furthermore, by measuring exocytosis at the single granule level, we showed, that during all stages of cell division, secretory granules were competent for regulated exocytosis. In conclusion, our data shed new light on the complex molecular machinery of secretory granule redistribution during cell division, which facilitates their release from the F-actin-rich cortex and active transport along spindle microtubules.

  8. Immunohistochemical demonstration of Clara cell antigen in lung tumors of bronchiolar origin induced by N-nitrosodiethylamine in Syrian golden hamsters.

    Science.gov (United States)

    Rehm, S.; Takahashi, M.; Ward, J. M.; Singh, G.; Katyal, S. L.; Henneman, J. R.

    1989-01-01

    Both alveolar type II cells and Clara cells have been suggested as cells of origin of human bronchioloalveolar lung carcinomas and other pulmonary neoplasms, based on the presence of cell specific markers identified by immunocytochemical methods. Alveolar type II cell origin of solid and papillary lung tumors of the mouse has been demonstrated, and Clara cells have been suggested as cell of origin for hamster pulmonary neoplasms. Therefore, chemically induced bronchiolar hyperplasias and pulmonary neoplasms of Syrian golden hamsters were analyzed by avidin-biotin immunohistochemistry to localize a hamster-specific Clara cell antigen (CCA) and keratin. The hamsters had been treated subcutaneously with multiple doses of N-nitrosodiethylamine (NDEA). Proliferative lesions of low cuboidal, tall columnar, or pleomorphic cells were present within bronchioles or adjacent to airways in the alveolar parenchyma. Frequently areas of squamous cell differentiation were present focally or diffusely that were immunoreactive for cytokeratin. Immunoreactivity for cytokeratin was also noted for hyperplastic bronchiolar neuroepithelial bodies. Cellular hyperplasias extending out into the alveolar parenchyma contained ciliated cells and frequently consisted of cells immunoreactive for CCA, showing them to be of bronchiolar Clara cell origin. Tumors developed from bronchiolar cell hyperplasias localized within bronchioles and from bronchiolar cells lining former alveolar walls. Neoplastic growth patterns were tubulo-papillary, forming loose networks or densely cellular areas. Immunoreactivity for cytoplasmic CCA was found in 50% of the tumors and was seen most frequently in small cuboidal cells and larger, vacuolated cells scattered throughout the neoplasms. In summary, evidence is presented that NDEA-induced pulmonary tumors of the Syrian golden hamster originated from cells lining bronchioles and from extrabronchiolar Clara cell hyperplasias of the terminal bronchioles. As the

  9. Immunocytochemical localization of the surfactant apoprotein and Clara cell antigen in chemically induced and naturally occurring pulmonary neoplasms of mice.

    Science.gov (United States)

    Ward, J. M.; Singh, G.; Katyal, S. L.; Anderson, L. M.; Kovatch, R. M.

    1985-01-01

    The localization of surfactant apoprotein (SAP) and the Clara cell antigen(s) (CCA) was studied in naturally occurring and experimentally induced pulmonary hyperplasias and neoplasms by avidin-biotin peroxidase complex (ABC) immunocytochemistry. Lungs of B6C3F1 and A strain mice with naturally occurring lesions, B6C3F1 mice given injections of N-nitrosodiethylamine (DEN), BALB/c nu/nu or nu/+ mice exposed transplacentally on Day 16 of gestation to ethylnitrosourea (ENU), or BALB/c nu/+ mice exposed to ENU at 8-12 weeks of age were preserved in formalin or Bouin's fixative. After ABC immunocytochemistry, SAP was found in the cytoplasm of normal alveolar Type II cells; in the majority of cells in focal alveolar and solid hyperplasias originating in peribronchiolar or peripheral locations; and in solid, tubular, papillary, and mixed adenomas and carcinomas. The larger mixed-pattern neoplasms and small or large tubular neoplasms usually had the least number of cells with SAP. The majority of large papillary adenomas and carcinomas in BALB/c mice exposed to ENU and in untreated A strain mice contained SAP in the nuclei of many neoplastic cells but only in the cytoplasm of a few neoplastic cells. CCA was found in normal Clara cells of bronchi and bronchioles but not in any hyperplastic or neoplastic lesion of any mouse studied. This study provided immunocytochemical evidence that the vast majority of naturally occurring and experimentally induced pulmonary neoplasms of mice are alveolar Type II cell adenomas and carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:3883798

  10. Do Neural Cells Communicate with Endothelial Cells via Secretory Exosomes and Microvesicles?

    Directory of Open Access Journals (Sweden)

    Neil R. Smalheiser

    2009-01-01

    Full Text Available Neurons, glial, cells, and brain tumor cells tissues release small vesicles (secretory exosomes and microvesicles, which may represent a novel mechanism by which neuronal activity could influence angiogenesis within the embryonic and mature brain. If CNS-derived vesicles can enter the bloodstream as well, they may communicate with endothelial cells in the peripheral circulation and with cells concerned with immune surveillance.

  11. The use of lectins as markers for differentiated secretory cells in planarians.

    Science.gov (United States)

    Zayas, Ricardo M; Cebrià, Francesc; Guo, Tingxia; Feng, Junjie; Newmark, Phillip A

    2010-11-01

    Freshwater planarians have reemerged as excellent models to investigate mechanisms underlying regeneration. The introduction of molecular tools has facilitated the study of planarians, but cell- and tissue-specific markers are still needed to examine differentiation of most cell types. Here we report the utility of fluorescent lectin-conjugates to label tissues in the planarian Schmidtea mediterranea. We show that 16 lectin-conjugates stain planarian cells or tissues; 13 primarily label the secretory cells, their cytoplasmic projections, and terminal pores. Thus, we examined regeneration of the secretory system using lectin markers and functionally characterized two genes expressed in the secretory cells: marginal adhesive gland-1 (mag-1) and Smed-reticulocalbin1 (Smed-rcn1). RNAi knockdown of these genes caused a dramatic reduction of secretory cell lectin staining, suggesting a role for mag-1 and Smed-rcn1 in secretory cell differentiation. Our results provide new insights into planarian secretory system regeneration and add new markers for labeling several planarian tissues.

  12. Evaluation of beta-cell secretory capacity using glucagon-like peptide 1

    DEFF Research Database (Denmark)

    Vilsbøll, Tina; Nielsen, Mette Toft; Krarup, T

    2000-01-01

    Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients.......Beta-cell secretory capacity is often evaluated with a glucagon test or a meal test. However, glucagon-like peptide 1 (GLP-1) is the most insulinotropic hormone known, and the effect is preserved in type 2 diabetic patients....

  13. Histological and histochemical characterization of the secretory cells of Choeradoplana iheringi Graff, 1899 (Platyhelminthes: Tricladida: Terricola

    Directory of Open Access Journals (Sweden)

    S. A. de Souza

    Full Text Available The present study aims at providing a detailed description of the histology, as well as the first histochemical characterization, of the secretory cells of the epidermis, pharynx, and copulatory organs of Choeradoplana iheringi, in order to give further support to studies on the physiology of these organs. The secretory cells are distinguished on the basis of secretion morphology and its staining properties, using trichrome methods and histochemical reactions. Four cell types open through the epidermis of Ch. iheringi, three of them secreting basic protein and a fourth containing glycosaminoglycan mucins. The epidermal lining cells store glycogen. In the pharynx, four secretory cell types were distinguished. Two types produce glycoprotein, a third type secretes basic protein, and another one produces glycosaminoglycan mucins. In the male copulatory organs, the prostatic vesicle receives four secretory cell types containing basic protein, except for one type which produces glycoprotein. The two secretory cell types opening into the male atrium secrete, respectively, glycoprotein, and glycosaminoglycan mucins. In the female copulatory organs, the female atrium and its proximal diverticulum, the vagina, receive two types of secretory cells producing, respectively, basic protein and glycosaminoglycan mucins. Another secretory cell type constitutes the so-called shell glands which open into the common glandular duct, secreting basic protein. The lining cells of the male and female atria produce a mucous secretion containing glycosaminoglycans. In addition, the lining epithelium of the female atrium presents an apical secretion of a proteic nature. The occurrence of a kind of spermatophore is reported for the first time for a species of Choeradoplana. This structure is located in the male or female atria in different specimens, and characterized by erythrophil, xanthophil, and/or mixed secretions associated with sperm.

  14. Modulation of dendritic cell function by Trichomonas vaginalis-derived secretory products.

    Science.gov (United States)

    Song, Min-Ji; Lee, Jong-Joo; Nam, Young Hee; Kim, Tae-Gyun; Chung, Youn Wook; Kim, Mikyoung; Choi, Ye-Eun; Shin, Myeong Heon; Kim, Hyoung-Pyo

    2015-02-01

    Trichomoniasis caused by the parasitic protozoan Trichomonas vaginalis is the most common sexually transmitted disease in the world. Dendritic cells are antigen presenting cells that initiate immune responses by directing the activation and differentiation of naïve T cells. In this study, we analyzed the effect of Trichomonas vaginalis-derived Secretory Products on the differentiation and function of dendritic cells. Differentiation of bone marrow-derived dendritic cells in the presence of T. vaginalis-derived Secretory Products resulted in inhibition of lipopolysaccharide-induced maturation of dendritic cells, down-regulation of IL-12, and up-regulation of IL-10. The protein components of T. vaginalis-derived Secretory Products were shown to be responsible for altered function of bone marrow- derived dendritic cells. Chromatin immunoprecipitation assay demonstrated that IL-12 expression was regulated at the chromatin level in T. vaginalis-derived Secretory Productstreated dendritic cells. Our results demonstrated that T. vaginalis- derived Secretory Products modulate the maturation and cytokine production of dendritic cells leading to immune tolerance.

  15. The cell outgrowth secretory endosome (COSE): a specialized compartment involved in neuronal morphogenesis.

    Science.gov (United States)

    Alberts, Philipp; Galli, Thierry

    2003-10-01

    The role of intracellular membrane trafficking in cellular morphogenesis is still unclear. We propose here a prominent function of a recently identified compartment that we propose to call the cell outgrowth secretory endosome (COSE), the exocytosis of which is controlled by the v-SNARE TIVAMP and by cell-cell adhesion.

  16. Localization of Cyclo-Oxygenase and Prostaglandin E2 in the Secretory Granule of the Mast Cell

    Science.gov (United States)

    1989-01-01

    cascade during exocytosis. Keywords: Cyclo-oxygenase; Prostaglandin E2; Secretory granules; Mast cell ; Exocytosis; Lipid mediators; Inflammation; Arachidonic acid; Eicosanoids; Immunocytochemistry; Reprints. (KT)

  17. Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells

    DEFF Research Database (Denmark)

    Poulsen, Mona Dam; Hansen, Gert Helge; Dabelsteen, Erik

    1993-01-01

    Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part...... labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein...

  18. The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium.

    Science.gov (United States)

    Rawlins, Emma L; Okubo, Tadashi; Xue, Yan; Brass, David M; Auten, Richard L; Hasegawa, Hiroshi; Wang, Fan; Hogan, Brigid L M

    2009-06-05

    To directly test the contribution of Scgb1a1(+) Clara cells to postnatal growth, homeostasis, and repair of lung epithelium, we generated a Scgb1a1-CreER "knockin" mouse for lineage-tracing these cells. Under all conditions tested, the majority of Clara cells in the bronchioles both self-renews and generates ciliated cells. In the trachea, Clara cells give rise to ciliated cells but do not self-renew extensively. Nevertheless, they can contribute to tracheal repair. In the postnatal mouse lung, it has been proposed that bronchioalveolar stem cells (BASCs) which coexpress Scgb1a1 (Secretoglobin1a1) and SftpC (Surfactant Protein C), contribute descendants to both bronchioles and alveoli. The putative BASCs were lineage labeled in our studies. However, we find no evidence for the function of a special BASC population during postnatal growth, adult homeostasis, or repair. Rather, our results support a model in which the trachea, bronchioles, and alveoli are maintained by distinct populations of epithelial progenitor cells.

  19. Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasis

    DEFF Research Database (Denmark)

    Carobbio, Stefania; Frigerio, Francesca; Rubi, Blanca

    2009-01-01

    Insulin exocytosis is regulated in pancreatic ss-cells by a cascade of intracellular signals translating glucose levels into corresponding secretory responses. The mitochondrial enzyme glutamate dehydrogenase (GDH) is regarded as a major player in this process, although its abrogation has not bee...... weight gain was preserved. The results demonstrate that GDH is essential for the full development of the secretory response in beta-cells. However, maximal secretory capacity is not required for maintenance of glucose homeostasis in normo-caloric conditions....

  20. Rab3D is critical for secretory granule maturation in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Tanja Kögel

    Full Text Available Neuropeptide- and hormone-containing secretory granules (SGs are synthesized at the trans-Golgi network (TGN as immature secretory granules (ISGs and complete their maturation in the F-actin-rich cell cortex. This maturation process is characterized by acidification-dependent processing of cargo proteins, condensation of the SG matrix and removal of membrane and proteins not destined to mature secretory granules (MSGs. Here we addressed a potential role of Rab3 isoforms in these maturation steps by expressing their nucleotide-binding deficient mutants in PC12 cells. Our data show that the presence of Rab3D(N135I decreases the restriction of maturing SGs to the F-actin-rich cell cortex, blocks the removal of the endoprotease furin from SGs and impedes the processing of the luminal SG protein secretogranin II. This strongly suggests that Rab3D is implicated in the subcellular localization and maturation of ISGs.

  1. Intestinal Mucus Gel and Secretory Antibody are Barriers to Campylobacter jejuni Adherence to INT 407 Cells

    Science.gov (United States)

    1987-06-01

    An in vitro mucus assay was developed to study the role of mucus gel and secretory immunoglobulin A (sIgA) in preventing attachment of Campylobacter ... jejuni to INT 407 cells. An overlay of rabbit small intestinal mucus was found to impede the attachment of C. jejuni to a monolayer of INT 407 cells

  2. Network reconstruction of the mouse secretory pathway applied on CHO cell transcriptome data

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Kaas, Christian Schrøder; Brandl, Julian

    2017-01-01

    of the literature on the yeast, human, and mouse secretory pathway, we have compiled a comprehensive catalogue of characterized proteins with functional annotation and their interconnectivity. Thus we have established the most elaborate reconstruction (RECON) of the functional secretion pathway network to date...... regulation of protein secretion than healthy mouse cells.  Conclusions: The RECON of the secretory pathway represents a strong tool for interpretation of data related to protein secretion as illustrated with transcriptomic data of Chinese Hamster Ovary (CHO) cells, the main platform for mammalian protein...

  3. Zinc transport complexes contribute to the homeostatic maintenance of secretory pathway function in vertebrate cells.

    Science.gov (United States)

    Ishihara, Kaori; Yamazaki, Tomohiro; Ishida, Yoko; Suzuki, Tomoyuki; Oda, Kimimitsu; Nagao, Masaya; Yamaguchi-Iwai, Yuko; Kambe, Taiho

    2006-06-30

    Zinc transporters play important roles in a wide range of biochemical processes. Here we report an important function of ZnT5/ZnT6 hetero-oligomeric complexes in the secretory pathway. The activity of human tissue-nonspecific alkaline phosphatase (ALP) expressed in ZnT5(-)ZnT7(-/-) cells was significantly reduced compared with that expressed in wild-type cells as in the case of endogenous chicken tissue-nonspecific ALP activity. The inactive human tissue-nonspecific ALP in ZnT5(-)ZnT7(-/-) cells was degraded by proteasome-mediated degradation without being trafficked to the plasma membrane. ZnT5(-)ZnT7(-/-) cells showed exacerbation of the unfolded protein response as did the wild-type cells cultured under a zinc-deficient condition, revealing that both complexes play a role in homeostatic maintenance of secretory pathway function. Furthermore, we showed that expression of ZnT5 mRNA was up-regulated by the endoplasmic reticulum stress in various cell lines. The up-regulation of the hZnT5 transcript was mediated by transcription factor XBP1 through the TGACGTGG sequence in the hZnT5 promoter, and this sequence was highly conserved in the ZnT5 genes of mouse and chicken. These results suggest that zinc transport into the secretory pathway is strictly regulated for the homeostatic maintenance of secretory pathway function in vertebrate cells.

  4. The Role of Adenoid Mast Cells in the Pathogenesis of Secretory Otitis Media

    Directory of Open Access Journals (Sweden)

    M. Faruk Oktay

    2007-01-01

    Full Text Available To investigate the possible role of adenoid mast cells in the etiology of secretory otitis media. Between 2001-2002, 25 patients with chronic adenoitis and chronic secretory otitis media and 25 patients with isolated adenoid hypertrophy were included to the study. Adenoidectomy performed to the all patients under general anesthesia. Adenoidectomy specimens were evaluated under the light microscopy and the number of mast cells were calculated for each patient. The number of mast cells were compared between two groups. The number of mast cells were between 4-84 in the otitis media with effusion and adenoid hypertrophy group (median:52, however it was between 2-63 (median: 23 in the isolated adenoid hypertrophy group. When comparing the two groups using Mann-Withney U test, the number of mast cells found to be significantly higher in the chronic secretory otitis media group (p<0.001.Based on our findings there is a relationship between increased adenoid mast cells and otitis media with effusion and these cells may have a possible role in the etiology of chronic secretory otitis media.

  5. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

    Directory of Open Access Journals (Sweden)

    Gianni García-Faroldi

    Full Text Available BACKGROUND: Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG present within the granules. Polyamines (putrescine, spermidine and spermine are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules. METHODOLOGY/PRINCIPAL FINDINGS: Spermidine was released by mouse bone marrow derived mast cells (BMMCs after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  6. File list: InP.Utr.05.AllAg.Fallopian_tube_secretory_epithelial_cell [Chip-atlas[Archive

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  14. Synthesis of Prostaglandins and Eicosanoids by the Mast Cell Secretory Granule

    Science.gov (United States)

    1988-01-01

    constituents of the so-called "slow reacting substance of anaphylaxis" (SRS-A) (1,3). Like many other cell types, the mast cell can incorporate exogenous...arachidonic acid into its cellular phospholipid. The stimulation of mast cells which have been pre-loaded with radioactive arachidonic acid can result in...synthesis of eicosanoids has not been identified. Recently, we found that the secretory granule of the quiescent mast cell contains a large amount of matrix

  15. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Steffen Nyegaard

    Full Text Available Secretory phospholipase A2 (sPLA2 is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2's do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50-60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2.

  16. Secretory leukocyte proteinase inhibitor-competent DNA deposits are potent stimulators of plasmacytoid dendritic cells

    DEFF Research Database (Denmark)

    Skrzeczynska-Moncznik, Joanna; Wlodarczyk, Agnieszka; Zabieglo, Katarzyna

    2012-01-01

    Secretory leukocyte proteinase inhibitor (SLPI) is a well-established inhibitor of serine proteases such as human neutrophil elastase (HNE) and a NF-κB regulatory agent in immune cells. In this paper, we report that SLPI plays a previously uncharacterized role in regulating activation of plasmacy...

  17. Nuclear DNA content and ultrastructure of secretory cells of Vicia faba L. stigma

    Directory of Open Access Journals (Sweden)

    Bogdan Wróbel

    2014-01-01

    Full Text Available The object of study was the level of nuclear DNA and the ultrastructural transformations in the secretory cells of the stigma in Vicia faba L. It has been found that the stigmal cells which are active in biogenesis and exudate secretion are diploid cells whose differentiation starts from 2C DNA level. The presence of a population of nuclei with an amount DNA of about 2.5 C suggests that the metabolic activity of those cells may be regulated through supplementary incomplete replication. The ultrastructural transformations of secretory cells point to three stages of biogenesis and secretion of exudate. Stage I, before the start of the cell's secretory functions, is characterized by the development of the protein synthesizing apparatus and the activity of dictyosomes. In development stage II vesicular electron-transparent exudate is secreted. Stage III of exudate biogenesis is production of lipids. They form mainly in the plastids and are secreted with the involvement of the cell's vacuolar system.

  18. Kinetic evaluation of cell membrane hydrolysis during apoptosis by human isoforms of secretory phospholipase A2.

    OpenAIRE

    Olson, Erin D.; Nelson, Jennifer; Griffith, Katalyn; Nguyen, Thaothanh; Streeter, Michael; Wilson-Ashworth, Heather A.; Michael H Gelb; Judd, Allan M.; Bell, John D.

    2010-01-01

    Some isoforms of secretory phospholipase A2 (sPLA2) distinguish between healthy and damaged or apoptotic cells. This distinction reflects differences in membrane physical properties. Because various sPLA2 isoforms respond differently to properties of artificial membranes such as surface charge, they should also behave differently as these properties evolve during a dynamic physiological process such as apoptosis. To test this idea, S49 lymphoma cell death was induced by glucocorticoid (6–48 h...

  19. p172: An alveolar type II and Clara cell specific protein with late developmental expression and upregulation by hyperoxic lung injury.

    Science.gov (United States)

    Girod, C E; Shin, D H; Hershenson, M B; Solway, J; Dahl, R; Miller, Y E

    1996-06-01

    The epithelium of the alveolus and distal airway meets unique requirements, functioning as a gas exchange membrane and barrier to alveolar flooding by vascular contents as well as to bloodstream contamination by airborne toxins and pathogens. Gene products specifically expressed by this epithelium, notably the surfactant apoproteins, have had important clinical application. No cell surface antigen specific for alveolar type II and Clara cells has been described. We report the biochemical characterization, tissue and developmental expression, and upregulation by injury of a 172 kD protein recognized by a monoclonal antibody, 3F9, synthesized in response to immunization with freshly isolated rat alveolar type II cells. p172 is expressed in a polarized fashion by the apical surface of rat alveolar type II and Clara cells. An immunohistochemical survey of various rat tissues and organs reveals lung specificity. p172 is first detectable in rare epithelial cells at 19 days of gestation, a time when the fully differentiated alveolar type II cell is identified by the first detection of lamellar bodies. There is a dramatic increase in p172 expression just prior to birth. Hyperoxic lung injury results in increased expression of p172. The upregulation of p172 by hyperoxia and its cell-specific expression suggests an important adaptive function.

  20. Could the gene coding for human uteroglobin (clara cell 10 kDa protein) be a candidate gene for atopy?

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, A.B.; Peri, A.; Miele, L. [SDG, Bethesda, MD (United States)] [and others

    1994-09-01

    It has been proposed that human immune response to allergens is genetically determined. Most of these allergic responses are directed to environmental proteins and are mediated by immunoglobulin E (IgE). These allergic disorders (eg. allergic asthma) are commonly known as atopy. IgE activates phospholipase A{sub 2} (PLA{sub 2}) which hydrolyzes cell membrane phospholipids generating free fatty acids, such as arachidonic acid (AA). AA is utilized as the substrate for the generation of pro-inflammatory eicosanoids and platelet activating factor (PAF). These agents can cause inflammation as well as bronchoconstriction, hallmarks of asthma. IgE-induced mast cell degranulation and accumulation of basophils and eosinophils in the lung are also characteristic immunological processes commonly found in atopic asthma. Recent investigations suggest that a group I PLA{sub 2} may be associated with the secretory granules of these cells. An inverse relationship between the levels of eicosanoids and hUG has been found in the nasopharyngeal lavage fluid of children with viral infections of the upper respiratory tract, often a precipitating factor in asthma. Results of genetic linkage studies mapped a putative atopy gene in human chromosome 11q{sup 13}, the same region in which we localized the hUG gene. Moreover, a genetic linkage between atopic IgE responses and chromosome 11q{sup 13} has been reported. In addition, hUG is: (i) a potent inhibitor of PLA{sub 2} activity, (ii) a potent antiinflammatory/immunomodulatory and antichemotactic protein and has a hitherto undetermined receptor-mediated activity. Taken together, these findings suggest that a mutation either in the hUG or its receptor genes may manifest symptoms characteristic of atopy. Hence, we raise the question whether hUG is a candidate gene for this disease.

  1. The secretory peptide gene EPF1 enforces the stomatal one-cell-spacing rule.

    Science.gov (United States)

    Hara, Kenta; Kajita, Ryoko; Torii, Keiko U; Bergmann, Dominique C; Kakimoto, Tatsuo

    2007-07-15

    Stomata are innovations of land plants that allow regulated gas exchange. Stomatal precursor cells are produced by asymmetric cell division, and once formed, signal their neighbors to inhibit the formation of stomatal precursors in direct contact. We report a gene of Arabidopsis thaliana, EPIDERMAL PATTERNING FACTOR 1 (EPF1) that encodes a small secretory peptide expressed in stomatal cells and precursors and that controls stomatal patterning through regulation of asymmetric cell division. EPF1 activity is dependent on the TOO MANY MOUTHS receptor-like protein and ERECTA family receptor kinases, suggesting that EPF1 may provide a positional cue interpreted by these receptors.

  2. Intracellular ion concentrations and cell volume during cholinergic stimulation of eccrine secretory coil cells

    Energy Technology Data Exchange (ETDEWEB)

    Takemura, T.; Sato, F.; Saga, K.; Suzuki, Y.; Sato, K. (Univ. of Iowa College of Medicine, Iowa City (USA))

    1991-02-01

    Methacholine (MCh)-induced changes in intracellular concentrations of Na, K, and Cl (( Na)i, (K)i, and (Cl)i, respectively) and in cellular dry mass (a measure of cell shrinkage) were examined in isolated monkey eccrine sweat secretory coils by electron probe X-ray microanalysis using the peripheral standard method. To further confirm the occurrence of cell shrinkage during MCh stimulation, the change in cell volume of dissociated clear and dark cells were directly determined under a light microscope equipped with differential interference contrast (DIC) optics. X-ray microanalysis revealed a biphasic increase in cellular dry mass in clear cells during continuous MCh stimulation; an initial increase of dry mass to 158% (of control) followed by a plateau at 140%, which correspond to the decrease in cell volume of 37 and 29%, respectively. The latter agrees with the MCh-induced cell shrinkage of 29% in dissociated clear cells. The MCh-induced increase in dry mass in myoepithelial cells was less than half that of clear cells. During the steady state of MCh stimulation, both (K+)i and (Cl)i of clear cells decreased by about 45%, whereas (Na)i increased in such a way to maintain the sum of (Na) i + (K)i constant. There was a small (12-15 mM) increase in (Na)i and a decrease in (K)i in myoepithelial cells during stimulation with MCh. Dissociated dark cells failed to significantly shrink during MCh stimulation. The decrease in (Cl)i in the face of constant (Na)i + (K)i suggests the accumulation of unknown anion(s) inside the clear cell during MCh stimulation.

  3. Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells.

    Science.gov (United States)

    Kishida, Kunihiro; Pearce, Sarah C; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P

    2017-06-01

    Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers. We identified nutrient sensing cell type(s) by increased expression of fructolytic genes in response to a fructose challenge. Organoids comprised primarily of enterocytes, Paneth, or goblet, but not ISC, cells responded specifically to fructose without affecting nonfructolytic genes. Sensing was independent of Wnt and Notch modulators and of glucose concentrations in the medium but required fructose absorption and metabolism. More mature enterocyte- and goblet-enriched organoids exhibited stronger fructose responses. Remarkably, enterocyte organoids, upon forced dedifferentiation to reacquire ISC characteristics, exhibited a markedly extended lifespan and retained fructose sensing ability, mimicking responses of some dedifferentiated cancer cells. Using an innovative approach, we discovered that nutrient sensing is likely repressed in progenitor ISCs then irreversibly derepressed during specification into sensing-competent absorptive or secretory lineages, the surprising capacity of Paneth and goblet cells to detect fructose, and the important role of differentiation in modulating nutrient sensing.NEW & NOTEWORTHY Small intestinal stem cells differentiate into several

  4. Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length.

    Science.gov (United States)

    Schott, Daniel H; Collins, Ruth N; Bretscher, Anthony

    2002-01-01

    Myosins are molecular motors that exert force against actin filaments. One widely conserved myosin class, the myosin-Vs, recruits organelles to polarized sites in animal and fungal cells. However, it has been unclear whether myosin-Vs actively transport organelles, and whether the recently challenged lever arm model developed for muscle myosin applies to myosin-Vs. Here we demonstrate in living, intact yeast that secretory vesicles move rapidly toward their site of exocytosis. The maximal speed varies linearly over a wide range of lever arm lengths genetically engineered into the myosin-V heavy chain encoded by the MYO2 gene. Thus, secretory vesicle polarization is achieved through active transport by a myosin-V, and the motor mechanism is consistent with the lever arm model.

  5. Reversal by EGTA of the enhanced secretory responsiveness of mast cells due to treatment with ouabain

    DEFF Research Database (Denmark)

    Johansen, Torben; Knudsen, T; Bertelsen, Niels Haldor

    1990-01-01

    The effect of EGTA on the enhancement by ouabain of compound 48/80-induced secretion from mast cells was compared with the effect on the Na(+)-K+ pump activity. The time-dependent secretory enhancement by ouabain was blocked by addition of EGTA to the cell suspension concomitantly with the addition...... of ouabain, and EGTA caused a large increase in the pump activity. Addition of 10 microM EGTA to ouabain-treated cells stopped but did not reverse the enhancement. The experiments show that the effect of ouabain was due to changes in a calcium pool utilized in compound 48/80-induced secretion following...

  6. The Ultrastructure of Secretory Cells of the Islets of Langerhans in South American Catfish Rhamdia quelen

    Directory of Open Access Journals (Sweden)

    Laura Luchini

    2015-01-01

    Full Text Available The present work shows that a detailed description of the ultrastructure of the secretory cells of the South American catfish Rhamdia quelen pancreatic islets is presented. Evidence is offered to support the contention that the α-granules consist of a central and an outer portion of different electron densities and solubilities, that the δ-cells are most probably morphologically altered but viable α-cells, and that the β-granules possibly possess a repeating substructure and may therefore represent an intracellular crystalline storage form of insulin.

  7. Monoclonal Antibodies as Probes for Unique Antigens in Secretory Cells of Mixed Exocrine Organs

    Science.gov (United States)

    Basbaum, C. B.; Mann, J. K.; Chow, A. W.; Finkbeiner, W. E.

    1984-07-01

    In the past, it has been difficult to identify the secretory product and control mechanisms associated with individual cell types making up mixed exocrine organs. This report establishes the feasibility of using immunological methods to characterize both the biochemical constituents and regulatory mechanisms associated with secretory cells in the trachea. Monoclonal antibodies directed against components of tracheal mucus were produced by immunizing mice with dialyzed, desiccated secretions harvested from tracheal organ culture. An immunofluorescence assay revealed that of the total 337 hybridomas screened, 100 produced antibodies recognizing goblet cell granules; 64, gland cell granules; and 3, antigen confined to the ciliated apical surface of the epithelium. The tracheal goblet cell antibody described in this report was strongly cross-reactive with intestinal goblet cells, as well as with a subpopulation of submandibular gland cells, but not with cells of Brunner's glands or the ciliated cell apical membrane. The serous cell antibody was not cross-reactive with goblet, Brunner's gland, or submandibular cells, or the ciliated cell apical membrane. The antibody directed against the apical membrane of ciliated cells did not cross-react with gland or goblet cells or the apical membrane of epithelial cells in the duodenum. Monoclonal antibodies, therefore, represent probes by which products unique to specific cells or parts of cells in the trachea can be distinguished. The antibodies, when used in enzyme immunoassays, can be used to quantitatively monitor secretion by individual cell types under a variety of physiological and pathological conditions. They also provide the means for purification and characterization of cell-specific products by immunoaffinity chromatography.

  8. Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

    DEFF Research Database (Denmark)

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte;

    2009-01-01

    in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep......Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study...... into the crypts. This cell population was also positive for lysozyme and alpha-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP...

  9. The Fas pathway is involved in pancreatic β cell secretory function

    Science.gov (United States)

    Schumann, Desiree M.; Maedler, Kathrin; Franklin, Isobel; Konrad, Daniel; Størling, Joachim; Böni-Schnetzler, Marianne; Gjinovci, Asllan; Kurrer, Michael O.; Gauthier, Benoit R.; Bosco, Domenico; Andres, Axel; Berney, Thierry; Greter, Melanie; Becher, Burkhard; Chervonsky, Alexander V.; Halban, Philippe A.; Mandrup-Poulsen, Thomas; Wollheim, Claes B.; Donath, Marc Y.

    2007-01-01

    Pancreatic β cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in β cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates β cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a β cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient β cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased β cell mass. Up-regulation of FLIP enhanced NF-κB activity via NF-κB-inducing kinase and RelB. This led to increased PDX-1 and insulin production independent of changes in cell turnover. The results support a previously undescribed role for the Fas pathway in regulating insulin production and release. PMID:17299038

  10. Spatial partitioning of secretory cargo from Golgi resident proteins in live cells

    Directory of Open Access Journals (Sweden)

    White Jamie

    2001-10-01

    Full Text Available Abstract Background To maintain organelle integrity, resident proteins must segregate from itinerant cargo during secretory transport. However, Golgi resident enzymes must have intimate access to secretory cargo in order to carry out glycosylation reactions. The amount of cargo and associated membrane may be significant compared to the amount of Golgi membrane and resident protein, but upon Golgi exit, cargo and resident are efficiently sorted. How this occurs in live cells is not known. Results We observed partitioning of the fluorescent Golgi resident T2-CFP and fluorescent cargo proteins VSVG3-YFP or VSVG3-SP-YFP upon Golgi exit after a synchronous pulse of cargo was released from the ER. Golgi elements remained stable in overall size, shape and relative position as cargo emptied. Cargo segregated from resident rapidly by blebbing into micron-sized domains that contained little or no detectable resident protein and that appeared to be continuous with the parent Golgi element. Post-Golgi transport carriers (TCs exited repeatedly from these domains. Alternatively, entire cargo domains exited Golgi elements, forming large TCs that fused directly with the plasma membrane. However, domain formation did not appear to be an absolute prerequisite for TC exit, since TCs also exited directly from Golgi elements in the absence of large domains. Quantitative cargo-specific photobleaching experiments revealed transfer of cargo between Golgi regions, but no discrete intra-Golgi TCs were observed. Conclusions Our results establish domain formation via rapid lateral partitioning as a general cellular strategy for segregating different transmembrane proteins along the secretory pathway and provide a framework for consideration of molecular mechanisms of secretory transport.

  11. De novo epidermal regeneration using human eccrine sweat gland cells: higher competence of secretory over absorptive cells.

    Science.gov (United States)

    Pontiggia, Luca; Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Oliveira, Carol; Braziulis, Erik; Klar, Agnieszka S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

    2014-06-01

    In our previous work, we showed that human sweat gland-derived epithelial cells represent an alternative source of keratinocytes to grow a near normal autologous epidermis. The role of subtypes of sweat gland cells in epidermal regeneration and maintenance remained unclear. In this study, we compare the regenerative potential of both secretory and absorptive sweat gland cell subpopulations. We demonstrate the superiority of secretory over absorptive cells in forming a new epidermis on two levels: first, the proliferative and colony-forming efficiencies in vitro are significantly higher for secretory cells (SCs), and second, SCs show a higher frequency of successful epidermis formation as well as an increase in the thickness of the formed epidermis in the in vitro and in vivo functional analyses using a 3D dermo-epidermal skin model. However, the ability of forming functional skin substitutes is not limited to SCs, which supports the hypothesis that multiple subtypes of sweat gland epithelial cells hold regenerative properties, while the existence and exact localization of a keratinocyte stem cell population in the human eccrine sweat gland remain elusive.

  12. Secretory clusterin inhibits osteoclastogenesis by attenuating M-CSF-dependent osteoclast precursor cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Bongkun; Kang, Soon-Suk [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Kang, Sang-Wook [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Min, Bon-Hong [Department of Pharmacology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Lee, Eun-Jin; Song, Da-Hyun; Kim, Sang-Min [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Song, Youngsup [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Yoon, Seung-Yong [Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Chang, Eun-Ju, E-mail: ejchang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Department of Anatomy and Cell Biology, Cell Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736 (Korea, Republic of)

    2014-07-18

    Highlights: • We describe the expression and secretion of clusterin in osteoclasts. • Endogenous clusterin deficiency does not affect osteoclast formation. • Exogenous treatment with secretory clusterin decreases osteoclast differentiation. • Secretory clusterin attenuates osteoclast precursor cell proliferation by inhibiting M-CSF-mediated ERK activation. - Abstract: Secretory clusterin (sCLU)/apolipoprotein J is a multifunctional glycoprotein that is ubiquitously expressed in various tissues. Reduced sCLU in the joints of patients with bone erosive disease is associated with disease activity; however, its exact role has yet to be elucidated. Here, we report that CLU is expressed and secreted during osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs) that are treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). CLU-deficient BMMs obtained from CLU{sup −/−} mice exhibited no significant alterations in OC differentiation in comparison with BMMs obtained from wild-type mice. In contrast, exogenous sCLU treatment significantly inhibited OC formation in both BMMs and OC precursor cultures. The inhibitory effect of sCLU was more prominent in BMMs than OC precursor cultures. Interestingly, treating BMMs with sCLU decreased the proliferative effects elicited by M-CSF and suppressed M-CSF-induced ERK activation of OC precursor cells without causing apoptotic cell death. This study provides the first evidence that sCLU reduces OC formation by inhibiting the actions of M-CSF, thereby suggesting its protective role in bone erosion.

  13. [Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance].

    Science.gov (United States)

    Popović, Ljiljana; Zamaklar, Miroslava; Lalić, Katarina; Vasović, Olga

    2006-01-01

    Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA beta index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA beta) and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA beta index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

  14. Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance

    Directory of Open Access Journals (Sweden)

    Popović Ljiljana

    2006-01-01

    Full Text Available Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA β index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA β and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA β index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

  15. Rab Proteins and the Secretory Pathway: The Case of Rab18 in Neuroendocrine Cells

    Directory of Open Access Journals (Sweden)

    RAFAEL eVAZQUEZ-MARTINEZ

    2011-01-01

    Full Text Available The secretory pathway is a process characteristic of cells specialized in secretion such as endocrine cells and neurons. It consists of different stages that are dependent on specific transport of proteins in vesicular-tubular carriers. Biochemical analyses have unveiled a number of protein families that confer identity to carrier vesicles and specificity to their transport. Among them is the family of Rab proteins, Ras-like small GTPases that anchor to the surface of transport vesicles and participate in vesicle formation from the donor compartment, transport along cytoskeletal tracks, and docking and fusion with the acceptor compartment. All of these functions are accomplished through the recruitment of effector proteins, such as sorting adaptors, tethering factors, kinases, phosphatases and motors. The numerous Rab proteins have distinct subcellular distributions throughout the endomembrane system, which ensures efficient cargo transfer. Rab proteins act as molecular switches that alternate between a cytosolic GDP-bound, inactive form and a membrane-associated GTP-bound, active conformation. Cycling between inactive and active states is a highly regulated process that enables Rabs to confer spatio-temporal precision to the different stages through which a vesicle passes during its lifespan. This review focuses on our current knowledge on Rab functioning, from their structural features to the multiple regulatory proteins and effectors that control Rab activity and translate Rab function. Furthermore, we also summarize the information available on a particular Rab protein, Rab18, which has been linked to the control of secretory granule traffic in neuroendocrine cells.

  16. Multiple effects of the phenylhydrazone derivative FCCP on the secretory pathway in rat plasma cells.

    Science.gov (United States)

    Antoine, J C; Jouanne, C

    1986-10-01

    We studied the sensitivity of the last steps of the secretory process of antibody-producing cells to carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) and sodium azide (NaN3), agents which lower the cellular ATP content by inhibiting oxidative phosphorylation and mitochondrial electron transport, respectively. Popliteal lymph node cells or purified plasma cells from rats immunized against horseradish peroxidase were incubated with the drugs. The rate of secretion of anti-HRP antibodies was measured by an enzyme-linked immunoadsorbent assay or after biosynthetic labeling with L-[3H]fucose. FCCP as well as NaN3 were shown to rapidly inhibit (in less than 5 min) the secretion of immunoglobulins (Ig) and to partially block the release of fucosylated Ig. This indicates that the drugs inhibit the transport of Ig from the Golgi apparatus (GA) (where fucose is added to Ig) to the plasma membrane. However, the degree of inhibition reached 40 to 50% with NaN3 and 70 to 80% with FCCP, whereas both drugs similarly depleted ATP stores by 45 to 55%. These results are consistent with multiple effects of FCCP on the secretion pathway of Ig. As a tentative explanation, we suggest that FCCP, because of its protonophore properties, not only reduces cellular ATP levels but may also neutralize the Golgi or post-Golgi acidic compartments recently shown to be involved in the transport of plasma membrane and secretory proteins.

  17. Calcineurin is universally involved in vesicle endocytosis at neuronal and nonneuronal secretory cells.

    Science.gov (United States)

    Wu, Xin-Sheng; Zhang, Zhen; Zhao, Wei-Dong; Wang, Dongsheng; Luo, Fujun; Wu, Ling-Gang

    2014-05-22

    Calcium influx triggers and accelerates endocytosis in nerve terminals and nonneuronal secretory cells. Whether calcium/calmodulin-activated calcineurin, which dephosphorylates endocytic proteins, mediates this process is highly controversial for different cell types, developmental stages, and endocytic forms. Using three preparations that previously produced discrepant results (i.e., large calyx-type synapses, conventional cerebellar synapses, and neuroendocrine chromaffin cells containing large dense-core vesicles), we found that calcineurin gene knockout consistently slowed down endocytosis, regardless of cell type, developmental stage, or endocytic form (rapid or slow). In contrast, calcineurin and calmodulin blockers slowed down endocytosis at a relatively small calcium influx, but did not inhibit endocytosis at a large calcium influx, resulting in false-negative results. These results suggest that calcineurin is universally involved in endocytosis. They may also help explain the discrepancies among previous pharmacological studies. We therefore suggest that calcineurin should be included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis.

  18. Regulation by L channels of Ca(2+)-evoked secretory responses in ouabain-treated chromaffin cells.

    Science.gov (United States)

    De Pascual, Ricardo; Colmena, Inés; Ruiz-Pascual, Lucía; Baraibar, Andrés Mateo; Egea, Javier; Gandía, Luis; García, Antonio G

    2016-10-01

    It is known that the sustained depolarisation of adrenal medullary bovine chromaffin cells (BCCs) with high K(+) concentrations produces an initial sharp catecholamine release that subsequently fades off in spite depolarisation persists. Here, we have recreated a sustained depolarisation condition of BCCs by treating them with the Na(+)/K(+) ATPase blocker ouabain; in doing so, we searched experimental conditions that permitted the development of a sustained long-term catecholamine release response that could be relevant during prolonged stress. BCCs were perifused with nominal 0Ca(2+) solution, and secretion responses were elicited by intermittent application of short 2Ca(2+) pulses (Krebs-HEPES containing 2 mM Ca(2+)). These pulses elicited a biphasic secretory pattern with an initial 30-min period with secretory responses of increasing amplitude and a second 30-min period with steady-state, non-inactivating responses. The initial phase was not due to gradual depolarisation neither to gradual increases of the cytosolic calcium transients ([Ca(2+)]c) elicited by 2Ca(2+) pulses in BBCs exposed to ouabain; both parameters increased soon after ouabain addition. Νifedipine blocked these responses, and FPL64176 potentiated them, suggesting that they were triggered by Ca(2+) entry through non-inactivating L-type calcium channels. This was corroborated by nifedipine-evoked blockade of the L-type Ca(2+) channel current and the [Ca(2+)]c transients elicited by 2Ca(2+) pulses. Furthermore, the plasmalemmal Na(+)/Ca(2+) exchanger (NCX) blocker SEA0400 caused a mild inhibition followed by a large rebound increase of the steady-state secretory responses. We conclude that these two phases of secretion are mostly contributed by Ca(2+) entry through L calcium channels, with a minor contribution of Ca(2+) entry through the reverse mode of the NCX.

  19. An FNA pitfall: Mammary analog secretory carcinoma mistaken for acinic cell carcinoma due to cytoplasmic granules

    Directory of Open Access Journals (Sweden)

    Nouf Hijazi, MD

    2014-12-01

    Full Text Available In the salivary gland, a key differential feature of Mammary analog secretory carcinoma (MASC from acinic cell carcinoma (ACC is the lack of cytoplasmic granules. We report a case of a parotid mass incorrectly diagnosed on fine needle aspirate as acinic cell carcinoma due to many cells with basophilic granules suggesting serous acinar differention. Tumor resection revealed a tumor consistent with low grade adenocarcinoma that had eosinophilic, microvacuolar cytoplasm with distinct basophilic granules staining with PASD and mucicarmine. The diagnosis of MASC was confirmed with stains for GCDF-15, mammoglobin, and S100 and FISH consistent with a t(12;15 translocation. Relying on the absence of cytoplasmic granules as a feature to distinguish ACC from MASC is a diagnostic pitfall.

  20. Mitochondrial calcium in the life and death of exocrine secretory cells.

    Science.gov (United States)

    Voronina, Svetlana; Tepikin, Alexei

    2012-07-01

    The remarkable recent discoveries of the proteins mediating mitochondrial Ca(2+) transport (reviewed in this issue) provide an exciting opportunity to utilise this new knowledge to improve our fundamental understanding of relationships between Ca(2+) signalling and bioenergetics and, importantly, to improve the understanding of diseases in which Ca(2+) toxicity and mitochondrial malfunction play a crucial role. Ca(2+) is an important activator of exocrine secretion, a regulator of the bioenergetics of exocrine cells and a contributor to exocrine cell damage. Exocrine secretory cells, exocrine tissues and diseases affecting exocrine glands (like Sjögren's syndrome and acute pancreatitis) will, therefore, provide worthy research areas for the application of this new knowledge of the Ca(2+) transport mechanisms in mitochondria.

  1. Extracellular magnesium decreases the secretory response of rat peritoneal mast cells to compound 48/80 in vitro

    DEFF Research Database (Denmark)

    Bertelsen, Niels Haldor; Johansen, Torben

    1991-01-01

    Exposure of rat peritoneal mast cells to magnesium in the absence of extracellular calcium resulted in a time- and dose-dependent decrease in the secretory response induced by compound 48/80. The decrease was prevented by a low extracellular concentration of calcium. Furthermore, the decreased...... and the secretory stimulus. A dose-dependent decrease in antigen induced histamine secretion that was reversed by calcium was also observed. Exposure of the mast cells to magnesium for 15 min resulted in a parallel decrease in histamine secretion and in the cellular content of 45Ca2+. These observations suggest...... secretory responsiveness was dose-dependently restored by the addition of calcium to the cells simultaneously with compound 48/80. Preincubation with magnesium also inhibited antigen-induced histamine secretion in a dose-dependent manner. This was reversed by the simultaneous addition of calcium...

  2. Long-term primary culture of secretory cells of Bothrops jararaca venom gland for venom production in vitro.

    Science.gov (United States)

    Yamanouye, Norma; Kerchove, Celine Marie; Moura-da-Silva, Ana Maria; Carneiro, Sylvia M; Markus, Regina P

    2006-01-01

    This protocol details the optimal conditions to establish a long-term primary culture of secretory cells from the venom gland of the Bothrops jararaca snake. Furthermore, these conditions allow the production and secretion of venom into the culture medium. Snake venom is a rich source of active molecules and has been used for bioprospection studies. However, obtaining enough venom from snakes is a major obstacle. Secretory cells of venom glands are capable of producing active toxins. Therefore, a culture of secretory cells is a good in vitro system to acquire the venom of snakes without capturing the animal from the wild. The protocol described here provides a rapid (approximately 4 h) and reproducible means of producing sufficient amounts of snake venom for biological investigations.

  3. Secretory Transactivating Transcription-apoptin fusion protein induces apoptosis in hepatocellular carcinoma HepG2 cells

    Institute of Scientific and Technical Information of China (English)

    Su-Xia Han; Jin-Lu Ma; Yi Lv; Chen Huang; Hai-Hua Liang; Kang-Min Duan

    2008-01-01

    AIM: To determine whether SP-TAT-apoptin induces apoptosis and also maintains its tumor cell specificity.METHODS: In this study, we designed a secretory protein by adding a secretory signal peptide (SP) to the N terminus of Transactivating Transcription (TAT)-apoptin (SP-TAT-apoptin), to test the hypothesis that it gains an additive bystander effect as an anti-cancer therapy. We used an artificial human secretory SP whose amino acid sequence and corresponding cDNA sequence were generated by the SP hidden Markov model.RESULTS: In human liver carcinoma HepG2 cells, SP-TAT-apoptin expression showed a diffuse pattern in the early phase after transfection. After 48h, however, it translocated into the nuclear compartment and caused massive apoptotic cell death, as determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and annexin-V binding assay. SP-TAT-apoptin did not, however, cause any cell death in non-malignant human umbilical vein endothelial cells (HUVECs). Most importantly, the conditioned medium from Chinese hamster ovary (CHO) cells transfected with SP-TAT-apoptin also induced significant cell death in HepG2 cells, but not in HUVECs.CONCLUSION: The data demonstrated that SP-TAT-apoptin induces apoptosis only in malignant cells, and its secretory property might greatly increase its potency once it is delivered in vivo for cancer therapy.

  4. Epidermal cell density is autoregulated via a secretory peptide, EPIDERMAL PATTERNING FACTOR 2 in Arabidopsis leaves.

    Science.gov (United States)

    Hara, Kenta; Yokoo, Toshiya; Kajita, Ryoko; Onishi, Takaaki; Yahata, Saiko; Peterson, Kylee M; Torii, Keiko U; Kakimoto, Tatsuo

    2009-06-01

    Regulation of the number of cells is critical for development of multicellular organisms. During plant epidermal development, a protodermal cell first makes a fate decision of whether or not to be the meristemoid mother cell (MMC), which undergoes asymmetric cell division forming a meristemoid and its sister cell. The MMC-derived lineage produces all stomatal guard cells and a large proportion of non-guard cells. We demonstrate that a small secretory peptide, EPIDERMAL PATTERING FACTOR 2 (EPF2), is produced by the MMC and its early descendants, and negatively regulates the density of guard and non-guard epidermal cells. Our results suggest that EPF2 inhibits cells from adopting the MMC fate in a non-cell-autonomous manner, thus limiting the number of MMCs. This feedback loop is critical for regulation of epidermal cell density. The amino acid sequence of EPF2 resembles that of EPF1, which is known to control stomatal positioning. Over-expression of EPF1 also inhibits stomatal development, but EPF1 can act only on a later developmental process than EPF2. Overexpression and promoter swapping experiments suggested that the protein functions of EPF1 and EPF2, rather than the expression patterns of the genes, are responsible for the specific functions. Although targets of EPF1 and EPF2 are different, both EPF1 and EPF2 require common putative receptor components TOO MANY MOUTHS (TMM), ERECTA (ER), ERECTA LIKE 1 (ERL1) and ERL2 in order to function.

  5. Ionic and secretory response of pancreatic islet cells to minoxidil sulfate

    Energy Technology Data Exchange (ETDEWEB)

    Antoine, M.H.; Hermann, M.; Herchuelz, A.; Lebrun, P. (Laboratory of Pharmacology, Brussels Free University School of Medicine (Belgium))

    1991-07-01

    Minoxidil sulfate is an antihypertensive agent belonging to the new class of vasodilators, the K+ channel openers. The present study was undertaken to characterize the effects of minoxidil sulfate on ionic and secretory events in rat pancreatic islets. The drug unexpectedly provoked a concentration-dependent decrease in 86Rb outflow. This inhibitory effect was reduced in a concentration-dependent manner by glucose and tolbutamide. Minoxidil sulfate did not affect 45Ca outflow from islets perfused in the presence of extracellular Ca++ and absence or presence of glucose. However, in islets exposed to a medium deprived of extracellular Ca++, the drug provoked a rise in 45Ca outflow. Whether in the absence or presence of extracellular Ca++, minoxidil sulfate increased the cytosolic free Ca++ concentration of islet cells. Lastly, minoxidil sulfate increased the release of insulin from glucose-stimulated pancreatic islets. These results suggest that minoxidil sulfate reduces the activity of the ATP-sensitive K+ channels and promotes an intracellular translocation of Ca++. The latter change might account for the effect of the drug on the insulin-releasing process. However, the secretory response to minoxidil sulfate could also be mediated, at least in part, by a modest Ca++ entry.

  6. Syntaxin clusters assemble reversibly at sites of secretory granules in live cells.

    Science.gov (United States)

    Barg, S; Knowles, M K; Chen, X; Midorikawa, M; Almers, Wolfhard

    2010-11-30

    Syntaxin resides in the plasma membrane, where it helps to catalyze membrane fusion during exocytosis. The protein also forms clusters in cell-free and granule-free plasma-membrane sheets. We imaged the interaction between syntaxin and single secretory granules by two-color total internal reflection microscopy in PC12 cells. Syntaxin-GFP assembled in clusters at sites where single granules had docked at the plasma membrane. Clusters were intermittently present at granule sites, as syntaxin molecules assembled and disassembled in a coordinated fashion. Recruitment to granules required the N-terminal domain of syntaxin, but not the entry of syntaxin into SNARE complexes. Clusters facilitated exocytosis and disassembled once exocytosis was complete. Syntaxin cluster formation defines an intermediate step in exocytosis.

  7. Isoprenoid biosynthesis. Metabolite profiling of peppermint oil gland secretory cells and application to herbicide target analysis.

    Science.gov (United States)

    Lange, B M; Ketchum, R E; Croteau, R B

    2001-09-01

    Two independent pathways operate in plants for the synthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of all isoprenoids. The mevalonate pathway is present in the cytosol, whereas the recently discovered mevalonate-independent pathway is localized to plastids. We have used isolated peppermint (Mentha piperita) oil gland secretory cells as an experimental model system to study the effects of the herbicides fosmidomycin, phosphonothrixin, methyl viologen, benzyl viologen, clomazone, 2-(dimethylamino)ethyl diphosphate, alendronate, and pamidronate on the pools of metabolites related to monoterpene biosynthesis via the mevalonate-independent pathway. A newly developed isolation protocol for polar metabolites together with an improved separation and detection method based on liquid chromatography-mass spectrometry have allowed assessment of the enzyme targets for a number of these herbicides.

  8. [The role of mitochondrial uniporter in calcium-homeostasis of the exorbital lacrimal gland secretory cells].

    Science.gov (United States)

    Kotliarova, A B; Merlavs'kyĭ, V M; Dorosh, O M; Man'ko, V V

    2014-01-01

    The role of mitochondrial calcium-uniporter in calcium-homeostasis maintenance and correlations of calcium-uniporter with other calcium-transport systems of the rat exorbital lacrimal gland secretory cells were studied. The experiments were performed on intact and digitonin-permeabilized cells. The interdependence of calcium-uniporter and other calcium-transporting systems functioning was estimated on the basis of additivity of their inhibitors/agonists effects, which was accompanied with a decrease in the Ca2+ content in the gland cells. It was found that in conditions of simultaneously inhibition of sarco endoplasmic reticulum Ca2+-ATPase (SERCA) and mitochondrial calcium-uniporter Ca2+ passively released from different calcium stores, because the effects of these calcium-transport systems inhibitors (thapsigargin and ruthenium red, respectively) were additive. Similarly, the processes of inositol-1,4,5-trisphosphate receptors (IP3Rs) activation and calcium-uniporter inhibition were additive. In contrast, the effects of ryanodine and ruthenium red on the Ca2+ content in cells were significantly non-additive. In addition, ryanodine at concentrations 1-3 μM reduced respiration rate of studied cells in dose-dependent manner, and this effect was persisted at cells preincubation with ruthenium red or tapsigargin. Thus, besides the activation of ryanodine receptors (RyRs) in endoplasmic reticulum, ryanodine inhibits Ca2+ influx to the mitochondrial matrix, that was insensitive to ruthenium red.

  9. Serglycin determines secretory granule repertoire and regulates natural killer cell and cytotoxic T lymphocyte cytotoxicity.

    Science.gov (United States)

    Sutton, Vivien R; Brennan, Amelia J; Ellis, Sarah; Danne, Jill; Thia, Kevin; Jenkins, Misty R; Voskoboinik, Ilia; Pejler, Gunnar; Johnstone, Ricky W; Andrews, Daniel M; Trapani, Joseph A

    2016-03-01

    The anionic proteoglycan serglycin is a major constituent of secretory granules in cytotoxic T lymphocyte (CTL)/natural killer (NK) cells, and is proposed to promote the safe storage of the mostly cationic granule toxins, granzymes and perforin. Despite the extensive defects of mast cell function reported in serglycin gene-disrupted mice, no comprehensive study of physiologically relevant CTL/NK cell populations has been reported. We show that the cytotoxicity of serglycin-deficient CTL and NK cells is severely compromised but can be partly compensated in both cell types when they become activated. Reduced intracellular granzyme B levels were noted, particularly in CD27(+) CD11b(+) mature NK cells, whereas serglycin(-/-) TCR-transgenic (OTI) CD8 T cells also had reduced perforin stores. Culture supernatants from serglycin(-/-) OTI T cells and interleukin-2-activated NK contained increased granzyme B, linking reduced storage with heightened export. By contrast, granzyme A was not significantly reduced in cells lacking serglycin, indicating differentially regulated trafficking and/or storage for the two granzymes. A quantitative analysis of different granule classes by transmission electronmicroscopy showed a selective loss of dense-core granules in serglycin(-/-) CD8(+) CTLs, although other granule types were maintained quantitatively. The findings of the present study show that serglycin plays a critical role in the maturation of dense-core cytotoxic granules in cytotoxic lymphocytes and the trafficking and storage of perforin and granzyme B, whereas granzyme A is unaffected. The skewed retention of cytotoxic effector molecules markedly reduces CTL/NK cell cytotoxicity, although this is partly compensated for as a result of activating the cells by physiological means.

  10. Expression of ODC Antizyme Inhibitor 2 (AZIN2 in Human Secretory Cells and Tissues.

    Directory of Open Access Journals (Sweden)

    Tiina Rasila

    Full Text Available Ornithine decarboxylase (ODC antizyme inhibitor 2 (AZIN2, originally called ODCp, is a regulator of polyamine synthesis that we originally identified and cloned. High expression of ODCp mRNA was found in brain and testis. We reported that AZIN2 is involved in regulation of cellular vesicle transport and / or secretion, but the ultimate physiological role(s of AZIN2 is still poorly understood. In this study we used a peptide antibody (K3 to human AZIN2 and by immunohistochemistry mapped its expression in various normal tissues. We found high expression in the nervous system, in type 2 pneumocytes in the lung, in megakaryocytes, in gastric parietal cells co-localized with H,K-ATPase beta subunit, in selected enteroendocrine cells, in acinar cells of sweat glands, in podocytes, in macula densa cells and epithelium of collecting ducts in the kidney. The high expression of AZIN2 in various cells with secretory or vesicle transport activity indicates that the polyamine metabolism regulated by AZIN2 is more significantly involved in these events than previously appreciated.

  11. Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells.

    Science.gov (United States)

    Falcón, Cristian; Carranza, Franco; Martínez, Fernando F; Knubel, Carolina P; Masih, Diana T; Motrán, Claudia C; Cervi, Laura

    2010-09-15

    Fasciola hepatica is a helminth trematode that migrates through the host tissues until reaching bile ducts where it becomes an adult. During its migration the parasite releases different excretory-secretory products (ESP), which are in contact with the immune system. In this study, we focused on the effect of ESP on the maturation and function of murine bone marrow derived-dendritic cells (DC). We found that the treatment of DC with ESP failed to induce a classical maturation of these cells, since ESP alone did not activate DC to produce any cytokines, although they impaired the ability of DC to be activated by TLR ligands and also their capacity to stimulate an allospecific response. In addition, using an in vitro ovalbumin peptide-restricted priming assay, ESP-treated DC exhibited a capacity to drive Th2 and regulatory T cell (Treg) polarization of CD4(+) cells from DO11.10 transgenic mice. This was characterized by increased IL-4, IL-5, IL-10 and TGF-beta production and the expansion of CD4(+)CD25(+)Foxp3(+) cells. Our results support the hypothesis that ESP from F. hepatica modulate the maturation and function of DC as part of a generalized immunosuppressive mechanism that involves a bias towards a Th2 response and Treg development.

  12. Lactadherin inhibits secretory phospholipase A2 activity on pre-apoptotic leukemia cells

    DEFF Research Database (Denmark)

    Nyegaard, Steffen; Novakovic, Valerie A.; Rasmussen, Jan Trige

    2013-01-01

    Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2’s do not bind to plasma membranes...

  13. From differentiation to proliferation: The secretory amyloid precursor protein as a local mediator of growth in thyroid epithelial cells

    OpenAIRE

    Pietrzik, Claus Ulrich; Hoffmann, Jens; Stöber, Kai; Chen, Chun-yan; Bauer, Christoph; Otero, Deborah A.C.; Roch, Jean-Marc; Herzog, Volker

    1998-01-01

    In various species, thyrotropin (TSH) is known to stimulate both differentiation and proliferation of thyroid follicle cells. This cell type has also been shown to express members of the Alzheimer amyloid precursor (APP) protein family and to release the secretory N-terminal domain of APP (sAPP) in a TSH-dependent fashion. In this study on binding to the cell surfaces, exogenously added recombinant sAPP stimulated phosphorylation mediated by mitogen-activated protein kinase and effectively ev...

  14. Protection of Human Colon Cells from Shiga Toxin by Plant-based Recombinant Secretory IgA

    Science.gov (United States)

    Nakanishi, Katsuhiro; Morikane, Shota; Ichikawa, Shiori; Kurohane, Kohta; Niwa, Yasuo; Akimoto, Yoshihiro; Matsubara, Sachie; Kawakami, Hayato; Kobayashi, Hirokazu; Imai, Yasuyuki

    2017-01-01

    Shiga toxin is a major virulence factor of food-poisoning caused by Escherichia coli such as O157:H7. Secretory immunoglobulin (Ig) A (SIgA) is supposed to prevent infection of the mucosal surface and is a candidate agent for oral immunotherapy. We previously established a recombinant monoclonal antibody (mAb) consisting of variable regions from a mouse IgG mAb specific for the binding subunit of Shiga toxin 1 (Stx1) and the Fc region of mouse IgA. Here we produced a secretory form of the recombinant IgA (S-hyIgA) with transgenic Arabidopsis thaliana plant. All the S-hyIgA cDNAs (heavy, light, J chain and secretory component) were expressed under the control of a bidirectional promoter of a chlorophyll a/b-binding protein of A. thaliana without using a viral promoter. The plant-based S-hyIgA exhibited antigen binding, and was modified with plant-specific N-linked sugar chains. The Ig heavy chain and secretory components were observed in an intracellular protein body-like structure of the transgenic leaves on immuno-electron microscopy. An extract of the transgenic leaves neutralized the cytotoxicity of Stx1 toward butyrate-treated Caco-2 cells, a human colon carcinoma cell line. These results will contribute to the development of edible therapeutic antibodies such as those for the treatment of mucosal infection. PMID:28368034

  15. THE EFFECT OF CURCUMIN ON SECRETORY ACTIVITY, PROLIFERATION AND APOPTOSIS OF THE PORCINE OVARIAN GRANULOSA CELLS

    Directory of Open Access Journals (Sweden)

    Attila Kádasi

    2012-08-01

    Full Text Available The aim of this in vitro study was to examine the effect of natural plant (Curcuma longa molecule curcumin on secretory activity, proliferation and apoptosis of porcine granulosa cells. The secretion of steroid hormones (progesterone, testosterone, accumulation of PCNA (marker of proliferation and bax (marker of apoptosis in granulosa cells of swine ovaries after curcumin treatment at the doses 0, 1, 10, 100 μg.mL-1 was determined by RIA and immunocytochemistry. It was observed that, addition of curcumin stimulated progesterone (at doses 1 and 10 μg.mL-1, but not 100 μg.mL-1 and testosterone at (100 μg.mL-1 but not 1 and 10 μg.mL-1 release. The number of cells contained PCNA was down-regulated by curcumin administration (at dose of 10 μg.mL-1, but not of 1 and 100 μg.mL-1. Bax expression was stimulated by curcumin at all doses added. Our results suggest a direct effect of curcumin on ovarian functions: steroidogenesis, proliferation and apoptosis. This could suggest antireproductive properties of curcumin in swine ovaries.

  16. Effect of vagus nerve stimulation on the secretory-granule volume of the principal cells of the mouse gallbladder epithelium.

    Science.gov (United States)

    Wahlin, T; Hulliger, M; Axelsson, H

    1979-07-01

    Experiments in mice were performed in order to investigate whether vagal activity could affect glycoprotein secretion from gallbladder principal cells. This cell type was studied with the electron microscope in control animals and after electric stimulation of the right or left nervus vagus. The volume density of glycoprotein containing granules was determined using morphometry. It was found that stimulation of the left vagus nerve significantly reduced the relative cellular volume of secretory granules in the principal cells of the gallbladder. Right vagus stimulation was accompanied by a weak but insignificant increase in secretory granule content. It is suggested that the left vagus nerve may exert a direct influence on glycoprotein secretion from gallbladder principal cells.

  17. Agglutinating secretory IgA preserves intestinal epithelial cell integrity during apical infection by Shigella flexneri.

    Science.gov (United States)

    Mathias, Amandine; Longet, Stéphanie; Corthésy, Blaise

    2013-08-01

    Shigella flexneri, by invading intestinal epithelial cells (IECs) and inducing inflammatory responses of the colonic mucosa, causes bacillary dysentery. Although M cells overlying Peyer's patches are commonly considered the primary site of entry of S. flexneri, indirect evidence suggests that bacteria can also use IECs as a portal of entry to the lamina propria. Passive delivery of secretory IgA (SIgA), the major immunoglobulin secreted at mucosal surfaces, has been shown to protect rabbits from experimental shigellosis, but no information exists as to its molecular role in maintaining luminal epithelial integrity. We have established that the interaction of virulent S. flexneri with the apical pole of a model intestinal epithelium consisting of polarized Caco-2 cell monolayers resulted in the progressive disruption of the tight junction network and actin depolymerization, eventually resulting in cell death. The lipopolysaccharide (LPS)-specific agglutinating SIgAC5 monoclonal antibody (MAb), but not monomeric IgAC5 or IgGC20 MAbs of the same specificity, achieved protective functions through combined mechanisms, including limitation of the interaction between S. flexneri and epithelial cells, maintenance of the tight junction seal, preservation of the cell morphology, reduction of NF-κB nuclear translocation, and inhibition of proinflammatory mediator secretion. Our results add to the understanding of the function of SIgA-mediated immune exclusion by identifying a mode of action whereby the formation of immune complexes translates into maintenance of the integrity of epithelial cells lining the mucosa. This novel mechanism of protection mediated by SIgA is important to extend the arsenal of effective strategies to fight against S. flexneri mucosal invasion.

  18. Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription.

    OpenAIRE

    Shimon, I; Hüttner, A; Said, J; Spirina, O M; Melmed, S

    1996-01-01

    We have shown previously that human prolactinomas express transforming sequences of the heparin-binding secretory transforming gene (hst) which encodes fibroblast growth factor-4 (FGF-4). To elucidate the role of hst in pituitary tumorigenesis we treated primary rat pituitary and pituitary tumor cell cultures with recombinant FGF-4 and also stably transfected pituitary cell lines with full-length human hst cDNA. Transfectants were screened for hst mRNA expression and FGF-4 production. FGF-4 (...

  19. Kinetic Evaluation of Cell Membrane Hydrolysis during Apoptosis by Human Isoforms of Secretory Phospholipase A2*

    Science.gov (United States)

    Olson, Erin D.; Nelson, Jennifer; Griffith, Katalyn; Nguyen, Thaothanh; Streeter, Michael; Wilson-Ashworth, Heather A.; Gelb, Michael H.; Judd, Allan M.; Bell, John D.

    2010-01-01

    Some isoforms of secretory phospholipase A2 (sPLA2) distinguish between healthy and damaged or apoptotic cells. This distinction reflects differences in membrane physical properties. Because various sPLA2 isoforms respond differently to properties of artificial membranes such as surface charge, they should also behave differently as these properties evolve during a dynamic physiological process such as apoptosis. To test this idea, S49 lymphoma cell death was induced by glucocorticoid (6–48 h) or calcium ionophore. Rates of membrane hydrolysis catalyzed by various concentrations of snake venom and human groups IIa, V, and X sPLA2 were compared after each treatment condition. The data were analyzed using a model that evaluates the adsorption of enzyme to the membrane surface and subsequent binding of substrate to the active site. Results were compared temporally to changes in membrane biophysics and composition. Under control conditions, membrane hydrolysis was confined to the few unhealthy cells present in each sample. Increased hydrolysis during apoptosis and necrosis appeared to reflect substrate access to adsorbed enzyme for the snake venom and group X isoforms corresponding to weakened lipid-lipid interactions in the membrane. In contrast, apoptosis promoted initial adsorption of human groups V and IIa concurrent with phosphatidylserine exposure on the membrane surface. However, this observation was inadequate to explain the behavior of the groups V and IIa enzymes toward necrotic cells where hydrolysis was reduced or absent. Thus, a combination of changes in cell membrane properties during apoptosis and necrosis capacitates the cell for hydrolysis differently by each isoform. PMID:20139082

  20. P2X7 receptors trigger ATP exocytosis and modify secretory vesicle dynamics in neuroblastoma cells.

    Science.gov (United States)

    Gutiérrez-Martín, Yolanda; Bustillo, Diego; Gómez-Villafuertes, Rosa; Sánchez-Nogueiro, Jesús; Torregrosa-Hetland, Cristina; Binz, Thomas; Gutiérrez, Luis Miguel; Miras-Portugal, María Teresa; Artalejo, Antonio R

    2011-04-01

    Previously, we reported that purinergic ionotropic P2X7 receptors negatively regulate neurite formation in Neuro-2a (N2a) mouse neuroblastoma cells through a Ca(2+)/calmodulin-dependent kinase II-related mechanism. In the present study we used this cell line to investigate a parallel though faster P2X7 receptor-mediated signaling pathway, namely Ca(2+)-regulated exocytosis. Selective activation of P2X7 receptors evoked exocytosis as assayed by high resolution membrane capacitance measurements. Using dual-wavelength total internal reflection microscopy, we have observed both the increase in near-membrane Ca(2+) concentration and the exocytosis of fluorescently labeled vesicles in response to P2X7 receptor stimulation. Moreover, activation of P2X7 receptors also affects vesicle motion in the vertical and horizontal directions, thus, involving this receptor type in the control of early steps (docking and priming) of the secretory pathway. Immunocytochemical and RT-PCR experiments evidenced that N2a cells express the three neuronal SNAREs as well as vesicular nucleotide and monoamine (VMAT-1 and VMAT-2) transporters. Biochemical measurements indicated that ionomycin induced a significant release of ATP from N2a cells. Finally, P2X7 receptor stimulation and ionomycin increased the incidence of small transient inward currents, reminiscent of postsynaptic quantal events observed at synapses. Small transient inward currents were dependent on extracellular Ca(2+) and were abolished by Brilliant Blue G, suggesting they were mediated by P2X7 receptors. Altogether, these results suggest the existence of a positive feedback mechanism mediated by P2X7 receptor-stimulated exocytotic release of ATP that would act on P2X7 receptors on the same or neighbor cells to further stimulate its own release and negatively control N2a cell differentiation.

  1. Clara Cell Protein Expression in Mechanically Ventilated Term and Preterm Infants with Respiratory Distress Syndrome and at Risk of Bronchopulmonary Dysplasia: A Pilot Study

    Directory of Open Access Journals (Sweden)

    José Guzmán-Bárcenas

    2017-01-01

    Full Text Available The aim of this pilot study was to determine Clara cell protein (CC16 concentration in bronchoalveolar lavages (BAL fluid from full-term and preterm (<37 weeks’ gestational age neonates requiring respiratory support, having symptoms of neonatal respiratory distress syndrome, and at risk of bronchopulmonary dysplasia (BPD. We hypothesized that CC16 may be predictive of BPD diagnosis regardless of gestational age. BAL fluid CC16 was measured by ELISA at birth and at day 7 of life. Both groups that developed BPD showed significantly decreased BAL fluid CC16 levels compared to those infants that did not develop the disease. CC16 positively correlated with diagnosis of BPD and negatively with the severity of the disease. These results suggest that BAL fluid CC16 levels may have a diagnostic value at day 7 for BPD in both term and preterm infants. This study demonstrates the potential utility of BAL fluid CC16 levels as a biomarker for BPD in term infants.

  2. Mast cell mediators: Their differential release and the secretory pathways involved

    Directory of Open Access Journals (Sweden)

    Tae Chul eMoon

    2014-11-01

    Full Text Available Mast cells (MC are widely distributed throughout the body and are common at mucosal surfaces, a major host-environment interface. MC are functionally and phenotypically heterogeneous depending on the microenvironment in which they mature. Although MC have been classically viewed as effector cells of IgE-mediated allergic diseases, they are also recognized as important in host defense, innate and acquired immunity, homeostatic responses, and immunoregulation. MC activation can induce release of preformed mediators such as histamine from their granules, as well as release of de novo synthesized lipid mediators, cytokines and chemokines that play diverse roles, not only in allergic reactions but also in numerous physiological and pathophysiological responses. Indeed, MC release their mediators in a discriminating and chronological manner, depending upon the stimuli involved and their signaling cascades (e.g., IgE-mediated or Toll Like Receptor-mediated. However, the precise mechanisms underlying differential mediator release in response to these stimuli are poorly known. This review summarizes our knowledge of MC mediators and will focus on what is known about the discriminatory release of these mediators dependent upon diverse stimuli, MC phenotypes and species of origin, as well as on the intracellular synthesis, storage and secretory processes involved.

  3. Molecular mechanisms involved in secretory vesicle recruitment to the plasma membrane in beta-cells.

    Science.gov (United States)

    Varadi, Aniko; Ainscow, E K; Allan, V J; Rutter, G A

    2002-04-01

    Glucose stimulates the release of insulin in part by activating the recruitment of secretory vesicles to the cell surface. While this movement is known to be microtubule-dependent, the molecular motors involved are undefined. Active kinesin was found to be essential for vesicle translocation in live beta-cells, since microinjection of cDNA encoding dominant-negative KHC(mut) (motor domain of kinesin heavy chain containing a Thr(93)-->Asn point mutation) blocked vesicular movements. Moreover, expression of KHC(mut) strongly inhibited the sustained, but not acute, stimulation of secretion by glucose. Thus, vesicles released during the first phase of insulin secretion exist largely within a translocation-independent pool. Kinesin-driven anterograde movement of vesicles is then necessary for the sustained (second phase) of insulin release. Kinesin may, therefore, represent a novel target for increases in intracellular ATP concentrations in response to elevated extracellular glucose and may be involved in the ATP-sensitive K+channel-independent stimulation of secretion by the sugar.

  4. Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis.

    Science.gov (United States)

    Yagami, Tatsurou; Ueda, Keiichi; Asakura, Kenji; Hata, Satoshi; Kuroda, Takayuki; Sakaeda, Toshiyuki; Takasu, Nobuo; Tanaka, Kazushige; Gemba, Takefumi; Hori, Yozo

    2002-01-01

    Expression of group IIA secretory phospholipase A2 (sPLA2-IIA) is documented in the cerebral cortex (CTX) after ischemia, suggesting that sPLA2-IIA is associated with neurodegeneration. However, how sPLA2-IIA is involved in the neurodegeneration remains obscure. To clarify the pathologic role of sPLA2-IIA, we examined its neurotoxicity in rats that had the middle cerebral artery occluded and in primary cultures of cortical neurons. After occlusion, sPLA2 activity was increased in the CTX. An sPLA2 inhibitor, indoxam, significantly ameliorated not only the elevated activity of the sPLA2 but also the neurodegeneration in the CTX. The neuroprotective effect of indoxam was observed even when it was administered after occlusion. In primary cultures, sPLA2-IIA caused marked neuronal cell death. Morphologic and ultrastructural characteristics of neuronal cell death by sPLA2-IIA were apoptotic, as evidenced by condensed chromatin and fragmented DNA. Before apoptosis, sPLA2-IIA liberated arachidonic acid (AA) and generated prostaglandin D2 (PGD2), an AA metabolite, from neurons. Indoxam significantly suppressed not only AA release, but also PGD2 generation. Indoxam prevented neurons from sPLA2-IIA-induced neuronal cell death. The neuroprotective effect of indoxam was observed even when it was administered after sPLA2-IIA treatment. Furthermore, a cyclooxygenase-2 inhibitor significantly prevented neurons from sPLA2-IIA-induced PGD2 generation and neuronal cell death. In conclusion, sPLA2-IIA induces neuronal cell death via apoptosis, which might be associated with AA metabolites, especially PGD2. Furthermore, sPLA2 contributes to neurodegeneration in the ischemic brain, highlighting the therapeutic potential of sPLA2-IIA inhibitors for stroke.

  5. Membrane secretory component is cleaved on the cell surface of rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Musil, L.S.; Baenziger, J.U.

    1986-03-05

    Transcellular transport of polymeric IgA from serum to bile by rat hepatocytes is mediated by a 105Kd membranous form of secretory component (mSC). In the presence or absence of IgA, mSC is cleaved and released into bile as a soluble 80Kd protein (fSC). They used monolayer cultures of rat hepatocytes, which synthesize mSC and efficiently cleave it to fSC, to determine the site of this conversion. (/sup 35/S)Cys-mSC accumulated in hepatocytes in the presence of leupeptin and was released as fSC when hepatocytes were placed in leupeptin-free media at 37/sup 0/. Small amounts of fSC were also produced when leupeptin was removed at 4/sup 0/, suggesting cleavage might occur on the cell membrane. Lactoperoxidase-catalyzed iodination of hepatocytes at 4/sup 0/ selectively labeled surface mSC which remained trypsin sensitive at 4/sup 0/. Hepatocytes maintained at 4/sup 0/ released significant amounts of /sup 125/I-mSC as fSC. Anti-SC antiserum reduced fSC generation at 4/sup 0/ by 70%. Following incubation at 37/sup 0/ for 10 min, /sup 125/I-mSC became resistant to degradation by trypsin and no production of fSC was seen if the cells were returned to 4/sup 0/. /sup 125/I-mSC was also cleaved to fSC following disruption by Dounce homogenization if cells were maintained at 4/sup 0/ following iodination but not if they were incubated at 37/sup 0/ for 10 min. They propose that mSC is cleaved to fSC at the plasma membrane but not intracellularly. This may reflect localization of the protease at the cell surface in a bile canalicular-like domain.

  6. The Story of Clara Pickle

    Institute of Scientific and Technical Information of China (English)

    问号

    2005-01-01

    Everyone in town knew Clara Pickle.She was asdear and sw eet as anyone could be.In fact,it wasClara Pickle's good nature that gother in trouble.O ne day a grey cat w andered into Clara’skitchen.Clara,who lived alone,took the cat in.Shewas glad for the com pany.The nextm orning she letthecat out for a breath of fresh air.W hen the cat cam eback that afternoon,he was no longer alone.H e hadbrought his entire fam ily and m ost ofhis friends.Therewere thirty-four cats in all。Clare,sweet soul that she was,adopte...

  7. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

  8. Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic beta-cells.

    Science.gov (United States)

    Eto, Kazuhiro; Yamashita, Tokuyuki; Hirose, Kenzo; Tsubamoto, Yoshiharu; Ainscow, Edward K; Rutter, Guy A; Kimura, Satoshi; Noda, Mitsuhiko; Iino, Masamitsu; Kadowaki, Takashi

    2003-08-01

    We studied acute changes of secretory vesicle pH in pancreatic beta-cells with a fluorescent pH indicator, lysosensor green DND-189. Fluorescence was decreased by 0.66 +/- 0.10% at 149 +/- 16 s with 22.2 mM glucose stimulation, indicating that vesicular pH was alkalinized by approximately 0.016 unit. Glucose-responsive pH increase was observed when cytosolic Ca2+ influx was blocked but disappeared when an inhibitor of glycolysis or mitochondrial ATP synthase was present. Glutamate dimethyl ester (GME), a plasma membrane-permeable analog of glutamate, potentiated glucose-stimulated insulin secretion at 5 mM without changing cellular ATP content or cytosolic Ca2+ concentration ([Ca2+]). Application of GME at basal glucose concentration decreased DND-189 fluorescence by 0.83 +/- 0.19% at 38 +/- 2 s. These results indicated that the acutely alkalinizing effect of glucose on beta-cell secretory vesicle pH was dependent on glucose metabolism but independent of modulations of cytosolic [Ca2+]. Moreover, glutamate derived from glucose may be one of the mediators of this alkalinizing effect of glucose, which may have potential relevance to the alteration of secretory function by glutamate.

  9. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    Directory of Open Access Journals (Sweden)

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  10. The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development.

    Directory of Open Access Journals (Sweden)

    Vida Praitis

    2013-05-01

    Full Text Available Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R and ryanodine receptors (RyR, which release calcium into the cytosol, are important regulators of cell migration. Similarly, proteins that return calcium to secretory stores are likely to be important for cell migration. The secretory protein calcium ATPase (SPCA is a Golgi-localized protein that transports calcium from the cytosol into secretory stores. SPCA has established roles in protein processing, metal homeostasis, and inositol-trisphosphate signaling. Defects in the human SPCA1/ATP2C1 gene cause Hailey-Hailey disease (MIM# 169600, a genodermatosis characterized by cutaneous blisters and fissures as well as keratinocyte cell adhesion defects. We have determined that PMR-1, the Caenorhabditis elegans ortholog of SPCA1, plays an essential role in embryogenesis. Pmr-1 strains isolated from genetic screens show terminal phenotypes, such as ventral and anterior enclosure failures, body morphogenesis defects, and an unattached pharynx, which are caused by earlier defects during gastrulation. In Pmr-1 embryos, migration rates are significantly reduced for cells moving along the embryo surface, such as ventral neuroblasts, C-derived, and anterior-most blastomeres. Gene interaction experiments show changing the activity of itr-1/IP3R and unc-68/RyR modulates levels of embryonic lethality in Pmr-1 strains, indicating pmr-1 acts with these calcium channels to regulate cell migration. This analysis reveals novel genes involved in C. elegans cell migration, as well as a new role in cell migration for the highly conserved SPCA gene family.

  11. The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development.

    Science.gov (United States)

    Praitis, Vida; Simske, Jeffrey; Kniss, Sarah; Mandt, Rebecca; Imlay, Leah; Feddersen, Charlotte; Miller, Michael B; Mushi, Juliet; Liszewski, Walter; Weinstein, Rachel; Chakravorty, Adityarup; Ha, Dae-Gon; Schacht Farrell, Angela; Sullivan-Wilson, Alexander; Stock, Tyson

    2013-05-01

    Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R) and ryanodine receptors (RyR), which release calcium into the cytosol, are important regulators of cell migration. Similarly, proteins that return calcium to secretory stores are likely to be important for cell migration. The secretory protein calcium ATPase (SPCA) is a Golgi-localized protein that transports calcium from the cytosol into secretory stores. SPCA has established roles in protein processing, metal homeostasis, and inositol-trisphosphate signaling. Defects in the human SPCA1/ATP2C1 gene cause Hailey-Hailey disease (MIM# 169600), a genodermatosis characterized by cutaneous blisters and fissures as well as keratinocyte cell adhesion defects. We have determined that PMR-1, the Caenorhabditis elegans ortholog of SPCA1, plays an essential role in embryogenesis. Pmr-1 strains isolated from genetic screens show terminal phenotypes, such as ventral and anterior enclosure failures, body morphogenesis defects, and an unattached pharynx, which are caused by earlier defects during gastrulation. In Pmr-1 embryos, migration rates are significantly reduced for cells moving along the embryo surface, such as ventral neuroblasts, C-derived, and anterior-most blastomeres. Gene interaction experiments show changing the activity of itr-1/IP3R and unc-68/RyR modulates levels of embryonic lethality in Pmr-1 strains, indicating pmr-1 acts with these calcium channels to regulate cell migration. This analysis reveals novel genes involved in C. elegans cell migration, as well as a new role in cell migration for the highly conserved SPCA gene family.

  12. The regulated secretory pathway in CD4(+ T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse.

    Directory of Open Access Journals (Sweden)

    Clare Jolly

    2011-09-01

    Full Text Available Direct cell-cell spread of Human Immunodeficiency Virus type-1 (HIV-1 at the virological synapse (VS is an efficient mode of dissemination between CD4(+ T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear. We have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary CD4(+ T cells from normal individuals and patients with Chediak-Higashi Syndrome and report that the HIV-1 VS displays a regulated secretion phenotype that shares features with polarized secretion at the T cell immunological synapse (IS. Cell-cell contact at the VS re-orientates the microtubule organizing center (MTOC and organelles within the HIV-1-infected T cell towards the engaged target T cell, concomitant with polarization of viral proteins. Directed secretion of proteins at the T cell IS requires specialized organelles termed secretory lysosomes (SL and we show that the HIV-1 envelope glycoprotein (Env localizes with CTLA-4 and FasL in SL-related compartments and at the VS. Finally, CD4(+ T cells that are disabled for regulated secretion are less able to support productive cell-to-cell HIV-1 spread. We propose that HIV-1 hijacks the regulated secretory pathway of CD4(+ T cells to enhance its dissemination.

  13. The Regulated Secretory Pathway in CD4+ T cells Contributes to Human Immunodeficiency Virus Type-1 Cell-to-Cell Spread at the Virological Synapse

    Science.gov (United States)

    Jolly, Clare; Welsch, Sonja; Michor, Stefanie; Sattentau, Quentin J.

    2011-01-01

    Direct cell-cell spread of Human Immunodeficiency Virus type-1 (HIV-1) at the virological synapse (VS) is an efficient mode of dissemination between CD4+ T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear. We have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary CD4+ T cells from normal individuals and patients with Chediak-Higashi Syndrome and report that the HIV-1 VS displays a regulated secretion phenotype that shares features with polarized secretion at the T cell immunological synapse (IS). Cell-cell contact at the VS re-orientates the microtubule organizing center (MTOC) and organelles within the HIV-1-infected T cell towards the engaged target T cell, concomitant with polarization of viral proteins. Directed secretion of proteins at the T cell IS requires specialized organelles termed secretory lysosomes (SL) and we show that the HIV-1 envelope glycoprotein (Env) localizes with CTLA-4 and FasL in SL-related compartments and at the VS. Finally, CD4+ T cells that are disabled for regulated secretion are less able to support productive cell-to-cell HIV-1 spread. We propose that HIV-1 hijacks the regulated secretory pathway of CD4+ T cells to enhance its dissemination. PMID:21909273

  14. Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.

    Science.gov (United States)

    Chaiyadet, Sujittra; Smout, Michael; Johnson, Michael; Whitchurch, Cynthia; Turnbull, Lynne; Kaewkes, Sasithorn; Sotillo, Javier; Loukas, Alex; Sripa, Banchob

    2015-10-01

    Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south

  15. CLARA: CLAS12 Reconstruction and Analysis Framework

    Science.gov (United States)

    Gyurgyan, V.; Mancilla, S.; Oyarzún, R.

    2016-10-01

    In this paper we present SOA based CLAS12 event Reconstruction and Analyses (CLARA) framework. CLARA design focus is on two main traits: real-time data stream processing, and service-oriented architecture (SOA) in a flow based programming (FBP) paradigm. Data driven and data centric architecture of CLARA presents an environment for developing agile, elastic, multilingual data processing applications. The CLARA framework presents solutions capable of processing large volumes of data interactively and substantially faster than batch systems.

  16. CLARA: CLAS12 Reconstruction and Analysis Framework

    Energy Technology Data Exchange (ETDEWEB)

    Gyurjyan, Vardan [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Matta, Sebastian Mancilla [Santa Maria U., Valparaiso, Chile; Oyarzun, Ricardo [Santa Maria U., Valparaiso, Chile

    2016-11-01

    In this paper we present SOA based CLAS12 event Reconstruction and Analyses (CLARA) framework. CLARA design focus is on two main traits: real-time data stream processing, and service-oriented architecture (SOA) in a flow based programming (FBP) paradigm. Data driven and data centric architecture of CLARA presents an environment for developing agile, elastic, multilingual data processing applications. The CLARA framework presents solutions capable of processing large volumes of data interactively and substantially faster than batch systems.

  17. Subcellular localization of SV2 and other secretory vesicle components in PC12 cells by an efficient method of preembedding EM immunocytochemistry for cell cultures

    DEFF Research Database (Denmark)

    Tanner, V A; Ploug, Thorkil; Tao-Cheng, J H

    1996-01-01

    We demonstrated the subcellular localization of SV2, a transmembrane protein associated with neuroendocrine secretory vesicles, in NGF-treated PC12 cells by preembedding EM immunocytochemistry (ICC), using a small gold probe followed by silver enhancement. The use of a multiwell chamber slide...

  18. Impact of simulated microgravity on the secretory and adhesive activity of cultured human vascular endothelial cells.

    Science.gov (United States)

    Rudimov, Evgeny; Buravkova, Ludmila; Pogodina, Margarita; Andrianova, Irina

    The layer of vascular endothelial cells (ECs) is a dynamic,disseminated organ that perform the function of an interface between the blood and vascular wall. The endothelial monolayer is able to quickly respond to changes in the microenvironment due to its synthesis of vasoactive substances, chemokines, adhesion molecules expression, etc. ECs are highly sensitive to gravitational changes and capable of short-term and long-term responses (Sangha et al., 2001; Buravkova et al., 2005; Infanger et al., 2006, 2007. However, the question remains how to reflect the impact of microgravity on endothelium under the inflammatory process. Therefore, the aim of this study was to investigate secretory and adhesive activity of human umbilical vein endothelial cells (HUVECs) during simulated microgravity and TNF-a activation. HUVECs were isolated according to Gimbrone et al. (1978) in modification A. Antonov (1981) and used for experiments at 2-4 passages. HUVECs were activated by low level of TNF-a (2 ng/ml). Microgravity was generated by Random Positioning Machine (RPM, Dutch Space, Leiden) placed into the thermostat at 37°C. After 24 hours of clinorotation we measured adhesion molecules expression on the cell surface (ICAM-1, VCAM-1, PECAM-1, E-selectin, CD144, endoglin (CD105)) and cell viability using a flow cytometry. To evaluate the level of target gene expression was used the real time RT-PCR. IL-6 and IL-8 concentration was measured in the conditioned medium of HUVECs by using the ELISA test. We found that simulated microgravity within 24 hours caused a decrease of ICAM-1, CD144, and E-selectin expression, at the same time not affect the cell viability, endoglin and PECAM-1 expression on the surface HUVEC. Furthermore, there were no changes of the level of IL-6 and IL-8 gene expression and their products in the culture medium. TNF-activated HUVECs showed an increase in gene expression of interleukins and molecules involved in the adhesion process, which also was confirmed

  19. Plasma wakefield acceleration at CLARA facility in Daresbury Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Xia, G., E-mail: guoxing.xia@manchester.ac.uk [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); Nie, Y. [Deutsche Elektronen-Synchrotron DESY, Hamburg (Germany); Mete, O.; Hanahoe, K. [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); Dover, M.; Wigram, M.; Wright, J.; Zhang, J. [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); Smith, J. [Tech-X UK Corporation, Daresbury Innovation Centre, Warrington (United Kingdom); Pacey, T.; Li, Y. [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); Wei, Y.; Welsch, C. [The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); University of Liverpool, Liverpool (United Kingdom)

    2016-09-01

    A plasma accelerator research station (PARS) has been proposed to study the key issues in electron driven plasma wakefield acceleration at CLARA facility in Daresbury Laboratory. In this paper, the quasi-nonlinear regime of beam driven plasma wakefield acceleration is analysed. The wakefield excited by various CLARA beam settings are simulated by using a 2D particle-in-cell (PIC) code. For a single drive beam, an accelerating gradient up to 3 GV/m can be achieved. For a two bunch acceleration scenario, simulation shows that a witness bunch can achieve a significant energy gain in a 10–50 cm long plasma cell.

  20. Urethral glands of the male mouse contain secretory component and immunoglobulin A plasma cells and are targets of testosterone.

    Science.gov (United States)

    Parr, M B; Ren, H P; Russell, L D; Prins, G S; Parr, E L

    1992-12-01

    The occurrence and possible functions of mucosal immunity in the male urogenital tract have not been extensively investigated. In this study we used immunolabeling to localize secretory component (SC) and immunoglobulin (Ig) A in the urogenital tract of the male mouse. SC was located in the ventral prostate, while SC and IgA plasma cells were both detected in the urethral glands in the pelvic and bulbous portions of the urethra. SC and IgA were not observed elsewhere in the urogenital tract. We also examined the ventral prostate and urethral glands of sham-castrated, oil-treated castrated, and testosterone-treated castrated mice. There was a striking reduction in the size of the ventral prostate and urethral glands in oil-treated castrates compared to the other two groups, based on gross and histological morphology. Morphometric analysis showed that the cell and nuclear sizes of the urethral gland acinar cells were reduced after castration and restored to normal size by testosterone treatment. Androgen receptors (AR) were localized in the nuclei of urethral gland cells by immunocytochemistry using anti-AR antibodies. Labeling of SC and IgA plasma cells was similar in the urethral glands and ventral prostates of sham- and testosterone-treated castrates, but was reduced or absent at these sites in oil-treated castrates. These studies show that the ventral prostate and urethral glands may be sites for secretory immunity in the male murine urogenital tract, and that the urethral glands are targets for testosterone.

  1. Hydrogen sulfide induces hyperpolarization and decreases the exocytosis of secretory granules of rat GH3 pituitary tumor cells.

    Science.gov (United States)

    Mustafina, Alsu N; Yakovlev, Aleksey V; Gaifullina, Aisylu Sh; Weiger, Thomas M; Hermann, Anton; Sitdikova, Guzel F

    2015-10-02

    The aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16-19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (KATP) by glibenclamide or by diazoxide, respectively. In whole-cell recordings NaHS increased the amplitude of KATP currents, induced by hyperpolarizing pulses and subsequent application of glibenclamide decreased currents to control levels. Using the fluorescent dye FM 1-43 exocytosis of secretory granules was analyzed in basal and stimulated conditions (high K(+) external solution). Prior application of NaHS decreased the fluorescence of the cell membrane in both conditions which links with activation of KATP currents (basal secretion) and activation of KATP currents and BK-currents (stimulated exocytosis). We suggest that H2S induces hyperpolarization of GH3 cells by activation of KATP channels which results in a truncation of spontaneous action potentials and a decrease of hormone release.

  2. Functional expression of a Kir2.1-like inwardly rectifying potassium channel in mouse mammary secretory cells.

    Science.gov (United States)

    Kamikawa, Akihiro; Ishikawa, Toru

    2014-02-01

    K(+) channels in mammary secretory (MS) cells are believed to play a role in transcellular electrolyte transport and thus determining ionic composition of the aqueous phase of milk. However, direct evidence for specific K(+) channel activity in native MS cells is lacking at the single-cell level. Here, we show for the first time that an inwardly rectifying K(+) (Kir) channel is functionally expressed in fully differentiated MS cells that were freshly isolated from the mammary gland of lactating mice. Using the standard whole cell patch-clamp technique, we found that mouse MS cells consistently displayed a K(+) current, whose electrophysiological properties are similar to those previously reported for Kir2.x channels, particularly Kir2.1: 1) current-voltage relationship with strong inward rectification, 2) slope conductance approximately proportional to the square root of external K(+) concentration, 3) voltage- and time-dependent and high-affinity block by external Ba(2+), and 4) voltage-dependent inhibition by external Cs(+). Accordingly, RT-PCR analysis revealed the gene expression of Kir2.1, but not Kir2.2, Kir2.3, and Kir2.4, in lactating mouse mammary gland, and immunohistochemical staining showed Kir2.1 protein expression in the secretory cells. Cell-attached patch recordings from MS cells revealed that a 31-pS K(+) channel with strong inward rectification was likely active at the resting membrane potential. Collectively, the present work demonstrates that a functional Kir2.1-like channel is expressed in lactating mouse MS cells. We propose that the channel might be involved, at least in part, in secretion and/or preservation of ionic components of milk stored into the lumen of these cells.

  3. The Relationship between the Ionic Composition of the Environment and the Secretory Activity of the Endocrine Cell Types of Stannius Corpuscles in the Teleost Gasterosteus aculeatus

    NARCIS (Netherlands)

    Wendelaar Bonga, S.E.; Greven, J.A.A.; Veenhuis, M.

    1976-01-01

    The corpuscles of Stannius of threespined sticklebacks contain two glandular cell types of presumed endocrine nature. To elucidate the function of both cell types the secretory activity of the cells was studied in fully adapted seawater and freshwater fishes and in specimens transferred from sea

  4. Characterization of phospholipids in insulin secretory granules and mitochondria in pancreatic beta cells and their changes with glucose stimulation.

    Science.gov (United States)

    MacDonald, Michael J; Ade, Lacmbouh; Ntambi, James M; Ansari, Israr-Ul H; Stoker, Scott W

    2015-04-24

    The lipid composition of insulin secretory granules (ISG) has never previously been thoroughly characterized. We characterized the phospholipid composition of ISG and mitochondria in pancreatic beta cells without and with glucose stimulation. The phospholipid/protein ratios of most phospholipids containing unsaturated fatty acids were higher in ISG than in whole cells and in mitochondria. The concentrations of negatively charged phospholipids, phosphatidylserine, and phosphatidylinositol in ISG were 5-fold higher than in the whole cell. In ISG phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin, fatty acids 12:0 and 14:0 were high, as were phosphatidylserine and phosphatidylinositol containing 18-carbon unsaturated FA. With glucose stimulation, the concentration of many ISG phosphatidylserines and phosphatidylinositols increased; unsaturated fatty acids in phosphatidylserine increased; and most phosphatidylethanolamines, phosphatidylcholines, sphingomyelins, and lysophosphatidylcholines were unchanged. Unsaturation and shorter fatty acid length in phospholipids facilitate curvature and fluidity of membranes, which favors fusion of membranes. Recent evidence suggests that negatively charged phospholipids, such as phosphatidylserine, act as coupling factors enhancing the interaction of positively charged regions in SNARE proteins in synaptic or secretory vesicle membrane lipid bilayers with positively charged regions in SNARE proteins in the plasma membrane lipid bilayer to facilitate docking of vesicles to the plasma membrane during exocytosis. The results indicate that ISG phospholipids are in a dynamic state and are consistent with the idea that changes in ISG phospholipids facilitate fusion of ISG with the plasma membrane-enhancing glucose-stimulated insulin exocytosis.

  5. Illuminating cellular structure and function in the early secretory pathway by multispectral 3D imaging in living cells

    Science.gov (United States)

    Rietdorf, Jens; Stephens, David J.; Squire, Anthony; Simpson, Jeremy; Shima, David T.; Paccaud, Jean-Pierre; Bastiaens, Philippe I.; Pepperkok, Rainer

    2000-04-01

    Membrane traffic between the endoplasmic reticulum (ER) and the Golgi complex is regulated by two vesicular coat complexes, COPII and COPI. COPII has been implicated in selective packaging of anterograde cargo into coated transport vesicles budding from the ER. COPI-coated vesicles are proposed to mediate recycling of proteins from the Golgi complex to the ER. We have used multi spectral 3D imaging to visualize COPI and COPII behavior simultaneously with various GFP-tagged secretory markers in living cells. This shows that COPII and COPI act sequentially whereby COPI association with anterograde transport complexes is involved in microtubule-based transport and the en route segregation of ER recycling molecules from secretory cargo within TCS in transit to the Golgi complex. We have also investigated the possibility to discriminate spectrally GFP fusion proteins by fluorescence lifetime imaging. This shows that at least two, and possibly up to three GFP fusion proteins can be discriminated and localized in living cells using a single excitation wavelength and a single broad band emission filter.

  6. Excretory/secretory products of Fasciola hepatica but not recombinant phosphoglycerate kinase induce death of human hepatocyte cells.

    Science.gov (United States)

    Bąska, Piotr; Norbury, Luke J; Wiśniewski, Marcin; Januszkiewicz, Kamil; Wędrychowicz, Halina

    2013-06-01

    The liver fluke Fasciola hepatica infects a wide range of hosts, and has a considerable impact on the agriculture industry, mainly through infections of sheep and cattle. Further, human infection is now considered of public health importance and is hyperendemic in some regions. The fluke infection causes considerable damage to the hosts' liver. However, the mechanisms of liver destruction have not yet been completely elucidated. In the present report we incubated a human liver cell line in the presence of either F. hepatica excretory/secretory material (FhES) or recombinant phosphoglycerate kinase (FhPGK). Dosedependent cytotoxicity in the presence of FhES was observed, indicating that FhES is capable of killing human hepatocytes, supporting a role for FhES in damaging host liver cells during infection; while treatment with a recombinant intracellular protein - FhPGK, had no impact on cell survival.

  7. PLACENTAL SECRETORY FACTORS INFLUENCE TO THP-1 CELLS PHENOTYPE AND THP-1 CELLS TRANSENDOTHELIAL MIGRATION

    Directory of Open Access Journals (Sweden)

    O. I. Stepanova

    2013-01-01

    Full Text Available Decidual and placental macrophage pools are renewed due to its transendothelial monocyte migration from peripheral blood. Tissue macrophages control placental development and provide fetomaternal immunological tolerance. Preeclamptic pregnancy is accompanied by increased monocyte migration to decidual tissue and local inflammatory events. Regulatory mechanisms of monocyte recruitment to placental and decidual tissues is still unclear. Therefore we investigated the influence soluble placental factors (SPFs during the first- and third-trimester normal pregnancy, as compared to effects of these factors in preeclamptic pregnancy. We studied biological actions of SPF upon transendothelial migration of monocyte-like THP-1 cells and their phenotypic pattern. Transendothelial migration of THP-1 cells was more intensive with firsttrimester SPFs from normal pregnancy, when compared with third-trimester samples, and it was accompanied by decreased CD11a expression. SPFs from pre-eclamptic pregnancy caused an increase in transendothelial migration of THP-1 cells, as compared to SPFs from normal pregnancies, being accompanied by increased CD11b expression. The present study was supported by grants ГК №  02.740.11.0711, НШ-3594.2010.7, МД-150.2011.7 and a grant from St.-Petersburg Goverment for young scientists.

  8. Secretory function of ovarian cells and myometrial contractions in cow are affected by chlorinated insecticides (chlordane, heptachlor, mirex) in vitro.

    Science.gov (United States)

    Wrobel, Michael Hubert; Mlynarczuk, Jaroslaw

    2017-01-01

    The aim of the study was to investigate the effect of chlordane, heptachlor and mirex, on hormonal regulation of the force of myometrial contractions. Myometrial, endometrial, granulosa and luteal cells as well as strips of myometrium from non-pregnant cows were incubated with three insecticides at environmentally relevant doses (0.1, 1 or 10ng/ml). None of the insecticides affected the viability of studied cells. Chlordane stimulated, while heptachlor and mirex inhibited, secretion of testosterone and estradiol from granulosa cells as well as secretion of progesterone from luteal cells, respectively. Secretion of oxytocin (OT) from granulosa cells was increased after incubation with all studied insecticides. Only mirex stimulated OT secretion from luteal cells, while heptachlor inhibited this effect. None of them affected synthesis of OT in luteal cells and prostaglandins (PGF2 and PGE2) secretion from uterine cells, except PGE2 secretion from endometrial cells was decreased when the cells were incubated with 0.1ng/ml of chlordane. Basal and OT-stimulated myometrial contractions were increased by mirex and decreased by heptachlor. The data show that the insecticides altered secretory function of ovarian cells. Heptachlor and mirex affected also myometrial contractions in vitro, but uterine secretion of prostaglandins were not involved in the mechanism of that adverse effect of insecticides. The data indicate on potential of these insecticides to disturb fertilisation, blastocyst implantation or even the length of gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine.

    Science.gov (United States)

    Flasse, Lydie C; Stern, David G; Pirson, Justine L; Manfroid, Isabelle; Peers, Bernard; Voz, Marianne L

    2013-04-15

    Notch signaling has a fundamental role in stem cell maintenance and in cell fate choice in the intestine of different species. Canonically, Notch signaling represses the expression of transcription factors of the achaete-scute like (ASCL) or atonal related protein (ARP) families. Identifying the ARP/ASCL genes expressed in the gastrointestinal tract is essential to build the regulatory cascade controlling the differentiation of gastrointestinal progenitors into the different intestinal cell types. The expression of the ARP/ASCL factors was analyzed in zebrafish to identify, among all the ARP/ASCL factors found in the zebrafish genome, those expressed in the gastrointestinal tract. ascl1a was found to be the earliest factor detected in the intestine. Loss-of-function analyses using the pia/ascl1a mutant, revealed that ascl1a is crucial for the differentiation of all secretory cells. Furthermore, we identify a battery of transcription factors expressed during secretory cell differentiation and downstream of ascl1a. Finally, we show that the repression of secretory cell fate by Notch signaling is mediated by the inhibition of ascl1a expression. In conclusion, this work identifies Ascl1a as a key regulator of the secretory cell lineage in the zebrafish intestine, playing the same role as Atoh1 in the mouse intestine. This highlights the diversity in the ARP/ASCL family members acting as cell fate determinants downstream from Notch signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. A Western Blot-based Investigation of the Yeast Secretory Pathway Designed for an Intermediate-Level Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Hood-DeGrenier, Jennifer K.

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in…

  11. A Western Blot-based Investigation of the Yeast Secretory Pathway Designed for an Intermediate-Level Undergraduate Cell Biology Laboratory

    Science.gov (United States)

    Hood-DeGrenier, Jennifer K.

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in…

  12. Inflammatory cues modulate the expression of secretory product genes, Golgi sulfotransferases and sulfomucin production in LS174T cells.

    Science.gov (United States)

    Croix, Jennifer A; Bhatia, Shikha; Gaskins, H Rex

    2011-12-01

    The signals that mediate goblet cell expression of specific mucin chemotypes are poorly defined. Animal and in vitro studies show that acidomucin chemotypes may be altered by inflammation and changes in intestinal microbiota. To examine factors that may elicit this response, human adenocarcinoma-derived LS174T cells, which have a goblet cell-like phenotype and produce both sulfo- and sialomucins, were used to examine the effects of selected microbial and host factors on expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production. Expression of genes encoding mucin 2 (MUC2), resistin-like molecule β (RETNLB), and trefoil factor 3 (TFF3) and Golgi sulfotransferases, carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), was measured by quantitative reverse transcriptase-polymerase chain reaction following treatment with bacterial flagellin, tumor necrosis factor α (TNF-α) or the mucogenic cytokine interleukin-13 (IL-13). Expression of the toll-like receptor 5 (TLR5) gene was also analysed. Sulfomucin expression was examined via high-iron diamide/alcian blue (HID/AB) histochemistry and immunofluorescent staining for the Sulfo Le(a) antigen, which is synthesized in part by GAL3ST2. Flagellin, IL-13 and TNF-α all significantly increased GAL3ST2, MUC2, TFF3 and TLR5 expression, while only IL-13 increased RETNLB and CHST5 expression. Based on HID/AB histochemistry, mucin sulfation was significantly increased in response to both flagellin and IL-13 but not TNF-α. Only treatment with flagellin increased the expression of the Sulfo Le(a) antigen. Collectively, these results indicate that bacterial flagellin, IL-13 and TNF-α differentially modulate the expression of goblet cell secretory product genes, sulfotransferases and sulfomucin production.

  13. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Copp& #233; , Jean-Philippe; Patil, Christopher; Rodier, Francis; Sun, Yu; Munoz, Denise; Goldstein, Joshua; Nelson, Peter; Desprez, Pierre-Yves; Campisi, Judith

    2008-10-24

    Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

  14. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Coppé

    Full Text Available Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP, which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that "senescent" mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen, do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3% oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-alpha. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP.

  15. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Coppé

    2008-12-01

    Full Text Available Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

  16. Adverse influence of coumestrol on secretory function of bovine luteal cells in the first trimester of pregnancy.

    Science.gov (United States)

    Młynarczuk, J; Wróbel, M H; Kotwica, J

    2013-07-01

    Coumestrol is one of a few biologically active substances present in leguminous plants, which are widely used as fodder for ruminants. Depending on the doses, coumestrol acts on the reproductive processes as an estrogen-like factor or antiestrogen to evoke a decrease in ovulation frequency, elongation of estrous cycle duration. The aim of the current investigations was to study the influence of coumestrol on secretory function of luteal cells obtained from first trimester of pregnant cows. Luteal cells (2.5 × 10(5) /mL) from 3rd to 5th, 6th to 8th, and 9th to 12th week of pregnancy were preincubated for 24 h and incubated with coumestrol (1 × 10(-6) M) for successive 48 h and the medium concentrations of progesterone (P4), oxytocin (OT), prostaglandin (PG) E2 and F2α were determined. Moreover, the expression of mRNA for neurophysin-I/oxytocin (NP-I/OT; precursor of OT) and peptidyl-glycine-α-amidating mono-oxygenase (PGA, an enzyme responsible for post-translational OT synthesis) was determined after 8 h of treatment. Coumestrol did not affect P4 secretion but increased the secretion of OT from the cells collected at all stages of gestation studied. Hence, the ratio of P4 to OT was markedly decreased. Simultaneously, coumestrol increased the expression of NP-I/OT mRNA during 9th to 12th weeks of pregnancy, and mRNA for PGA during 3rd to 5th and 9th to 12th weeks of gestation. Furthermore, coumestrol decreased PGE2 secretion from luteal cells in all studied stages of pregnancy, while it affected PGF2α metabolite (PGFM) concentration only from week 3 to 5 of pregnancy. Obtained results suggest that coumestrol impairs secretory function of the corpus luteum (CL) and this way it can affect the maintenance of pregnancy in the cow.

  17. Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility.

    Science.gov (United States)

    Roach, Gillian; Heath Wallace, Rachel; Cameron, Amy; Emrah Ozel, Rifat; Hongay, Cintia F; Baral, Reshica; Andreescu, Silvana; Wallace, Kenneth N

    2013-04-15

    The vertebrate intestinal epithelium is renewed continuously from stem cells at the base of the crypt in mammals or base of the fold in fish over the life of the organism. As stem cells divide, newly formed epithelial cells make an initial choice between a secretory or enterocyte fate. This choice has previously been demonstrated to involve Notch signaling as well as Atonal and Her transcription factors in both embryogenesis and adults. Here, we demonstrate that in contrast to the atoh1 in mammals, ascl1a is responsible for formation of secretory cells in zebrafish. ascl1a-/- embryos lack all intestinal epithelial secretory cells and instead differentiate into enterocytes. ascl1a-/- embryos also fail to induce intestinal epithelial expression of deltaD suggesting that ascl1a plays a role in initiation of Notch signaling. Inhibition of Notch signaling increases the number of ascl1a and deltaD expressing intestinal epithelial cells as well as the number of developing secretory cells during two specific time periods: between 30 and 34hpf and again between 64 and 74hpf. Loss of enteroendocrine products results in loss of anterograde motility in ascl1a-/- embryos. 5HT produced by enterochromaffin cells is critical in motility and secretion within the intestine. We find that addition of exogenous 5HT to ascl1a-/- embryos at near physiological levels (measured by differential pulse voltammetry) induce anterograde motility at similar levels to wild type velocity, distance, and frequency. Removal or doubling the concentration of 5HT in WT embryos does not significantly affect anterograde motility, suggesting that the loss of additional enteroendocrine products in ascl1a-/- embryos also contributes to intestinal motility. Thus, zebrafish intestinal epithelial cells appear to have a common secretory progenitor from which all subtypes form. Loss of enteroendocrine cells reveals the critical need for enteroendocrine products in maintenance of normal intestinal motility.

  18. Dense core secretory vesicles revealed as a dynamic Ca2+ store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera

    Science.gov (United States)

    Mitchell, Kathryn J.; Pinton, Paolo; Varadi, Aniko; Tacchetti, Carlo; Ainscow, Edward K.; Pozzan, Tullio; Rizzuto, Rosario; Rutter, Guy A.

    2001-01-01

    The role of dense core secretory vesicles in the control of cytosolic-free Ca2+ concentrations ([Ca2+]c) in neuronal and neuroendocrine cells is enigmatic. By constructing a vesicle-associated membrane protein 2–synaptobrevin.aequorin chimera, we show that in clonal pancreatic islet β-cells: (a) increases in [Ca2+]c cause a prompt increase in intravesicular-free Ca2+ concentration ([Ca2+]SV), which is mediated by a P-type Ca2+-ATPase distinct from the sarco(endo) plasmic reticulum Ca2+-ATPase, but which may be related to the PMR1/ATP2C1 family of Ca2+ pumps; (b) steady state Ca2+ concentrations are 3–5-fold lower in secretory vesicles than in the endoplasmic reticulum (ER) or Golgi apparatus, suggesting the existence of tightly bound and more rapidly exchanging pools of Ca2+; (c) inositol (1,4,5) trisphosphate has no impact on [Ca2+]SV in intact or permeabilized cells; and (d) ryanodine receptor (RyR) activation with caffeine or 4-chloro-3-ethylphenol in intact cells, or cyclic ADPribose in permeabilized cells, causes a dramatic fall in [Ca2+]SV. Thus, secretory vesicles represent a dynamic Ca2+ store in neuroendocrine cells, whose characteristics are in part distinct from the ER/Golgi apparatus. The presence of RyRs on secretory vesicles suggests that local Ca2+-induced Ca2+ release from vesicles docked at the plasma membrane could participate in triggering exocytosis. PMID:11571310

  19. Dense core secretory vesicles revealed as a dynamic Ca(2+) store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera.

    Science.gov (United States)

    Mitchell, K J; Pinton, P; Varadi, A; Tacchetti, C; Ainscow, E K; Pozzan, T; Rizzuto, R; Rutter, G A

    2001-10-01

    The role of dense core secretory vesicles in the control of cytosolic-free Ca(2+) concentrations ([Ca(2+)](c)) in neuronal and neuroendocrine cells is enigmatic. By constructing a vesicle-associated membrane protein 2-synaptobrevin.aequorin chimera, we show that in clonal pancreatic islet beta-cells: (a) increases in [Ca(2+)](c) cause a prompt increase in intravesicular-free Ca(2+) concentration ([Ca(2+)]SV), which is mediated by a P-type Ca(2+)-ATPase distinct from the sarco(endo) plasmic reticulum Ca(2+)-ATPase, but which may be related to the PMR1/ATP2C1 family of Ca(2+) pumps; (b) steady state Ca(2+) concentrations are 3-5-fold lower in secretory vesicles than in the endoplasmic reticulum (ER) or Golgi apparatus, suggesting the existence of tightly bound and more rapidly exchanging pools of Ca(2+); (c) inositol (1,4,5) trisphosphate has no impact on [Ca(2+)](SV) in intact or permeabilized cells; and (d) ryanodine receptor (RyR) activation with caffeine or 4-chloro-3-ethylphenol in intact cells, or cyclic ADPribose in permeabilized cells, causes a dramatic fall in [Ca(2+)](SV). Thus, secretory vesicles represent a dynamic Ca(2+) store in neuroendocrine cells, whose characteristics are in part distinct from the ER/Golgi apparatus. The presence of RyRs on secretory vesicles suggests that local Ca(2+)-induced Ca(2+) release from vesicles docked at the plasma membrane could participate in triggering exocytosis.

  20. Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R.L.; Austen, K.F. (Brigham and Women' s Hospital, Boston, MA (USA)); Fox, C.C.; Lichtenstein, L.M. (Johns Hopkins School of Medicine, Baltimore, MD (USA))

    1988-04-01

    The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of {sup 35}S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although ({sup 35}S)heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. The authors demonstrate that human lung mast cells of 96% purity incorporate ({sup 35}S)sulfate into separate heparin and chondroitin sulfate proteoglycans in an {approx}2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin ({sup 35}S)sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin ({sup 35}S)sulfate E proteoglycans and the ({sup 35}S)heparin proteoglycans were exocytosed from the ({sup 35}S)sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of {sup 35}S-labeled proteoglycans reside in the secretory granules of these human lung mast cells.

  1. Isolation of a sesquiterpene synthase expressing in specialized epithelial cells surrounding the secretory cavities in rough lemon (Citrus jambhiri).

    Science.gov (United States)

    Uji, Yuya; Ozawa, Rika; Shishido, Hodaka; Taniguchi, Shiduku; Takabayashi, Junji; Akimitsu, Kazuya; Gomi, Kenji

    2015-05-15

    Volatile terpenoids such as monoterpenes and sesquiterpenes play multiple roles in plant responses and are synthesized by terpene synthases (TPSs). We have previously isolated a partial TPS gene, RlemTPS4, that responds to microbial attack in rough lemon. In this study, we isolated a full length RlemTPS4 cDNA from rough lemon. RlemTPS4 localized in the cytosol. The recombinant RlemTPS4 protein was obtained using a prokaryotic expression system and GC-MS analysis of the terpenes produced by the RlemTPS4 enzymatic reaction determined that RlemTPS4 produces some sesquiterpenes such as δ-elemene. The RlemTPS4 gene was specifically expressed in specialized epithelial cells surrounding the oil secretory cavities in rough lemon leaf tissue.

  2. Isoprenoid Biosynthesis. Metabolite Profiling of Peppermint Oil Gland Secretory Cells and Application to Herbicide Target Analysis1

    Science.gov (United States)

    Lange, B. Markus; Ketchum, Raymond E.B.; Croteau, Rodney B.

    2001-01-01

    Two independent pathways operate in plants for the synthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the central intermediates in the biosynthesis of all isoprenoids. The mevalonate pathway is present in the cytosol, whereas the recently discovered mevalonate-independent pathway is localized to plastids. We have used isolated peppermint (Mentha piperita) oil gland secretory cells as an experimental model system to study the effects of the herbicides fosmidomycin, phosphonothrixin, methyl viologen, benzyl viologen, clomazone, 2-(dimethylamino)ethyl diphosphate, alendronate, and pamidronate on the pools of metabolites related to monoterpene biosynthesis via the mevalonate-independent pathway. A newly developed isolation protocol for polar metabolites together with an improved separation and detection method based on liquid chromatography-mass spectrometry have allowed assessment of the enzyme targets for a number of these herbicides. PMID:11553758

  3. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding ...

  4. Prospective Isolation of Bronchiolar Stem Cells Based Upon Immunophenotypic and Autofluorescence Characteristics

    Science.gov (United States)

    Teisanu, Roxana M.; Lagasse, Eric; Whitesides, John F.; Stripp, Barry R.

    2009-01-01

    Bronchiolar stem cells have been functionally defined in vivo on the basis of their resistance to chemical (naphthalene) injury, their infrequent proliferation relative to other progenitor cell types, and their coexpression of the airway and alveolar secretory cell markers Clara cell secretory protein and pro-surfactant protein C, respectively. Cell surface markers that have previously been used for their prospective isolation included Sca-1 and CD34. Using transgenic animal models associated with stem cell expansion, ablation, and lineage tracing, we demonstrate that CD34pos cells do not belong to the airway epithelial lineage and that cell surface Sca-1 immunoreactivity does not distinguish between bronchiolar stem and facultative transit-amplifying (Clara) cell populations. Furthermore, we show that high autofluorescence (AFhigh) is a distinguishing characteristic of Clara cells allowing for the fractionation of AFlow bronchiolar stem cells. On the basis of these data we show that the defining phenotype of the bronchiolar stem cell is CD45neg CD31neg CD34neg Sca-llow AFlow. This refinement in the definition of bronchiolar stem cells provides a critical tool by which to assess functional and molecular distinctions between bronchiolar stem cells and the more abundant pool of facultative transit-amplifying (Clara) cells. PMID:19056905

  5. Pob1 ensures cylindrical cell shape by coupling two distinct rho signaling events during secretory vesicle targeting.

    Science.gov (United States)

    Nakano, Kentaro; Toya, Mika; Yoneda, Aki; Asami, Yukiko; Yamashita, Akira; Kamasawa, Naomi; Osumi, Masako; Yamamoto, Masayuki

    2011-06-01

    Proper cell morphogenesis requires the co-ordination of cell polarity, cytoskeletal organization and vesicle trafficking. The Schizosaccharomyces pombe mutant pob1-664 has a curious lemon-like shape, the basis of which is not understood. Here, we found abundant vesicle accumulation in these cells, suggesting that Pob1 plays a role in vesicle trafficking. We identified Rho3 as a multicopy suppressor of this phenotype. Because Rho3 function is related to For3, an actin-polymerizing protein, and Sec8, a component of the exocyst complex, we analyzed their functional relationship with Pob1. Pob1 was essential for the formation of actin cables (by interacting with For3) and for the polarized localization of Sec8. Although neither For3 nor Sec8 is essential for polarized growth, their simultaneous disruption prevented tip growth and yielded a lemon-like cell morphology similar to pob1-664. Thus, Pob1 may ensure cylindrical cell shape of S. pombe by coupling actin-mediated vesicle transport and exocyst-mediated vesicle tethering during secretory vesicle targeting.

  6. AtGRIP protein locates to the secretory vesicles of trans Golgi-network in Arabidopsis root cap cells

    Institute of Scientific and Technical Information of China (English)

    CHEN Ying; ZHANG Wei; ZHAO Lei; LI Yan

    2008-01-01

    GRIP domain proteins, locating to the trans-Golgi network, are thought to play an essential role in Golgi apparatus trafficking in yeast and animal cells. In the present study, AtGRIP cDNA was amplified by reverse transcriptase PCR from RNA isolated from Arabidopsis seedling. The GST fusion protein of AtGRIP was affinity-purified and its rabbit polyclonal antibody was obtained. Immuno-blotting with the purified anti-AtGRIP polyclonal antibody demonstrated that the molecular mass of AtGRIP protein is about 92 kD, and its expression is not tissue-specific in Arabidopsis. Immunoflourescent labeling and confocal microscopy revealed that the AtGRIP protein was co-localized with Golgi stacks in Arabidop-sis root cells. Immuno-gold labeling and electron microscopy observation showed that AtGRIP protein was mainly located to the membrane of the secretory vesicles of trans-Golgi network in Arabidopsis root cap cells. Taken together, these results indicate that the localization of GRIP domain proteins be-tween plants and animal cells are conserved. These results also suggest that the AtGRIP may be in-volved in regulating the formation or sorting of Golgi-associated vesicles in plant cells.

  7. Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic beta-cells.

    Science.gov (United States)

    Varadi, Aniko; Ainscow, Edward K; Allan, Victoria J; Rutter, Guy A

    2002-11-01

    Recruitment of secretory vesicles to the cell surface is essential for the sustained secretion of insulin in response to glucose. At present, the molecular motors involved in this movement, and the mechanisms whereby they may be regulated, are undefined. To investigate the role of kinesin family members, we labelled densecore vesicles in clonal beta-cells using an adenovirally expressed, vesicle-targeted green fluorescent protein (phogrin.EGFP), and employed immunoadsorption to obtain highly purified insulin-containing vesicles. Whereas several kinesin family members were expressed in this cell type, only conventional kinesin heavy chain (KHC) was detected in vesicle preparations. Expression of a dominant-negative KHC motor domain (KHC(mut)) blocked all vesicular movements with velocity >0.4 micro m second(-1), which demonstrates that kinesin activity was essential for vesicle motility in live beta-cells. Moreover, expression of KHC(mut) strongly inhibited the sustained, but not acute, stimulation of secretion by glucose. Finally, vesicle movement was stimulated by ATP dose-dependently in permeabilized cells, which suggests that glucose-induced increases in cytosolic [ATP] mediate the effects of the sugar in vivo, by enhancing kinesin activity. These data therefore provide evidence for a novel mechanism whereby glucose may enhance insulin release.

  8. Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion.

    Science.gov (United States)

    Katgı, Abdullah; Sevindik, Ömür Gökmen; Gökbulut, Aysun Adan; Özsan, Güner Hayri; Yüksel, Faize; Solmaz, Şerife Medeni; Alacacıoğlu, İnci; Özcan, Mehmet Ali; Demirkan, Fatih; Baran, Yusuf; Pişkin, Özden

    2015-10-01

    There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability. © The Author(s) 2014.

  9. Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons.

    Science.gov (United States)

    Wei, S; Ong, W Y; Thwin, M M; Fong, C W; Farooqui, A A; Gopalakrishnakone, P; Hong, W

    2003-01-01

    Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis. External application of group IIA sPLA2 (purified crotoxin subunit B or purified human synovial sPLA2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.

  10. JAM-A promotes wound healing by enhancing both homing and secretory activities of mesenchymal stem cells.

    Science.gov (United States)

    Wu, Minjuan; Ji, Shizhao; Xiao, Shichu; Kong, Zhengdong; Fang, He; Zhang, Yunqing; Ji, Kaihong; Zheng, Yongjun; Liu, Houqi; Xia, Zhaofan

    2015-10-01

    The homing ability and secretory function of mesenchymal stem cells (MSCs) are key factors that influence cell involvement in wound repair. These factors are controlled by multilayer regulatory circuitry, including adhesion molecules, core transcription factors (TFs) and certain other regulators. However, the role of adhesion molecules in this regulatory circuitry and their underlying mechanism remain undefined. In the present paper, we demonstrate that an adhesion molecule, junction adhesion molecule A (JAM-A), may function as a key promoter molecule to regulate skin wound healing by MSCs. In in vivo experiments, we show that JAM-A up-regulation promoted both MSC homing to full-thickness skin wounds and wound healing-related cytokine secretion by MSCs. In vitro experiments also showed that JAM-A promoted MSC proliferation and migration by activating T-cell lymphoma invasion and metastasis 1 (Tiam1). We suggest that JAM-A up-regulation can increase the proliferation, cytokine secretion and wound-homing ability of MSCs, thus accelerating the repair rate of full-thickness skin defects. These results may provide insights into a novel and potentially effective approach to improve the efficacy of MSC treatment.

  11. Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte-derived dendritic cells.

    Science.gov (United States)

    Rehman, Z U; Knight, J S; Koolaard, J; Simpson, H V; Pernthaner, A

    2015-12-01

    The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy.

  12. Clara细胞在兔肺缺血再灌注损伤中的作用%Role of Clara cells in lung ischemia-reperfusion injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    李戈辉; 李李; 沈金美; 裴万敏

    2010-01-01

    目的 探讨Clara细胞在兔肺缺血再灌注(IR)损伤中的作用.方法 健康家兔24只.随机分为3组(n=8):假手术组(S组)、IR组、肺Clara细胞剥除+IR组(CIR组).CIR组置于萘气体浓度为89.28 mg/m3的气体箱中12 h,S组和IR组置于无萘气体箱中12 h.取出正常饲养24 h后.IR组和CIR组采用阻断左肺门60 min,再灌注120 min的方法制备肺IR模型,S组不予阻断肺门.于再灌注120 min时采集颈动脉血样5 ml,测定血清TNF-α和总蛋白浓度,收集支气管肺泡灌洗液(BALF),计数WBC、中性粒细胞(PMN),计算PMN百分比,取肺组织测定MDA含量和湿/干重比值(W/D比值),观察病理学改变和Clara细胞的分布情况.结果 S组肺泡完整,肺实质无炎性细胞浸润,可见较多的Clara细胞;IR组肺不张伴肺气肿,肺间质增宽水肿,中度炎性细胞浸润,肺泡腔内有淡黄色渗出,渗出物有WBC,亦可见较多的Clara细胞;CIR组炎性细胞浸润严重,肺泡腔内渗出物多.WBC较多,血管腔变窄,甚至出现无复流现象,Clara细胞少见.与S组比较,IR组和CIR组BALF中WBC计数、PMN百分比、血清TNF-α浓度、肺组织MDA含量及W/D比值升高(P<0.05 );与IR组比较,CIR组BALF中WBC计数、PMN百分比、血清TNF-α浓度、肺组织MDA含量及W/D比值升高(P<0.05).结论 肺IR损伤时兔肺内Clara细胞通过抑制炎性反应产生内源性的保护作用.%Objective To investigate the role of Clara cells in lung ischemia-reperfusion (I/R) injury in rabbits.Methods Twenty-four healthy 10-12 month old rabbits of either sex weighing 1.5-2.0 kg were randomly divided into 3 groups ( n = 8 each) ; group A sham operation (group S) ; group B lung I/R and group C Clara cell elimination+ lung I/R. The animals were anesthetized with iv pentobarbital 30 mg/kg , tracheostomized and mechanically ventilated. In group B and C lung I/R was induced by clamping the left hilum of lung for 60 min followed by 120 min repeffusion. In group C Clara ceils

  13. Histological characterization of the special venom secretory cells in the stinger of rays in the northern waters of Persian Gulf and Oman Sea.

    Science.gov (United States)

    Dehghani, Hadi; Sajjadi, Mir Masoud; Parto, Paria; Rajaian, Hamid; Mokhlesi, Amin

    2010-06-01

    Rays are common elasmobranches in the northern waters of Persian Gulf and Oman Sea that may have one or more mineralized serrated stingers on the whip-like tail. The stingers are covered by epidermal cells among which some can produce venom. When these animals are dorsally touched, the stinger can be introduced into the aggressor by a whip reflex mechanism of the tail when the pectoral fins are touched, causing severe mechanical injuries and inoculating the venom. The exact localization of the venom secretory cells in the stinger of different species is controversial, but it is known that the cells are preferentially located in the ventro-lateral grooves in marine stingrays. A comparative morphological characterization of the stinger epidermal tissue of different ray species in the northern part of Persian Gulf and Oman Sea was carried out in this study. EDTA was used for decalcification of stings and conventional histological processes were subsequently employed. The results indicated that structure of dermis and epidermis layers of stings in all species are similar to the structure of corresponding layers in other parts of fish's body. The results of the present study have shown that all examined species of Dasyatidae family, but not Myliobatidae and Gymnuridae families, had venom secretory cells. Distribution of venom secretory cells varies in each species and is often located around or inside the stinger ventro-lateral grooves. These differences among the stingers of various species may explain the envenomation severity in these species. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. Key role of mast cells and their major secretory products in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He

    2004-01-01

    Hirtoncally, mast cells were known as a key cell type involved in type I hypersensitivity Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the iieum and colon of patients with IBD, which was accompanied by great changes of the content in mart cells such as dramatically increaed expression of TNFα, IL-16 and substance P.The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of petienta with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD.However, Iittle is known of the actions of histamine, tryptase,chymase and carboxypeptidase in IBD. Over the lart decade,heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the petienis showed good clinical and laberatory respense with no senous advere effectd. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast colls to amplify their own activationdegranulation signals in an autocrine or paracrine mannec.The hypethesis is that mast cell secretogogues induce mart cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 recepton.Whereas released tryptase acts similarly to hirtamine, but activates mart cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the

  15. Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

    DEFF Research Database (Denmark)

    Schulz, Anna M; Stutte, Susanne; Hogl, Sebastian

    2015-01-01

    Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42...... disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up-regulation of intracellular molecules to the cell surface....

  16. The position of mitochondria and ER in relation to that of the secretory sites in chromaffin cells.

    Science.gov (United States)

    Villanueva, José; Viniegra, Salvador; Gimenez-Molina, Yolanda; García-Martinez, Virginia; Expósito-Romero, Giovanna; del Mar Frances, Maria; García-Sancho, Javier; Gutiérrez, Luis M

    2014-12-01

    Knowledge of the distribution of mitochondria and endoplasmic reticulum (ER) in relation to the position of exocytotic sites is relevant to understanding the influence of these organelles in tuning Ca(2+) signals and secretion. Confocal images of probes tagged to mitochondria and the F-actin cytoskeleton revealed the existence of two populations of mitochondria, one that was cortical and one that was perinuclear. This mitochondrial distribution was also confirmed by using electron microscopy. In contrast, ER was sparse in the cortex and more abundant in deep cytoplasmic regions. The mitochondrial distribution might be due to organellar transport, which experiences increasing restrictions in the cell cortex. Further study of organelle distribution in relation to the position of SNARE microdomains and the granule fusion sites revealed that a third of the cortical mitochondria colocalized with exocytotic sites and another third located at a distance closer than two vesicle diameters. ER structures were also present in the vicinity of secretory sites but at a lower density. Therefore, mitochondria and ER have a spatial distribution that suggests a specialized role in modulation of exocytosis that fits with the role of cytosolic Ca(2+) microdomains described previously. © 2014. Published by The Company of Biologists Ltd.

  17. Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions

    Science.gov (United States)

    Vendelova, Emilia; Camargo de Lima, Jeferson; Lorenzatto, Karina Rodrigues; Monteiro, Karina Mariante; Mueller, Thomas; Veepaschit, Jyotishman; Grimm, Clemens; Brehm, Klaus; Hrčková, Gabriela; Lutz, Manfred B.; Ferreira, Henrique B.

    2016-01-01

    Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts. PMID:27736880

  18. Secretory phospholipase A2-mediated neuronal cell death involves glutamate ionotropic receptors

    DEFF Research Database (Denmark)

    de Turco, Elena B; Diemer, Nils Henrik; Bazan, Nicolas G

    2002-01-01

    To define the significance of glutamate ionotropic receptors in sPLA -mediated neuronal cell death we used the NMDA receptor antagonist MK-801 and the AMPA receptor antagonist PNQX. In primary neuronal cell cultures both MK-801 and PNQX inhibited sPLA - and glutamate-induced neuronal death. [ H]A...

  19. Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro.

    Directory of Open Access Journals (Sweden)

    Justin Komguep Nono

    Full Text Available BACKGROUND: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E.multilocularis, by excretory/secretory (E/S-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. METHODOLOGY/PRINCIPAL FINDINGS: We established cultivation systems for exposing DC to live material from early (oncosphere, chronic (metacestode and late (protoscolex infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naïve T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. CONCLUSIONS: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The

  20. Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells

    Science.gov (United States)

    Schulz, Anna M.; Stutte, Susanne; Hogl, Sebastian; Luckashenak, Nancy; Dudziak, Diana; Leroy, Céline; Forné, Ignasi; Imhof, Axel; Müller, Stephan A.; Brakebusch, Cord H.; Lichtenthaler, Stefan F.

    2015-01-01

    Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 deficiency renders DCs phenotypically mature as they up-regulate the co-stimulatory molecule CD86 from intracellular storages to the cell surface. Cdc42 knockout DCs also accumulate high amounts of invariant chain–major histocompatibility complex (MHC) class II complexes at the cell surface, which cannot efficiently present peptide antigens (Ag’s) for priming of Ag-specific CD4 T cells. Proteome analyses showed a significant reduction in lysosomal MHC class II–processing proteins, such as cathepsins, which are lost from DCs by enhanced secretion. As these effects on DCs can be mimicked by chemical actin disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up-regulation of intracellular molecules to the cell surface. PMID:26553928

  1. The Fas pathway is involved in pancreatic beta cell secretory function

    DEFF Research Database (Denmark)

    Schumann, Desiree M; Maedler, Kathrin; Franklin, Isobel

    2007-01-01

    Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending......-kappaB-inducing kinase and RelB. This led to increased PDX-1 and insulin production independent of changes in cell turnover. The results support a previously undescribed role for the Fas pathway in regulating insulin production and release....

  2. The role of secretory immunoglobulin A in the natural sensing of commensal bacteria by mouse Peyer's patch dendritic cells.

    Science.gov (United States)

    Rol, Nicolas; Favre, Laurent; Benyacoub, Jalil; Corthésy, Blaise

    2012-11-16

    The mammalian gastrointestinal (GI) tract harbors a diverse population of commensal species collectively known as the microbiota, which interact continuously with the host. From very early in life, secretory IgA (SIgA) is found in association with intestinal bacteria. It is considered that this helps to ensure self-limiting growth of the microbiota and hence participates in symbiosis. However, the importance of this association in contributing to the mechanisms ensuring natural host-microorganism communication is in need of further investigation. In the present work, we examined the possible role of SIgA in the transport of commensal bacteria across the GI epithelium. Using an intestinal loop mouse model and fluorescently labeled bacteria, we found that entry of commensal bacteria in Peyer's patches (PP) via the M cell pathway was mediated by their association with SIgA. Preassociation of bacteria with nonspecific SIgA increased their dynamics of entry and restored the reduced transport observed in germ-free mice known to have a marked reduction in intestinal SIgA production. Selective SIgA-mediated targeting of bacteria is restricted to the tolerogenic CD11c(+)CD11b(+)CD8(-) dendritic cell subset located in the subepithelial dome region of PPs, confirming that the host is not ignorant of its resident commensals. In conclusion, our work supports the concept that SIgA-mediated monitoring of commensal bacteria targeting dendritic cells in the subepithelial dome region of PPs represents a mechanism whereby the host mucosal immune system controls the continuous dialogue between the host and commensal bacteria.

  3. Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory/secretory product

    Institute of Scientific and Technical Information of China (English)

    Chanitra Thuwajit; Peti Thuwajit; Kazuhiko Uchida; Daoyot Daorueang; Sasithorn Kaewkes; Sopit Wongkham; Masanao Miwa

    2006-01-01

    AIM: To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory (ES) product.METHODS: NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA (cDNA) array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR.RESULTS: Among a total of 15 000 genes/ESTs, 239genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O. viverrini ES product. The expression level of signal transduction genes; pkC, pdgfrα, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC, eps 8 and tgfβ 1/4 which are the downstream signaling molecules of either epidermal growth factor (EGF) or transforming growth factor-β (TGF-β) showed statistical significance (P < 0.05). CONCLUSION: O. viverrini ES product stimulates the significant changes of gene expression in several

  4. MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors.

    Science.gov (United States)

    Badi, Ileana; Burba, Ilaria; Ruggeri, Clarissa; Zeni, Filippo; Bertolotti, Matteo; Scopece, Alessandro; Pompilio, Giulio; Raucci, Angela

    2015-11-01

    Arterial aging is a major risk factor for the occurrence of cardiovascular diseases. The aged artery is characterized by endothelial dysfunction and vascular smooth muscle cells altered physiology together with low-grade chronic inflammation. MicroRNA-34a (miR-34a) has been recently implicated in cardiac, endothelial, and endothelial progenitor cell senescence; however, its contribution to aging-associated vascular smooth muscle cells phenotype has not been explored so far. We found that miR-34a was highly expressed in aortas isolated from old mice. Moreover, its well-known target, the longevity-associated protein SIRT1, was significantly downregulated during aging in both endothelial cells and vascular smooth muscle cells. Increased miR-34a as well as decreased SIRT1 expression was also observed in replicative-senescent human aortic smooth muscle cells. miR-34a overexpression in proliferative human aortic smooth muscle cells caused cell cycle arrest along with enhanced p21 protein levels and evidence of cell senescence. Furthermore, miR-34a ectopic expression induced pro-inflammatory senescence-associated secretory phenotype molecules. Finally, SIRT1 protein significantly decreased upon miR-34a overexpression and restoration of its levels rescued miR-34a-dependent human aortic smooth muscle cells senescence, but not senescence-associated secretory phenotype factors upregulation. Taken together, our findings suggest that aging-associated increase of miR-34a expression levels, by promoting vascular smooth muscle cells senescence and inflammation through SIRT1 downregulation and senescence-associated secretory phenotype factors induction, respectively, may lead to arterial dysfunctions.

  5. Structures, Components and Functions of Secretory Tissues in Houttuynia cordata

    Institute of Scientific and Technical Information of China (English)

    Xi-Lu Ni; Li Peng; Wen-Zhe Liu

    2007-01-01

    Houttuynia cordata Thunb., traditionally used as a therapeutic plant in folk medicine, has shown antioxidant and anticancer activities.The species, as a core component of paleoherbs, is normally characterized based on the presence of different types of secretory tissue: oil cells, three types of secretory cells and glandular hairs.The aim of this work was to study the structural, componential, and the functional characteristics of the secretory tissues in both the floral and vegetative parts.The results indicate that oll cells and secretory cells are distributed in all organs of the plant, while glandular hairs are situated on the aerial stems and leaves.Both oil cells and glandular hairs initiate from the protoderm, but their developmental processes are different.Although three types of secretory cells initiate from different primary meristems, the developmental pattems of different secretory cells are the same.Also, although the origins of secretory cells are different from oil cells, their early developmental processes are the same.Histochemical results show that oil cells, secretory cells and glandular hairs produce flavonoids, phenolic compounds, tannins, lipids, aldehyde and ketone-compounds.In addition, there are terpenoids and pectic-like substances in oil cells, alkaloids in secretory cells of aerial stems, and terpenoids and alkaloids in glandular hairs.These compounds play very important roles in protecting plants from being eaten by herbivores (herbivory) and infected by microbial pathogens.The oil cell and secretory cell, as unicellular secretory tissues, are intermediates between the primitive surface glandular and secretory cavity and canal during the evolution of secretory structures.

  6. Morphological and biochemical analysis of the secretory pathway in melanoma cells with distinct metastatic potential

    NARCIS (Netherlands)

    Ayala, [No Value; Babia, T; Baldassarre, M; Pompeo, A; Fabra, A; Kok, JW; Luini, A; Buccione, R; Egea, G

    1999-01-01

    In this report, we have investigated whether alterations of the morphological and functional aspects of the biosecretory membrane system are associated with the metastatic potential of tumor cells. To this end, we have analyzed the morphology of the Golgi complex, the cytoskeleton organization and m

  7. Senescent cells and their secretory phenotype as targets for cancer therapy

    NARCIS (Netherlands)

    Velarde, Michael C; Demaria, Marco; Campisi, Judith

    2013-01-01

    Cancer is a devastating disease that increases exponentially with age. Cancer arises from cells that proliferate in an unregulated manner, an attribute that is countered by cellular senescence. Cellular senescence is a potent tumor-suppressive process that halts the proliferation, essentially

  8. CLARA: an integrated clinical research administration system.

    Science.gov (United States)

    Bian, Jiang; Xie, Mengjun; Hogan, William; Hutchins, Laura; Topaloglu, Umit; Lane, Cheryl; Holland, Jennifer; Wells, Thomas

    2014-10-01

    Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning.

  9. A Western blot-based investigation of the yeast secretory pathway designed for an intermediate-level undergraduate cell biology laboratory.

    Science.gov (United States)

    Hood-Degrenier, Jennifer K

    2008-01-01

    The movement of newly synthesized proteins through the endomembrane system of eukaryotic cells, often referred to generally as the secretory pathway, is a topic covered in most intermediate-level undergraduate cell biology courses. An article previously published in this journal described a laboratory exercise in which yeast mutants defective in two distinct steps of protein secretion were differentiated using a genetic reporter designed specifically to identify defects in the first step of the pathway, the insertion of proteins into the endoplasmic reticulum (Vallen, 2002). We have developed two versions of a Western blotting assay that serves as a second way of distinguishing the two secretory mutants, which we pair with the genetic assay in a 3-wk laboratory module. A quiz administered before and after students participated in the lab activities revealed significant postlab gains in their understanding of the secretory pathway and experimental techniques used to study it. A second survey administered at the end of the lab module assessed student perceptions of the efficacy of the lab activities; the results of this survey indicated that the experiments were successful in meeting a set of educational goals defined by the instructor.

  10. In situ localization of gene transcriptions for monoterpene synthesis in irregular parenchymic cells surrounding the secretory cavities in rough lemon (Citrus jambhiri).

    Science.gov (United States)

    Yamasaki, Yumiko; Akimitsu, Kazuya

    2007-11-01

    A cDNA (RlemispF) encoding 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, an enzyme of the methyl erythritol phosphate (MEP) pathway, and two homologs (RlemTPS1 and RlemTPS2) of citrus monoterpene synthase cDNA were isolated from the rough lemon (Citrus jambhiri). Transient localization of all or a part of RlemispF fused to a green fluorescence protein using particle gun-mediated DNA delivery localized RlemispF in the chloroplast. Transcripts of RlemispF and other monoterpene synthase genes are constitutively expressed in leaves of rough lemon. Transcript accumulations of RlemispF and RlemTPS1 were not induced by microbe attacks, but microbe attack weakly induced RlemTPS2 expression. Wounding decreased RlemispF expression. RlemispF and two different monoterpene synthase genes were specifically expressed in the epithelial tissue cells with dense cytoplasm that surround secretory cavities, which form a broadly round package containing a large volume of essential oils composed of monoterpenes. Interestingly, although expressions of RlemTPS1 and RlemTPS2 were detected at both mature and developing secretory cavities, the RlemispF-expressing cells were found more at around developing secretory cavities.

  11. Two distinct secretory vesicle–priming steps in adrenal chromaffin cells

    OpenAIRE

    Liu, Yuanyuan; Schirra, Claudia; Edelmann, Ludwig; Matti, Ulf; Rhee, JeongSeop; Hof, Detlef; Bruns, Dieter; Brose, Nils; Rieger, Heiko; Stevens, David R.; Rettig, Jens

    2010-01-01

    Priming of large dense-core vesicles (LDCVs) is a Ca2+-dependent step by which LDCVs enter a release-ready pool, involving the formation of the soluble N-ethyl-maleimide sensitive fusion protein attachment protein (SNAP) receptor complex consisting of syntaxin, SNAP-25, and synaptobrevin. Using mice lacking both isoforms of the calcium-dependent activator protein for secretion (CAPS), we show that LDCV priming in adrenal chromaffin cells entails two distinct steps. CAPS is required for primin...

  12. Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

    Science.gov (United States)

    Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

    2015-06-01

    Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs.

  13. The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Soo-Wan Nam

    2012-01-01

    Full Text Available The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs, which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05 notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL. AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.

  14. Clara Maass, yellow fever and human experimentation.

    Science.gov (United States)

    Chaves-Carballo, Enrique

    2013-05-01

    Clara Louise Maass, a 25-year-old American nurse, died of yellow fever on August 24, 1901, following experimental inoculation by infected mosquitoes in Havana, Cuba. The human yellow fever experiments were initially conducted by MAJ Walter Reed, who first used written informed consent and proved the validity of Finlay's mosquito-vector hypothesis. Despite informed consent form and an incentive of $100 in U.S. gold, human subjects were exposed to a deadly virus. The deaths of Clara Maass and two Spanish immigrants resulted in a public outcry and the immediate cessation of yellow fever human experiments in Cuba.

  15. The 2 MW Santa Clara Project

    Science.gov (United States)

    Eichenberger, Paul H.

    The City of Santa Clara, CA, USA, has hosted the world's first field demonstration of a molten carbonate fuel cell power plant. This US$46 million, 2 MW generator was a joint effort of five US utilities, the federal government, and two US research organizations. The demonstration used sixteen 125 kW stacks placed in four modules. The balance of plant (BOP) is the equipment that prepares and supplies the fuel to the stacks and converts the d.c. current to a.c. BOP construction started in April 1994, and was completed in June 1995. The BOP configuration allowed testing and development before installation of the four modules. The final full-temperature test was completed in February 1996. The four fuel cell modules were installed and cured, and power delivery began in April 1996. The plant operated for approximately 720 h at design output before electrical anomalies occurred and the plant was shut down for repairs. The plant restarted in August, but it soon became obvious that other problems had been caused by the electrical anomalies. The plant shut down and was reconfigured to a 1 MW plant. The restarted plant was ramped to 1 MW, but additional problems began to occur and the plant demonstration ended. The plant produced 2500 MWh, and operated at 1000°F, or higher, for over 5290 h. The plant set operational records, and demonstrated multistack, automatic control, and stable-field operation. Power quality met all standards with no measurable NOx or SOx output. The plant isolated itself from the grid during two major California, USA grid outages. The plant also experienced a shutdown of the automatic control system, and placed itself on hot standby using the mechanical field systems. The plant then restarted without incident.

  16. Two distinct secretory vesicle-priming steps in adrenal chromaffin cells.

    Science.gov (United States)

    Liu, Yuanyuan; Schirra, Claudia; Edelmann, Ludwig; Matti, Ulf; Rhee, JeongSeop; Hof, Detlef; Bruns, Dieter; Brose, Nils; Rieger, Heiko; Stevens, David R; Rettig, Jens

    2010-09-20

    Priming of large dense-core vesicles (LDCVs) is a Ca(2+)-dependent step by which LDCVs enter a release-ready pool, involving the formation of the soluble N-ethyl-maleimide sensitive fusion protein attachment protein (SNAP) receptor complex consisting of syntaxin, SNAP-25, and synaptobrevin. Using mice lacking both isoforms of the calcium-dependent activator protein for secretion (CAPS), we show that LDCV priming in adrenal chromaffin cells entails two distinct steps. CAPS is required for priming of the readily releasable LDCV pool and sustained secretion in the continued presence of high Ca(2+) concentrations. Either CAPS1 or CAPS2 can rescue secretion in cells lacking both CAPS isoforms. Furthermore, the deficit in the readily releasable LDCV pool resulting from CAPS deletion is reversed by a constitutively open form of syntaxin but not by Munc13-1, a priming protein that facilitates the conversion of syntaxin to the open conformation. Our data indicate that CAPS functions downstream of Munc13s but also interacts functionally with Munc13s in the LDCV-priming process.

  17. Regulation of lipid synthesis genes and milk fat production in human mammary epithelial cells during secretory activation.

    Science.gov (United States)

    Mohammad, Mahmoud A; Haymond, Morey W

    2013-09-15

    Expression of genes for lipid biosynthetic enzymes during initiation of lactation in humans is unknown. Our goal was to study mRNA expression of lipid metabolic enzymes in human mammary epithelial cell (MEC) in conjunction with the measurement of milk fatty acid (FA) composition during secretory activation. Gene expression from mRNA isolated from milk fat globule (MFG) and milk FA composition were measured from 6 h to 42 days postpartum in seven normal women. Over the first 96 h postpartum, daily milk fat output increased severalfold and mirrored expression of genes for all aspects of lipid metabolism and milk FA production, including lipolysis at the MEC membrane, FA uptake from blood, intracellular FA transport, de novo FA synthesis, FA and glycerol activation, FA elongation, FA desaturation, triglyceride synthesis, cholesterol synthesis, and lipid droplet formation. Expression of the gene for a key lipid synthesis regulator, sterol regulatory element-binding transcription factor 1 (SREBF1), increased 2.0-fold by 36 h and remained elevated over the study duration. Expression of genes for estrogen receptor 1, thyroid hormone-responsive protein, and insulin-induced 2 increased progressively to plateau by 96 h. In contrast, mRNA of peroxisome proliferator-activated receptor-γ decreased severalfold. With onset of lactation, increased de novo synthesis of FA was the most prominent change in milk FA composition and mirrored the expression of FA synthesis genes. In conclusion, milk lipid synthesis and secretion in humans is a complex process requiring the orchestration of a wide variety of pathways of which SREBF1 may play a primary role.

  18. Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells

    DEFF Research Database (Denmark)

    Olsen, Hervør L; Hoy, Marianne; Zhang, Wei;

    2003-01-01

    on phosphatidylinositol 4-kinase (PI 4-kinase) activity and that inhibition of this enzyme suppresses glucose-stimulated insulin secretion. Intracellular application of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] stimulated exocytosis by promoting the priming of secretory...

  19. 78 FR 66982 - Santa Clara Pueblo Disaster #NM-00039

    Science.gov (United States)

    2013-11-07

    ... ADMINISTRATION Santa Clara Pueblo Disaster NM-00039 AGENCY: U.S. Small Business Administration. ACTION: Notice... for the Santa Clara Pueblo (FEMA- 4151-DR), dated 10/29/2013. Incident: Severe Storms and Flooding... disaster: Primary Areas: Santa Clara Pueblo. The Interest Rates are: Percent For Physical Damage:...

  20. 27 CFR 9.126 - Santa Clara Valley.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Santa Clara Valley. 9.126... Santa Clara Valley. (a) Name. The name of the viticultural area described in this section is “Santa Clara Valley.” (b) Approved Maps. The appropriate maps for determining the boundaries of the...

  1. Two Rab proteins, vesicle-associated membrane protein 2 (VAMP-2) and secretory carrier membrane proteins (SCAMPs), are present on immunoisolated parietal cell tubulovesicles.

    Science.gov (United States)

    Calhoun, B C; Goldenring, J R

    1997-01-01

    The tubulovesicles of gastric parietal cells sequester H+/K+-ATPase molecules within resting parietal cells. Stimulation of parietal cell secretion elicits delivery of intracellular H+/K+-ATPase to the apically oriented secretory canaliculus. Previous investigations have suggested that this process requires the regulated fusion of intracellular tubulovesicles with the canalicular target membrane. We have sought to investigate the presence of critical putative regulators of vesicle fusion on immunoisolated gastric parietal cell tubulovesicles. Highly purified tubulovesicles were prepared by gradient fractionation and immunoisolation on magnetic beads coated with monoclonal antibodies against the alpha subunit of H+/K+-ATPase. Western blot analysis revealed the presence of Rab11, Rab25, vesicle-associated membrane protein 2 (VAMP-2) and secretory carrier membrane proteins (SCAMPs) on immunoisolated vesicles. The same cohort of proteins was recovered on vesicles immunoisolated with monoclonal antibodies against SCAMPs and VAMP-2. In contrast, whereas immunoreactivities for syntaxin 1A/1B and synaptosome-associated protein (SNAP-25) were present in gradient-isolated vesicles, none of the immunoreactivity was associated with immunoisolated vesicles. The observation of VAMP-2 and two Rab proteins on immunoisolated H+/K+-ATPase-containing tubulovesicles supports the role for tubulovesicles in a regulated vesicle fusion process. In addition, the presence of SCAMPs along with Rab11 and Rab25 implicates the tubulovesicles as a critical apical recycling vesicle population. PMID:9230141

  2. Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon

    NARCIS (Netherlands)

    Sasaki, Nobuo; Sachs, Norman; Wiebrands, Kay; Ellenbroek, Saskia I J; Fumagalli, Arianna; Lyubimova, Anna; Begthel, Harry; van den Born, Maaike; van Es, Johan H; Karthaus, Wouter R; Li, Vivian S W; López-Iglesias, Carmen; Peters, Peter J; van Rheenen, Jacco; van Oudenaarden, Alexander; Clevers, Hans

    2016-01-01

    Leucine-rich repeat-containing G-protein coupled receptor 5-positive (Lgr5(+)) stem cells reside at crypt bottoms of the small and large intestine. Small intestinal Paneth cells supply Wnt3, EGF, and Notch signals to neighboring Lgr5(+) stem cells. Whereas the colon lacks Paneth cells, deep crypt

  3. Variation and clinical significance of Clara cell protein in patients with pulmonary contusion%肺挫伤患者血清CC16的变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    吴峰; 丁伯应; 杨小龙; 任刚; 熊克品; 徐东

    2014-01-01

    目的:探讨肺挫伤患者血清人克拉拉细胞蛋白(Clara cell protein,CC16)水平变化及临床意义。方法:应用ELISA方法检测42例肺挫伤患者(实验Ⅰ组:轻-中度肺挫伤患者24例;实验Ⅱ组:重度肺挫伤患者18例)伤后24 h内及治疗后1 d、3 d、7 d、14 d血清CC16水平变化,并与16例健康体检者(对照组)血清CC16水平进行比较。结果:实验组各个时间点血清CC16水平均高于对照组,差异具有统计学意义( P<0.01)。伤后24 h内和治疗后1 d、3 d、7 d、14 d血清CC16水平之间均有差异( P<0.01),且有逐渐下降趋势。实验Ⅱ组各个时间点血清CC16水平均较实验Ⅰ组同时间点偏高,差异有统计学意义( P<0.01)。结论:肺挫伤患者伤后早期血清CC16水平明显上升,且随治疗进程逐渐下降。血清CC16水平上升与肺挫伤程度有密切关系。血清CC16水平变化可能为肺挫伤早期诊断提供生物学指标。%Objective:To investigate the variation and clinical significance of 16kDa Clara cell protein(CC16) in patients with pulmonary contusion. Methods:Forty-two patients with pulmonary contusion were divided into experimental group I(n=24,moderate pulmonary contusion)and experimental groupⅡ(n=18,severe pulmonary contusion).Enzyme-linked immunoadsordent assay (ELISA) was used to detect the serum levels of CC16 in the two groups of patients within 24 h after the incident and at day 1,3,7 and 14 after treatment.The results were compared with another 16 healthy subjects in-cluded as controls.Results:Serum CC16 level in each time point was higher in the two experimental groups than the controls(P<0.01).The difference was significant concerning the levels of CC16 measured within 24 h after contusion and at day 1,3,7 and 14 after treatment(P<0.01),yet the levels ten-ded to decline.In addition,the levels in each time point in experimental group II were somewhat higher than group

  4. Documentation of the Santa Clara Valley regional ground-water/surface-water flow model, Santa Clara Valley, California

    Science.gov (United States)

    Hanson, R.T.; Li, Zhen; Faunt, C.C.

    2004-01-01

    into upper- and lower-aquifer systems. Ground-water inflow occurs as natural recharge in the form of streamflow infiltration and areal infiltration of precipitation along stream channels, artificial recharge from infiltration of imported water at recharge ponds and along selected stream channels, and leakage along selected transmission pipelines. Ground-water outflow occurs as evapotranspiration, stream base flow, discharge through pumpage from wells, and subsurface flow to the San Francisco Bay. The geohydrologic framework of the regional ground-water flow system was represented as six model layers. The hydraulic properties were redefined on the basis of cell-based lithologic properties that were delineated in terms of aggregate thicknesses of coarse-grained, fine-grained, and mixed textural categories. The regional aquifer systems also are dissected by several laterally extensive faults that may form at least partial barriers to the lateral flow of ground water. The spatial extent of the ground-water flow model was extended and refined to cover the entire Santa Clara Valley, including the Evergreen subregion. The temporal discretization was refined and the period of simulation was extended to 197099. The model was upgraded to MODFLOW-2000 (MF2K) and was calibrated to fit historical ground-water levels, streamflow, and land subsidence for the period 197099. The revised model slightly overestimates measured water levels with an root-mean-square error of -7.34 feet. The streamflow generally shows a good match on gaged creeks and rivers for flows greater than 1.2 cubic feet per second. The revised model also fits the measured deformation at the borehole extensometer site located near San Jose within 16 to 27 percent and the extensometer site near Sunnyvale within 3 percent of the maximum measured seasonal deformation for the deepest extensometers. The total ground-water inflow and outflow of about 225,500 acre-feet per

  5. Engineering the cellular protein secretory pathway for enhancement of recombinant tissue plasminogen activator expression in Chinese hamster ovary cells: effects of CERT and XBP1s genes.

    Science.gov (United States)

    Rahimpour, Azam; Vaziri, Behrouz; Moazzami, Reza; Nematollahi, Leila; Barkhordari, Farzaneh; Kokabee, Leila; Adeli, Ahmad; Mahboudi, Fereidoun

    2013-08-01

    Cell line development is the most critical and also the most time-consuming step in the production of recombinant therapeutic proteins. In this regard, a variety of vector and cell engineering strategies have been developed for generating high-producing mammalian cells; however, the cell line engineering approach seems to show various results on different recombinant protein producer cells. In order to improve the secretory capacity of a recombinant tissue plasminogen activator (t-PA)-producing Chinese hamster ovary (CHO) cell line, we developed cell line engineering approaches based on the ceramide transfer protein (CERT) and X-box binding protein 1 (XBP1) genes. For this purpose, CERT S132A, a mutant form of CERT that is resistant to phosphorylation, and XBP1s were overexpressed in a recombinant t-PA-producing CHO cell line. Overexpression of CERT S132A increased the specific productivity of t-PA-producing CHO cells up to 35%. In contrast, the heterologous expression of XBP1s did not affect the t-PA expression rate. Our results suggest that CERTS132A- based secretion engineering could be an effective strategy for enhancing recombinant t- PA production in CHO cells.

  6. Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin.

    Science.gov (United States)

    Loveday, Emma-Kate; Diederich, Sandra; Pasick, John; Jean, François

    2015-01-01

    A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions.

  7. High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells

    Science.gov (United States)

    Khanaki, Korosh; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Darabi, Masoud; Mehdizadeh, Amir; Shabani, Mahdi; Rahimipour, Ali; Nouri, Mohammad

    2014-01-01

    Background: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. Objective: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. Materials and Methods: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. Results: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). Conclusion: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis. PMID:25709631

  8. Production of N-acetylgalactosaminyl-transferase 2 (GalNAc-T2) fused with secretory signal Igκ in insect cells.

    Science.gov (United States)

    Horynová, Milada; Takahashi, Kazuo; Hall, Stacy; Renfrow, Matthew B; Novak, Jan; Raška, Milan

    2012-02-01

    The human UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 2 (GalNAc-T2) is one of the key enzymes that initiate synthesis of hinge-region O-linked glycans of human immunoglobulin A1 (IgA1). We designed secreted soluble form of human GalNAc-T2 as a fusion protein containing mouse immunoglobulin light chain kappa secretory signal and expressed it using baculovirus and mammalian expression vectors. The recombinant protein was secreted by insect cells Sf9 and human HEK 293T cells in the culture medium. The protein was purified from the media using affinity Ni-NTA chromatography followed by stabilization of purified protein in 50mM Tris-HCl buffer at pH 7.4. Although the purity of recombinant GalNAc-T2 was comparable in both expression systems, the yield was higher in Sf9 insect expression system (2.5mg of GalNAc-T2 protein per 1L culture medium). The purified soluble recombinant GalNAc-T2 had an estimated molecular mass of 65.8kDa and its amino-acid sequence was confirmed by mass-spectrometric analysis. The enzymatic activity of Sf9-produced recombinant GalNAc-T2 was determined by the quantification of enzyme-mediated attachment of GalNAc to synthetic IgA1 hinge-region peptide as the acceptor and UDP-GalNAc as the donor. In conclusion, murine immunoglobulin kappa secretory signal was used for production of secreted enzymatically active GalNAc-T2 in insect baculovirus expression system.

  9. Activation of MAPK Is Required for ROS Generation and Exocytosis in HMC-1 Cells Induced by Trichomonas vaginalis-Derived Secretory Products.

    Science.gov (United States)

    Narantsogt, Giimaa; Min, Arim; Nam, Young Hee; Lee, Young Ah; Kim, Kyeong Ah; Agvaandaram, Gurbadam; Dorjsuren, Temuulen; El-Benna, Jamel; Shin, Myeong Heon

    2015-10-01

    Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47(phox) in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.

  10. A crucial role for the mitogen-activated protein kinase pathway in nicotinic cholinergic signaling to secretory protein transcription in pheochromocytoma cells.

    Science.gov (United States)

    Tang, K; Wu, H; Mahata, S K; O'Connor, D T

    1998-07-01

    The mitogen-activated protein kinase (MAPK) pathway plays a pivotal role in intracellular signaling, and this cascade may impinge on cAMP response elements (CREs) of target genes. Both the MAPK pathway and chromogranin A expression may be activated by cytosolic calcium influx, and calcium-dependent signals map onto the chromogranin A promoter proximal CRE. We therefore probed the role of the MAPK pathway in chromogranin A biosynthesis after secretory stimulation of PC12 pheochromocytoma cells by the nicotinic cholinergic pathway, the physiological secretory trigger. Chemical inhibition of either MAPK or MAPK kinase blocked the response of a transfected chromogranin A promoter to nicotine or protein kinase C activation [by phorbol-12-myristate-13-acetate (PMA)], although nicotine-evoked catecholamine secretion was unaffected. Activation of the MAP kinase cascade (Ras, Raf, MAPK, or CREB kinase) by cotransfection of pathway components stimulated the chromogranin A promoter. Cotransfection of MAPK pathway dominant negative mutants (for Raf, MAPK, or CREB kinase) blocked nicotinic or PMA activation of chromogranin A, although a dominant negative Ras mutant was without effect. MAPK pathway enzymatic activity was stimulated by both nicotine and PMA. Point mutations of the chromogranin A CRE suggested that this element was necessary in cis for stimulation by nicotine, PMA, or chemical activation of the MAPK pathway. Transfer of the CRE to a heterologous promoter conferred inducibility by not only nicotine or cAMP but also MAPK activation. Expression of the CREB antagonist KCREB blocked the response of the chromogranin A promoter to nicotine, cAMP, or MAPK pathway activation by either chemical stimulation or cotransfection of active cascade components. Chromogranin A mRNA responded to MAPK pathway manipulation in a fashion similar to the transfected chromogranin A promoter, in both direction and magnitude. We conclude that the MAPK pathway is a necessary intermediate in

  11. 77 FR 39726 - Land Acquisitions: Pueblo of Santa Clara

    Science.gov (United States)

    2012-07-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Land Acquisitions: Pueblo of Santa Clara AGENCY: Bureau of Indian Affairs... into trust for the Pueblo of Santa Clara on January 27, 2012. FOR FURTHER INFORMATION CONTACT:...

  12. Macrophageal/microglial cell activation and cerebral injury induced by excretory-secretory products secreted by Paragonimus westermani.

    Science.gov (United States)

    Lee, Jae-Chul; Cho, Geum-Sil; Kwon, Jae Hyun; Shin, Myeong Heon; Lim, Ji Hyae; Kim, Won-Ki

    2006-02-01

    Cerebral paragonimiasis causes various neurological disorders including seizures, visual impairment and hemiplegia. The excretory-secretory product (ESP) released by Paragonimus westermani has a cysteine protease activity and plays important roles in its migration in the host tissue and modulation of host immune responses. To gain more insight into the pathogenesis of ESP in the brain, we investigated the inflammatory reaction and cerebral injury following microinjection of ESP into rat striatum. The size of injury was maximally observed 3 days after microinjection of ESP and then declined to control levels as astrocytes have repopulated the injury. ED1-positive monocytes and microglia were confluently found inside the injury. The mRNA expression of inducible nitric oxide synthase (iNOS) occurred as early as 9h after ESP injection and then declined to control levels within 1 day. The iNOS inhibitor aminoguanidine largely decreased the expression of iNOS but did not reduce the size of lesion caused by ESP. Interestingly, however, heat inactivation of ESP caused a decrease of injury formation with no altered expression of iNOS. The data indicate that ESP produces brain tissue injury by recruiting activated monocytes/microglia via heat-labile protease activity.

  13. Evolution of apicomplexan secretory organelles

    Science.gov (United States)

    Gubbels, Marc-Jan; Duraisingh, Manoj T.

    2013-01-01

    The alveolate superphylum includes many free-living and parasitic organisms, which are united by the presence of alveolar sacs lying proximal to the plasma membrane, providing cell structure. All species comprising the apicomplexan group of alveolates are parasites and have adapted to the unique requirements of the parasitic lifestyle. Here the evolution of apicomplexan secretory organelles that are involved in the critical process of egress from one cell and invasion of another is explored. The variations within the Apicomplexa and how these relate to species-specific biology will be discussed. In addition, recent studies have identified specific calcium-sensitive molecules that coordinate the various events and regulate the release of these secretory organelles within apicomplexan parasites. Some aspects of this machinery are conserved outside the Apicomplexa, and are beginning to elucidate the conserved nature of the machinery. Briefly, the relationship of this secretion machinery within the Apicomplexa will be discussed, compared with free-living and predatory alveolates, and how these might have evolved from a common ancestor. PMID:23068912

  14. Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2015-07-01

    Full Text Available Background/Aims: IgA nephropathy (IgAN is the most common form of primary glomerulonephritis, and often aggravates by mucosal infection. Secretory IgA (SIgA is the dominant immunoglobulin in mucosal immunity, and is deposited in the mesangium in IgAN. The biological effects of SIgA on mesangial cells are poorly understood. Methods: Deposition of SIgA in frozen renal sections from IgAN patients was detected and the association between deposition of SIgA and patients characteristics was analyzed. The biological effects of SIgA and polymeric IgA (pIgA on human renal mesangial cells were compared. We also studied the molecular mechanism of microRNA regulating the inflammatory effects of SIgA on mesangial cells. Results: Fifty-five of 176 patients had SIgA deposition with higher incidence of infection history and hematuria, lower serum cystatin C, β2 microglobulin, blood urea nitrogen and T-grade in the Oxford classification, compared with patients without SIgA deposition. SIgA stimulated mesangial cells at a higher ratio of proliferation and higher production of interleukin (IL-6, IL-8, monocyte chemotactic protein 1, transforming growth factor-β1 and fibronectin, compared with SIgA from healthy volunteers. The proliferation and cytokines production in mesangial cells stimulated by SIgA were significantly lower than that stimulated by pIgA. miR-16 targeted the 3′-untranslated region of IL-6 and suppressed its translation in mesangial cells induced by SIgA. Conclusions: The biological effects of SIgA on mesangial cells differ from those of pIgA. SIgA stimulates mesangial cell proliferation and production of proinflammatory cytokines. IL-6 production is regulated by miR-16 in mesangial cells.

  15. Secretory Structure, Histochemistry and Phytochemistry Analyses of Stimulant Plant

    Science.gov (United States)

    Umah, C.; Dorly; Sulistyaningsih, Y. C.

    2017-03-01

    Plants that are used as stimulant supposed to contains various metabolit compounds that are produced or secreted by secretory structures. This study aimed to identify the secretory structure of plant used as stimulant and chemical compounds accumulated in it. The secretory structure and its histochemistry were observed on plant material that are used as herbal ingredient. Phytochemical content was analyzed by using a qualitative test. The result showed that the idioblast cells and secretory cavities were found in the leaves of Decaspermum fruticosum, and Polyalthia rumphii. Most idioblast cells contained lipophilic substances and terpenoids or alkaloids, while secretory cavity contained alkaloid. Phytochemical analysis for D. fruticosum, and P. rumphii contain terpenoids, phenols, steroids, and flavonoids

  16. Measurement of the intracellular ph in human stomach cells: a novel approach to evaluate the gastric acid secretory potential of coffee beverages.

    Science.gov (United States)

    Weiss, Carola; Rubach, Malte; Lang, Roman; Seebach, Elisabeth; Blumberg, Simone; Frank, Oliver; Hofmann, Thomas; Somoza, Veronika

    2010-02-10

    As the consumption of coffee beverages sometimes is reported to cause gastric irritation, for which an increased stomach acid secretion is one of the promoting factors, different processing technologies such as steam-treatment have been developed to reduce putative stomach irritating compounds. There is evidence-based data neither on the effect of detailed processing variations nor on individual coffee components affecting the proton secretory activity (PSA). This work aimed at developing a screening model suitable for investigating the effects of commercial coffee beverages and components thereof on human parietal cells. Human gastric cancer cells (HGT-1) were treated with reconstituted freeze-dried coffee beverages prepared from customary coffee products such as regular coffee (RC, n = 4), mild bean coffee (MBC, n = 5), stomach friendly coffee (SFC, n = 4), and SFC decaffeinated (SFCD, n = 3). PSA was analyzed by flow cytometry using the pH-sensitive dye SNARF-AM. Treatment of the cells with MBC did not result in a PSA different from RC treatment (p component analysis of putative stomach irritating compounds revealed significantly reduced contents of (beta)N-alkanoyl-5-hydroxytryptamides, caffeine, N-methylpyridinium, and catechol in SFCD compared to RC. However, none of these compounds seem to act as the sole key bioactive reducing the PSA of SFCD, since their contents in MBC and SFC samples were not different from those in RC samples, although the PSA of these beverages was significantly lower than that of reconstituted freeze-dried RC beverage.

  17. Influence of 4-hydroxylated polychlorinated biphenyls on the secretory function of bovine ovarian cells: role of the steroidogenic factor-1 receptor.

    Science.gov (United States)

    Mlynarczuk, Jaroslaw; Kotwica, Jan

    2015-04-01

    The hydroxy-derivatives (OHPCBs) of polychlorinated biphenyls (PCBs) can accumulate in the tissues of the reproductive tract in animals and humans and may still have estrogen-like properties. Moreover, the "orphan" nuclear receptor Steroidogenic Factor-1 (SF-1) can be the target of PCBs. The aim of the present study was to determine the effect 4OH4CB and 4OH3CB on the secretion of estradiol (E2), progesterone (P4), and oxytocin (OT) from granulosa cells of follicles 1cm in diameter and from luteal cells collected at four stages of the estrous cycle of cows. Furthermore, the possibility that 4OHPCBs have an effect on OT synthesis and secretion via the SF receptor was studied using receptor blocker (F0160). Used OHPCBs increased the secretion of P4 from the granulosa cells of follicles of both sizes and increased the secretion of OT from follicles with a diameter of >1cm. These increases were inhibited by an SF-1 receptor blocker. In luteal cells, 4OH3CB increased the secretion of P4 and OT from luteal cells at all phases of the estrous cycle, while 4OH4CB increased OT secretion during the first half of the estrous cycle. Concomitant with the increase in OT secretion from the cells, an increase in the expression of OT precursor mRNA (NP-I/OT) was observed. This effect was inhibited by SF-1 receptor blocker. These results indicate that 4OHPCBs impair the secretory function of ovarian steroidogenic cells by disrupting steroidogenesis and increasing OT secretion, and the receptor SF-1 appears to be essentially involved in these processes.

  18. Detection of intestinal intraepithelial lymphocytes, goblet cells and secretory IgA in the intestinal mucosa during Newcastle disease virus infection.

    Science.gov (United States)

    Sun, Quan; Shang, Yunlian; She, Ruiping; Jiang, Taozhen; Wang, Decheng; Ding, Ye; Yin, Jun

    2013-12-01

    Newcastle disease, which is caused by Newcastle disease virus (NDV), is a highly contagious viral disease of poultry and other bird species. The mucosa is the first line of defence to invading pathogens, including NDV, and it has been confirmed that the mucosa can contribute to host protection. This study was conducted to evaluate the intestinal mucosal immunology in NDV infection. Forty specific-pathogen-free chickens were divided into two groups, 20 birds in each group. Group 1 was inoculated with NDV by the intravenous route. Group 2 was used as the control group and was given sterile phosphate-buffered saline by the same route. At 24, 48, 72, and 96 h post infection (h.p.i.), five chickens from each treatment were killed. Samples of the duodenum, jejunum, and ileum were collected to quantify intestinal intraepithelial lymphocytes (IEL), goblet cells and secretory IgA (sIgA) by cytochemistry and immunohistochemistry analysis. The results indicated that IEL were increased from 24 to 72 h.p.i. in the infected tissues, and were significantly higher than in the control group at 48 h.p.i. (P lining of the intestinal mucosa. These data suggest that IEL, goblet cells, and sIgA were involved in the intestinal mucosal immunity against NDV infection.

  19. Effects of Statins and Xuezhikang on the Expression of Secretory Phospholipase A2, Group IIA in Rat Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Xie, Qiang; Zhang, Dan

    2017-02-07

    Atherosclerosis is a multifactorial vascular disease characterized by formation of inflammatory lesions. Secretory phospholipase A2, group IIA (sPLA2-IIA) is involved in this process and plays a critical role. However, the exact role of sPLA2-IIA in cardiovascular inflammation is more complicated and remains unclear. Furthermore, both statins and Xuezhikang (XZK) are widely used in the prevention and treatment of cardiovascular disease risk because of their pleiotropic effects on the cardiovascular system. However, their effects on sPLA2-IIA are still controversial. We investigated the regulation of sPLA2-IIA by rat thoracic aorta smooth muscle cells (VSMCs) in culture. Cells were first incubated with IL-1β alone to induce expression of sPLA2-IIA and then treated with several concentrations of statins or XZK for different times in the absence or presence of IL-1β. We tested the expression of sPLA2-IIA, including sPLA2-IIA mRNA, protein, as well as activity. We found that statins or IL-1β increase the expression of sPLA2-IIA in VSMCs and the effect is based on a synergetic relationship between them. However, for the first time, we observed that XZK effectively reduces sPLA2-IIA expression in IL-1β-treated VSMCs. Our findings may shine a new light on the clinical use of XZK and statins in the prevention and treatment of atherosclerosis-related thrombosis.

  20. Neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor (SLPI by lung epithelial cells: role of charge of the proteinase-inhibitor complex

    Directory of Open Access Journals (Sweden)

    Hiemstra Pieter S

    2008-08-01

    Full Text Available Abstract Background Secretory leukoproteinase inhibitor (SLPI is an important inhibitor of neutrophil elastase (NE, a proteinase implicated in the pathogenesis of lung diseases such as COPD. SLPI also has antimicrobial and anti-inflammatory properties, but the concentration of SLPI in lung secretions in COPD varies inversely with infection and the concentration of NE. A fall in SLPI concentration is also seen in culture supernatants of respiratory cells exposed to NE, for unknown reasons. We investigated the hypothesis that SLPI complexed with NE associates with cell membranes in vitro. Methods Respiratory epithelial cells were cultured in the presence of SLPI, varying doses of proteinases over time, and in different experimental conditions. The likely predicted charge of the complex between SLPI and proteinases was assessed by theoretical molecular modelling. Results We observed a rapid, linear decrease in SLPI concentration in culture supernatants with increasing concentration of NE and cathepsin G, but not with other serine proteinases. The effect of NE was inhibited fully by a synthetic NE inhibitor only when added at the same time as NE. Direct contact between NE and SLPI was required for a fall in SLPI concentration. Passive binding to cell culture plate materials was able to remove a substantial amount of SLPI both with and without NE. Theoretical molecular modelling of the structure of SLPI in complex with various proteinases showed a greater positive charge for the complex with NE and cathepsin G than for other proteinases, such as trypsin and mast cell tryptase, that also bind SLPI but without reducing its concentration. Conclusion These data suggest that NE-mediated decrease in SLPI is a passive, charge-dependent phenomenon in vitro, which may correlate with changes observed in vivo.

  1. Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

    DEFF Research Database (Denmark)

    Hansen, Henning Gram; Pristovsek, Nusa; Kildegaard, Helene Faustrup;

    2017-01-01

    Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottle...

  2. Estuarine ecology : A report on Santa Clara County Wetlands

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report on the Santa Clara County wetlands was written just prior to the establishment of the San Francisco Bay National Wildlife Refuge. The report summarizes...

  3. A plasma wakefield acceleration experiment using CLARA beam

    Energy Technology Data Exchange (ETDEWEB)

    Xia, G., E-mail: guoxing.xia@cockcroft.ac.uk [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); Angal-Kalinin, D.; Clarke, J. [STFC/ASTeC, Daresbury, Warrington (United Kingdom); Smith, J. [Tech-X UK Corporation, Daresbury Innovation Centre, Warrington (United Kingdom); Cormier-Michel, E. [Tech-X Corporation, Boulder, CO (United States); Jones, J.; Williams, P.H.; Mckenzie, J.W.; Militsyn, B.L. [STFC/ASTeC, Daresbury, Warrington (United Kingdom); Hanahoe, K.; Mete, O. [School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom); The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); Aimidula, A.; Welsch, C.P. [The Cockcroft Institute, Sci-Tech Daresbury, Daresbury, Warrington (United Kingdom); The University of Liverpool, Liverpool (United Kingdom)

    2014-03-11

    We propose a Plasma Accelerator Research Station (PARS) based at proposed FEL test facility CLARA (Compact Linear Accelerator for Research and Applications) at Daresbury Laboratory. The idea is to use the relativistic electron beam from CLARA, to investigate some key issues in electron beam transport and in electron beam driven plasma wakefield acceleration, e.g. high gradient plasma wakefield excitation driven by a relativistic electron bunch, two bunch experiment for CLARA beam energy doubling, high transformer ratio, long bunch self-modulation and some other advanced beam dynamics issues. This paper presents the feasibility studies of electron beam transport to meet the requirements for beam driven wakefield acceleration and presents the plasma wakefield simulation results based on CLARA beam parameters. Other possible experiments which can be conducted at the PARS beam line are also discussed.

  4. A plasma wakefield acceleration experiment using CLARA beam

    CERN Document Server

    Xia, G; Clarke, J; Smith, J; Cormier-Michel, E; Jones, J; Williams, P H; Mckenzie, J W; Militsyn, B L; Hanahoe, K; Mete, O; Aimidula, A; Welsch, C P

    2014-01-01

    We propose a Plasma Accelerator Research Station (PARS) based at proposed FEL test facility CLARA (Compact Linear Accelerator for Research and Applications) at Daresbury Laboratory. The idea is to use the relativistic electron beam from CLARA, to investigate some key issues in electron beam transport and in electron beam driven plasma wakefield acceleration, e.g. high gradient plasma wakefield excitation driven by a relativistic electron bunch, two bunch experiment for CLARA beam energy doubling, high transformer ratio, long bunch self-modulation and some other advanced beam dynamics issues. This paper presents the feasibility studies of electron beam transport to meet the requirements for beam driven wakefield acceleration and presents the plasma wakefield simulation results based on CLARA beam parameters. Other possible experiments which can be conducted at the PARS beam line are also discussed.

  5. Uptake of ascorbic acid by freshly isolated cells and secretory granules from the intermediate lobe of ox hypophyses

    DEFF Research Database (Denmark)

    Zhou, A; Matsumoto, T; Farver, O

    1990-01-01

    of uptake occurred when mechanically isolated cells were incubated with increasing ascorbic acid concentrations up to 0.6 mM. But if such cells were purified on a Percoll gradient, a clear saturation of uptake could be observed. Acetylsalicylic acid reduced the uptake markedly. When cells loaded with L-[14C......Mechanically isolated cells from the intermediate lobe of ox hypophyses contained 40.6 +/- 3.7 nmol mg-1 protein (mean +/- SE, n = 5) of ascorbic acid. They accumulated radioactivity time dependently, on incubation with L-[14C]ascorbic acid in ionic medium dominated by NaCl. No definite saturation......]ascorbic acid were homogenized and placed on a Percoll gradient, the radioactivity was recovered in several subcellular fractions. Decrease of the Na+ concentration or presence of ouabain in the medium did not cause noticeable changes in uptake by non-purified cells, whereas uptake by purified cells was clearly...

  6. Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and IL-10 secretion from intestinal epithelial cells (IPEC-1).

    Science.gov (United States)

    Parthasarathy, G; Mansfield, L S

    2005-08-10

    Immune responses to gastrointestinal helminth infections have received increasing attention due to similarities to allergen-induced responses. In fact, the whipworm parasite of swine, Trichuris suis, has been used in beginning clinical trials as an antidote to inflammatory bowel disease. This strategy was based on this similarity and the recognition that other worms have been documented to induce anti-inflammatory responses in the host. In an effort to understand the basis for this response, we hypothesized that the proteins and peptides secreted by T. suis stimulate local intestinal epithelial cells to produce anti-inflammatory cytokines. To test this hypothesis in a correlate system of the natural swine host, T. suis excretory secretory products (ESP) were used to treat both differentiated and undifferentiated intestinal pig epithelial cells (IPEC-1) in vitro as a model for the effect on villus tip and crypt epithelial cells in the vicinity of the worms. IPEC-1 were exposed to low-level doses (0.3mg/ml) of T. suis ESP, and IL-4, IL-6 and IL-10 cytokine responses were measured by an enzyme-linked immunosorbant assay (ELISA). IL-6 was the predominant cytokine produced, accompanied by moderate IL-10 secretion from both differentiated and undifferentiated cells. As expected, IL-4 was not produced by IPEC-1. Additionally, IL-6 and IL-10 cytokines were produced within 24h, suggesting that these two cytokines form part of the primary host response to T. suis infections. These data suggest that T. suis ESP could enhance host immune responses and modulation through the induction of enteric IL-6 and IL-10.

  7. Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes.

    Directory of Open Access Journals (Sweden)

    Courtney K Burrows

    2016-07-01

    Full Text Available Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL mapping study to identify common regulatory (expression single nucleotide polymorphisms (eSNPs in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR of 1%. After pruning for strong LD (r2 >0.95, we tested for associations between eSNPs and fecundability (the ability to get pregnant, measured as the length of the interval to pregnancy, in 117 women. Two eSNPs were associated with fecundability at a FDR of 5%; both were in the HLA region and were eQTLs for the TAP2 gene (P = 1.3x10-4 and the HLA-F gene (P = 4.0x10-4, respectively. The effects of these SNPs on fecundability were replicated in an independent sample. The two eSNPs reside within or near regulatory elements in decidualized human endometrial stromal cells. Our study integrating eQTL mapping in a primary tissue with association studies of a related phenotype revealed novel genes and associated alleles with independent effects on fecundability, and identified a central role for two HLA region genes in human implantation success.

  8. Delineation of glutamate pathways and secretory responses in pancreatic islets with β-cell-specific abrogation of the glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Vetterli, Laurène; Carobbio, Stefania; Pournourmohammadi, Shirin;

    2012-01-01

    In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated ...

  9. [Endoplasmic-mitochondrial Ca(2+)-functional unit: dependence of respiration of secretory cells on activity of ryanodine- and IP3 - sensitive Ca(2+)-channels].

    Science.gov (United States)

    Velykopols'ka, O Iu; Man'ko, B O; Man'ko, V V

    2012-01-01

    Using Clark oxygen electrode, dependence of mitochondrial functions on Ca(2+)-release channels activity of Chironomus plumosus L. larvae salivary glands suspension was investigated. Cells were ATP-permeabilized in order to enable penetration of exogenous oxidative substrates. Activation of plasmalemmal P2X-receptors (as well as P2Y-receptors) per se does not modify the endogenous respiration of salivary gland suspension. That is, Ca(2+)-influx from extracellular medium does not influence functional activity of mitochondria, although they are located along the basal part of the plasma membrane. Activation of RyRs intensifies endogenous respiration and pyruvate-malate-stimulated respiration, but not succinate-stimulated respiration. Neither activation of IP3Rs (via P2Y-receptors activation), nor their inhibition alters endogenous respiration. Nevertheless, IP3Rs inhibition by 2-APB intensifies succinate-stimulated respiration. All abovementioned facts testify that Ca2+, released from stores via channels, alters functional activity of mitochondria, and undoubtedly confirm the existence of endoplasmic-mitochondrial Ca(2+)-functional unit in Ch. plumosus larvae salivary glands secretory cells. In steady state of endoplasmic-mitochondrial Ca(2+)-functional unit the spontaneous activity of IP3Rs is observed; released through IP3Rs, Ca2+ is accumulated in mitochondria via uniporter and modulates oxidative processes. Activation of RyRs induces the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to the active state, which is required to intensify cell respiration and oxidative phosphorylation. As expected, the transition of endoplasmic-mitochondrial Ca(2+)-functional unit to inactivated state (i. e. inhibition of Ca(2+)-release channels at excessive [Ca2+]i) limits the duration of signal transduction, has protective nature and prevents apoptosis.

  10. Docking of Secretory Vesicles Is Syntaxin Dependent

    Science.gov (United States)

    de Wit, Heidi; Cornelisse, L. Niels; Toonen, Ruud F.G.; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones. PMID:17205130

  11. Docking of secretory vesicles is syntaxin dependent.

    Directory of Open Access Journals (Sweden)

    Heidi de Wit

    Full Text Available Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones.

  12. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) ß-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) ß-cells....

  13. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Plomgaard, Peter; Berney, Thierry;

    2011-01-01

    Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.......Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells....

  14. Component composition of essential oils and ultrastructure of secretory cells of resin channel needles Juniperus communis (Cupressaceae

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    N. V. Gerling

    2015-12-01

    Full Text Available The results of determining the qualitative and quantitative composition of essential oil Juniperus communis, growing under the canopy of spruce blueberry sphagnum subzone middle taiga. Juniperus communis essential oil is liquid light yellow color. The content of essential oil was 0.46 % in shoots with needles. 37 substances of components identified. Mass fraction of components in the essential oil of Juniperus communis reached 89 %. The highest percentage of occupied fraction of monoterpenes (82.3 %, the proportion of sesquiterpenes less than 0.5 % of the total composition of essential oils, alcohols 3.5 and 0.7 % esters. In monoterpenes fraction predominant α-pinene (24.5–32.6 %, β-pinene (15–20.3 % and α-phellandrene (6.4–8.8 %. Essential oil of Juniperus communis is characterized by high content of monoterpenoids in contrast to other conifers of the taiga zone. All stages of biosynthesis essential oils occur in the epithelial cells of the resin channel (terpenoidogennyh cells. An oval shape have epithelial cells of the resin channel needles in transverse sections the Juniperus communis, which is situated vacuole in the center. Large number of lipid globules (up to 40 noted in the hyaloplasm of explored cells. Leucoplasts surrounded by membranes of smooth endoplasmic reticulum in cross sections of epithelial cells in resin channel of juniper. Endoplasmic reticulum is poorly developed in epithelial cells, which corresponds to the low content of sesquiterpenes in the needles during the study period. Development of large leucoplasts and large number of mitochondria associated with predominance of synthesis monoterpenoids the in the epithelium cells resin channel.

  15. Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

    Science.gov (United States)

    Nath, S; Kadasi, A; Grossmann, R; Sirotkin, A V; Kolesarova, A; Talukdar, A D; Choudhury, M D

    2015-01-01

    Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

  16. Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH.

    Science.gov (United States)

    Sirotkin, A V; Benco, A; Tandlmajerova, A; Vasícek, D; Kotwica, J; Darlak, K; Valenzuela, F

    2008-11-01

    The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosis-related (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P(4)), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P(4), and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P(4), but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P(4) secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P(4) secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary.

  17. DNA structures decorated with cathepsin G/secretory leukocyte proteinase inhibitor stimulate IFNI production by plasmacytoid dendritic cells

    DEFF Research Database (Denmark)

    Skrzeczynska-Moncznik, Joanna; Wlodarczyk, Agnieszka; Banas, Magdalena

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) and neutrophils are detected in psoriatic skin lesions and implicated in the pathogenesis of psoriasis. pDCs specialize in the production of type I interferon (IFNI), a cytokine that plays an important role in chronic autoimmune-like inflammation, including pso...

  18. Molecular bases of K+ secretory cells in the inner ear: shared and distinct features between birds and mammals

    Science.gov (United States)

    Wilms, Viviane; Köppl, Christine; Söffgen, Chris; Hartmann, Anna-Maria; Nothwang, Hans Gerd

    2016-01-01

    In the cochlea, mammals maintain a uniquely high endolymphatic potential (EP), which is not observed in other vertebrate groups. However, a high [K+] is always present in the inner ear endolymph. Here, we show that Kir4.1, which is required in the mammalian stria vascularis to generate the highly positive EP, is absent in the functionally equivalent avian tegmentum vasculosum. In contrast, the molecular repertoire required for K+ secretion, specifically NKCC1, KCNQ1, KCNE1, BSND and CLC-K, is shared between the tegmentum vasculosum, the vestibular dark cells and the marginal cells of the stria vascularis. We further show that in barn owls, the tegmentum vasculosum is enlarged and a higher EP (~+34 mV) maintained, compared to other birds. Our data suggest that both the tegmentum vasculosum and the stratified stria vascularis evolved from an ancestral vestibular epithelium that already featured the major cell types of the auditory epithelia. Genetic recruitment of Kir4.1 specifically to strial melanocytes was then a crucial step in mammalian evolution enabling an increase in the cochlear EP. An increased EP may be related to high-frequency hearing, as this is a hallmark of barn owls among birds and mammals among amniotes. PMID:27680950

  19. Cloning of the Zygosaccharomyces bailii GAS1 homologue and effect of cell wall engineering on protein secretory phenotype

    Directory of Open Access Journals (Sweden)

    Dato Laura

    2010-01-01

    Full Text Available Abstract Background Zygosaccharomyces bailii is a diploid budding yeast still poorly characterized, but widely recognised as tolerant to several stresses, most of which related to industrial processes of production. Because of that, it would be very interesting to develop its ability as a cell factory. Gas1p is a β-1,3-glucanosyltransglycosylase which plays an important role in cell wall construction and in determining its permeability. Cell wall defective mutants of Saccharomyces cerevisiae and Pichia pastoris, deleted in the GAS1 gene, were reported as super-secretive. The aim of this study was the cloning and deletion of the GAS1 homologue of Z. bailii and the evaluation of its deletion on recombinant protein secretion. Results The GAS1 homologue of Z. bailii was cloned by PCR, and when expressed in a S. cerevisiae GAS1 null mutant was able to restore the parental phenotype. The respective Z. bailii Δgas1 deleted strain was obtained by targeted deletion of both alleles of the ZbGAS1 gene with deletion cassettes having flanking regions of ~400 bp. The morphological and physiological characterization of the Z. bailii null mutant resulted very similar to that of the corresponding S. cerevisiae mutant. As for S. cerevisiae, in the Z. bailii Δgas1 the total amount of protein released in the medium was significantly higher. Moreover, three different heterologous proteins were expressed and secreted in said mutant. The amount of enzymatic activity found in the medium was almost doubled in the case of the Candida rugosa lipase CRL1 and of the Yarrowia lipolytica protease XPR2, while for human IL-1β secretion disruption had no relevant effect. Conclusions The data presented confirm that the engineering of the cell wall is an effective way to improve protein secretion in yeast. They also confirmed that Z. bailii is an interesting candidate, despite the knowledge of its genome and the tools for its manipulation still need to be improved. However, as

  20. The secretory synapse: the secrets of a serial killer.

    Science.gov (United States)

    Bossi, Giovanna; Trambas, Christina; Booth, Sarah; Clark, Richard; Stinchcombe, Jane; Griffiths, Gillian M

    2002-11-01

    Cytotoxic T lymphocytes (CTLs) destroy their targets by a process involving secretion of specialized granules. The interactions between CTLs and target can be very brief; nevertheless, adhesion and signaling proteins segregate into an immunological synapse. Secretion occurs in a specialized secretory domain. Use of live and fixed cell microscopy allows this secretory synapse to be visualized both temporally and spatially. The combined use of confocal and electron microscopy has produced some surprising findings, which suggest that the secretory synapse may be important both in delivering the lethal hit and in facilitating membrane transfer from target to CTL. Studies on the secretory synapse in wild-type and mutant CTLs have been used to identify proteins involved in secretion. Further clues as to the signals required for secretion are emerging from comparisons of inhibitory and activating synapses formed by natural killer cells.

  1. SCR96, a small cysteine-rich secretory protein of Phytophthora cactorum, can trigger cell death in the Solanaceae and is important for pathogenicity and oxidative stress tolerance.

    Science.gov (United States)

    Chen, Xiao-Ren; Li, Yan-Peng; Li, Qi-Yuan; Xing, Yu-Ping; Liu, Bei-Bei; Tong, Yun-Hui; Xu, Jing-You

    2016-05-01

    Peptides and small molecules produced by both the plant pathogen Phytophthora and host plants in the apoplastic space mediate the relationship between the interplaying organisms. Various Phytophthora apoplastic effectors, including small cysteine-rich (SCR) secretory proteins, have been identified, but their roles during interaction remain to be determined. Here, we identified an SCR effector encoded by scr96, one of three novel genes encoding SCR proteins in P. cactorum with similarity to the P. cactorum phytotoxic protein PcF. Together with the other two genes, scr96 was transcriptionally induced throughout the developmental and infection stages of the pathogen. These genes triggered plant cell death (PCD) in the Solanaceae, including Nicotiana benthamiana and tomato. The scr96 gene did not show single nucleotide polymorphisms in a collection of P. cactorum isolates from different countries and host plants, suggesting that its role is essential and non-redundant during infection. Homologues of SCR96 were identified only in oomycetes, but not in fungi and other organisms. A stable protoplast transformation protocol was adapted for P. cactorum using green fluorescent protein as a marker. The silencing of scr96 in P. cactorum caused gene-silenced transformants to lose their pathogenicity on host plants and these transformants were significantly more sensitive to oxidative stress. Transient expression of scr96 partially recovered the virulence of gene-silenced transformants on plants. Overall, our results indicate that the P. cactorum scr96 gene encodes an important virulence factor that not only causes PCD in host plants, but is also important for pathogenicity and oxidative stress tolerance.

  2. In vitro effect of leptin on anterior pituitary cells LH secretory activity during early pregnancy in pig.

    Science.gov (United States)

    Siawrys, G; Gajewska, A

    2017-03-28

    Leptin modulates reproductive activity but its potential influence on LH secretion from anterior pituitary (AP) cells during implantation period in pigs (days 14-16 of pregnancy) remained unexplored. This study focused on determination whether leptin affects basal and GnRH-induced LH secretion and intracellular accumulation and whether leptin receptor (OB-Rb) mRNA is expressed in the AP gland during implantation in pigs. Four individual AP glands were developed into separate primary cultures. 2×105 cells/ml were preincubated (72 h) and next, for 3.5 h, experimentally treated with GnRH (100 ng/ml), leptin (10-11, 10-9, 10-7, 10-6 M) alone, or given in respective combinations with GnRH. In the AP gland, OB-Rb mRNA expression was determined by real-time PCR method. Leptin activated LH secretion and its concentration-dependent effect was observed as stimulation shown in a full range tested (culture 1) and exhibited only at 10-6 M (culture 2). A pooled data analysis revealed that basal LH secretion increased at 10-9, 10-7 and 10-6 M, but GnRH-induced LH release decreased at 10-6 M. Leptin down-regulated GnRH-induced LH secretion in all cultures, but only culture 3 exhibited sensitivity for all concentrations tested. Basal LH accumulation was activated in culture 1 (at 10-11 M) and inhibited in culture 4 (at 10-9 M). In the presence of GnRH leptin up-regulated LH accumulation with individual culture leptin-sensitivity (culture 1-3), while down-regulated LH accumulation in culture 4. Obtained data indicate that OB-Rb mRNA is expressed in the AP gland and leptin alone and in combination with GnRH specifically modulates LH activity during early pregnancy in pigs.

  3. En el Cincuentenario del Hospital Santa Clara

    Directory of Open Access Journals (Sweden)

    Gilberto Rueda Pérez

    1992-12-01

    Full Text Available

    El 16 de julio de 1942 nace el Hospital Sanatorio Antituberculoso Santa Clara en Santafé de Bogotá.
    Un siglo atrás, casi a la fecha, en 1843, nace en Alemania Roberto Koch, quien, 60 años antes de la fundación del Hospital, el 24 de marzo de 1882, presenta al mundo el descubrimiento del Micobacterium Tuberculosis, germen causante de la enfermedad que ataca alhombre desde sus más remotos orígenes y que aún nos acompaña, especialmente en los países subdesarrollados, causando severo impacto en la salud de las poblaciones más necesitadas, apesar de los grandes avances alcanzados en el campo de la Medicina a nivel mundial.
    Por haber sido destinado el Hospital altratamiento de los tuberculosos, destino que aún conserva primordialmente aunque, como se verá posteriormente, sus camas reciben enfermos de medicina general dada la evolución de los tratamientos y la modernización de los esquemas terapéuticos, se justifica ampliamente mencionar aquí los principales avances relacionados con el control de la Tuberculosis a través de los tiempos hasta la fundación del Hospital.

    Estos se pueden resumir así:

    • 'HIPOCRATES (460-377 a. C.:describe la consunción y la llama tisis; lanza el concepto de herencia que perdura por siglos.
    • ARISTOTELES(324-284a. C.:habla del contagio a través de la respiración.
    • CELSO (siglo I a. C.: describe el tubérculo y señala tres formas de consunción: atrofia, caquexia y tisis.
    • GALENO(181-261 d. C.: la agrupa con otras enfermedades transmisibles: la peste, la sarna, etc.
    • EDADMEDIA(sigloVII alXIIId. C.:se destaca únicamente como aporte nuevo Maimonides, filósofo judío radicado en Granada (11351204,quien describe la tisis de los animales.

    Posteriormente Girolamo Fracastoro (1478-1553, nacido en Verona,la asimila a la viruela y lanza la teoría microbiana.

    • PARACELSO(1493-1541pregona que: los

    • Zymophagy: Selective Autophagy of Secretory Granules

      Directory of Open Access Journals (Sweden)

      Maria I. Vaccaro

      2012-01-01

      Full Text Available Timing is everything. That's especially true when it comes to the activation of enzymes created by the pancreas to break down food. Pancreatic enzymes are packed in secretory granules as precursor molecules called zymogens. In physiological conditions, those zymogens are activated only when they reach the gut, where they get to work releasing and distributing nutrients that we need to survive. If this process fails and the enzymes are prematurely activated within the pancreatic cell, before they are released from the gland, they break down the pancreas itself causing acute pancreatitis. This is a painful disease that ranges from a mild and autolimited process to a severe and lethal condition. Recently, we demonstrated that the pancreatic acinar cell is able to switch on a refined mechanism that could explain the autolimited form of the disease. This is a novel selective form of autophagy named zymophagy, a cellular process to specifically detect and degrade secretory granules containing activated enzymes before they can digest the organ. In this work, we revise the molecules and mechanisms that mediate zymophagy, a selective autophagy of secretory granules.

    • Neutrophil predominance in induced sputum from asthmatic patients: Therapeutic implications and role of clara cell 16-KD protein Predominio de neutrófilos en esputo inducido de asmáticos: Implicancias terapéuticas y rol de la proteína 16-kD de la célula clara

      Directory of Open Access Journals (Sweden)

      Elisa M. Uribe Echevarría

      2011-08-01

      Full Text Available Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d. or montelukast (10 mg/d for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP or neutrophil predominance (NP, and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.El eosinófilo es considerado la célula protagonista principal en el asma; sin embargo, a menudo se observan discordancias entre las manifestaciones clínicas y la respuesta de los pacientes al tratamiento. Nos propusimos determinar la ocurrencia de predominio de neutrófilos en el asma e identificar las caracter

    • SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

      Science.gov (United States)

      Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

      2016-10-01

      Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.

    • RFP tags for labeling secretory pathway proteins

      Energy Technology Data Exchange (ETDEWEB)

      Han, Liyang; Zhao, Yanhua [State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Zhang, Xi; Peng, Jianxin [College of Life Sciences, Central China Normal University, Wuhan 430079, Hubei (China); Xu, Pingyong, E-mail: pyxu@ibp.ac.cn [Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Huan, Shuangyan, E-mail: shuangyanhuan@163.com [State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 (China); Zhang, Mingshu, E-mail: mingshu1984@gmail.com [Key Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

      2014-05-09

      Highlights: • Membrane protein Orai1 can be used to report the fusion properties of RFPs. • Artificial puncta are affected by dissociation constant as well as pKa of RFPs. • Among tested RFPs mOrange2 is the best choice for secretory protein labeling. - Abstract: Red fluorescent proteins (RFPs) are useful tools for live cell and multi-color imaging in biological studies. However, when labeling proteins in secretory pathway, many RFPs are prone to form artificial puncta, which may severely impede their further uses. Here we report a fast and easy method to evaluate RFPs fusion properties by attaching RFPs to an environment sensitive membrane protein Orai1. In addition, we revealed that intracellular artificial puncta are actually colocalized with lysosome, thus besides monomeric properties, pKa value of RFPs is also a key factor for forming intracellular artificial puncta. In summary, our current study provides a useful guide for choosing appropriate RFP for labeling secretory membrane proteins. Among RFPs tested, mOrange2 is highly recommended based on excellent monomeric property, appropriate pKa and high brightness.

    • Natural Law, Santa Clara, and the Supreme Court.

      Science.gov (United States)

      Rodgers, Raymond S.; Lujan, Phillip

      The court case, "Santa Clara Pueblo, et al. v. Julia Martinez, et al.," is the subject of this paper. It gives the background of the case of a woman whose children were refused admittance to tribal rolls because of an ordinance prohibiting the enrollment of children whose father is not a tribal member. The paper gives the arguments of…

    • ["The piano trio" Robert Schumann, Clara Schumann and Johannes Brahms].

      Science.gov (United States)

      Albretsen, C S

      1998-12-10

      The relationship between the pianist and composer Clara Schumann and the composers Robert Schumann and Johannes Brahms has for a century been an interesting topic. Clara and Robert Schumann both suffered separation from their mothers during early childhood. Johannes Brahms was intensely spoiled by his mother. Robert Schumann needed a structuring wife in his adult life, while Johannes Brahms turned to be afraid of intrusive women. Robert Schumann's psychotic breakdown in February 1854 had a complex background: a hypomanic state, some marital problems, a stressful journey with musical appearances, and possibly a difficulty in differentiating between himself and his new friend Johannes Brahms. As for Clara Schumann, who lost her mother before the age of five, musical activities became her way of overcoming the difficulties of life. She was able to support Robert in his lunatic asylum and their seven children growing up in three separate towns. The chronic diseases of the sons: schizophrenia, polyarthritis and tuberculosis made a deep impression on her and her fingers and hands were periodically immobilised with severe pain. For four decades Johannes was her able "son" and Clara was his "mother", at a safe distance.

    • 78 FR 67210 - Santa Clara Pueblo Disaster #NM-00038

      Science.gov (United States)

      2013-11-08

      ... ADMINISTRATION Santa Clara Pueblo Disaster NM-00038 AGENCY: U.S. Small Business Administration. ACTION: Notice...: Submit completed loan applications to: U.S. Small Business Administration, Processing and Disbursement... of Disaster Assistance, U.S. Small Business Administration, 409 3rd Street, SW., Suite...

    • Cultural Contact through Musical Poetry in Clara Janes's "Kampa"

      Science.gov (United States)

      Faszer-McMahon, Debra

      2009-01-01

      Clara Janes's "Kampa" is a love song dedicated to the renowned Czech poet Vladimir Holan. The work includes a musical and lyrical composition performed on tape, and its unconventional musical mode offers an alternative to divisions between western and non-western literary and musical forms. The poetry of "Kampa" presents musical methods of…

    • Escaping Slavery: "Sweet Clara and the Freedom Quilt."

      Science.gov (United States)

      Miller, Sue Ann

      This lesson uses the picture book "Sweet Clara and the Freedom Quilt" by Deborah Hopkinson and an interactive website to enhance third- through fifth-grade students' understanding of the Underground Railroad and slavery, development of reading comprehension skills, and application of mapping skills. During three 45-60 minute lessons,…

    • NKCC1 and NHE1 are abundantly expressed in the basolateral plasma membrane of secretory coil cells in rat, mouse, and human sweat glands

      DEFF Research Database (Denmark)

      Nejsum, Lene Niemann; Prætorius, Jeppe; Nielsen, Søren

      2005-01-01

      1 (NHE1) protein has been localized to both the duct and secretory coil of human sweat duct; however, the NHE1 abundance in the duct was not compared with that in the secretory coil. The aim of this study was to test whether mRNA encoding NKCC1, NKCC2, and Na(+)-coupled acid-base transporters...... and the corresponding proteins are expressed in rodent sweat glands and, if expressed, to determine the cellular and subcellular localization in rat, mouse, and human eccrine sweat glands. NKCC1 mRNA was demonstrated in rat palmar tissue, including sweat glands, using RT-PCR, whereas NKCC2 mRNA was absent. Also, NHE1 m...... palmar skin by immunoblotting, whereas NKCC2, NHE2, and NHE3 proteins were not detected. Immunohistochemistry was performed using sections from rat, mouse, and human palmar tissue. Immunoperoxidase labeling revealed abundant expression of NKCC1 and NHE1 in the basolateral domain of secretory coils of rat...

    • Carbon isotope geochemistry of the Santa Clara River

      Science.gov (United States)

      Masiello, Caroline A.; Druffel, Ellen R. M.

      2001-06-01

      The Santa Clara River is a prototypical small mountainous river, with a headwater height greater than 1000 m and a basin area smaller than 10,000 m 2. Although individual small mountainous rivers export trivial amounts of sediment and carbon to the ocean, as a group these rivers may export a major fraction (as much as 50%) of the total global river sediment flux [Milliman and Syvitski, 1992], making their geochemistry relevant the study of the ocean's carbon cycle. In addition, many small rivers export sediment in a few high flux events, causing massive, sporadic discharge of carbon onto coastal shelves, discharge conditions very different from those of large rivers. This class of rivers is an end-member of the river-ocean carbon exchange system,. opposite the Earth's largest river, the Amazon. The carbon mass and isotopic properties of the Santa Clara River are significantly different from previously studied large rivers. During the 1997-1998 winter, all Santa Clara carbon pools were old, with flux-weighted average Δl4C values of-428±76‰ for particulate organic carbon, -73±31‰ for dissolved organic carbon, and-644±58‰ for black carbon. The age of exported carbon is primarily due to the deep erosion of old soils and not to inclusion of fossil fuel carbon. Additionally, the δ13C signatures of exported carbon pools were high relative to terrestrial carbon, bearing a signature quite similar to marine carbon (average particulate organic carbon (POC) δ13C = -22.2±0.8‰). The Santa Clara's estuary is small and drains onto the narrow eastern Pacific coastal margin, exporting this old soil organic matter directly into the ocean. If the Santa Clara export patterns are representative of this class of rivers, they may be a significant source of refractory terrestrial carbon to the ocean.

    • Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice

      Directory of Open Access Journals (Sweden)

      Hongyu Li

      2015-03-01

      Conclusions: Together with our previous studies, the current data reveal a conserved role for BIG3 in regulating alpha- and beta-cell functions. We propose that BIG3 negatively regulates hormone production at the secretory granule biogenesis stage and that such regulatory mechanism may be used in secretory pathways of other endocrine cells.

    • Non secretory multiple myeloma – a case report

      Directory of Open Access Journals (Sweden)

      Kartika W. Taroeno-Hariadi

      2007-12-01

      Full Text Available A rare variant of multiple mieloma, non-secretory multiple myeloma (NSM, is reported. Diagnosis of NSM is made by presentations of lytic bone lesions with bone pain, anemia, slight hypercalcemia, good renal function, negative results of protein and immunoelectrophoresis detecting monoclonal gammopathy, and positive clonal proliferation of plasma cells and atypical plasma cells in bone marrow biopsy. Immunophenotypic study resulted negative pan-B cell antigens and positive CD 79a. Patient condition was improved after institution of combination chemotherapy and 1 year afterward. (Med J Indones 2007; 16:257-60Keywords: multiple myeloma, non-secretory multiple myeloma, diagnosis, management

    • 78 FR 66756 - Santa Clara Pueblo; Amendment No. 1 to Notice of a Major Disaster Declaration

      Science.gov (United States)

      2013-11-06

      ... SECURITY Federal Emergency Management Agency Santa Clara Pueblo; Amendment No. 1 to Notice of a Major... amends the notice of a major disaster declaration for the Santa Clara Pueblo (FEMA-4147-DR), dated... disaster declaration for the Santa Clara Pueblo is hereby amended to include Public Assistance...

    • 78 FR 64233 - Santa Clara Pueblo; Major Disaster and Related Determinations

      Science.gov (United States)

      2013-10-28

      ... SECURITY Federal Emergency Management Agency Santa Clara Pueblo; Major Disaster and Related Determinations... Presidential declaration of a major disaster for the Santa Clara Pueblo (FEMA-4147-DR), dated September 27... Santa Clara Pueblo resulting from severe storms and flooding during the period of July 19-21, 2013,...

    • 76 FR 9640 - Prevailing Rate Systems: Santa Clara, CA, Tulsa County, OK, and Angelina County, TX

      Science.gov (United States)

      2011-02-22

      ..., ``Santa Clara,'' which was abolished as a NAF FWS wage area by a final rule (74 FR 9951) published on... MANAGEMENT 5 CFR Part 532 RIN 3206-AM22 Prevailing Rate Systems: Santa Clara, CA, Tulsa County, OK, and... of California by removing the entry for ``Santa Clara.'' 0 3. Appendix D to subpart B is amended...

    • Fine structure of the Caenorhabditis elegans secretory-excretory system.

      Science.gov (United States)

      Nelson, F K; Albert, P S; Riddle, D L

      1983-02-01

      The secretory-excretory system of C. elegans, reconstructed from serial-section electron micrographs of larvae, is composed of four cells, the nuclei of which are located on the ventral side of the pharynx and adjacent intestine. (1) The pore cell encloses the terminal one-third of the excretory duct which leads to an excretory pore at the ventral midline. (2) The duct cell surrounds the excretory duct with a lamellar membrane from the origin of the duct at the excretory sinus to the pore cell boundary. (3) A large H-shaped excretory cell extends bilateral canals anteriorly and posteriorly nearly the entire length of the worm. The excretory sinus within the cell body joins the lumena of the canals with the origin of the duct. (4) A binucleate, A-shaped gland cell extends bilateral processes anteriorly from cell bodies located just behind the pharynx. These processes are fused at the anterior tip of the cell, where the cell enters the circumpharyngeal nerve ring. The processes are also joined at the anterior edge of the excretory cell body, where the excretory cell and gland are joined to the duct cell at the origin of the duct. Secretory granules may be concentrated in the gland near this secretory-excretory junction. Although the gland cells of all growing developmental stages stain positively with paraldehyde-fuchsin, the gland of the dauer larva stage (a developmentally arrested third-stage larva) does not stain, nor do glands of starved worms of other stages. Dauer larvae uniquely lack secretory granules, and the gland cytoplasm is displaced by a labyrinth of large, transparent spaces. Exit from the dauer stage results in the return of active secretory morphology in fourth-stage larvae.

  1. Calcium dynamics in catecholamine-containing secretory vesicles

    OpenAIRE

    Moreno, Alfredo; Domínguez Lobatón, María Carmen; Santo Domingo, Jaime; Vay, Laura; Hernández-SanMiguel, Esther; Rizzuto, Rosario; Montero, Mayte; Álvarez, Javier

    2005-01-01

    Producción Científica We have used an aequorin chimera targeted to the membrane of the secretory granules to monitor the free [Ca2+] inside them in neurosecretory PC12 cells. More than 95% of the probe was located in a compartment with an homogeneous [Ca2+] around 40 M. Cell stimulation with either ATP, caffeine or high-K+ depolarization increased cytosolic [Ca2+] and decreased secretory granule [Ca2+] ([Ca2+]SG). Inositol-(1,4,5)- trisphosphate, cyclic ADP ribose and nicotinic a...

  2. Fasciola hepatica excretory-secretory products induce CD4+T cell anergy via selective up-regulation of PD-L2 expression on macrophages in a Dectin-1 dependent way.

    Science.gov (United States)

    Guasconi, Lorena; Chiapello, Laura S; Masih, Diana T

    2015-07-01

    Fasciola hepatica excretory-secretory products (FhESP) induce immunomodulatory effects on macrophages. Previously, we demonstrated that these effects are dependent on Dectin-1. Therefore, the aim of this study was to determine how this affects the CD4 T-cells immune response. We observed that FhESP induce an increased expression of PD-L2 in macrophages via Dectin-1. Furthermore, in co-cultures with CD4 T-cell we observed a suppressive effect on proliferative response, down-modulation of IFN-γ and up-modulation of IL-10 via Dectin-1 on macrophages. These results suggest that FhESP induce T-cell anergy via selective up-regulation of PD-L2 expression on macrophages in a Dectin-1 dependent way.

  3. Influence of continuous light and darkness on the secretory pinealocytes of Heteropneustes fossilis

    Indian Academy of Sciences (India)

    S Srivastava

    2003-09-01

    In an earlier study on Heteropneustes fossilis, evidence of secretory activity in the pinealocytes had been demonstrated at the electron microscopic (EM) level and it was found to exist in two phases: a secretory phase (light cells) and a storage phase (dark cells). In the present investigation, H. fossilis was subjected to artificial photoperiods of continuous illumination and continuous darkness for a period of ten days and the effect on the secretory pinealocytes was studied at the EM level. Marked results were observed within the short period of ten days emphasizing the role of environmental photoperiod on the secretory activity of the pinealocytes. During continuous illuminated phase, both light and dark cells were observed: the light cells showed intense secretory activity and dark cells a storage one. During the dark phase both types of cells were present but in different metabolic states and neither of the cells demonstrated synthetic nor storage activity. Light cells were metabolically active but not secretory active and dark cells showed a necrotic condition. Phagocytotic activity of the dark cells was also seen. Intense neural activity was also observed during exposure to both the artificial photoperiods. The results highlight the role of light on the secretory activities of the pinealocytes of the catfish pineal organ.

  4. NKCC1 and NHE1 are abundantly expressed in the basolateral plasma membrane of secretory coil cells in rat, mouse, and human sweat glands

    DEFF Research Database (Denmark)

    Nejsum, Lene Niemann; Prætorius, Jeppe; Nielsen, Søren

    2005-01-01

    In isolated sweat glands, bumetanide inhibits sweat secretion. The mRNA encoding bumetanide-sensitive Na(+)-K(+)-Cl(-) cotransporter (NKCC) isoform 1 (NKCC1) has been detected in sweat glands; however, the cellular and subcellular protein localization is unknown. Na(+)/H(+) exchanger (NHE) isoform...... 1 (NHE1) protein has been localized to both the duct and secretory coil of human sweat duct; however, the NHE1 abundance in the duct was not compared with that in the secretory coil. The aim of this study was to test whether mRNA encoding NKCC1, NKCC2, and Na(+)-coupled acid-base transporters...... and the corresponding proteins are expressed in rodent sweat glands and, if expressed, to determine the cellular and subcellular localization in rat, mouse, and human eccrine sweat glands. NKCC1 mRNA was demonstrated in rat palmar tissue, including sweat glands, using RT-PCR, whereas NKCC2 mRNA was absent. Also, NHE1 m...

  5. Some features of secretory systems in plants.

    Science.gov (United States)

    Juniper, B E; Gilchrist, A J; Robins, R J

    1977-09-01

    Recent work on secretion in plants is reviewed, with emphasis on the anatomy and physiology of root cap cells in higher plants, the stalked glands of Drosera capensis, and the secretory mechanism of Dionaea muscipula. Cells of the root cap of higher plants switch from a geo-perceptive role to one of mucilage secretion at maturation. Features of this process, the role of the Golgi and the pathway for mucilage distribution are reviewed. In contrast, the stalked glands of the leaves of Drosera capensis are much longer lived and have a complex anatomy. The mechanisms for mucilage secretion, protein absorption and the role of the cell membranes in the internal secretion of the protein are described, using data from X-ray microscopv. The secretion of fluid and protein by Dionaea is stimulated by various nitrogen-containing compounds. Uric acid, often excreted by captured insects, is particularly effective in this respect.

  6. Secretory function of adipose tissue.

    Science.gov (United States)

    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

    There are two kinds of adipose tissue in mammals: white adipose tissue - WAT and brown adipose tissue - BAT. The main function of WAT is accumulation of triacylglycerols whereas the function of BAT is heat generation. At present, WAT is also considered to be an endocrine gland that produces bioactive adipokines, which take part in glucose and lipid metabolism. Considering its endocrine function, the adipose tissue is not a homogeneous gland but a group of a few glands which act differently. Studies on the secretory function of WAT began in 1994 after discovery of leptin known as the satiation hormone, which regulates body energy homeostasis and maintainence of body mass. Apart from leptin, the following belong to adipokines: adiponectin, resistin, apelin, visfatin and cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic, anti-inflammatory and anti-atherogenic activity. It plays a key role in carbohydrate and fat metabolism. Resistin exerts a counter effect compared to adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin stimulates insulin secretion and increases insulin sensitivity and glucose uptake by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity of tissues. TNF evokes insulin resistance by blocking insulin receptors and inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from adipose tissue. It causes insulin resistance by decreasing the expression of insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion, and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is insulin and leptin resistance as well as the production of inflammatory cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that excess of adipose tissue, especially visceral adipose tissue, leads to the development of a chronic subclinical

  7. Development and essential oil content of secretory glands of sage (Salvia officinalis)

    Energy Technology Data Exchange (ETDEWEB)

    Venkatachalam, K.V.; Kjonaas, R.; Croteau, R.

    1984-09-01

    Scanning electron microscopy of sage (Salvia officinalis L.) leave confirmed the presence of two basic types of glandular trichomes consisting of a capitate stalked form containing a multicellular stalk and surmounted by a unicellular secretory head, and a capitate sessile form containing a unicellular stalk and unicellular, or multicellular, secretory head. In the latter type, secretory activity and filling of the subcuticular cavity may begin at virtually any stage of the division cycle affording fully developed glands containing from one to twelve cells in the secretory head. Gas liquid chromatographic analysis of the oil content of the most numerous gland species (capitate stalked, capitate sessile with one and with eight secretory cells) indicated only minor quantitative differences in essential oil composition. Thus, each gland type is capable of producing the four major monoterpene families (p-menthanes, pinanes, bornanes and thujanes) characteristic of sage. 21 references, 2 figures.

  8. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    Directory of Open Access Journals (Sweden)

    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  9. Clara E. Lida. Caleidoscopio del exilio. Actores, memoria, identidades

    Directory of Open Access Journals (Sweden)

    Rose Duroux

    2010-07-01

    Full Text Available Desde mediados de la década de 1980 he publicado y disertado sobre el exilio español en México en diversos foros académicos. Ello me ha permitido explorar distintas facetas vinculadas con el tema y recibir comentarios y sugerencias valiosas. De alguna manera, con la suma de todas estas miradas se construyeron los fragmentos que, como en los giros de un caleidoscopio, combinan reflexiones e imágenes a la vez complementarias y nuevas.Clara E. Lida Soixante-dix ans après la fin de la Guerre d’Es...

  10. TREATMENT SYSTEM FOR WASTEWATER AT VILLA CLARA WATER MANAGEMENT COMPANY

    Directory of Open Access Journals (Sweden)

    Floramis Pérez Martín

    2016-04-01

    Full Text Available The aim of this paper is to assess the current operating and safety conditions of biological treatment systems for wastewater in the centers of swinish and poultry breeding at Villa Clara Water Management Company, with the purpose of setting a group of organizational, technical and human measures that contributes to prevent contamination and minimize biological risks. In this way it can be guaranteed the protection to the workers, the facilities, community and the environment, to have a sure occupational atmosphere in the organization. As a result of the evaluation the factors that affect the operation of the biodigestion system and the security of the process are defined.

  11. Carbon isotope geochemistry of the Santa Clara River

    OpenAIRE

    2001-01-01

    The Santa Clara River is a prototypical small mountainous river, with a headwater height greater than 1000 m and a basin area smaller than 10,000 m 2. Although individual small mountainous rivers export trivial amounts of sediment and carbon to the ocean, as a group these rivers may export a major fraction (as much as 50%) of the total global river sediment flux [Milliman and Syvitski, 1992], making their geochemistry relevant the study of the ocean's carbon cycle. In addition, many small riv...

  12. Spectroscopic studies with the PRISMA-CLARA set-up

    Energy Technology Data Exchange (ETDEWEB)

    Fioretto, E; Corradi, L; Angelis, G de; Napoli, D R; Sahin, E; Silvestri, R; Stefanini, A M; Valiente-Dobon, J J [INFN - Laboratori Nazionali di Legnaro, Viale dell' Universita 2, Legnaro (PD), I-35020 (Italy); Bazzacco, D; Beghini, S; Farnea, E; Lenzi, S M; Lunardi, S; Mason, P; Mengoni, D; Montagnoli, G; Scarlassara, F; Ur, C A [Dipartimento di Fisica dell' Universita di Padova and INFN, Via Marzolo 8, Padova, I-35131 (Italy); Gadea, A [Instituto de Fisica Corpuscolar, CSIC-Universidad de Valencia, Valencia, E-46071 (Spain); Pollarolo, G, E-mail: enrico.fioretto@lnl.infn.i [Dipartimento di Fisica Teorica dell' Universita di Torino and INFN, Via P. Giuria 1, Torino, I-10125 (Italy)

    2010-01-01

    The large solid angle magnetic spectrometer for heavy ions PRISMA, installed at Laboratori Nazionali di Legnaro (LNL), was operated up to the end of March 2008 in conjunction with the highly efficient CLARA set-up. It allowed to carry out nuclear structure and reaction mechanism studies in several mass regions of the nuclide chart. Results obtained in the vicinity of the island of inversion and for the heavy iron and chromium isotopes are presented in this contribution. The status of the new focal plane detectors specifically designed for light ions and slow moving heavy ions is also reported.

  13. Excretory-secretory products of Giardia lamblia induce interleukin-8 production in human colonic cells via activation of p38, ERK1/2, NF-κB and AP-1.

    Science.gov (United States)

    Lee, H-Y; Hyung, S; Lee, N Y; Yong, T-S; Han, S-H; Park, S-J

    2012-04-01

    Giardia lamblia, a pathogen causing diarrhoeal outbreaks, is interesting how it triggers immune response in the human epithelial cells. This study defined the crucial roles of signalling components involved in G. lamblia-induced cytokine production in human epithelial cells. Incubation of the gastrointestinal cell line HT-29 with G. lamblia GS trophozoites triggered production of interleukin (IL)-1β, IL-8 and tumour necrosis factor (TNF)-α. IL-8 production was not significantly decreased by physically separating the HT-29 cells and G. lamblia GS trophozoites. Indeed, treatment of HT-29 with G. lamblia excretory-secretory products (ESP) induced IL-8 production. Electrophoretic mobility gel shift and transfection assays using mutagenized IL-8 promoter reporter plasmids indicated that IL-8 production by G. lamblia ESP occurs through activation of two transcriptional factors, nuclear factor kappaB (NF-κB) and activator protein 1 (AP-1) in HT-29 cells. In addition, activation of two mitogen-activated protein kinases (MAPKs), p38 and ERK1/2, was also detected in the HT-29 cells stimulated with G. lamblia ESP. Selective inhibition of these MAPKs resulted in decreased production of ESP-induced IL-8. These results indicate that activation of p38, ERK1/2 MAPK, NF-κB and AP-1 comprises the signalling pathway responsible for IL-8 production by G. lamblia ESP.

  14. Structural superposition in fault systems bounding Santa Clara Valley, California

    Science.gov (United States)

    Graymer, Russell W.; Stanley, Richard G.; Ponce, David A.; Jachens, Robert C.; Simpson, Robert W.; Wentworth, Carl M.

    2015-01-01

    Santa Clara Valley is bounded on the southwest and northeast by active strike-slip and reverse-oblique faults of the San Andreas fault system. On both sides of the valley, these faults are superposed on older normal and/or right-lateral normal oblique faults. The older faults comprised early components of the San Andreas fault system as it formed in the wake of the northward passage of the Mendocino Triple Junction. On the east side of the valley, the great majority of fault displacement was accommodated by the older faults, which were almost entirely abandoned when the presently active faults became active after ca. 2.5 Ma. On the west side of the valley, the older faults were abandoned earlier, before ca. 8 Ma and probably accumulated only a small amount, if any, of the total right-lateral offset accommodated by the fault zone as a whole. Apparent contradictions in observations of fault offset and the relation of the gravity field to the distribution of dense rocks at the surface are explained by recognition of superposed structures in the Santa Clara Valley region.

  15. Hydrogeologic framework of the Santa Clara Valley, California

    Science.gov (United States)

    Hanson, Randall T.

    2015-01-01

    The hydrologic framework of the Santa Clara Valley in northern California was redefined on the basis of new data and a new hydrologic model. The regional groundwater flow systems can be subdivided into upper-aquifer and lower-aquifer systems that form a convergent flow system within a basin bounded by mountains and hills on three sides and discharge to pumping wells and the southern San Francisco Bay. Faults also control the flow of groundwater within the Santa Clara Valley and subdivide the aquifer system into three subregions.After decades of development and groundwater depletion that resulted in substantial land subsidence, Santa Clara Valley Water District (SCVWD) and the local water purveyors have refilled the basin through conservation and importation of water for direct use and artificial recharge. The natural flow system has been altered by extensive development with flow paths toward major well fields. Climate has not only affected the cycles of sedimentation during the glacial periods over the past million years, but interannual to interdecadal climate cycles also have affected the supply and demand components of the natural and anthropogenic inflows and outflows of water in the valley. Streamflow has been affected by development of the aquifer system and regulated flow from reservoirs, as well as conjunctive use of groundwater and surface water. Interaquifer flow through water-supply wells screened across multiple aquifers is an important component to the flow of groundwater and recapture of artificial recharge in the Santa Clara Valley. Wellbore flow and depth-dependent chemical and isotopic data indicate that flow into wells from multiple aquifers, as well as capture of artificial recharge by pumping of water-supply wells, predominantly is occurring in the upper 500 ft (152 m) of the aquifer system. Artificial recharge represents about one-half of the inflow of water into the valley for the period 1970–1999. Most subsidence is occurring below 250 ft

  16. Secretory breast cancer. Case report.

    Science.gov (United States)

    Lombardi, A; Maggi, S; Bersigotti, L; Lazzarin, G; Nuccetelli, E; Amanti, C

    2013-04-01

    Secretory carcinoma of the breast is a rare tumor initially described in children but occurring equally in adult population. This unusual breast cancer subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases. However, surgery is still considered the most appropriate treatment for this pathology. We describe the case of a 50 -year-old woman who has undergone a breast conservative surgery for a little tumor, preoperatively diagnosticated by a fine needle aspiration biopsy (FNAB) as a well differentiated infiltrating carcinoma.

  17. Groundwater quality in the Santa Clara River Valley, California

    Science.gov (United States)

    Burton, Carmen A.; Landon, Matthew K.; Belitz, Kenneth

    2011-01-01

    The Santa Clara River Valley (SCRV) study unit is located in Los Angeles and Ventura Counties, California, and is bounded by the Santa Monica, San Gabriel, Topatopa, and Santa Ynez Mountains, and the Pacific Ocean. The 460-square-mile study unit includes eight groundwater basins: Ojai Valley, Upper Ojai Valley, Ventura River Valley, Santa Clara River Valley, Pleasant Valley, Arroyo Santa Rosa Valley, Las Posas Valley, and Simi Valley (California Department of Water Resources, 2003; Montrella and Belitz, 2009). The SCRV study unit has hot, dry summers and cool, moist winters. Average annual rainfall ranges from 12 to 28 inches. The study unit is drained by the Ventura and Santa Clara Rivers, and Calleguas Creek. The primary aquifer system in the Ventura River Valley, Ojai Valley, Upper Ojai Valley, and Simi Valley basins is largely unconfined alluvium. The primary aquifer system in the remaining groundwater basins mainly consists of unconfined sands and gravels in the upper portion and partially confined marine and nonmarine deposits in the lower portion. The primary aquifer system in the SCRV study unit is defined as those parts of the aquifers corresponding to the perforated intervals of wells listed in the California Department of Public Health (CDPH) database. Public-supply wells typically are completed in the primary aquifer system to depths of 200 to 1,100 feet below land surface (bls). The wells contain solid casing reaching from the land surface to a depth of about 60-700 feet, and are perforated below the solid casing to allow water into the well. Water quality in the primary aquifer system may differ from the water in the shallower and deeper parts of the aquifer. Land use in the study unit is approximately 40 percent (%) natural (primarily shrubs, grassland, and wetlands), 37% agricultural, and 23% urban. The primary crops are citrus, avocados, alfalfa, pasture, strawberries, and dry beans. The largest urban areas in the study unit are the cities of

  18. 78 FR 67382 - Santa Clara Pueblo; Major Disaster and Related Determinations

    Science.gov (United States)

    2013-11-12

    ... SECURITY Federal Emergency Management Agency Santa Clara Pueblo; Major Disaster and Related Determinations... Presidential declaration of a major disaster for the Santa Clara Pueblo (FEMA-4151-DR), dated October 24, 2013... Act''), as follows: I have determined that the damage to the lands associated with the Santa...

  19. Lipids implicated in the journey of a secretory granule: from biogenesis to fusion.

    Science.gov (United States)

    Tanguy, Emeline; Carmon, Ophélie; Wang, Qili; Jeandel, Lydie; Chasserot-Golaz, Sylvette; Montero-Hadjadje, Maité; Vitale, Nicolas

    2016-06-01

    The regulated secretory pathway begins with the formation of secretory granules by budding from the Golgi apparatus and ends by their fusion with the plasma membrane leading to the release of their content into the extracellular space, generally following a rise in cytosolic calcium. Generation of these membrane-bound transport carriers can be classified into three steps: (i) cargo sorting that segregates the cargo from resident proteins of the Golgi apparatus, (ii) membrane budding that encloses the cargo and depends on the creation of appropriate membrane curvature, and (iii) membrane fission events allowing the nascent carrier to separate from the donor membrane. These secretory vesicles then mature as they are actively transported along microtubules toward the cortical actin network at the cell periphery. The final stage known as regulated exocytosis involves the docking and the priming of the mature granules, necessary for merging of vesicular and plasma membranes, and the subsequent partial or total release of the secretory vesicle content. Here, we review the latest evidence detailing the functional roles played by lipids during secretory granule biogenesis, recruitment, and exocytosis steps. In this review, we highlight evidence supporting the notion that lipids play important functions in secretory vesicle biogenesis, maturation, recruitment, and membrane fusion steps. These effects include regulating various protein distribution and activity, but also directly modulating membrane topology. The challenges ahead to understand the pleiotropic functions of lipids in a secretory granule's journey are also discussed. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015).

  20. Tar Creek study, Sargent oil field, Santa Clara County, California

    Science.gov (United States)

    Wagner, David L.; Fedasko, Bill; Carnahan, J.R.; Brunetti, Ross; Magoon, Leslie B.; Lillis, Paul G.; Lorenson, T.D.; Stanley, Richard G.

    2002-01-01

    Field work in the Tar Creek area of Sargent oil field was performed June 26 to 28, 2000. The Santa Clara County study area is located in Sections, 30, 31, and 32, Township 11 South, Range 4 East, M.D.B&M; and in Sections 25 and 36, Township 11 South, Range 3 East, M.D.B.&M., north and south of Tar Creek, west of Highway 101. The work was a cooperative effort of the California Department of Conservation's Division of Oil, Gas, and Geothermal Resources (DOGGR), California Geological Survey (CGS), and the United States Geological Survey (USGS). The purpose of the project was to map the stratigraphy and geologic structure (David Wagner, CGS); sample oil for age dating (Les Magoon, USGS); and search for undocumented wells plus conduct a GPS survey of the area (Bill Fedasko, J.P. Carnahan, and Ross Brunetti, DOGGR)

  1. Muscle as a secretory organ

    DEFF Research Database (Denmark)

    Pedersen, Bente K

    2013-01-01

    of several hundred secreted peptides. This finding provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. In addition, several myokines exert their effects within the muscle itself. Many...... evidence has identified skeletal muscle as a secretory organ. We have suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects should be classified as "myokines." The muscle secretome consists...... proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute in the mediation of the health benefits of exercise....

  2. Muscle as a secretory organ.

    Science.gov (United States)

    Pedersen, Bente K

    2013-07-01

    Skeletal muscle is the largest organ in the body. Skeletal muscles are primarily characterized by their mechanical activity required for posture, movement, and breathing, which depends on muscle fiber contractions. However, skeletal muscle is not just a component in our locomotor system. Recent evidence has identified skeletal muscle as a secretory organ. We have suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either autocrine, paracrine, or endocrine effects should be classified as "myokines." The muscle secretome consists of several hundred secreted peptides. This finding provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs such as adipose tissue, liver, pancreas, bones, and brain. In addition, several myokines exert their effects within the muscle itself. Many proteins produced by skeletal muscle are dependent upon contraction. Therefore, it is likely that myokines may contribute in the mediation of the health benefits of exercise.

  3. Regulation of secretory granule size by the precise generation and fusion of unit granules.

    Science.gov (United States)

    Hammel, Ilan; Lagunoff, David; Galli, Stephen J

    2010-07-01

    Morphometric evidence derived from studies of mast cells, pancreatic acinar cells and other cell types supports a model in which the post-Golgi processes that generate mature secretory granules can be resolved into three steps: (1) fusion of small, Golgi-derived progranules to produce immature secretory granules which have a highly constrained volume; (2) transformation of such immature granules into mature secretory granules, a process often associated with a reduction in the maturing granule's volume, as well as changes in the appearance of its content and (3) fusion of secretory granules of the smallest size, termed 'unit granules', forming granules whose volumes are multiples of the unit granule's volume. Mutations which perturb this process can cause significant pathology. For example, Chediak-Higashi syndrome / lysosomal trafficking regulator (CHS)/(Lyst) mutations result in giant secretory granules in a number of cell types in human beings with the Chediak-Higashi syndrome and in 'beige' (Lyst(bg)/Lyst(bg)) mice. Analysis of the secretory granules of mast cells and pancreatic acinar cells in Lyst-deficient beige mice suggests that beige mouse secretory granules retain the ability to fuse randomly with other secretory granules no matter what the size of the fusion partners. By contrast, in normal mice, the pattern of granule-granule fusion occurs exclusively by the addition of unit granules, either to each other or to larger granules. The normal pattern of fusion is termed unit addition and the fusion evident in cells with CHS/Lyst mutations is called random addition. The proposed model of secretory granule formation has several implications. For example, in neurosecretory cells, the secretion of small amounts of cargo in granules constrained to a very narrow size increases the precision of the information conveyed by secretion. By contrast, in pancreatic acinar cells and mast cells, large granules composed of multiple unit granules permit the cells to store

  4. Progressive quality control of secretory proteins in the early secretory compartment by ERp44.

    Science.gov (United States)

    Sannino, Sara; Anelli, Tiziana; Cortini, Margherita; Masui, Shoji; Degano, Massimo; Fagioli, Claudio; Inaba, Kenji; Sitia, Roberto

    2014-10-01

    ERp44 is a pH-regulated chaperone of the secretory pathway. In the acidic milieu of the Golgi, its C-terminal tail changes conformation, simultaneously exposing the substrate-binding site for cargo capture and the RDEL motif for ER retrieval through interactions with cognate receptors. Protonation of cysteine 29 in the active site allows tail movements in vitro and in vivo. Here, we show that conserved histidine residues in the C-terminal tail also regulate ERp44 in vivo. Mutants lacking these histidine residues retain substrates more efficiently. Surprisingly, they are also O-glycosylated and partially secreted. Co-expression of client proteins prevents secretion of the histidine mutants, forcing tail opening and RDEL accessibility. Client-induced RDEL exposure allows retrieval of proteins from distinct stations along the secretory pathway, as indicated by the changes in O-glycosylation patterns upon overexpression of different partners. The ensuing gradients might help to optimize folding and assembly of different cargoes. Endogenous ERp44 is O-glycosylated and secreted by human primary endometrial cells, suggesting possible pathophysiological roles of these processes.

  5. 76 FR 72972 - Notice of Realty Action: Competitive Sale of Public Land in Santa Clara County, CA

    Science.gov (United States)

    2011-11-28

    ... Bureau of Land Management Notice of Realty Action: Competitive Sale of Public Land in Santa Clara County... approximately 23.42 acres, more or less, in Santa Clara County, California. The public land would be sold for... described contains 23.42 acres, more or less, in Santa Clara County, California. Appraised fair market...

  6. 76 FR 16812 - Notice of Realty Action: Modified Competitive Bid Sale of Public Land in Santa Clara County, CA

    Science.gov (United States)

    2011-03-25

    ... Notice of Realty Action: Modified Competitive Bid Sale of Public Land in Santa Clara County, CA AGENCY... approximately 9.27 acres in Santa Clara County, California, for not less than the appraised fair market value of..., more or less, in Santa Clara County. The public land was originally identified as suitable for...

  7. 75 FR 8106 - Don Edwards San Francisco Bay National Wildlife Refuge, Alameda, Santa Clara, and San Mateo...

    Science.gov (United States)

    2010-02-23

    ... Fish and Wildlife Service Don Edwards San Francisco Bay National Wildlife Refuge, Alameda, Santa Clara... located in Alameda, Santa Clara, and San Mateo Counties of California. We provide this notice in... in Alameda, Santa Clara, and San Mateo Counties of California, consists of several non...

  8. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

    DEFF Research Database (Denmark)

    Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M

    2013-01-01

    Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here...... for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine cells and support an important role of PICK1/ICA69 in maintenance of metabolic homeostasis.......Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here......, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation...

  9. Oil Secretory System in Vegetative Organs of Three Arnica Taxa: Essential Oil Synthesis, Distribution and Accumulation.

    Science.gov (United States)

    Kromer, Krystyna; Kreitschitz, Agnieszka; Kleinteich, Thomas; Gorb, Stanislav N; Szumny, Antoni

    2016-05-01

    Arnica, a genus including the medicinal species A. montana, in its Arbo variety, and A. chamissonis, is among the plants richest in essential oils used as pharmaceutical materials. Despite its extensive use, the role of anatomy and histochemistry in the internal secretory system producing the essential oil is poorly understood. Anatomical sections allowed differentiation between two forms of secretory structures which differ according to their distribution in plants. The first axial type is connected to the vascular system of all vegetative organs and forms canals lined with epithelial cells. The second cortical type is represented by elongated intercellular spaces filled with oil formed only between the cortex cells of roots and rhizomes at maturity, with canals lacking an epithelial layer.Only in A. montana rhizomes do secretory structures form huge characteristic reservoirs. Computed tomography illustrates their spatial distribution and fusiform shape. The axial type of root secretory canals is formed at the interface between the endodermis and cortex parenchyma, while, in the stem, they are located in direct contact with veinal parenchyma. The peripheral phloem parenchyma cells are arranged in strands around sieve tube elements which possess a unique ability to accumulate large amounts of oil bodies. The cells of phloem parenchyma give rise to the aforementioned secretory structures while the lipid components (triacylglycerols) stored there support the biosynthesis of essential oils by later becoming a medium in which these oils are dissolved. The results indicate the integrity of axial secretory structures forming a continuous system in vegetative plant organs.

  10. Secretory structures of Ipomoea asarifolia: anatomy and histochemistry

    OpenAIRE

    Martins,Fabiano M.; Lima,Jamile F.; Ana Angélica S. Mascarenhas; Thayane P. Macedo

    2012-01-01

    Ipomoea asarifolia (Desr.) Roem. & Schult., Convolvulaceae, is a weed that infests agricultural areas and is toxic to cattle. In spite of its toxicity, the leaves of this plant are used in traditional remedies in the state of Bahia, Brazil. The present work describes the leaf anatomy of I. asarifolia and characterizes the exudates of its secretory structures. The leaves have a unistratified epidermis composed of ordinary cells with straight to slightly sinuous anticlinal walls and thin cu...

  11. Discovery and characterization of secretory IgD in rainbow trout: secretory IgD is produced through a novel splicing mechanism

    Science.gov (United States)

    Ramirez-Gomez, F.; Greene, W.; Rego, K.; Hansen, J.D.; Costa, G.; Kataria, P.; Bromage, E.S.

    2012-01-01

    The gene encoding IgH δ has been found in all species of teleosts studied to date. However, catfish (Ictalurus punctatus) is the only species of fish in which a secretory form of IgD has been characterized, and it occurs through the use of a dedicated δ-secretory exon, which is absent from all other species examined. Our studies have revealed that rainbow trout (Oncorhynchus mykiss) use a novel strategy for the generation of secreted IgD. The trout secretory δ transcript is produced via a run-on event in which the splice donor site at the end of the last constant domain exon (D7) is ignored and transcription continues until a stop codon is reached 33 nt downstream of the splice site, resulting in the production of an in-frame, 11-aa secretory tail at the end of the D7 domain. In silico analysis of several published IgD genes suggested that this unique splicing mechanism may also be used in other species of fish, reptiles, and amphibians. Alternative splicing of the secretory δ transcript resulted in two δ-H chains, which incorporated Cμ1 and variable domains. Secreted IgD was found in two heavily glycosylated isoforms, which are assembled as monomeric polypeptides associated with L chains. Secretory δ mRNA and IgD+ plasma cells were detected in all immune tissues at a lower frequency than secretory IgM. Our data demonstrate that secretory IgD is more prevalent and widespread across taxa than previously thought, and thus illustrate the potential that IgD may have a conserved role in immunity.

  12. Impairment of intestinal barrier and secretory function as well as egg excretion during intestinal schistosomiasis occur independently of mouse mast cell protease-1.

    NARCIS (Netherlands)

    Rychter, J.; van Nassauw, L.; Brown, J.K.; van Marck, E.; Knight, P.A.; Miller, H.R.P.; Kroese, A.; Timmermans, J.P.

    2010-01-01

    Deposition of Schistosoma mansoni eggs in the intestinal mucosa is associated with recruitment of mucosal mast cells (MMC) expressing mouse mast cell protease-1 (mMCP-1). We investigated the involvement of mMCP-1 in intestinal barrier disruption and egg excretion by examining BALB/c mice lacking mMC

  13. Modeling the Cienega de Santa Clara, Sonora, Mexico

    Science.gov (United States)

    Huckelbridge, K. H.; Hidalgo, H.; Dracup, J.; Ibarra Obando, S. E.

    2002-12-01

    The Cienega de Santa Clara is a created wetland located in the Colorado River Delta (CRD), in Sonora, Mexico. It is sustained by agricultural return flows from the Wellton-Mohawk Irrigation District in Arizona and the Mexicali Valley in Mexico. As one of the few wetlands remaining in the CRD, it provides critical habitat for several species of fish and birds, including several endangered species such as the desert pupfish (Cyprinodon macularius) and the Yuma clapper rail (Rallus longirostris yumanensis). However, this habitat may be in jeopardy if the quantity and quality of the agricultural inflows are significantly altered. This study seeks to develop a model that describes the dynamics of wetland hydrology, vegetation, and water quality as a function of inflow variability and salinity loading. The model is divided into four modules set up in sequence. For a given time step, the sequence begins with the first module, which utilizes basic diffusion equations to simulate mixing processes in the shallow wetland when the flow and concentration of the inflow deviate from the baseline. The second module develops a vegetated-area response to the resulting distribution of salinity in the wetland. Using the new area of vegetation cover determined by the second module and various meteorological variables, the third module calculates the evapotranspiration rate for the wetland, using the Penman-Montieth equation. Finally, the fourth module takes the overall evapotranspiration rate, along with precipitation, inflow and outflow and calculates the new volume of the wetland using a water balance. This volume then establishes the initial variables for the next time step. The key outputs from the model are salinity concentration, area of vegetation cover, and wetland volume for each time step. Results from this model will illustrate how the wetland's hydrology, vegetation, and water quality are altered over time under various inflow scenarios. These outputs can ultimately be used

  14. MiR-100-3p and miR-877-3p regulate overproduction of IL-8 and IL-1β in mesangial cells activated by secretory IgA from IgA nephropathy patients.

    Science.gov (United States)

    Liang, Yan; Zhao, Guoqiang; Tang, Lin; Zhang, Junjun; Li, Tianfang; Liu, Zhangsuo

    2016-10-01

    IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, characterized by mesangial deposition of pathogenic IgA and the injury to mesangial cells. Our previous studies indicate that secretory IgA (SIgA) plays an important role in the pathogenesis of IgAN, and miR-16 is involved in destructive process in mesangial cells mediated by the SIgA from IgAN patients. Our current study aimed to study the role of miRNAs in the effect of SIgA from IgAN patients on mesangial cells. MicroRNA microarray and cytokines assay were performed to obtain the differential microRNAs expression profile in human renal mesangial cells stimulated by SIgA from IgAN patients (P-SIgA) with the cells treated by SIgA from healthy subjects (N-SgA) as control. The microRNAs with the most significant differences in microarray analysis were validated by quantitative RT-PCR. Among them, miR-100-3p and miR-877-3p were selected to predict target gene related to cytokines detecting in this study. Fifty-six differentially expressed microRNAs were chosen and 17 microRNAs with the most prominent changes were validated. Compared with N-SIgA, P-SIgA increased the production of interleukin (IL)-1β, IL-8, monocyte chemotactic protein-1 and transforming growth factor-β1. In addition, we for the first time demonstrated that over-production of IL-8 induced by the SIgA was regulated by down-expression of miR-100-3p in mesangial cells. Similarly, IL-1β over-production was regulated by down-expression of miR-877-3p. Our findings represent a pathogenic microRNAs expression profiling in human mesangial cells activated by P-SIgA. Furthermore, we provide a new explanation characterizing the molecular mechanism responsible for the regulation of IL-1β and IL-8 production in P-SIgA-triggered mesangial cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Chronic Insulin Exposure Induces ER Stress and Lipid Body Accumulation in Mast Cells at the Expense of Their Secretory Degranulation Response.

    Directory of Open Access Journals (Sweden)

    William E Greineisen

    Full Text Available Lipid bodies (LB are reservoirs of precursors to inflammatory lipid mediators in immunocytes, including mast cells. LB numbers are dynamic, increasing dramatically under conditions of immunological challenge. We have previously shown in vitro that insulin-influenced lipogenic pathways induce LB biogenesis in mast cells, with their numbers attaining steatosis-like levels. Here, we demonstrate that in vivo hyperinsulinemia resulting from high fat diet is associated with LB accumulation in murine mast cells and basophils. We characterize the lipidome of purified insulin-induced LB, and the shifts in the whole cell lipid landscape in LB that are associated with their accumulation, in both model (RBL2H3 and primary mast cells. Lipidomic analysis suggests a gain of function associated with LB accumulation, in terms of elevated levels of eicosanoid precursors that translate to enhanced antigen-induced LTC4 release. Loss-of-function in terms of a suppressed degranulation response was also associated with LB accumulation, as were ER reprogramming and ER stress, analogous to observations in the obese hepatocyte and adipocyte. Taken together, these data suggest that chronic insulin elevation drives mast cell LB enrichment in vitro and in vivo, with associated effects on the cellular lipidome, ER status and pro-inflammatory responses.

  16. The Ultra-structure Observation of Glandular Hairs Secretory Cell of Flue-cured Tobacco%烤烟腺毛分泌细胞的超微结构观察

    Institute of Scientific and Technical Information of China (English)

    薛晓明; 张晶; 于丽杰

    2011-01-01

    为了解和掌握烤烟腺毛分泌细胞中分泌物产生、转运及分泌的过程和规律,通过透射电子显微镜观察了烤烟的长柄腺毛和短柄腺毛分泌细胞的超微结构.结果表明:2种类型腺毛的分泌细胞在超微结构上特性比较相似,但优势细胞器的分布不同,结构完整的发达的叶绿体在长柄腺毛分泌细胞的细胞质内大量存在,可以初步认定叶绿体参与了腺毛分泌产物的生物合成;在2类腺毛中均有大量的内质网、线粒体、液泡和少数的高尔基体,这些细胞器与腺毛的分泌活动有密切的关系.2种腺毛中都观察到细胞间隙和胞质外空间的产生和扩大,以及其中存在的嗜锇物质,2处是分泌产物的临时储藏所,分泌产物在细胞中的分布可得到分泌物的储存和释放途径.%Ultra-structure of the flue-cured tobacco was observed by transmission electron microscope (TEM) to understand and master the process and regulation of generation, transportation and secretion of the secretion from glandular hairs secretory cell of flue-cured tobacco. The results showed that the ultra-structure of the long-stem glandular hairs was very similar to the short-stem glandular hairs, but the distribution of advantageous cell was different and there were plenty of well structured and developed chloroplasts in the long-stem glandular cell. It can be affirmed that chloroplast has been involved in the biosynthesis of glandular secreta. A large amount of endoplasmic, reticulum, mitochondria, vacuole and a few of golgiosome existed in the two kinds of glandular hairs. These organelles were greatly related with the secretory of glandular hairs cell. With the space appearance and expansion of intercellular and cytoplasm external and osmiophilic materials, it was proved that the two places were both temporary storage sites of secreta and the pathway of secreta storage and release can be investigated by observing the secreta's distribution

  17. RNAi knockdown of parafusin inhibits the secretory pathway.

    Science.gov (United States)

    Liu, Li; Wyroba, Elzbieta; Satir, Birgit H

    2011-10-01

    Several glycolytic enzymes and their isoforms have been found to be important in cell signaling unrelated to glycolysis. The involvement of parafusin (PFUS), a member of the phosphoglucomutase (PGM) superfamily with no phosphoglucomutase activity, in Ca(2+)-dependent exocytosis has been controversial. This protein was first described in Paramecium tetraurelia, but is widely found. Earlier work showed that parafusin is a secretory vesicle scaffold component with unusual post-translational modifications (cyclic phosphorylation and phosphoglucosylation) coupled to stages in the exocytic process. Using RNAi, we demonstrate that parafusin synthesis can be reversibly blocked, with minor or no effect on other PGM isoforms. PFUS knockdown produces an inhibition of dense core secretory vesicle (DCSV) synthesis leading to an exo(-) phenotype. Although cell growth is unaffected, vesicle content is not packaged properly and no new DCSVs are formed. We conclude that PFUS and its orthologs are necessary for proper scaffold maturation. Because of this association, parafusin is an important signaling component for regulatory control of the secretory pathway.

  18. Secretory TAT-peptide-mediated protein transduction of LIF receptor α-chain distal cytoplasmic motifs into human myeloid HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Q. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Xiong, J. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Lu, J. [Office of Medical Education, Training Department, Second Military Medical University, Shanghai (China); Xu, S. [Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China); Li, Y. [State Food and Drug Administration of China,Huangdao Branch, Qingdao (China); Zhong, X.P.; Gao, G.K. [Department of Hyperbaric Medicine, No. 401 Hospital of PLA, Qingdao (China); Liu, H.Q. [2Department of Histology and Embryology, Faculty of Basic Medical Sciences, Second Military Medical University, Shanghai (China)

    2012-06-22

    The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.

  19. Resistin, a fat-derived secretory factor, promotes metastasis of MDA-MB-231 human breast cancer cells through ERM activation.

    Science.gov (United States)

    Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Lee, Yong Woo; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo

    2016-01-05

    Resistin, an adipocyte-secreted factor, is known to be elevated in breast cancer patients. However, the molecular mechanism by which resistin acts is not fully understood. The aim of this study was to investigate whether resistin could stimulate invasion and migration of breast cancer cells. Here, we report that resistin stimulated invasion and migration of breast cancer cells as well as phosphorylation of c-Src. Inhibition of c-Src blocked resistin-induced breast cancer cell invasion. Resistin increased intracellular calcium concentration, and chelation of intracellular calcium blocked resistin-mediated activation of Src. Resistin also induced phosphorylation of protein phosphatase 2A (PP2A). Inhibition of c-Src blocked resistin-mediated PP2A phosphorylation. In addition, resistin increased phosphorylation of PKCα. Inhibition of PP2A enhanced resistin-induced PKCα phosphorylation, demonstrating that PP2A activity is critical for PKCα phosphorylation. Resistin also increased phosphorylation of ezrin, radixin, and moesin (ERM). Additionally, ezrin interacted with PKCα, and resistin promoted co-localization of ezrin and PKCα. Either inhibition of c-Src and PKCα or knock-down of ezrin blocked resistin-induced breast cancer cells invasion. Moreover, resistin increased expression of vimentin, a key molecule for cancer cell invasion. Knock-down of ezrin abrogated resistin-induced vimentin expression. These results suggest that resistin play as a critical regulator of breast cancer metastasis.

  20. Effects of exposure to electromagnetic radiation at 835 MHz on growth, morphology and secretory characteristics of a mast cell analogue, RBL-2H3.

    Science.gov (United States)

    Donnellan, M; McKenzie, D R; French, P W

    1997-07-01

    A mast cell line, RBL-2H3, was exposed to 835 MHz for 20 minutes, three times per day for 7 days at a power density of 8.1 +/- 3 mW/cm2. From day 4 onwards, it was observed that the rate of DNA synthesis and cell replication increased, that actin distribution and cell morphology became altered, and the amount of beta-hexosaminidase (a marker of granule secretion) released in response to a calcium ionophore was significantly enhanced, in comparison to unexposed cultures. There were no effects seen on levels of cytoskeletal protein synthesis or of beta-actin mRNA. Morphological changes persisted following subculture for at least 7 days in the absence of further exposure. It is hypothesized that effects of exposure to an electromagnetic field at 835 MHz may be mediated via a signal transduction pathway.

  1. The CREC family, a novel family of multiple EF-hand, low-affinity Ca(2+)-binding proteins localised to the secretory pathway of mammalian cells

    DEFF Research Database (Denmark)

    Honoré, B; Vorum, H

    2000-01-01

    (2+)-regulated activities. Recent evidence has been obtained that some CREC family members are involved in pathological activities such as malignant cell transformation, mediation of the toxic effects of snake venom toxins and putative participation in amyloid formation. Udgivelsesdato: 2000-Jan-21...

  2. Taenia taeniaeformis: inhibition of rat testosterone production by excretory-secretory product of the cultured metacestode.

    Science.gov (United States)

    Rikihisa, Y; Lin, Y C; Fukaya, T

    1985-06-01

    In 3- to 5-month-old male Sprague-Dawley rats infected with the hepatic metacestode, Taenia taeniaeformis, the serum testosterone level was significantly lower than in comparable uninfected controls. By transmission electron microscopy, testicular Leydig cells of infected rats had less smooth endoplasmic reticulum than control Leydig cells. Cultured metacestodes isolated from the hepatic cysts secreted or excreted substances into the incubation medium. The effect of the excretory-secretory product on testosterone concentration in the sera and testes of 15-day-old rats was examined. Subcutaneous injection of 50-200 micrograms of excretory-secretory product/0.1 ml saline/rat for 2 days significantly reduced human chorionic gonadotropin-stimulated serum and testicular testosterone concentrations. Furthermore, the effect of the excretory-secretory product on isolated rat Leydig cell testosterone production was examined. Rat Leydig cells produced testosterone in vitro and, in the presence of 50 IU human chorionic gonadotropin/ml incubation medium, they responded with approximately 100% increase in testosterone production. Addition of 2-10 micrograms excretory-secretory product protein/ml of culture medium significantly reduced the testosterone production by rat Leydig cells in vitro. These results indicate that excretory-secretory product of cultured T. taeniaeformis metacestodes has a direct inhibitory effect on Leydig cell testosterone production under stimulation with human chorionic gonadotropin.

  3. Platelet-Rich Plasma Increases Growth and Motility of Adipose Tissue-Derived Mesenchymal Stem Cells and Controls Adipocyte Secretory Function.

    Science.gov (United States)

    D'Esposito, Vittoria; Passaretti, Federica; Perruolo, Giuseppe; Ambrosio, Maria Rosaria; Valentino, Rossella; Oriente, Francesco; Raciti, Gregory A; Nigro, Cecilia; Miele, Claudia; Sammartino, Gilberto; Beguinot, Francesco; Formisano, Pietro

    2015-10-01

    Adipose tissue-derived mesenchymal stem cells (Ad-MSC) and platelet derivatives have been used alone or in combination to achieve regeneration of injured tissues. We have tested the effect of platelet-rich plasma (PRP) on Ad-MSC and adipocyte function. PRP increased Ad-MSC viability, proliferation rate and G1-S cell cycle progression, by at least 7-, 2-, and 2.2-fold, respectively, and reduced caspase 3 cleavage. Higher PRP concentrations or PRPs derived from individuals with higher platelet counts were more effective in increasing Ad-MSC growth. PRP also accelerated cell migration by at least 1.5-fold. However, PRP did not significantly affect mature adipocyte viability, differentiation and expression levels of PPAR-γ and AP-2 mRNAs, while it increased leptin production by 3.5-fold. Interestingly, PRP treatment of mature adipocytes also enhanced the release of Interleukin (IL)-6, IL-8, IL-10, Interferon-γ, and Vascular Endothelial Growth Factor. Thus, data are consistent with a stimulatory effect of platelet derivatives on Ad-MSC growth and motility. Moreover, PRP did not reduce mature adipocyte survival and increased the release of pro-angiogenic factors, which may facilitate tissue regeneration processes.

  4. Secretory carcinoma of breast mimicking an abscess: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    K Bharathi

    2015-01-01

    Full Text Available Secretory carcinoma is a rare type of breast carcinoma usually seen in the young females, and it is also called as "Juvenile carcinoma." We report here a case of secretory carcinoma in an elderly female with an unusual clinical presentation. She had a painful swelling in left breast of 6 cm × 5 cm size for the past 6 months. Skin over the swelling was inflamed and ulcerated. Mammogram findings favored a chronic infected hematoma/abscess. Fine needle aspirate (FNA is a murky fluid admixed with blood and was reported as acute inflammatory lesion. 2 weeks later she developed nipple retraction and an increase in size of the swelling. Fine needle aspiration cytology (FNAC was repeated again from firm areas and in multiple points of swelling. To our surprise, FNA smears revealed dysplastic ductal epithelial cells with minimal atypia. Modified radical mastectomy was planned. Histopathological examination confirmed the mass as secretory carcinoma, a rare variant of ductal carcinoma of the breast. Postoperative chemotherapy and radiotherapy was started. We report this case to emphasize that FNAC can be repeated in suspicious cases and should be correlated clinico-radiologically to give a preoperative diagnosis.

  5. Drug-induced secretory diarrhea: A role for CFTR.

    Science.gov (United States)

    Moon, Changsuk; Zhang, Weiqiang; Sundaram, Nambirajan; Yarlagadda, Sunitha; Reddy, Vadde Sudhakar; Arora, Kavisha; Helmrath, Michael A; Naren, Anjaparavanda P

    2015-12-01

    Many medications induce diarrhea as a side effect, which can be a major obstacle to therapeutic efficacy and also a life-threatening condition. Secretory diarrhea can be caused by excessive fluid secretion in the intestine under pathological conditions. The cAMP/cGMP-regulated cystic fibrosis transmembrane conductance regulator (CFTR) is the primary chloride channel at the apical membrane of intestinal epithelial cells and plays a major role in intestinal fluid secretion and homeostasis. CFTR forms macromolecular complexes at discreet microdomains at the plasma membrane, and its chloride channel function is regulated spatiotemporally through protein-protein interactions and cAMP/cGMP-mediated signaling. Drugs that perturb CFTR-containing macromolecular complexes in the intestinal epithelium and upregulate intracellular cAMP and/or cGMP levels can hyperactivate the CFTR channel, causing excessive fluid secretion and secretory diarrhea. Inhibition of CFTR chloride-channel activity may represent a novel approach to the management of drug-induced secretory diarrhea.

  6. Elastic stresses and plastic deformations in 'Santa Clara' tomato fruits caused by package dependent compression

    Directory of Open Access Journals (Sweden)

    PEREIRA ADRIANA VARGAS

    2000-01-01

    Full Text Available The objective of this work was to study the fruit compression behavior aiming to develop new tomato packages. Deformations caused by compression forces were observed inside packages and in individual 'Santa Clara' tomato fruit. The forces applied by a transparent acrylic lever to the fruit surface caused pericarp deformation and the flattened area was proportional to the force magnitude. The deformation was associated to the reduction in the gas volume (Vg, caused by expulsion of the air from the loculus cavity and reduction in the intercellular air volume of the pericarp. As ripening advanced, smaller fractions of the Vg reduced by the compressive force were restored after the stress was relieved. The lack of complete Vg restoration was an indication of permanent plastic deformations of the stressed cells. Vg regeneration (elastic recovery was larger in green fruits than in the red ones. The ratio between the applied force and the flattened area (flattening pressure, which depends on cell turgidity, decreased during ripening. Fruit movements associated with its depth in the container were observed during storage in a transparent glass container (495 x 355 x 220 mm. The downward movement of the fruits was larger in the top layers because these movements seem to be driven by a summation of the deformation of many fruits in all layers.

  7. An inside job: subversion of the host secretory pathway by intestinal pathogens.

    Science.gov (United States)

    Sharp, Tyler M; Estes, Mary K

    2010-10-01

    The cellular secretory pathway, composed of the endoplasmic reticulum, Golgi apparatus, and cellular vesicles, mediates the intracellular trafficking of proteins and lipids. Gastrointestinal pathogens frequently affect the functions of enterocytes, the differentiated cells involved in secretion and absorption of extracellular molecules. Microbial pathogenesis can be enhanced by altering the trafficking of key molecules such as brush border enzymes, soluble immune mediators such as cytokines and chemokines, and MHC Class I molecules, all of which rely on the secretory pathway for their appropriate cellular localization. This review focuses on our current understanding of the distinct mechanisms employed by enteric pathogens to antagonize the secretory pathway. Many pathogens encode individual or multiple proteins to antagonize the secretory pathway, including disrupting the trafficking of vesicles between the endoplasmic reticulum, Golgi, and plasma membrane. This antagonism allows for increased pathogenesis and can assist, directly or indirectly, in microbial replication. Virtually all arms of the secretory pathway are targeted by intestinal pathogens, supporting the pathogenic significance of shutting this pathway down. This review summarizes the mechanisms utilized by gut pathogens to disrupt the cellular secretory pathway and addresses potential therapeutic targets to combat these highly prevalent and burdensome microbes.

  8. Superfund Record of Decision (EPA Region 9): Intel Santa Clara III Superfund site, Santa Clara, CA. (First remedial action), September 1990. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1990-09-20

    The Intel (Santa Clara III) site includes a plant that performs quality control testing of chemicals and electrical testing of semiconductors in Santa Clara, Santa Clara County, California. The site is in a predominantly industrial area, and overlies a major ground regional source of ground water, the Santa Clara Valley ground water basin. In 1982, the State conducted a leak detection program, which identified VOC contamination in an onsite shallow aquifer. Possible sources for the contamination may include the accidental dumping of solvents into an acid neutralization tank, accidental spills near an above-ground solvent storage facility, and cleaning of solvent-contaminated pipes during plant construction. It has been determined that no onsite source is presently contributing to ground water contamination. Since 1985, Intel has been pumping and treating ground water using granular activated carbon as an Initial Remedial Measure (IRM). The Record of Decision (ROD) addresses a final solution for restoring ground water to its beneficial use. The primary contaminants of concern affecting the ground water are VOCs including TCE.

  9. REGISTRO HOSPITALARIO DE INFARTO AGUDO DE MIOCARDIO EN SANTA CLARA / Hospital registry of acute miocardial infarction in Santa Clara

    Directory of Open Access Journals (Sweden)

    Alberto Morales Salinas

    2010-09-01

    Full Text Available Resumen Introducción y objetivos: En Cuba las estadísticas vitales de la morbi-mortalidad por infarto agudo de miocardio proceden de pequeñas áreas de salud. El objetivo fue identificar las principales características y conducta hospitalaria de los pacientes con infarto a través de un registro hospitalario de infarto. Métodos: Se monitorizaron los casos de infarto ocurridos en pacientes de 45 a 74 años de edad y residentes en Santa Clara, durante los años 2007 y 2008. Las fuentes de información fueron: listados de egresos hospitalarios, registros hospitalarios de infarto de miocardio, certificados de defunción y registros de autopsias nosocomiales. Se utilizó la metodología MONICA (MONItoring Trends and Determinants in CArdiovascular Disease Project. Resultados: Se registraron 297 pacientes con infarto. El 62,7 % de los varones y el 46,8 % de las mujeres recibieron tratamiento de reperfusión. Las letalidades hospitalarias en varones y mujeres fueron de 25,3 % y 45 %. Las variables que se relacionaron con una mayor mortalidad fueron la edad, el sexo femenino, la frecuencia cardíaca alta, el infarto de topografía anterior, la creatinina elevada, así como los antecedentes personales de cardiopatía isquémica previa y diabetes mellitus. Mientras que el tratamiento con fibrinolíticos y/o betabloqueadores se correlacionaron inversamente con la mortalidad. Conclusiones: Existió una elevada prevalencia de dislipidemia desconocida y letalidad hospitalaria a 28 días; así como una baja utilización de las estrategias cruentas. La hipertensión sistólica al ingreso se relacionó con un mejor pronóstico. / Abstract Introduction and objectives: In Cuba, the vital statistics of morbi-mortality due to acute myocardial infarction come from small health areas. The objective of this study was to identify the main characteristics and hospital management of patients with myocardial infarction, through a hospital registry of infarctions

  10. Wave propagation and site response in the Santa Clara Valley

    Science.gov (United States)

    Fletcher, Joe B.; Boatwright, J.; Lindh, A.G.

    2003-01-01

    Forty-two portable digital instruments were deployed across the Santa Clara Valley from June until early November 1998; this array recorded 14 small and moderate local events and 7 large teleseismic events. We analyze the ground motion from these events to determine station delays and relative site amplification within the Valley. P waves from an event at the southern edge of the valley are early (??t > -0.35 sec) at stations over an axial ridge in the basement interface in the middle of the valley, but late (??t < 0.20 sec) for stations over the Cupertino and Evergreen basins to either side. The S-wave delays are approximately twice as large. Teleseismic P-waves from an M = 7.0 event beneath the Bonin Islands show a similar pattern in travel-time delays. The P waves are amplified by factors of 1.5-3 for frequencies below 2 Hz at stations within either basin, compared with stations on the axial ridge. The P-wave coda appear enhanced at 2-3 sec, but coda Q estimates at frequencies from 0.2 to 1.1 Hz are not markedly different at stations over the basin compared with stations on the ridge with the possible exceptions of consistently high values over the northern end of the Evergreen Basin. We invert the S-wave spectra for site-specific attenuation and amplification from the 14 local events by assuming a common source spectra for each event, 1/r geometrical spreading, and constraining the inversion using the 30-m velocity profile at four stations in the array. The largest amplifications occurred in the 1- to 6-Hz band at stations near the northwest edge of the Evergreen basin. While the highest amplifications occur at stations with the lowest S-wave velocities, the scatter obscures the correlation between velocity and amplification. The stations in the basins are characterized by higher attenuation than the stations on the basement ridge.

  11. Distribution and structure of internal secretory reservoirs on the vegetative organs of Inula helenium L. (Asteraceae

    Directory of Open Access Journals (Sweden)

    Aneta Sulborska

    2012-12-01

    Full Text Available The aim of the study was to investigate the structure and topography of endogenous secretory tissues of Inula helenium L. By using light and electron microscopy, morphological and anatomical observations of stems, leaves and rhizomes were made. It was shown that in the stems secretory cavities were situated in the vicinity of phloem and xylem bundles. The number of the reservoirs reached its maximum value (34 at shoot flowerig termination, whereas the cavities with the largest diameter were observed at full flowering stage (44.6 µm. In the leaf petioles and midribs, the reservoirs also accompanied the vascular bundles, and their number and size increased along with the growth of the assimilation organs. Observations of the cross sections of the rhizomes revealed the presence of several rings of secretory reservoirs. The measurements of the cavities showed that as a rule the reservoirs with a larger dimension were located in the phelloderm, whereas the smallest ones in the xylem area. The secretory cavities located in the stems and leaves developed by schizogenesis, whereas the rhizome reservoirs were probably formed schizolisygenously. The cells lining the reservoirs formed a one - four-layered epithelium. Observed in TEM, the secretory cells of the mature cavities located in the rhizomes were characterised by the presence of a large central vacuole, whereas the protoplast was largely degraded. Fibrous elements of osmophilic secretion and numerous different coloured vesicles could be distinguished in it. The cell walls formed, from the side of the reservoir lumen, ingrowths into the interior of the epithelial cells. Between the cell wall and the plasmalemma of the glandular cells, a brighter periplasmatic zone with secretory vesicles was observed.

  12. Secretory immunity with special reference to the oral cavity

    Directory of Open Access Journals (Sweden)

    Per Brandtzaeg

    2013-03-01

    Full Text Available The two principal antibody classes present in saliva are secretory IgA (SIgA and IgG; the former is produced as dimeric IgA by local plasma cells (PCs in the stroma of salivary glands and is transported through secretory epithelia by the polymeric Ig receptor (pIgR, also named membrane secretory component (SC. Most IgG in saliva is derived from the blood circulation by passive leakage mainly via gingival crevicular epithelium, although some may be locally produced in the gingiva or salivary glands. Gut-associated lymphoid tissue (GALT and nasopharynx-associated lymphoid tissue (NALT do not contribute equally to the pool of memory/effector B cells differentiating to mucosal PCs throughout the body. Thus, enteric immunostimulation may not be the best way to activate the production of salivary IgA antibodies although the level of specific SIgA in saliva may still reflect an intestinal immune response after enteric immunization. It remains unknown whether the IgA response in submandibular/sublingual glands is better related to B-cell induction in GALT than the parotid response. Such disparity is suggested by the levels of IgA in submandibular secretions of AIDS patients, paralleling their highly upregulated intestinal IgA system, while the parotid IgA level is decreased. Parotid SIgA could more consistently be linked to immune induction in palatine tonsils/adenoids (human NALT and cervical lymph nodes, as supported by the homing molecule profile observed after immune induction at these sites. Several other variables influence the levels of antibodies in salivary secretions. These include difficulties with reproducibility and standardization of immunoassays, the impact of flow rate, acute or chronic stress, protein loss during sample handling, and uncontrolled admixture of serum-derived IgG and monomeric IgA. Despite these problems, saliva is an easily accessible biological fluid with interesting scientific and clinical potentials.

  13. Secretory structures of Ipomoea asarifolia: anatomy and histochemistry

    Directory of Open Access Journals (Sweden)

    Fabiano M. Martins

    2012-02-01

    Full Text Available Ipomoea asarifolia (Desr. Roem. & Schult., Convolvulaceae, is a weed that infests agricultural areas and is toxic to cattle. In spite of its toxicity, the leaves of this plant are used in traditional remedies in the state of Bahia, Brazil. The present work describes the leaf anatomy of I. asarifolia and characterizes the exudates of its secretory structures. The leaves have a unistratified epidermis composed of ordinary cells with straight to slightly sinuous anticlinal walls and thin cuticles. Paracytic stomata are found on both surfaces of the leaves at the same level as the ordinary epidermal cells. Trichomes producing polysaccharide secretions occur on the petiole and leaf blade and are considered colleters. The mesophyll is dorsiventral and the vascular bundle of the central vein is bicollateral. Two opposed nectaries occur on the petiole near the leaf blade. Each nectary is composed of a small canal with internal ramifications and numerous secretory trichomes. The laticiferous glands are articulated, not anastomosed, and are composed of large diameter cells with thin cell walls. The secretions of the laticiferous glands are lipidic.

  14. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate...

  15. Clara Haber, nee Immerwahr (1870-1915): Life, Work and Legacy.

    Science.gov (United States)

    Friedrich, Bretislav; Hoffmann, Dieter

    2016-03-01

    We examine the life, work, and legacy of Clara Haber, nee Immerwahr, who became the first woman to earn a doctorate from the University of Breslau, in 1900. In 1901 she married the chemist Fritz Haber. With no employment available for female scientists, Clara freelanced as an instructor in the continued education of women, mainly housewives, while struggling not to become a housewife herself. Her duties as a designated head of a posh household hardly brought fulfillment to her life. The outbreak of WWI further exacerbated the situation, as Fritz Haber applied himself in extraordinary ways to aid the German war effort. The night that he celebrated the "success" of the first chlorine cloud attack, Clara committed suicide. We found little evidence to support claims that Clara was an outspoken pacifist who took her life because of her disapproval of Fritz Haber's involvement in chemical warfare. We conclude by examining "the myth of Clara Immerwahr" that took root in the 1990s from the perspective offered by the available scholarly sources, including some untapped ones.

  16. Clara Haber, nee Immerwahr (1870–1915): Life, Work and Legacy

    Science.gov (United States)

    2016-01-01

    Abstract We examine the life, work, and legacy of Clara Haber, nee Immerwahr, who became the first woman to earn a doctorate from the University of Breslau, in 1900. In 1901 she married the chemist Fritz Haber. With no employment available for female scientists, Clara freelanced as an instructor in the continued education of women, mainly housewives, while struggling not to become a housewife herself. Her duties as a designated head of a posh household hardly brought fulfillment to her life. The outbreak of WWI further exacerbated the situation, as Fritz Haber applied himself in extraordinary ways to aid the German war effort. The night that he celebrated the “success” of the first chlorine cloud attack, Clara committed suicide. We found little evidence to support claims that Clara was an outspoken pacifist who took her life because of her disapproval of Fritz Haber's involvement in chemical warfare. We conclude by examining “the myth of Clara Immerwahr” that took root in the 1990s from the perspective offered by the available scholarly sources, including some untapped ones. PMID:27099403

  17. Amylase expression in taste receptor cells of rat circumvallate papillae.

    Science.gov (United States)

    Merigo, Flavia; Benati, Donatella; Cecchini, Maria Paola; Cristofoletti, Mirko; Osculati, Francesco; Sbarbati, Andrea

    2009-06-01

    The chemical composition of the luminal content is now accepted to have a profound influence on the performance of chemosensory receptors. Gustatory and intestinal chemoreceptors have in common their expression of molecules involved in taste sensing and signal transduction pathways. The recent finding that enterocytes of the duodenal epithelium are capable of expressing luminal pancreatic amylase suggests that taste cells of the gustatory epithelium might, in the same way, express salivary amylase in the oral cavity. Therefore, we investigated amylase expression in rat circumvallate papillae by using analyses involving immunohistochemistry, Western blot, and reverse transcription with the polymerase chain reaction. In addition, we used double-labeling confocal laser microscopy to compare amylase immunolabeling with that of the following markers: protein gene product 9.5 (PGP 9.5) and chromogranin A (CgA) for endocrine cells, alpha-gustducin and phospholipase C beta 2 (PLC beta 2) as taste-signaling molecules, and cystic fibrosis transmembrane regulator (CFTR) and Clara-cell-specific secretory protein of 10-kDa (CC10) as secretory markers. The results showed that amylase was present in some taste bud cells; its immunoreactivity was observed in subsets of cells that expressed CgA, alpha-gustducin, PLC beta 2, CFTR, or CC10. PGP 9.5 immunoreactivity was never colocalized with amylase. The data suggest that amylase-positive cells constitute an additional subset of taste receptor cells also associated with chemoreceptorial and/or secretory molecules, confirming the occurrence of various pathways in taste buds.

  18. A highly sensitive assay for monitoring the secretory pathway and ER stress.

    Directory of Open Access Journals (Sweden)

    Christian E Badr

    Full Text Available BACKGROUND: The secretory pathway is a critical index of the capacity of cells to incorporate proteins into cellular membranes and secrete proteins into the extracellular space. Importantly it is disrupted in response to stress to the endoplasmic reticulum that can be induced by a variety of factors, including expression of mutant proteins and physiologic stress. Activation of the ER stress response is critical in the etiology of a number of diseases, such as diabetes and neurodegeneration, as well as cancer. We have developed a highly sensitive assay to monitor processing of proteins through the secretory pathway and endoplasmic reticulum (ER stress in real-time based on the naturally secreted Gaussia luciferase (Gluc. METHODOLOGY/PRINCIPLE FINDINGS: An expression cassette for Gluc was delivered to cells, and its secretion was monitored by measuring luciferase activity in the conditioned medium. Gluc secretion was decreased down to 90% when these cells were treated with drugs that interfere with the secretory pathway at different steps. Fusing Gluc to a fluorescent protein allowed quantitation and visualization of the secretory pathway in real-time. Expression of this reporter protein did not itself elicit an ER stress response in cells; however, Gluc proved very sensitive at sensing this type of stress, which is associated with a temporary decrease in processing of proteins through the secretory pathway. The Gluc secretion assay was over 20,000-fold more sensitive as compared to the secreted alkaline phosphatase (SEAP, a well established assay for monitoring of protein processing and ER stress in mammalian cells. CONCLUSIONS/SIGNIFICANCE: The Gluc assay provides a fast, quantitative and sensitive technique to monitor the secretory pathway and ER stress and its compatibility with high throughput screening will allow discovery of drugs for treatment of conditions in which the ER stress is generally induced.

  19. Secretory pathway Ca2+/Mn2+-ATPase isoform 2 and lactation: specific localization of plasmalemmal and secretory pathway Ca2+ pump isoforms in the mammary gland

    Energy Technology Data Exchange (ETDEWEB)

    Faddy, Helen M.; Smart, Chanel E.; Xu, Ren; Lee, Genee Y.; Kenny, Paraic A.; Feng, Mingye; Rao, Rajini; Brown, Melissa A.; Bissell, Mina J.; Roberts-Thomson, Sarah J.; Monteith, Gregory R.

    2008-04-09

    The supply of calcium to the developing neonate via milk is an important physiological process. Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely mediated via the secretory pathway. However, recent studies suggest that a specific isoform of the plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during different stages of development. SPCA2 levels increased over 35 fold during lactation, while SPCA1 increased only a modest two fold. The potential importance of SPCA2 in lactation was also highlighted by its localization to luminal secretory cells of the mammary gland during lactation, while SPCA1 was expressed throughout the cells of the mammary gland. We also observed major differences in the localization of PMCA2 and PMCA1 during lactation. Using the SCp2 mouse mammary epithelial cell 3D culture model, differences in the sub-cellular distribution of PMCA2 and PMCA1 were clear. These studies highlight the likely specific roles of PMCA2 and SPCA2 in lactation, and link the recently characterized SPCA2 calcium pump to the supply of calcium into milk and the regulation of Golgi resident enzymes important in lactation. They also indicate that calcium transport into milk is a complex interplay between apical and secretory pathways.

  20. Changes of Clara cell protein and interferon-γ in lungs with fetal growth retardation in fetal rats%宫内生长受限胎鼠肺组织Clara细胞蛋白与干扰素γ的变化

    Institute of Scientific and Technical Information of China (English)

    刘晓梅; 田宝玲; 焦伊胜; 袁正伟; 刘彩霞

    2014-01-01

    目的 研究孕期营养不良造成的宫内生长受限(IUGR)胎鼠肺组织Clara细胞蛋白(CCSP)和调控其转录表达的细胞因子干扰素-γ(IFN-γ)的变化及相互联系,探讨其与肺部疾病发生的相关性.方法 采用孕期全程低蛋白饮食法建立大鼠IUGR模型,孕第20.5天(足月21.5 d)剖腹取胎鼠,分离其肺脏,肺组织切片HE染色后观察其肺组织病理变化,酶联免疫分析法检测其血清和肺组织中CCSP和IFN-γ水平.采用荧光定量反转录-聚合酶链式反应技术检测胎鼠肺脏中IFN-γ mRNA和CCSP mRNA表达.结果 低蛋白组胎鼠体质量和湿肺质量均低于对照组;IUGR胎鼠肺组织切片放射性肺泡计数降低,提示IUGR组胎鼠肺泡数量减少,肺泡平均线性截距增加.IUGR组胎鼠肺组织CCSP mRNA和蛋白水平均低于对照组(P均<0.05),其血浆CCSP蛋白水平亦明显低于对照组(P<0.05).IUGR胎鼠血循环和肺组织IFN-γ水平均明显低于对照组(P均<0.05).结论 宫内营养不良引起胎鼠肺组织结构发生改变,IFN-γ表达降低,可能抑制CCSP基因的转录和表达,从而诱发产后早期乃至后期肺部疾病.%Objective To determine the effects of intrauterine growth retardation(IUGR) caused by malnutrition during pregnancy on the lung structure and expression of Clara cell protein (CCSP) and interferon (IFN)-γ in the fetal lungs,and to explore their relation ship with pulmonary disease.Methods Fetal rats from maternal protein-malnutrition dams were studied on day 20(term 21.5 day).The lung pathology was examined by means of Hematoxylin and eosin(HE) stain.Plasma was collected to determine the CCSP and IFN-γ concentration.Lungs were harvested to measure the expression of CCSP and IFN-γ mRNA by using fluorescent quantization reverse transcription (RT)-PCR and the levels of CCSP and IFN-γ protein were assessed by using enzyme-linked immunosorbent assay.Results Malnutrition fetus body weight significantly less compared

  1. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance

    DEFF Research Database (Denmark)

    Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M;

    2013-01-01

    Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here...... was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported...... dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus...

  2. Spatially explicit West Nile virus risk modeling in Santa Clara County, California.

    Science.gov (United States)

    Konrad, Sarah K; Miller, Scott N; Reeves, Will K; Tietze, Noor S

    2009-06-01

    A geographic information system model designed to identify regions at risk for West Nile virus (WNV) transmission was calibrated and tested with data collected in Santa Clara County, California. American Crows that died from WNV infection in 2005 provided spatial and temporal ground truth. When the model was run with parameters based on Culex tarsalis infected with the NY99 genotype of the virus, it underestimated WNV occurrence in Santa Clara Co. The parameters were calibrated to fit the field data by reducing the number of degree-days necessary to reach the mosquito's extrinsic incubation period from 109 to 76. The calibration raised model efficiency from 61% to 92% accuracy, and the model performed well the following year in Santa Clara Co.

  3. Predicting Secretory Proteins with SignalP

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2017-01-01

    SignalP is the currently most widely used program for prediction of signal peptides from amino acid sequences. Proteins with signal peptides are targeted to the secretory pathway, but are not necessarily secreted. After a brief introduction to the biology of signal peptides and the history...

  4. Neuronal damage by secretory phospholipase A2

    DEFF Research Database (Denmark)

    Rodriguez de Turco, Elena B; Diemer, Nils H; Bazan, Nicolas G

    2003-01-01

    Activation of cytosolic phospholipase A(2) (cPLA(2)) is an early event in brain injury, which leads to the formation and accumulation of bioactive lipids: platelet-activating factor (PAF), free arachidonic acid, and eicosanoids. A cross-talk between secretory PLA(2) (sPLA(2)) and cPLA(2) in neura...

  5. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  6. Auxilin facilitates membrane traffic in the early secretory pathway.

    Science.gov (United States)

    Ding, Jingzhen; Segarra, Verónica A; Chen, Shuliang; Cai, Huaqing; Lemmon, Sandra K; Ferro-Novick, Susan

    2016-01-01

    Coat protein complexes contain an inner shell that sorts cargo and an outer shell that helps deform the membrane to give the vesicle its shape. There are three major types of coated vesicles in the cell: COPII, COPI, and clathrin. The COPII coat complex facilitates vesicle budding from the endoplasmic reticulum (ER), while the COPI coat complex performs an analogous function in the Golgi. Clathrin-coated vesicles mediate traffic from the cell surface and between the trans-Golgi and endosome. While the assembly and structure of these coat complexes has been extensively studied, the disassembly of COPII and COPI coats from membranes is less well understood. We describe a proteomic and genetic approach that connects the J-domain chaperone auxilin, which uncoats clathrin-coated vesicles, to COPII and COPI coat complexes. Consistent with a functional role for auxilin in the early secretory pathway, auxilin binds to COPII and COPI coat subunits. Furthermore, ER-Golgi and intra-Golgi traffic is delayed at 15°C in swa2Δ mutant cells, which lack auxilin. In the case of COPII vesicles, we link this delay to a defect in vesicle fusion. We propose that auxilin acts as a chaperone and/or uncoating factor for transport vesicles that act in the early secretory pathway.

  7. Expression and interaction of secretory immunoglobulin A, interleukin 6, and dendritic cells in oral cancers%SIgA IL-6和树突状细胞在口腔癌中的表达及相互作用

    Institute of Scientific and Technical Information of China (English)

    张素欣; 尹克; 段玉芹; 陈彦平; 郭兰涛; 李天客; 陈中

    2013-01-01

      目的:探讨分泌型免疫球蛋白A(secretory immunoglobulin A,SIgA)、白细胞介素-6(interleukin-6,IL-6)和树突状细胞(dendritic cell,DC)在口腔癌中的表达和相互作用.方法:选取60例原发口腔癌患者为研究对象,20例健康志愿者唾液为正常对照,用ELISA法检测唾液中的SIgA、IL-6含量.用免疫组织化学法和流式细胞仪检测癌组织中CD1a、CD83、CD80及CD86的表达情况.经病理证实的20例良性肿瘤患者正常口腔黏膜组织为对照.结果:口腔癌患者唾液SIgA的含量明显低于对照组,IL-6的含量明显高于对照组,差异有统计学意义(P0.05),与临床分期及淋巴结转移呈负相关(P0.05). Correlation analysis showed that the CD80 and CD86 levels were negatively correlated with the clinical stage and lymph node metastases (P<0.05). Conclusion:The SIgA and IL-6 content can be used as auxiliary indicators for oral cancer diagnosis. The increasing IL-6 level could account for the decreased SIgA production. Immune deficiency occurs in the DCs of oral cancer patients, and the expression levels of CD80 and CD86 reflect this prognostic evaluation. IL-6 may inhibit the formation of SIgA and cause the immune tolerance of DC. Thus, the effective immune response is lost, thereby promoting carcinogenesis and the progress of oral cancer.

  8. A signal sequence is sufficient for green fluorescent protein to be routed to regulated secretory granules.

    Science.gov (United States)

    El Meskini, R; Jin, L; Marx, R; Bruzzaniti, A; Lee, J; Emeson, R; Mains, R

    2001-02-01

    To investigate trafficking in neuroendocrine cells, green fluorescent protein (GFP) tags were fused to various portions of the preproneuropeptide Y (NPY) precursor. Two neuroendocrine cell lines, AtT-20 corticotrope tumor cells and PC-12 pheochromocytoma cells, along with primary anterior pituitary cells, were examined. Expression of chimeric constructs did not disrupt trafficking or regulated secretion of endogenous ACTH and prohormone convertase 1 in AtT-20 cells. Western blot and immunocytochemical analyses demonstrated that the chimeric constructs remained intact, as long as the Lys-Arg cleavage site within preproNPY was deleted. GFP was stored in, and released from, regulated granules in cells expressing half of the NPY precursor fused to GFP, and also in cells in which only the signal sequence of preproNPY was fused to GFP. Thus, in neuroendocrine cells, entering the lumen of the secretory pathway is sufficient to target GFP to regulated secretory granules.

  9. Clara Barton: teacher, nurse, Civil War heroine, founder of the American Red Cross.

    Science.gov (United States)

    Evans, Gerald D

    2003-01-01

    Clara Barton was a nineteenth century woman driven to greatness. She was a teacher, a nurse, a Civil War heroine and founder of the American Red Cross. In order to cut a path into the future we must know where we have been. The story of Clara Barton is about someone who cut that path. It is about courage, overcoming obstacles, never giving up and doing the job that needs doing. What makes it fascinating is the human side, the weaknesses that coloured her life. We can learn from her journey as we develop our own path into the future.

  10. Reglas electorales claras: el objetivo de todo organismo encargado de organizar un torneo comicial

    Directory of Open Access Journals (Sweden)

    Alejandro J. Robles Leal

    2017-07-01

    Full Text Available La importancia de establecer reglas claras y que estas sean conocidas por todos los actores electorales coadyuva al desarrollo exitoso de una contienda electoral. El artículo analiza las sentencias 1532-E1-2017 y 2173-E1-2017 del Tribunal Supremo de Elecciones las cuales, en términos generales, han dejado clara la obligación que tienen los partidos políticos de definir las reglas que regirán las contiendas electorales dentro de las agrupaciones políticas.

  11. 31 flavors to 50 shades of grey: battling Phytophthoras in native habitats managed by the Santa Clara Valley Water District

    Science.gov (United States)

    Janet Hillman; Tedmund J. Swiecki; Elizabeth A. Bernhardt; Heather K. Mehl; Tyler B. Bourret; David Rizzo

    2017-01-01

    The Santa Clara Valley Water District (District) is a wholesale water supplier for 1.8 million people in Santa Clara County, California. Capital, water utility, and stream maintenance projects result in extensive, long-term mitigation requirements in riparian, wetland, and upland habitats throughout the county. In 2014, several restoration sites on the valley floor and...

  12. 76 FR 16811 - Notice of Realty Action: Direct Sale of Public Lands in Santa Clara County, CA

    Science.gov (United States)

    2011-03-25

    ... Bureau of Land Management Notice of Realty Action: Direct Sale of Public Lands in Santa Clara County, CA... public land are proposed for direct sale to the Santa Clara County Open Space Authority (Authority) in... parcels, isolated from other public lands. The BLM is proposing a direct sale to the Authority because...

  13. A spatial analysis of the Burrowing Owl (Speotyto cunicularia) population in Santa Clara County, California, using a geographic information system

    Science.gov (United States)

    Janice Taylor Buchanan

    1997-01-01

    A small population of Burrowing Owls (Speotyto cunicularia) is found in the San Francisco Bay Area, particularly in Santa Clara County. These owls utilize habitat that is dispersed throughout this heavily urbanized region. In an effort to establish a conservation plan for Burrowing Owls in Santa Clara County, a spatial analysis of owl distribution...

  14. See Us as We Are: Clara Chu--University of California at Los Angeles

    Science.gov (United States)

    Library Journal, 2005

    2005-01-01

    This article highlights the influence of Clara Chu, associate professor in the University of California at Los Angeles's (UCLA) Department of Information Studies. Her influence extends far beyond her campus. She works with many organizations to advance multiculturalism in librarianship. As a prolific researcher, writer, and speaker, Chu has given…

  15. Spatially Explicit West Nile Virus Risk Modeling in Santa Clara County, CA

    Science.gov (United States)

    A geographic information systems model designed to identify regions of West Nile virus (WNV) transmission risk was tested and calibrated with data collected in Santa Clara County, California. American Crows that died from WNV infection in 2005, provided spatial and temporal ground truth. When the mo...

  16. Clara Barton High School Bilingual Program. O.E.E. Evaluation Report, 1982-1983.

    Science.gov (United States)

    Collazo-Levy, Dora; Sica, Michael

    In 1982-83, the program evaluated here provided tutorial and supportive services to approximately 50 Spanish-speaking students of limited English proficiency (LEP) in grades 9-12 at Clara Barton High School, Brooklyn, New York. The program's main objective was to enable LEP students to function successfully in terms of language achievement and…

  17. Disparate effects of p24alpha and p24delta on secretory protein transport and processing.

    Directory of Open Access Journals (Sweden)

    Jeroen R P M Strating

    Full Text Available BACKGROUND: The p24 family is thought to be somehow involved in endoplasmic reticulum (ER-to-Golgi protein transport. A subset of the p24 proteins (p24alpha(3, -beta(1, -gamma(3 and -delta(2 is upregulated when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated to produce vast amounts of their major secretory cargo, the prohormone proopiomelanocortin (POMC. METHODOLOGY/PRINCIPAL FINDINGS: Here we find that transgene expression of p24alpha(3 or p24delta(2 specifically in the Xenopus melanotrope cells in both cases causes an effective displacement of the endogenous p24 proteins, resulting in severely distorted p24 systems and disparate melanotrope cell phenotypes. Transgene expression of p24alpha(3 greatly reduces POMC transport and leads to accumulation of the prohormone in large, ER-localized electron-dense structures, whereas p24delta(2-transgenesis does not influence the overall ultrastructure of the cells nor POMC transport and cleavage, but affects the Golgi-based processes of POMC glycomaturation and sulfation. CONCLUSIONS/SIGNIFICANCE: Transgenic expression of two distinct p24 family members has disparate effects on secretory pathway functioning, illustrating the specificity and non-redundancy of our transgenic approach. We conclude that members of the p24 family furnish subcompartments of the secretory pathway with specific sets of machinery cargo to provide the proper microenvironments for efficient and correct secretory protein transport and processing.

  18. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

    DEFF Research Database (Denmark)

    Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

    2009-01-01

    The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...

  19. Human neutrophil defensins and secretory leukocyte proteinase inhibitor in squamous metaplastic epithelium of bronchial airways.

    NARCIS (Netherlands)

    Aarbiou, J.; Schadewijk, A. van; Stolk, J.; Sont, J.K.; Boer, W.I.; Rabe, K.F.; Krieken, J.H.J.M. van; Mauad, T.; Hiemstra, P.S.

    2004-01-01

    OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the num

  20. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  1. First light measurements of the Total Solar Irradiance experiment CLARA on NORSAT-1

    Science.gov (United States)

    Schmutz, Werner

    2016-07-01

    NORSAT-1 is a Norwegian micro-satellite, which will be launched April 22, 2016. (In the future at the time of writing this abstract.) The satellite carries two scientific instruments and an AIS receiver for performing ship detection from space. One of the scientific instruments is a Compact Light-weight Absolute RAdiometer (CLARA) and the other is a Langmuir Probe instrument comprising four probes mounted on booms. The latter experiment will measure electron density and the platform's floating potential along the orbit. The University of Oslo provides the Langmuir probes. The radiometer experiment CLARA has been built by PMOD/WRC funded through the Swiss PRODEX program. It will measure Total Solar Irradiance with an instrument of novel design that is optimized for minimizing mass and size by still ensuring highest measuring accuracy and thermal stability. The radiometers of CLARA have been fully characterized as well as calibrated at the TRF facility. It is expected that the first light accuracy of the absolute measurement of Total Solar Irradiance will be better than pm0.3 W/m^{2, allowing to probe the current TSI composite for its absolute level. The presentation will give an overview of the CLARA instrument and its calibration. It is expected that at the time of the COSPAR conference the first light TSI value of CLARA/NORSAT-1 is ready for publication. Together with a previous absolute TSI measurements available for July 27, 2010 measured by PREMOS/PICARD the new absolute TSI measurement will be used to test the accuracy of long term TSI trend given by the relative TSI composite.

  2. Widespread occurrence of expressed fungal secretory peroxidases in forest soils.

    Science.gov (United States)

    Kellner, Harald; Luis, Patricia; Pecyna, Marek J; Barbi, Florian; Kapturska, Danuta; Krüger, Dirk; Zak, Donald R; Marmeisse, Roland; Vandenbol, Micheline; Hofrichter, Martin

    2014-01-01

    Fungal secretory peroxidases mediate fundamental ecological functions in the conversion and degradation of plant biomass. Many of these enzymes have strong oxidizing activities towards aromatic compounds and are involved in the degradation of plant cell wall (lignin) and humus. They comprise three major groups: class II peroxidases (including lignin peroxidase, manganese peroxidase, versatile peroxidase and generic peroxidase), dye-decolorizing peroxidases, and heme-thiolate peroxidases (e.g. unspecific/aromatic peroxygenase, chloroperoxidase). Here, we have repeatedly observed a widespread expression of all major peroxidase groups in leaf and needle litter across a range of forest ecosystems (e.g. Fagus, Picea, Acer, Quercus, and Populus spp.), which are widespread in Europe and North America. Manganese peroxidases and unspecific peroxygenases were found expressed in all nine investigated forest sites, and dye-decolorizing peroxidases were observed in five of the nine sites, thereby indicating biological significance of these enzymes for fungal physiology and ecosystem processes. Transcripts of selected secretory peroxidase genes were also analyzed in pure cultures of several litter-decomposing species and other fungi. Using this information, we were able to match, in environmental litter samples, two manganese peroxidase sequences to Mycena galopus and Mycena epipterygia and one unspecific peroxygenase transcript to Mycena galopus, suggesting an important role of this litter- and coarse woody debris-dwelling genus in the disintegration and transformation of litter aromatics and organic matter formation.

  3. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment

    NARCIS (Netherlands)

    De Proost, Ian; Pintelon, Isabel; Brouns, Inge; Kroese, A; Riccardi, Daniela; Kemp, Paul J.; Timmermans, Jean-Pierre; Adriaensen, Dirk

    2008-01-01

    Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of neuroendocrine cells invariably accompanied by Clara-like cells. Together with NEBs, Clara-like cells form the so-called "NEB microenvironment," which recently has been assigned a potential pulmonary stem cell niche. Conclusive

  4. Functional live cell imaging of the pulmonary neuroepithelial body microenvironment

    NARCIS (Netherlands)

    De Proost, Ian; Pintelon, Isabel; Brouns, Inge; Kroese, A; Riccardi, Daniela; Kemp, Paul J.; Timmermans, Jean-Pierre; Adriaensen, Dirk

    Pulmonary neuroepithelial bodies (NEBs) are densely innervated groups of neuroendocrine cells invariably accompanied by Clara-like cells. Together with NEBs, Clara-like cells form the so-called "NEB microenvironment," which recently has been assigned a potential pulmonary stem cell niche. Conclusive

  5. Analysis of protein localization and secretory pathway function using the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Vallen, Elizabeth

    2002-01-01

    The isolation and characterization of mutants has been crucial in understanding a number of processes in the field of cell biology. In this exercise, students examine the effects of mutations in the secretory pathway on protein localization. Yeast strains deficient for synthesis of histidinol dehydrogenase are transformed with a plasmid encoding a chimeric protein. The chimera contains a signal sequence fused to histidinol dehydrogenase. A strain with a defect in the translocation of secretory proteins into the endoplasmic reticulum (ER) accumulates sufficient histidinol dehydrogenase in the cytoplasm to grow on media lacking histidine. In contrast, yeast proficient for secretion, or yeast with secretion defects later in the pathway, are unable to grow on media lacking histidine. Student analysis of the experimental yeast transformants and appropriate controls allows investigation into the effects of conditional defects in the secretory pathway on both cell viability and protein localization. The exercise is usually performed in a manner that allows students to execute a number of techniques common in molecular biology laboratories, including plasmid minipreps, restriction digestions, and Southern blots. Student understanding and enjoyment of the exercise was assessed by laboratory reports, oral and written examinations, and questionnaires. After completion of these experiments, students can describe the utility of protein fusions, the roles of mutant analysis in cell biology, and the steps taken by proteins transiting the secretory pathway.

  6. A Highway for War and Peace: The Secretory Pathway in Plant-Microbe Interactions

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Xinnian Dong

    2011-01-01

    Secretion of proteins and other molecules is the primary means by which a cell interacts with its surroundings.The overall organization of the secretory system is remarkably conserved among eukaryotes, and many of the components have been investigated in detail in animal models. Plant cells, because of their sessile lifestyle, are uniquely reliant on the secretory pathway to respond to changes in their environments, either abiotic, such as the absence of nutrients, or biotic,such as the presence of predators or pathogens. In particular, most plant pathogens are extracellular, which demands a robust and efficient host secretory system directed at the site of attack. Here, we present a summary of recent advances in our understanding of the molecular details of the secretory pathway during plant-microbe interactions. Secretion is required not only for the delivery of antimicrobial molecules, but also for the biogenesis of cell surface sensors to detemicrobes. The deposition of extracellular material is important in the defense against classical bacterial pathogens as well as in the so-called 'non-host" resistance. Finally, boosting the protein secretion capacity is vital for avoiding infection as well as for achieving symbiosis, even though in the latter case, the microbes are engulfed in intracellular compartments.The emerging evidence indicates that secretion provides an essential interface between plant hosts and their associated microbial partners.

  7. Unique biological function of cathepsin L in secretory vesicles for biosynthesis of neuropeptides.

    Science.gov (United States)

    Funkelstein, Lydiane; Beinfeld, Margery; Minokadeh, Ardalan; Zadina, James; Hook, Vivian

    2010-12-01

    Neuropeptides are essential for cell-cell communication in the nervous and neuroendocrine systems. Production of active neuropeptides requires proteolytic processing of proneuropeptide precursors in secretory vesicles that produce, store, and release neuropeptides that regulate physiological functions. This review describes recent findings indicating the prominent role of cathepsin L in secretory vesicles for production of neuropeptides from their protein precursors. The role of cathepsin L in neuropeptide production was discovered using the strategy of activity-based probes for proenkephalin-cleaving activity for identification of the enzyme protein by mass spectrometry. The novel role of cathepsin L in secretory vesicles for neuropeptide production has been demonstrated in vivo by cathepsin L gene knockout studies, cathepsin L gene expression in neuroendocrine cells, and notably, cathepsin L localization in neuropeptide-containing secretory vesicles. Cathepsin L is involved in producing opioid neuropeptides consisting of enkephalin, β-endorphin, and dynorphin, as well as in generating the POMC-derived peptide hormones ACTH and α-MSH. In addition, NPY, CCK, and catestatin neuropeptides utilize cathepsin L for their biosynthesis. The neuropeptide-synthesizing functions of cathepsin L represent its unique activity in secretory vesicles, which contrasts with its role in lysosomes. Interesting evaluations of protease gene knockout studies in mice that lack cathepsin L compared to those lacking PC1/3 and PC2 (PC, prohormone convertase) indicate the key role of cathepsin L in neuropeptide production. Therefore, dual cathepsin L and prohormone convertase protease pathways participate in neuropeptide production. Significantly, the recent new findings indicate cathepsin L as a novel 'proprotein convertase' for production of neuropeptides that mediate cell-cell communication in health and disease.

  8. Mammary analogue secretory carcinoma of parotid: Is preoperative cytological diagnosis possible?

    Science.gov (United States)

    Oza, Nikita; Sanghvi, Kintan; Shet, Tanuja; Patil, Asawari; Menon, Santosh; Ramadwar, Mukta; Kane, Shubhada

    2016-06-01

    Mammary analogue secretory carcinoma is a recently recognized tumor of salivary gland with characteristic t(12;15)(q13;q25) that results in ETV6-NTRK3 fusion product. Distinguishing mammary analogue secretory carcinoma from other salivary gland tumors is important. Present study highlights cytologic findings in three cases of mammary analogue secretory carcinoma of parotid which facilitate preoperative diagnosis with the aid of ancillary diagnostic techniques. Fine needle aspiration cytology of parotid was performed on three cases after clinical examination. Immunocytochemistry for mammoglobin and S100 were performed. Parotidectomy was done in all cases. The corresponding hematoxylin and eosin stained slides and blocks of all cases were studied. Molecular analysis was done in one of the cases. Cases 1 and 3 revealed uniform atypical epithelial cells arranged in branching papillary pattern with few cells in microcystic pattern. Case 2 showed atypical cells arranged mainly in loose clusters and few singly dissociated. Individual cells revealed round nuclei, vesicular chromatin, prominent nucleoli and abundant finely vacuolated cytoplasm with metachromasia prominent in May-Grunwald-Giemsa smear (case 3). Characteristic hob-nail cells covering papillae were observed in cases 1 and 3. Immunocytochemistry showed strong positivity for mammoglobin and S100 thereby confirming the diagnosis of mammary analogue secretory carcinoma preoperatively. The diagnosis was in concordance with surgical specimen. Also, characteristic ETV6-NTRK3 translocation was confirmed in case 1. Increased awareness and high index of suspicion is necessary for the upfront diagnosis, more so for the papillary variant of mammary analogue secretory carcinoma. Immunocytochemistry aids in confirming this preoperative diagnosis, based on which treatment can be planned. Diagn. Cytopathol. 2016;44:519-525. © 2016 Wiley Periodicals, Inc.

  9. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Birgitte Holst

    Full Text Available Secretory vesicles in endocrine cells store hormones such as growth hormone (GH and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs domain protein PICK1 (protein interacting with C kinase 1 as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of

  10. PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance.

    Science.gov (United States)

    Holst, Birgitte; Madsen, Kenneth L; Jansen, Anna M; Jin, Chunyu; Rickhag, Mattias; Lund, Viktor K; Jensen, Morten; Bhatia, Vikram; Sørensen, Gunnar; Madsen, Andreas N; Xue, Zhichao; Møller, Siri K; Woldbye, David; Qvortrup, Klaus; Huganir, Richard; Stamou, Dimitrios; Kjærulff, Ole; Gether, Ulrik

    2013-01-01

    Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine

  11. THE ROLE OF SECRETORY GRANULES IN THE RADIOSENSITIVITY OF RAT SALIVARY-GLAND ACINI - A MORPHOLOGICAL-STUDY

    NARCIS (Netherlands)

    PETER, B; VANWAARDE, MAWH; VISSINK, A; GRAVENMADE, EJS; KONINGS, AWT

    1994-01-01

    The aim of this study was to investigate the radiosensitivity of salivary gland tissue pretreated with isoproterenol to establish a status of depletion of secretory granules in acinar cells at the time of irradiation. Nuclear aberrations and cell lysis were taken as parameters for cell death. Local

  12. The key target of neuroprotection after the onset of ischemic stroke:secretory pathway Ca2+-ATPase 1

    Institute of Scientific and Technical Information of China (English)

    Li-hua Li; Xiang-rong Tian; Zhi-ping Hu

    2015-01-01

    The regulatory mechanisms of cytoplasmic Ca2+ after myocardial infarction-induced Ca2+ over-load involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2+ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2+ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2+ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2+ showed an opposite effect. The expression of Gol-gi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was simi-lar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regu-lation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.

  13. Secretory carcinoma of the breast: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Youk, Ji Hyun; Ko, Kyung Hee; Kim, Gwang Il [Bundang CHA Hospital, Pochon CHA University, Seongnam, (Korea, Republic of)

    2008-07-15

    A secretory carcinoma of the breast is a rare, but clinically and histologically a distinct variant of the invasive ductal carcinoma, which has a slow growth pattern and a favorable prognosis. Few studies have reported the radiologic findings involved in a secretory carcinoma of the breast. We report the imaging findings of a secretory carcinoma of the breast in a 48-year-old woman, which were similar to those of a benign mass found on a mammography and sonography.

  14. Psychological distress and salivary secretory immunity.

    Science.gov (United States)

    Engeland, C G; Hugo, F N; Hilgert, J B; Nascimento, G G; Junges, R; Lim, H-J; Marucha, P T; Bosch, J A

    2016-02-01

    Stress-induced impairments of mucosal immunity may increase susceptibility to infectious diseases. The present study investigated the association of perceived stress, depressive symptoms, and loneliness with salivary levels of secretory immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were calculated to assess the differential effects of stress on immunoglobulin transport versus availability. This study involved 113 university students, in part selected on high scores on the UCLA Loneliness Scale and/or the Beck Depression Inventory. Stress levels were assessed using the Perceived Stress Scale. Unstimulated saliva was collected and analysed for total S-IgA and its subclasses, as well as SC and total salivary protein. Multiple linear regression analyses, adjusted for gender, age, health behaviours, and concentration effects (total protein) revealed that higher perceived stress was associated with lower levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels were associated with loneliness and depressive symptoms, indicative of enhanced transport activity, which explained a lower IgA1/SC ratio (loneliness and depression) and IgA2/SC ratio (depression). This is the first study to investigate the effects of protracted psychological stress across S-IgA subclasses and its transporter SC. Psychological stress was negatively associated with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter ratio that was associated with higher loneliness and depression suggested a relative immunoglobulin depletion, whereby availability was not keeping up with enhanced transport demand.

  15. Hijack it, Change it: How do Plant Viruses Utilize the Host Secretory Pathway for Efficient Viral Replication and Spread?

    Directory of Open Access Journals (Sweden)

    Camilo ePatarroyo

    2013-01-01

    Full Text Available The secretory pathway of eukaryotic cells has an elaborated set of endomembrane compartments involved in the synthesis, modification and sorting of proteins and lipids. The secretory pathway in plant cells shares many features with that in other eukaryotic cells but also has distinct characteristics important for fundamental cell and developmental processes and for proper immune responses. Recently, there has been evidence that the remodeling of this pathway, and often the formation of viral induced organelles, play an important role in viral replication and spread. The modification of the host secretory pathway seems to be a common feature among most single-stranded positive ss(+RNA and even some DNA viruses. In this review, we will present the recent advances in the organization and dynamics of the plant secretory pathway and the molecular regulation of membrane trafficking in the pathway. We will also discuss how different plant viruses may interact with the host secretory pathway for their efficient replication and spread, with a focus on Tobacco mosaic virus (TMV and Turnip mosaic virus (TuMV.

  16. Efeito de reguladores de crescimento em uva apirênica, cv. BRS Clara Effect of growth regulators on the seedless grape cv. BRS Clara

    Directory of Open Access Journals (Sweden)

    Jair Costa Nachtigal

    2005-08-01

    Full Text Available O presente trabalho teve por objetivo verificar o efeito da aplicação de diferentes concentrações do ácido giberélico (AG3, do thidiazuron (TDZ e do forchlorfenuron (CPPU no aumento do tamanho dos cachos e das bagas e no teor de sólidos solúveis totais de uva sem semente, cv. BRS Clara. As plantas foram conduzidas no sistema de latada, sobre o porta-enxerto IAC 572, no espaçamento 2,5 x 2,0m e com irrigação por microaspersão. Os experimentos foram conduzidos na Estação Experimental de Viticultura Tropical, da Embrapa Uva e Vinho, em Jales-SP. Os reguladores de crescimento foram aplicados via pulverização localizada no cacho, utilizando-se de concentrações de 0 a 4mg.L-1 de CPPU; 0 a 10mg.L-1 de TDZ, e de 0 a 90mg.L-1 de AG3, isolados ou em conjunto. De modo geral, a aplicação dos reguladores de crescimento promove a melhoria da qualidade dos cachos da cv. BRS Clara; o uso do TDZ e do CPPU em conjunto com o AG3 produz um efeito sinérgico, proporcionando melhor resposta do que o uso isolado do AG3; os tratamentos com 60mg.L-1 de AG3; 20mg.L-1 de AG3 + 4mg.L-1 de CPPU, e 10mg.L-1 de AG3 + 5mg.L-1 de TDZ proporcionam os melhores resultados para o aumento do diâmetro das bagas; a aplicação de AG3 antes da floração da cv. BRS Clara provoca abortamento excessivo, reduzindo a qualidade comercial dos cachos; a utilização de concentrações elevadas dos reguladores reduz o teor de sólidos solúveis totais.The objective of this study was to evaluate the effect of different concentrations of gibberellic acid (AG3, thidiazuron (TDZ and forchlorfenuron (CPPU on the size of bunches and berries and on the total soluble solids content, when applied in different concentrations on the seedless grapes, cv. BRS Clara. The grapevines were grafted on the rootstock IAC 572, trained in the pergola system and, spaced 2.5 x 2.0m and irrigated by micro sprinklers. The experiments were carried out at the Embrapa Grape and Wine Experimental

  17. Heterogeneity of secretory granules of silent pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R

    1988-01-01

    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...... approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas....

  18. Estimation of carbon sequestration by tree species in three farms in Villa Clara province

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    José Carlos García Hernández

    2016-03-01

    Full Text Available The research took place in two farms of the Cifuentes municipality and in a farm of the Santa Clara municipality, province of Villa Clara. It was carried out from November 2008 to May 2009, with the objective of estimating the capture of Carbon by common arboreal species in these farms. The plant biomass analyses were made according to the methodology of Mercadet and Álvarez (2005. Several parameters were analyzed. Age, height and perimeter of the plants were the most influential parameters on the amount of carbon sequestered. In this regard, we performed a multivariate curve fitting, showing the age of the plants the highest percent of dependence (54.89%. Palma Real with values between 0.81 and 0.84 t / plant and the Mango between 0.60 and 0.81 t /plant of retained Carbon, were the most outstanding in the capture of Carbon.

  19. Physical subdivision and description of the water-bearing sediments of the Santa Clara Valley, California

    Science.gov (United States)

    Wentworth, Carl M.; Jachens, Robert C.; Williams, Robert A.; Tinsley, John C.; Hanson, Randall T.

    2015-01-01

    A thick Quaternary alluvial section fills a sedimentary basin beneath the Santa Clara Valley, California, located within the San Andreas Fault system at the south end of San Francisco Bay. This section consists of an upper sequence about 1,000 feet thick containing eight sedimentary cycles and a lower fine-grained unit as thick as several hundred feet. Together these constitute the Quaternary Santa Clara Basin. The section overlies an irregular unconformity with more than 1,200 feet of relief cut into the underlying bedrock. This stratigraphy is determined through study of new wells and seismic reflection profiles, together with a sample of the many thousands of water wells in the valley. It represents a major change and improvement in understanding of the basin, particularly with regard to the upper cyclic sequence, which forms a large groundwater system that is an important resource in the San Francisco Bay region.

  20. The Architectonics of Luna Clara e Apolo Onze: a Metalinguistic Reflection

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    Marice Fiuza Geletkanicz

    2013-11-01

    Full Text Available This paper proposes a metalinguistic reflection about the methodological process from which resulted a master's degree thesis entitled Luna Clara e Apolo Onze: a creative organization of voices. More specifically, it intends to show how, from the foundations of dialogical discourse analysis, and from a preliminary examination of the corpus, the book of Adriana Falcão entitled Luna Clara e Apolo Onze, the author of the research developed a specific way of describing the authorial architectonics of a verbal work which integrates visual resources. It intends still to consider how, in the context of the dialogic conception of language, one can propose an object of study, and a specific way of studying it by considering a phenomenon such as a book and examining it by means of concepts compatible with this object, instead of applying ready-made categories.

  1. Histological and histochemical characterization of secretory cells of the male copulatory organs of Girardia anderlani (Platyhelminthes: Tricladida: Paludicola Caracterização histológica e histoquímica das células secretoras dos órgãos do aparelho copulador masculino de Girardia anderlani (Platyhelminthes: Tricladida: Paludicola

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    Dioneia C. da Vara

    2008-06-01

    Full Text Available Glands of the reproductive system are important for taxonomical identification of flatworms. We studied the histology and histochemical characteristics of the glands of the male copulatory apparatus in Girardia anderlani (KAWAKATSU & HAUSER, 1983. Specimens were fixed in reproductive state, i. e. during and following copulation at four, eight, 12 and 16 hours intervals. Secretory cells were distinguished on the basis of secretion morphology and their staining properties, using trichrome methods and histochemical reactions. Twelve secretory cell types and five main types of secretions were identified in the male copulatory apparatus: glycoproteic with and without tryptophan; glycosaminoglycidic; neutral mucopolysaccharidic; and proteic. Compared to other Girardia species, more diverse types of secretory cells comprise the glands of the male reproductive system. Histophysiological comparative studies of species of Girardia, in a reproductive state, are necessary to characterize the various regions of the copulatory apparatus as well as to understand the physiology of reproduction.Considerando a importância das glândulas do sistema reprodutor para a caracterização taxonômica de planárias, o presente trabalho objetiva fornecer uma descrição detalhada da histologia e a primeira caracterização histoquímica das glândulas do aparelho copulador masculino de Girardia anderlani (KAWAKATSU & HAUSER, 1983. A análise foi realizada em espécimes fixados em período reprodutivo, i. e., durante e após a cópula (períodos de quatro, oito, 12 e 16 horas. As células secretoras foram diferenciadas com base na morfologia da secreção e em sua coloração com métodos tricrômicos e reações histoquímicas. Doze tipos de células secretoras e cinco tipos principais de secreção foram identificados no aparelho copulador masculino de G. anderlani: glicoprotéica com e sem triptofano, glicosaminoglicídica, mucopolissacarídica neutra e protéica. Em

  2. Evaluation of animal control measures on pet demographics in Santa Clara County, California, 1993–2006

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    Philip H. Kass

    2013-02-01

    Full Text Available The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes. A prospective cross-sectional study of 1000 households was implemented in 2005 to evaluate characteristics of the owned and unowned population of dogs and cats in Santa Clara County, California. The same population was previously studied 12 years earlier. During this time period, the county instituted in 1994 and then subsequently disestablished a municipal spay/neuter voucher program for cats. Dog intakes declined from 1992–2005, as they similarly did for an adjacent county (San Mateo. However, cat intakes declined significantly more in Santa Clara County than San Mateo, with an average annual decline of approximately 700 cats for the 12 year period. Time series analysis showed a greater than expected decline in the number of cats surrendered to shelters in Santa Clara County during the years the voucher program was in effect (1994–2005. The net savings to the county by reducing the number of cat shelter intakes was estimated at approximately $1.5 million. The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes.

  3. Carcinoma odontogénico de células claras

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    Sergio Alberto Flores Alvarado

    2011-03-01

    Full Text Available El carcinoma odontogénico de células claras es un raro tumor odontogénico que se presenta principalmente en la parte anterior de la mandíbula, mayormente en mujeres entre la quinta y séptima década de vida. Se caracteriza histológicamente por redes de células con citoplasma claro mezcladas con células que contienen citoplasma eosinófilo. Es sumamente agresivo y puede presentar metástasis local o a distancia. Al emplearse el tratamiento por enucleación y curetaje, frecuentemente da lugar a recurrencia, por lo que se aconseja el tratamiento radical de resección mandibular hasta una zona libre de lesión. El carcinoma odontogénico de células claras debe ser considerado en el diagnóstico diferencial de tumores mandibulares que presenten células claras para el establecimiento del plan de tratamiento adecuado. Se debe incluir el seguimiento a largo plazo del paciente. Se presenta el caso de un paciente femenino de 69 años de edad, con una lesión presente en la región presinfisaria derecha, sin afectación de ganglios linfáticos regionales o metástasis aparente. Se efectuó osteotomía segmentaria mandibular y reconstrucción con placa de titanio.

  4. Evaluation of animal control measures on pet demographics in Santa Clara County, California, 1993-2006.

    Science.gov (United States)

    Kass, Philip H; Johnson, Karen L; Weng, Hsin-Yi

    2013-01-01

    The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes. A prospective cross-sectional study of 1000 households was implemented in 2005 to evaluate characteristics of the owned and unowned population of dogs and cats in Santa Clara County, California. The same population was previously studied 12 years earlier. During this time period, the county instituted in 1994 and then subsequently disestablished a municipal spay/neuter voucher program for cats. Dog intakes declined from 1992-2005, as they similarly did for an adjacent county (San Mateo). However, cat intakes declined significantly more in Santa Clara County than San Mateo, with an average annual decline of approximately 700 cats for the 12 year period. Time series analysis showed a greater than expected decline in the number of cats surrendered to shelters in Santa Clara County during the years the voucher program was in effect (1994-2005). The net savings to the county by reducing the number of cat shelter intakes was estimated at approximately $1.5 million. The measurable benefits of animal control programs are unknown and the aim of this study was to determine the impact of these programs on pet population changes.

  5. Superfund Record of Decision (EPA Region 9): Micro Storage/Intel Magnetics, Santa Clara, CA. (First remedial action), August 1991

    Energy Technology Data Exchange (ETDEWEB)

    1991-08-26

    The 3-acre Micro Storage/Intel Magnetics site consists of a former microcomputer disk drive manufacturing facility and a magnetic bubble production and testing facility in Santa Clara, Santa Clara County, California. In addition, the site overlies two shallow aquifers zones, which in turn, overlie the Santa Clara Valley ground water basin, the primary drinking water source for the 1.4 million residents of the Santa Clara Valley. As a result of possible improper storage procedures at both facilities, a number of State and EPA investigations identified VOCs including benzene, TCE, and TCA, and other organics in the ground water aquifer beneath the site. The Record of Decision (ROD) addresses ground water contaminated by past facility operations. The primary contaminants of concern affecting the ground water are VOCs including benzene, PCE, TCE, and toluene; and other organics. The selected remedial action for this site is included.

  6. Immunohistochemical demonstration of airway epithelial cell markers of guinea pig.

    Science.gov (United States)

    Li, Yong; Wang, Jing; He, Hai Yan; Ma, Ling Jie; Zeng, Jin; Deng, Guang Cun; Liu, Xiaoming; Engelhardt, John F; Wang, Yujiong

    2011-10-01

    The guinea pig (Cavea porcellus) is a mammalian non-rodent species in the Caviidae family. The sensitivity of the respiratory system and the susceptibility to infectious diseases allows the guinea pig to be a useful model for both infectious and non-infectious lung diseases such as asthma and tuberculosis. In this report, we demonstrated for the first time, the major cell types and composition in the guinea pig airway epithelium, using cell type-specific markers by immunohistochemical staining using the commercial available immunological reagents that cross-react with guinea pig. Our results revealed the availability of antibodies cross-reacting with airway epithelial cell types of basal, non-ciliated columnar, ciliated, Clara, goblet and alveolar type II cells, as well as those cells expressing Mucin 5AC, Mucin 2, Aquaporin 4 and Calcitonin Gene Related Peptide. The distribution of these various cell types were quantified in the guinea pig airway by immunohistochemical staining and were comparable with morphometric studies using an electron microscopy assay. Moreover, this study also demonstrated that goblet cells are the main secretory cell type in the guinea pig's airway, distinguishing this species from rats and mice. These results provide useful information for the understanding of airway epithelial cell biology and mechanisms of epithelial-immune integration in guinea pig models.

  7. Phosphorylation of αSNAP is Required for Secretory Organelle Biogenesis in Toxoplasma gondii.

    Science.gov (United States)

    Stewart, Rebecca J; Ferguson, David J P; Whitehead, Lachlan; Bradin, Clare H; Wu, Hong J; Tonkin, Christopher J

    2016-02-01

    Upon infection, apicomplexan parasites quickly invade host cells and begin a replicative cycle rapidly increasing in number over a short period of time, leading to tissue lysis and disease. The secretory pathway of these highly polarized protozoan parasites tightly controls, in time and space, the biogenesis of specialized structures and organelles required for invasion and intracellular survival. In other systems, regulation of protein trafficking can occur by phosphorylation of vesicle fusion machinery. Previously, we have shown that Toxoplasma gondii αSNAP - a protein that controls the disassembly of cis-SNARE complexes--is phosphorylated. Here, we show that this post-translational modification is required for the correct function of αSNAP in controlling secretory traffic. We demonstrate that during intracellular development conditional expression of a non-phosphorylatable form of αSNAP results in Golgi fragmentation and vesiculation of all downstream secretory organelles. In addition, we show that the vestigial plastid (termed apicoplast), although reported not to be reliant on Golgi trafficking for biogenesis, is also affected upon overexpression of αSNAP and is much more sensitive to the levels of this protein than targeting to other organelles. This work highlights the importance of αSNAP and its phosphorylation in Toxoplasma organelle biogenesis and exposes a hereto fore-unexplored mechanism of regulation of vesicle fusion during secretory pathway trafficking in apicomplexan parasites.

  8. Morphological, histochemical and immunohistochemical characterization of secretory production of the ciliary glands in the porcine eyelid

    Directory of Open Access Journals (Sweden)

    T Yasui

    2009-06-01

    Full Text Available In addition to performing general histology and cytology of the ciliary glands of the miniature pig, we studied the localization of glycoconjugates and b-defensins in these glands with the use of carbohydrate histochemical and immunohistochemical methods. The secretory cells of the glands were equipped with non-homogeneous secretory granules, a welldeveloped Golgi apparatus and rough endoplasmic reticulum. The secretory epithelium and luminal secretion of the glands contained large amounts of neutral and acidic glycoconjugates with various saccharide residues (a-L-Fuc, b-DGal, a-D-GalNAc and sialic acid. The sebaceous glands and tarsal glands also exhibited positive reactions to most of the histochemical methods. Additionally, the antimicrobial peptide group of b-defensins was demonstrated to be products of the ciliary glands, as well as the sebaceous glands and tarsal glands. The results obtained are discussed with regard to the specific function of the ciliary glandular secretions. These secretory products may be related to the moistening and general protection of the skin surface of the eyelid and ocular surface.

  9. Internal secretory structures in stems of Silphium perfoliatum L.

    Directory of Open Access Journals (Sweden)

    Aneta Sulborska

    2013-04-01

    Full Text Available Silphium perfoliatum L. (Asteraceae is a North American perennial used as a medicinal, fodder, honey-bearing, and ornamental plant as well as for remediation of degraded soils. The location and structure of secretory reservoirs in the stem were examined with the use of light microscopy in cup plant stems. The stems were analysed at various heights (0-2 cm above the root collar, ½ of the stem length, and 0-2 cm below the stem apex/inflorescence and in three vegetation phases (vegetative phase, full bloom, withering. The plants belonged to the collection of the Department of Vegetable Crops and Medicinal Plants of the University of Life Sciences in Lublin. It was found that the secretory canals formed two rings: an external ring situated at the height of sclerenchymatous sheaths and bundle phloem, and the internal ring located in an immediate proximity of the xylem. Two external secretory reservoirs, one on each side of the bundle, were present at larger bundles. No internal reservoirs were formed in the proximity of these bundles. At smaller bundles, there were reservoirs of the internal verticil, but there were no external reservoirs. The canals of the external verticil (23-29 were more numerous that in the internal verticil (17-19. In both cases, the largest number of reservoirs was observed at half the length of the stem, and the lowest number was in the apical part. The less numerous internal canals were larger in comparison with the external reservoirs. Depending on the plant developmental stage and location in the stem, the diameter of the external ring canals was 49-91 μm in cross section, and that of the canals of the internal verticil was 52-101 μm. The analysis of the different vegetation phases in the cup plant demonstrated that the canals had the largest diameters and were the most abundant in the withering phase. The canals evolved through gradual separation of cells (of schizogenous origin. In the cross section they exhibited a

  10. Identification of routing determinants in the cytosolic domain of a secretory granule-associated integral membrane protein.

    Science.gov (United States)

    Milgram, S L; Mains, R E; Eipper, B A

    1996-07-19

    We have investigated the trafficking of integral membrane peptidylglycine alpha-amidating monooxygenase (PAM) in the neuroendocrine AtT-20 cell line. This bifunctional enzyme has two domains which together catalyze the COOH-terminal alpha-amidation of peptidylglycine substrates yielding amidated products stored in secretory granules. As soluble proteins, both catalytic domains were independently targeted to secretory granules. In contrast, membrane PAM was largely localized to the trans-Golgi network (TGN). Upon truncation of its cytoplasmic COOH-terminal domain, membrane PAM was less efficiently cleaved by secretory granule enzymes and accumulated on the plasma membrane. When transferred to the lumenal domain of the interleukin 2 receptor alpha-chain (Tac protein), the cytoplasmic domain of PAM caused rerouting of Tac from the surface to the TGN and supported internalization of Tac antibody from the plasma membrane. To define sequences in the cytoplasmic domain of integral membrane PAM involved in its trafficking, we expressed PAM proteins containing truncations, deletions, or point mutations in the COOH-terminal cytoplasmic domain. PAM proteins were not retained in the TGN when half of the cytoplasmic domain was deleted; such proteins accumulated on the plasma membrane, were not efficiently internalized, and were cleaved to generate a bifunctional PAM protein that was not stored in secretory granules. A tyrosine-based internalization motif was identified, which was not required for efficient cleavage of full-length integral membrane PAM by secretory granule enzymes. Deletion of an 18-amino acid domain surrounding this Tyr residue both diminished cleavage of membrane PAM by secretory granule enzymes and eliminated internalization of PAM from the plasma membrane. The cytoplasmic domain is responsible for retaining membrane PAM in the TGN and for retrieving membrane PAM from the cell surface, while the lumenal catalytic domains of PAM appear to be responsible for

  11. Crescimento e desenvolvimento de frutos do tomateiro 'Santa Clara' e do seu mutante natural 'Firme' Growth and development of 'Santa Clara' tomato fruit and its mutant 'Firme'

    Directory of Open Access Journals (Sweden)

    Marcia Lima Moura

    2004-12-01

    Full Text Available Na região produtora de hortaliças de Viçosa, MG, identificaram-se plantas de tomate da cv. Santa Clara (Lycopersicon esculentum Mill., que apresentam senescência foliar precoce e estigmas amarelados, com frutos de coloração "amarelo-creme" quando imaturos e vermelho quando maduros, de maturação lenta, e mais firmes que o fenótipo normal. Objetivou-se com este trabalho avaliar o crescimento e desenvolvimento dos frutos normais e mutantes. O delineamento experimental foi de blocos casualizados com quatro repetições. Os frutos mutantes apresentaram matéria fresca total e diâmetro transversal e longitudinal menores do que o normal durante todo o seu desenvolvimento. A espessura do pericarpo foi significativamente menor nos frutos mutantes do que nos frutos normais, a partir dos 21 dias após a antese. Folhas medianas e basais de plantas mutantes apresentaram menores teores de clorofila do que o observado em plantas normais. O período de amadurecimento do fruto mutante foi de 14 dias, enquanto dos frutos normais foi de 7 dias, quando ligados à planta-mãe, demonstrando a maior longevidade dos frutos mutantes. Além disso, os frutos mutantes apresentaram atraso na elevação da produção de etileno durante o amadurecimento.'Santa Clara' tomato (Lycopersicon esculentum Mill. plants showing earlier leaf senescence and yellowish stigma, fruits with pale yellow when immature and red when reach full ripe stage, associated to a lower rate of ripening and firmer than the wild type, were found in Viçosa, MG. The objective of this study was to evaluate the fruit growth and development of the mutant and wild type tomatoes. Mutant fruits showed smaller total fresh weight than wild type throughout development and thinner pericarp after 21 days after flowering. Basal and intermediate mutant plant leaves showed lower chlorophyll levels. 'Santa Clara' fruit took 7 days to reach full red ripe stage, while mutant fruits took 14 days. Furthermore

  12. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

  13. Saturated fatty acids alter the late secretory pathway by modulating membrane properties.

    Science.gov (United States)

    Payet, Laurie-Anne; Pineau, Ludovic; Snyder, Ellen C R; Colas, Jenny; Moussa, Ahmed; Vannier, Brigitte; Bigay, Joelle; Clarhaut, Jonathan; Becq, Frédéric; Berjeaud, Jean-Marc; Vandebrouck, Clarisse; Ferreira, Thierry

    2013-12-01

    Saturated fatty acids (SFA) have been reported to alter organelle integrity and function in many cell types, including muscle and pancreatic β-cells, adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this study, using a yeast-based model that recapitulates most of the trademarks of SFA-induced lipotoxicity in mammalian cells, we demonstrate that these lipid species act at different levels of the secretory pathway. Ceramides mostly appear to modulate the induction of the unfolded protein response and the transcription of nutrient transporters destined to the cell surface. On the other hand, saturated PL, by altering membrane properties, directly impact vesicular budding at later steps in the secretory pathway, i.e. at the trans-Golgi Network level. They appear to do so by increasing lipid order within intracellular membranes which, in turn, alters the recruitment of loose lipid packing-sensing proteins, required for optimal budding, to nascent vesicles. We propose that this latter general mechanism could account for the well-documented deleterious impacts of fatty acids on the last steps of the secretory pathway in several cell types.

  14. The secretory pathway at 50: a golden anniversary for some momentous grains of silver.

    Science.gov (United States)

    Matlin, Karl S; Caplan, Michael J

    2017-01-15

    The secretory pathway along which newly synthesized secretory and membrane proteins traffic through the cell was revealed in two articles published 50 years ago. This discovery was the culmination of decades of effort to unite the power of biochemical and morphological methodologies in order to elucidate the dynamic nature of the cell's biosynthetic machinery. The secretory pathway remains a central paradigm of modern cell biology. Its elucidation 50 years ago inspired tremendous multidisciplinary and on-going efforts to understand the machinery that makes it run, the adaptations that permit it to serve the needs of specialized cell types, and the pathological consequences that arise when it is perturbed. © 2017 Matlin and Caplan. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  15. Developmental genetics of secretory vesicle acidification during Caenorhabditis elegans spermatogenesis.

    Science.gov (United States)

    Gleason, Elizabeth J; Hartley, Paul D; Henderson, Melissa; Hill-Harfe, Katherine L; Price, Paul W; Weimer, Robby M; Kroft, Tim L; Zhu, Guang-Dan; Cordovado, Suzanne; L'Hernault, Steven W

    2012-06-01

    Secretory vesicles are used during spermatogenesis to deliver proteins to the cell surface. In Caenorhabditis elegans, secretory membranous organelles (MO) fuse with the plasma membrane to transform spermatids into fertilization-competent spermatozoa. We show that, like the acrosomal vesicle of mammalian sperm, MOs undergo acidification during development. Treatment of spermatids with the V-ATPase inhibitor bafilomycin blocks both MO acidification and formation of functional spermatozoa. There are several spermatogenesis-defective mutants that cause defects in MO morphogenesis, including spe-5. We determined that spe-5, which is on chromosome I, encodes one of two V-ATPase B paralogous subunits. The spe-5 null mutant is viable but sterile because it forms arrested, multi-nucleate spermatocytes. Immunofluorescence with a SPE-5-specific monoclonal antibody shows that SPE-5 expression begins in spermatocytes and is found in all subsequent stages of spermatogenesis. Most SPE-5 is discarded into the residual body during spermatid budding, but a small amount remains in budded spermatids where it localizes to MOs as a discrete dot. The other V-ATPase B subunit is encoded by vha-12, which is located on the X chromosome. Usually, spe-5 mutants are self-sterile in a wild-type vha-12 background. However, an extrachromosomal transgene containing wild-type vha-12 driven by its own promoter allows spe-5 mutant hermaphrodites to produce progeny, indicating that VHA-12 can at least partially substitute for SPE-5. Others have shown that the X chromosome is transcriptionally silent in the male germline, so expression of the autosomally located spe-5 gene ensures that a V-ATPase B subunit is present during spermatogenesis.

  16. Fisiologia do amadurecimento na planta do tomate 'Santa Clara' e do mutante 'Firme' Physiology of vine-ripened tomato 'Santa Clara' and its mutant 'Firme'

    Directory of Open Access Journals (Sweden)

    Márcia Lima Moura

    2005-03-01

    Full Text Available O mutante natural de tomate 'Firme' da cv. Santa Clara tem frutos com coloração "amarelo-creme" quando imaturos, firmes e com amadurecimento lento. Estudou-se as alterações fisiológicas que ocorrem durante o processo de amadurecimento na planta de frutos de tomate da cv. Santa Clara e do mutante 'Firme'. Os frutos normais e mutantes foram colhidos em 6 diferentes estádios de maturidade, e em cada um deles foram avaliados a produção de etileno e CO2, os teores de açúcares solúveis totais do pericarpo e do tecido locular, e as atividades das enzimas oxidase do ACC e poligalacturonase. Os frutos mutantes apresentaram menores taxas respiratórias e de produção de etileno em todos os estádios de maturidade. A atividade da oxidase do ACC apresentou padrão de comportamento distinto durante o amadurecimento na planta dos frutos mutantes e normais, porém com semelhante atividade final. Os frutos mutantes apresentaram atraso no aumento da atividade da enzima poligalacturonase em relação aos frutos normais nas fases iniciais do amadurecimento. Frutos normais acumularam açúcares solúveis totais durante seu amadurecimento na planta, enquanto que nos frutos mutantes os teores foram inferiores nos estádios mais avançados do amadurecimento quando comparados com aqueles no início do climatério. O pericarpo dos frutos mutantes nos estádios mais avançados do amadurecimento teve teores de açúcares total inferiores.The natural tomato mutant 'Firme' from cv. Santa Clara presents a yellow-pale appearance when immature, firm texture and slow ripening. Some of the physiological changes throughout ripening of cv. Santa Clara and the natural mutant 'Firme' were evaluated on the vine. Fruit ethylene and CO2 production, locular and outer pericarp total soluble sugars content, ACC oxidase and poligalacturonase activities were evaluated in both genotypes at six maturity stages. Mutant fruits presented lower ethylene and CO2 production at all

  17. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

    Directory of Open Access Journals (Sweden)

    Sonia Gullón

    Full Text Available Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase and a Tat-dependent model protein (agarase in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

  18. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans.

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients' depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host.

  19. Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits Different Cellular Responses in Streptomyces lividans

    Science.gov (United States)

    Gullón, Sonia; Marín, Silvia; Mellado, Rafael P.

    2015-01-01

    Streptomyces lividans is considered an efficient host for the secretory production of homologous and heterologous proteins. To identify possible bottlenecks in the protein production process, a comparative transcriptomic approach was adopted to study cellular responses during the overproduction of a Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein (agarase) in Streptomyces lividans. The overproduction of the model secretory proteins via the Sec or the Tat route in S. lividans does elicit a different major cell response in the bacterium. The stringent response is a bacterial response to nutrients’ depletion, which naturally occurs at late times of the bacterial cell growth. While the induction of the stringent response at the exponential phase of growth may limit overall productivity in the case of the Tat route, the induction of that response does not take place in the case of the Sec route, which comparatively is an advantage in secretory protein production processes. Hence, this study identifies a potential major drawback in the secretory protein production process depending on the secretory route, and provides clues to improving S. lividans as a protein production host. PMID:26200356

  20. Calcium-containing phosphopeptides pave the secretory pathway for efficient protein traffic and secretion in fungi.

    Science.gov (United States)

    Martín, Juan F

    2014-01-01

    Casein phosphopeptides (CPPs) containing chelated calcium drastically increase the secretion of extracellular homologous and heterologous proteins in filamentous fungi. Casein phosphopeptides released by digestion of alpha - and beta-casein are rich in phosphoserine residues (SerP). They stimulate enzyme secretion in the gastrointestinal tract and enhance the immune response in mammals, and are used as food supplements. It is well known that casein phosphopeptides transport Ca2+ across the membranes and play an important role in Ca2+ homeostasis in the cells. Addition of CPPs drastically increases the production of heterologous proteins in Aspergillus as host for industrial enzyme production. Recent proteomics studies showed that CPPs alter drastically the vesicle-mediated secretory pathway in filamentous fungi, apparently because they change the calcium concentration in organelles that act as calcium reservoirs. In the organelles calcium homeostasis a major role is played by the pmr1 gene, that encodes a Ca2+/Mn2+ transport ATPase, localized in the Golgi complex; this transporter controls the balance between intra-Golgi and cytoplasmic Ca2+ concentrations. A Golgi-located casein kinase (CkiA) governs the ER to Golgi directionality of the movement of secretory proteins by interacting with the COPII coat of secretory vesicles when they reach the Golgi. Mutants defective in the casein-2 kinase CkiA show abnormal targeting of some secretory proteins, including cytoplasmic membrane amino acid transporters that in ckiA mutants are miss-targeted to vacuolar membranes. Interestingly, addition of CPPs increases a glyceraldehyde-3-phpshate dehydrogenase protein that is known to associate with microtubules and act as a vesicle/membrane fusogenic agent. In summary, CPPs alter the protein secretory pathway in fungi adapting it to a deregulated protein traffic through the organelles and vesicles what results in a drastic increase in secretion of heterologous and also of

  1. Secretory Carcinoma of the Breast: Report of Two Cases and Review of the Literature

    OpenAIRE

    2015-01-01

    Secretory carcinoma of the breast is an extremely rare subtype of breast cancer characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. The disease which was considered to be predominant in younger age group has been recognized in adult population too and tends to show slow growth and indolent behavior. The disease occurs preferentially in females and only 27 cases have been reported amongst males. An optimal treatment for the dis...

  2. The urethral glands of male mice in relation to depletion of secretory granules upon mating.

    Science.gov (United States)

    Parr, M B; de França, L R; Kepple, L; Ying, L; Parr, E L; Russell, L D

    1994-08-01

    The present study describes the effects of mating on urethral gland acinar cells in male mice. Histological and morphometric analysis demonstrated that there was a depletion of secretory granules in the urethral glands during mating. However, no change occurred in the rough endoplasmic reticulum containing tubular elements. The results indicate that the urethral glands are functional during mating. The timing of their granule depletion suggests that urethral gland secretions may contribute to the formation of semen or the copulation plug.

  3. Evidence for antimuscarinic acetylcholine receptor antibody-mediated secretory dysfunction in nod mice.

    Science.gov (United States)

    Nguyen, K H; Brayer, J; Cha, S; Diggs, S; Yasunari, U; Hilal, G; Peck, A B; Humphreys-Beher, M G

    2000-10-01

    Antibodies directed against general and specific target-organ autoantigens are present in the sera of human patients and animal models with autoimmune disease. The relevance of these autoantibodies to the disease process remains ambiguous in most cases. In autoimmune exocrinopathy (Sjögren's syndrome), autoantibodies to the intracellular nuclear proteins SSA/Ro and SSB/La, as well as the cell surface muscarinic cholinergic receptor (M3) are observed. To evaluate the potential role of these factors in the loss of secretory function of exocrine tissues, a panel of monoclonal and polyclonal antibodies was developed for passive transfer into the NOD animal model. Monoclonal antibodies to mouse SSB/La, rat M3 receptor, and a rabbit polyclonal antiparotid secretory protein antibody were obtained for this study. These antibody reagents were subsequently infused into NOD-scid mice. Saliva flow rates were subsequently monitored over a 72-hour period. Submandibular gland lysates were examined by Western blotting for alteration of the distribution of the water channel protein aquaporin (AQP). Evaluation of the secretory response indicated that only antibodies directed toward the extracellular domains of the M3 receptor were capable of mediating the exocrine dysfunction aspect of the clinical pathology of the autoimmune disease. In vitro stimulation with a muscarinic agonist of submandibular gland cells isolated from mice treated with anti-M3 antibody, but not saline or the isotype control, failed to translocate AQP to the plasma membrane. These findings define a clear role for the humoral immune response and the targeting of the cell surface M3 signal transduction receptor as primary events in the development of clinical symptoms of autoimmune exocrinopathy. Furthermore, the anti-M3 receptor activity may negatively affect the secretory response through perturbation of normal signal transduction events, leading to translocation of the epithelial cell water channel.

  4. Epidemiological and ecological characteristics of past dengue virus infection in Santa Clara, Peru.

    Science.gov (United States)

    Reiskind, M H; Baisley, K J; Calampa, C; Sharp, T W; Watts, D M; Wilson, M L

    2001-03-01

    To determine risk factors associated with dengue (DEN) virus infection among residents of Santa Clara, Peru, a rural Amazonian village near Iquitos, a cross-sectional serological, epidemiological and environmental survey was conducted. Demographic, social and behavioural information was obtained by standardized questionnaire from 1225 Santa Clara residents (61.3%) aged 5 years or older. Additional data were obtained on the environmental variables and immature mosquito species and abundance surrounding each household (n = 248). Sera that had been collected previously by the Peruvian Ministry of Health from residents were tested by an enzyme-linked immunosorbent assay (ELISA) for DEN virus IgG antibody. Antibody identity was verified as DEN by plaque reduction neutralization test. Data on individuals were analysed by univariate and multivariable methods, and independent sample t-tests. Spatial clustering was evaluated by comparing distances among DEN positive households. Overall, antibody prevalence was 29.4 % and more than doubled from the youngest to the oldest age groups, but did not differ by sex. Curiously, length of residence in Santa Clara was negatively associated with DEN virus antibodies. More frequent travel to Iquitos was positively associated with seroprevalence. Residents who obtained water from a river source rather than a local well also had significantly higher antibody prevalence. None of the environmental variables measured at each household corresponded to the patterns of antibody distribution. Of the larval mosquitoes found around residences, all were determined to be species other than Aedes. No evidence of spatial autocorrelation among antibody-positive households was detected. These results strongly suggested that recent DEN virus transmission did not occur in the village and that most infections of residents of this rural village were acquired while visiting the city of Iquitos.

  5. Human axillary apocrine glands: proteins involved in the apocrine secretory mechanism.

    Science.gov (United States)

    Stoeckelhuber, Mechthild; Schubert, Christoph; Kesting, Marco R; Loeffelbein, Denys J; Nieberler, Markus; Koehler, Claudia; Welsch, Ulrich

    2011-02-01

    The apocrine secretory mechanism is a mode of secretion by which the apical part of the cell cytoplasm is pinched off, which leads to the formation of an aposome. The distinct mechanism of formation and decapitation of the aposome is not well investigated. Only few proteins are known that are involved in this secretory mechanism. We studied the human axillary apocrine gland and looked at proteins associated with cytokinesis, a process that is comparable to the pinching-off mechanism of apocrine glandular cells. By immunohistochemistry, we detected actin, myosin II, cytokeratin 7 and 19, α- and β-tubulin, anillin, cofilin, syntaxin 2, vamp8/endobrevin and septin 2. In highly active glandular cells, these proteins are located at the base of the apical protrusion when the aposome is in the process of being released or are concentrated in the cap of the apical protrusion. These findings demonstrate new insights on apocrine secretory mechanisms and point to similarities to the terminal step of cytokinesis, which is regulated by a SNARE-mediated membrane fusion event.

  6. Caracterización de la mortalidad fetal tardía en Villa Clara.

    OpenAIRE

    Juan Antonio Suárez González; Mario Gutiérrez Machado; Alexis Corrales Gutiérrez

    2011-01-01

    Fundamento: Eventos como la mortalidad fetal tardía agreden la evolución normal esperada en el embarazo, con una connotación en la mujer, la pareja y la comunidad. Objetivo: Caracterizar la mortalidad fetal tardía según factores asociados. Métodos: Se realizó un estudio descriptivo de las 74 muertes fetales registradas en el Hospital Universitario Ginecoobstétrico Mariana Grajales de Santa Clara, durante los años 2009 y 2010. Se analizaron las variables: edad materna, antecedentes patológicos...

  7. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

    Science.gov (United States)

    Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

    2013-01-01

    The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

  8. Secretory Cavity Development and Its Relationship with the Accumulation of Essential Oil in Fruits of Citrus medica L. var. sarcodactylis (Noot.) Swingle

    Institute of Scientific and Technical Information of China (English)

    She-Jian Liang; Hong Wu; Xuan Lun; Dong-Wen Lu

    2006-01-01

    The developmental types of secretory cavities in Citrus remain controversial. The relationship between secretory cavity development and the accumulation of essential oil in fruits of Citrus species is also unknown. In order to develop better insights into these problems, histological, histochemical, and cytochemical methods were used to investigate secretory cavity development and the accumulation of essential oil at different developmental stages of fruits of Citrus medica L. var. sarcodactylis (Noot.) Swingle.The results indicate that the secretory cavity of the variety seemed to originate from an epidermal cell and a subepidermal cell. These two cells underwent successive divisions, resulting in the formation of two parts: (i) a conical cap; and (ii) a globular gland. The formation of the lumen was schizolysigenous. Regular changes in the size of vacuoles and the accumulation of essential oil were revealed during the process of secretory cavity development. In addition, when fruits were a light yellow or golden color, the structure of secretory cavities was well developed and the content of essential oil in a single fruit reached a maximum. It would be most appropriate to collect the fruit as a medicinal material at this time.

  9. Secretory products from thrombin-stimulated human platelets exert an inhibitory effect on NK-cytotoxic activity

    DEFF Research Database (Denmark)

    Skov Madsen, P; Hokland, P; Hokland, M

    1987-01-01

    decreased the NK-cytotoxicity by 40% +/- 4.3%, indicating the existence of secreted products from platelets as a source of NK-inhibiting substances. In contrast, no direct cytotoxic effect of these secretory products on the target cells (K562) was seen. Thus, normal human platelets, when stimulated...

  10. Secretory Duct Structure and Phytochemistry Compounds of Yellow Latex in Mangosteen Fruit

    Directory of Open Access Journals (Sweden)

    DORLY

    2008-09-01

    Full Text Available Yellow latex is the main problem in mangosteen agribusiness, because it is one factor lowering the fruit quality. The structure of yellow latex secretory ducts in the flower and fruit as well as in the root, stem and leaf of mangosteen (Garcinia mangostana L. seedling and the qualitative phytochemistry of yellow latex were studied. The ducts were branched, canal-like type. They were found in the exocarp, mesocarp, endocarp, aril of the fruit, flower, stem, and leaf. In the fruit, the biggest diameter of the secretory ducts was found in the endocarp. There were continuous secretory ducts from fruit stalk to the fruit. Ultrastructural observation showed that the ducts surrounded by specific epithelial cells, which were living cells containing dense cytoplasm with plastid, mitochondria and golgi apparatus organelles. The qualitative test indicated that the yellow latex collected from stem bark, outer part of fruit, young fruit pericarp, mature aril and young aril contained terpenoid, flavonoid and tannin, but not alkaloid, saponin and steroid, except in the young aril containing the steroid.

  11. Augmentation of arginase Ⅱ expression in the human endometrial epithelium in the secretory phase.

    Science.gov (United States)

    Tajima, Makiko; Harada, Tatsuya; Ishikawa, Tomonori; Iwahara, Yuki; Kubota, Toshiro

    2012-12-03

    L-arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to urea and L-ornithine. L-Ornithine is the principal precursor for the production of polyamines and L-proline, which are required for cell proliferation and collagen synthesis. Endothelial NOS is expressed in the human endometrial glandular epithelium, but the expression and physiological roles of arginase in the human endometrium are not clear. The objective of this study was to investigate the expression and distribution patterns of arginases Ⅰ (A-Ⅰ) and Ⅱ (A-Ⅱ) in the human endometrium by using immunohistochemistry, reverse transcription-polymerase chain reaction (RTPCR), and western blotting. A-Ⅰ and A-Ⅱ were detected by immunohistochemistry in human endometrial epithelial cells during the proliferative and secretory phases of the menstrual cycle. RT-PCR showed that A-Ⅰ and A-Ⅱ mRNA were expressed in human endometrial tissue. Western blotting analysis results showed the expression of A-Ⅱ protein. Immunohistochemistry and western blotting results showed that expression levels of A-Ⅱ were significantly higher in the secretory phase than in the proliferative phase. Increased A-Ⅱ levels in the secretory phase may be responsible for endometrial growth by increasing polyamines and proline products.

  12. Phenolic composition of the Brazilian seedless table grape varieties BRS Clara and BRS Morena.

    Science.gov (United States)

    Lago-Vanzela, Ellen Silva; Da-Silva, Roberto; Gomes, Eleni; García-Romero, Esteban; Hermosín-Gutiérrez, Isidro

    2011-08-10

    The detailed phenolic composition (anthocyanins, flavonols, hydroxycinnamic acid derivatives, stilbenes, and flavan-3-ols) in the skin and flesh of the new BRS Clara and BRS Morena seedless table grapes has been studied using HPLC-DAD-ESI-MS/MS. The two grapes, especially BRS Morena, contained high amounts of phenolic compounds, mainly located in their skins and qualitatively not different from those found in Vitis vinifera grapes. In addition, BRS Morena (a teinturier variety) showed qualitatively different phenolic compositions in its skin and flesh, mainly affecting the anthocyanin and flavonol profiles. Consistent with high phenolic contents, high antioxidant capacity values were registered for both grape varieties, especially for BRS Morena. Proanthocyanidins and hydroxycinnamoyl-tartaric acids were the major phenolic compounds found in BRS Clara and were also important in BRS Morena, although anthocyanins were the main phenolic compounds in the latter case. These results suggest that the entire grapes, including the skin, may potentially possess properties that are beneficial to human health. In this context, the BRS Morena grape can be considered as a high resveratrol producer.

  13. Bioaccumulation of selenium (Se) in the Cienega de Santa Clara wetland, Sonora, Mexico.

    Science.gov (United States)

    García-Hernández, J; Glenn, E P; Artiola, J; Baumgartner, D J

    2000-07-01

    The Cienega de Santa Clara, on the east side of the Colorado River delta, is a brackish wetland supported by agricultural drainage water from the United States that provides habitat for endangered fish and bird species. Bioaccumulation of selenium has created toxicity problems for wildlife in similar wetlands in the United States. This is the first selenium survey in the Cienega de Santa Clara. Ten sites were selected to collect water (dissolved), sediments (total), plants, invertebrates, and fish. Samples were collected from October 1996 to March 1997. Selenium was detected in all samples. Concentrations in water ranged from 5 to 19 microg/L and increased along a salinity gradient. Although water levels of selenium exceeded EPA criterion for protection of wildlife, levels in sediments (0.8-1.8 mg/kg), aquatic plants (0.03-0.17 mg/kg), and fish (2.5-5.1 mg/kg whole body, dry wt) did not exceed USFWS recommended levels. It is concluded from this study that the levels of selenium in water did not affect the overall health of the fish sampled. Therefore, it is important to maintain or improve the water quality entering this wetland to continue to have normal levels of Se in the food chain components.

  14. Granivorous birds and sorghum crop in the province of Villa Clara,Cuba

    Directory of Open Access Journals (Sweden)

    Orlando Miguel Saucedo Castillo

    2017-07-01

    Full Text Available In order to reduce the damages granivorous birds cause to sorghum (Sorghum bicolor L. Moench in the province of Villa Clara, Cuba, research based on the determination of the major endemic, migratory birds and their relationship with the distribution were made space of historical meteorological variables in the province in the seasonal behavior of birds in different climatic regions. Population to sorghum producers grouped in different forms surveys were conducted, which yielded a large database, such as the determination of the main grain-eating birds percentage damage incurred, varieties, grain color, growth stage and other indicators. Nine main species affecting sorghum grain-eating birds in our province were recorded; Passer domesticus, Lonchura malacca, Lonchura punctulata, Dives atroviolaceus, Passerina cyanea, Zonotrichia leucophrys, Columbina passerine, Zenaida macroura y Zenaida asiatica. The spatial distribution of meteorological variables and their relation to the seasonal behavior of birds in different climatic regions of the province was determined, based on record four preferential habitat areas. The results allowed us to provide companies and different forms of production in Villa Clara, the possibility of a varietal structure planting of sorghum on the basis of different preferential areas granivorous birds, together with the morphological and physiological characteristics of different genotypes introduced in agricultural production of the province and nationally.

  15. Are there salvage routes within the general secretory pathway in yeast?

    Science.gov (United States)

    Gozalbo, D; Martínez, J P; Sentandreu, R

    1992-04-01

    It is generally accepted that both extracellular protein secretion and plasma membrane expansion in yeast occur basically as in higher eukaryotic cells. In addition to the constitutive (default) secretory pathway, some specialized mammalian cells possess a regulated route which at present has not been detected in yeast. However, there is a body of experimental results suggesting that under certain circumstances export of integral plasma membrane and exocellular proteins may take place through alternative (salvage) pathways. The existence of these latter routes would enable the yeast cell to adapt more efficiently to distinct or adverse conditions requiring the secretion of discrete amounts of specific sets of proteins.

  16. Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Ekkapongpisit M

    2012-04-01

    Full Text Available Maneerat Ekkapongpisit1,*, Antonino Giovia1,*, Giuseppina Nicotra1, Matteo Ozzano1, Giuseppe Caputo2,3, Ciro Isidoro1 1Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy; 2Department of Chemistry, University of Turin, Turin, 3Cyanine Technology SpA, Torino, Italy *These authors contributed equally to this workBackground: For a safe ‘in vivo’ biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth.Aim and methods: In this work, mastocyte-like rat basophilic leukemia (RBL cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS nanoparticles (NPs and naked mesoporous silica (MPS 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging.Results: Our findings were that: (1 secretory granules of mastocytes are accessible by NPs via endocytosis; (2 PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3 PS NPs induce calcium-dependent exocytosis of inflammatory granules.Conclusion: These findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.Keywords: secretory lysosomes, inflammation, nanoparticles, vesicular traffic

  17. Santa Clara Valley water district multi-aquifer monitoring-well site, Coyote Creek Outdoor Classroom, San Jose, California

    Science.gov (United States)

    Hanson, R.T.; Newhouse, M.W.; Wentworth, C.M.; Williams, C.F.; Noce, T.E.; Bennett, M.J.

    2002-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Santa Clara Valley Water District (SCVWD), has completed the first of several multiple-aquifer monitoring-well sites in the Santa Clara Valley. This site monitors ground-water levels and chemistry in the one of the major historic subsidence regions south of San Jose, California, at the Coyote Creek Outdoor Classroom (CCOC) (fig. 1) and provides additional basic information about the geology, hydrology, geochemistry, and subsidence potential of the upper- and lower-aquifer systems that is a major source of public water supply in the Santa Clara Valley. The site also serves as a science education exhibit at the outdoor classroom operated by SCVWD.

  18. INCIDENCIA DE CARDIOPATÍAS DURANTE EL EMBARAZO EN LA PROVINCIA DE VILLA CLARA / Incidence of heart disease during pregnancy in Villa Clara province

    Directory of Open Access Journals (Sweden)

    Marilín C. Luna Alonso

    2012-07-01

    Full Text Available ResumenIntroducción y objetivos: Las enfermedades cardiovasculares constituyen la cuarta causa de muerte durante el período gravídico-puerperal, y un indicador de morbilidad y mortalidad para el producto de la concepción. El objetivo de esta investigación fue determinar el comportamiento de la cardiopatía en la embarazada, su atención médica y evolución durante y al final del embarazo. Método: Se realizó un estudio descriptivo, prospectivo, donde se analizaron 283 gestantes con diagnóstico de cardiopatía, atendidas en el Hospital Universitario Gineco-Obstétrico "Mariana Grajales" de Santa Clara, Villa Clara, en el período 2008-2010. La información se obtuvo mediante la revisión de las historias clínicas individuales, interrogatorio, examen físico completo, así como pruebas complementarias para establecer o confirmar el diagnóstico. Resultados: Se obtuvo una incidencia de 17,2 cardiopatías por cada mil gestantes y en el 59,7 % de ellas, la cardiopatía era adquirida; el prolapso valvular mitral fue la más frecuente (45 %. De las congénitas, el 36,8 % se trataba de una comunicación interauricular. Se utilizó antibioprofilaxis en el 96,8 % de las embarazadas y en el 96,1 % de ellas se mantuvo un seguimiento médico. El 92,6 % tenía clase funcional I y 4,6 % presentó complicación por su enfermedad. El 77,4 % parió entre las 37 y 42 semanas, y el 82,7 % tuvo parto eutócico. Conclusiones: Las gestantes cardiópatas fueron más frecuentes en edades entre 20 y 29 años, con predominio de las que no habían parido, captación entre las 13 y 24 semanas, y cardiopatías adquiridas. La atención médica que prevaleció fue la antibioprofilaxis y el seguimiento médico con evolución final del embarazo satisfactoria. / AbstractIntroduction and Objectives: Cardiovascular diseases are the fourth leading cause of death during the gravid-puerperal period, and an indicator of morbidity and mortality for the product of conception

  19. Caballos de tracción de la ciudad de Santa Clara, Cuba. III Glicemia y electrolitros (Traction horses of Santa Clara city, Cuba. III Glycaemia electrolytes

    Directory of Open Access Journals (Sweden)

    Julio César Castillo Cuenca

    2007-07-01

    Full Text Available Se realizó un estudio de bioquímica sanguínea glicemia y electrolitos (Na, K, Ca, Mg en 100 caballos machos castrados seleccionados al azar utilizados en el transporte local de pasajeros en la ciudad de Santa Clara, Cuba. La sangre se extrajo directamente de la yugular determinándose la glicemia mediante la técnica de la glucosa oxidasa y los electrolitos por espectrofotometría de absorción atómica. El análisis estadístico reveló diferencias altamente significativas al comparar los valores medios obtenidos de la glucosa y los electrolitos con los correspondientes a la media referencial para la especie. Exceptuando el potasio, en el resto de los parámetros la media real fue inferior a la referencial, aunque en todos los casos, estos valores se encuentran dentro del rango planteado. Los equinos están sometidos a un trabajo exhaustivo y prolongado, que afecta el correcto funcionamiento de su organismo y el incremento de la concentración de iones potasio en el plasma es un buen indicador del esfuerzo físico a que son sometidos los animales.

  20. Analysis of the radioactivity in the 'Elguea' spa, Villa Clara, Cuba; Analisis de la radiactividad en el balneario 'Elguea' , Villa Clara, Cuba

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez G, I.M.; Zerquera, J.T.; Carrazana G, J.; Capote F, E.; Rodriguez C, G. [CPHR, La Habana (Cuba)]. e-mail: isis@cphr.edu.cu

    2006-07-01

    The 'Elguea' spa, located in the north coast of the county of Villa Clara, Cuba, is considered one of those more important spas of Latin America. The waters of this spa are rich in salts of chlorine, sodium, bromine, sulfides and its contain radon. As a result of measurements of environmental gamma dose rates carried out in the area of the spa, its were considered levels of dose between 0.13 and 2.3 mSv. The obtained results motivated that it was carried out a characterization, from the radiological point of view, of the spa. This characterization is of supreme importance to be able to evaluate the impact that it has and the discharges of its waters on the environment, as well as, those dose that the population potentially affected can receive by these discharges. With this end its were carried out quantitative determinations of those existent natural more significant radionuclides in different environmental objects coming from the area of the spa and its surroundings, as well as one characterization gamma 'in situ' of the same one. The obtained results are present in this work. (Author)

  1. Establishing human lacrimal gland cultures with secretory function.

    Directory of Open Access Journals (Sweden)

    Shubha Tiwari

    Full Text Available PURPOSE: Dry eye syndrome is a multifactorial chronic disabling disease mainly caused by the functional disruptions in the lacrimal gland. The treatment involves palliation like ocular surface lubrication and rehydration. Cell therapy involving replacement of the gland is a promising alternative for providing long-term relief to patients. This study aimed to establish functionally competent lacrimal gland cultures in-vitro and explore the presence of stem cells in the native gland and the established in-vitro cultures. METHODS: Fresh human lacrimal gland from patients undergoing exenteration was harvested for cultures after IRB approval. The freshly isolated cells were evaluated by flow cytometry for expression of stem cell markers ABCG2, high ALDH1 levels and c-kit. Cultures were established on Matrigel, collagen and HAM and the cultured cells evaluated for the presence of stem cell markers and differentiating markers of epithelial (E-cadherin, EpCAM, mesenchymal (Vimentin, CD90 and myofibroblastic (α-SMA, S-100 origin by flow cytometry and immunocytochemistry. The conditioned media was tested for secretory proteins (scIgA, lactoferrin, lysozyme post carbachol (100 µM stimulation by ELISA. RESULTS: Native human lacrimal gland expressed ABCG2 (mean±SEM: 3.1±0.61%, high ALDH1 (3.8±1.26% and c-kit (6.7±2.0%. Lacrimal gland cultures formed a monolayer, in order of preference on Matrigel, collagen and HAM within 15-20 days, containing a heterogeneous population of stem-like and differentiated cells. The epithelial cells formed 'spherules' with duct like connections, suggestive of ductal origin. The levels of scIgA (47.43 to 61.56 ng/ml, lysozyme (24.36 to 144.74 ng/ml and lactoferrin (32.45 to 40.31 ng/ml in the conditioned media were significantly higher than the negative controls (p<0.05 for all comparisons. CONCLUSION: The study reports the novel finding of establishing functionally competent human lacrimal gland cultures in-vitro. It also

  2. Lifetime measurements of neutron-rich nuclei around {sup 48}Ca with the CLARA-PRISMA setup

    Energy Technology Data Exchange (ETDEWEB)

    Mengoni, D.; Farnea, E. [Dipartimento di Fisica dell' Universita, Padova (Italy); INFN, Sezione di Padova, Padova (Italy); Valiente-Dobon, J.J.; Latina, A. [Laboratori Nazionali di Legnaro, Istituto Nazionale di Fisica Nucleare, Legnaro (Italy); Gadea, A. [Laboratori Nazionali di Legnaro, Istituto Nazionale di Fisica Nucleare, Legnaro (Italy); CSIC-Universitat de Valencia, IFIC, Valencia (Spain); Dewald, A. [Institut fuer Kernphysik, Koeln Universitaet (Germany)

    2009-12-15

    The lifetimes of excited states in neutron-rich nuclei around the doubly-magic nucleus {sup 48}Ca have been measured using a novel technique that combines the Recoil Distance Doppler Shift method with the CLARA-PRISMA spectrometers. This is the first time such a method is applied to measure lifetimes of neutron-rich nuclei populated via a multinucleon transfer reaction. The experimental method are discussed and the results for Ca nuclei are compared with realistic simulations of the CLARA and PRISMA spectrometers. (orig.)

  3. Teucrium polium complex with molybdate enhance cultured islets secretory function.

    Science.gov (United States)

    Mohseni Salehi Monfared, Seyed Sajad; Pournourmohammadi, Shirin

    2010-02-01

    Islet transplantation has become a promising treatment in the therapy of type 1 diabetes. Its function improvement, after isolation and before transplantation, is crucial because of their loss both in number and function of islets after isolation procedures. Trace elements sodium orthovanadate (SOV) and sodium molybdate (SM), as well as medicinal plant Teucrium polium L. (TP), showed and possessed high beneficial antioxidative potential and even hypoglycemic properties via their effect on islets. We evaluated the effect of these components in combination on cultured islet function in order to improve pancreatic islet transplantation. Rat pancreatic islets were cultured for 24 h then incubated with different concentrations of TP (0.01 and 0.1 mg/mL) alone and in combination with SOV (1 mM) or SM (1 mM). Insulin concentration in buffer media was measured as islet secretory function. Administration of TP (0.01 mg/mL), SM, and SOV alone or in combination with each other significantly increased insulin secretion at high glucose concentration (16.7 mM); insulin secretion was significantly greater in the group containing both TP and SM than other treated groups (p molybdate with TP could improve islet cells function before transplantation.

  4. Water resources development in Santa Clara Valley, California: insights into the human-hydrologic relationship

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Jesse L. [Univ. of California, Berkeley, CA (United States)

    2000-06-01

    Groundwater irrigation is critical to food production and, in turn, to humankind's relationship with its environment. The development of groundwater in Santa Clara Valley, California during the early twentieth century is instructive because (1) responses to unsustainable resource use were largely successful; (2) the proposals for the physical management of the water, although not entirely novel, incorporated new approaches which reveal an evolving relationship between humans and the hydrologic cycle; and (3) the valley serves as a natural laboratory where natural (groundwater basin, surface watershed) and human (county, water district) boundaries generally coincide. Here, I investigate how water resources development and management in Santa Clara Valley was influenced by, and reflective of, a broad understanding of water as a natural resource, including scientific and technological innovations, new management approaches, and changing perceptions of the hydrologic cycle. Market demands and technological advances engendered reliance on groundwater. This, coupled with a series of dry years and laissez faire government policies, led to overdraft. Faith in centralized management and objective engineering offered a solution to concerns over resource depletion, and a group dominated by orchardists soon organized, fought for a water conservation district, and funded an investigation to halt the decline of well levels. Engineer Fred Tibbetts authored an elaborate water salvage and recharge plan that optimized the local water resources by integrating multiple components of the hydrologic cycle. Informed by government investigations, groundwater development in Southern California, and local water law cases, it recognized the limited surface storage possibilities, the spatial and temporal variability, the relatively closed local hydrology, the interconnection of surface and subsurface waters, and the value of the groundwater basin for its storage, transportation, and

  5. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Somanath, Sangeeta [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Partridge, Christopher J. [Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Churchill Hospital, University of Oxford, Oxford, OX3 7LJ (United Kingdom); Marshall, Catriona [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Rowe, Tony [CSL Limited, 45 Poplar Road, Parkville, Victoria 3052 (Australia); Turner, Mark D., E-mail: mark.turner@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS (United Kingdom)

    2016-04-29

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  6. A pediatric case of mammary analogue secretory carcinoma within the parotid.

    Science.gov (United States)

    Quattlebaum, S Craig; Roby, Brianne; Dishop, Megan K; Said, M Sherif; Chan, Kenny

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described entity in the differential diagnosis of salivary gland tumors. It is notable for a characteristic t(12;15)(p13;q25) translocation that results in a unique fusion protein, ETV6-NTRK3. While several studies have retrospectively identified this translocation in cases previously diagnosed as a different salivary malignancy, there have been relatively few cases where this translocation was identified on initial pathology results, and fewer still in a pediatric population. We present a case of a 15 year old female with a slowly enlarging, painless, left facial mass. MRI demonstrated a cystic mass extending into the deep lobe of the parotid, and she underwent parotidectomy. The tumor cells stained positive for S100 and CK19. ETV6 translocation was present, confirming the diagnosis. Mammary analogue secretory carcinoma is a recently described tumor of the salivary glands, which often masquerades as more common primary salivary gland tumors and cysts. More research is needed to characterize the typical behavior of this neoplasm and the optimal treatment regimen. With identification of its characteristic translocation, mammary analogue secretory carcinoma can be easily differentiated from its more prevalent counterparts, and should therefore remain within the differential of the pathologist and head and neck surgeon.

  7. Secretory vesicles are preferentially targeted to areas of low molecular SNARE density.

    Directory of Open Access Journals (Sweden)

    Lei Yang

    Full Text Available Intercellular communication is commonly mediated by the regulated fusion, or exocytosis, of vesicles with the cell surface. SNARE (soluble N-ethymaleimide sensitive factor attachment protein receptor proteins are the catalytic core of the secretory machinery, driving vesicle and plasma membrane merger. Plasma membrane SNAREs (tSNAREs are proposed to reside in dense clusters containing many molecules, thus providing a concentrated reservoir to promote membrane fusion. However, biophysical experiments suggest that a small number of SNAREs are sufficient to drive a single fusion event. Here we show, using molecular imaging, that the majority of tSNARE molecules are spatially separated from secretory vesicles. Furthermore, the motilities of the individual tSNAREs are constrained in membrane micro-domains, maintaining a non-random molecular distribution and limiting the maximum number of molecules encountered by secretory vesicles. Together our results provide a new model for the molecular mechanism of regulated exocytosis and demonstrate the exquisite organization of the plasma membrane at the level of individual molecular machines.

  8. Cellular responses to the expression of unstable secretory proteins in the filamentous fungus Aspergillus oryzae.

    Science.gov (United States)

    Yokota, Jun-Ichi; Shiro, Daisuke; Tanaka, Mizuki; Onozaki, Yasumichi; Mizutani, Osamu; Kakizono, Dararat; Ichinose, Sakurako; Shintani, Tomoko; Gomi, Katsuya; Shintani, Takahiro

    2017-03-01

    Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi. More recently, however, even highly expressed endogenous secretory proteins were found to evoke the UPR. These findings raise the question of whether the unfolded or misfolded state of proteins is selectively recognized by quality control mechanisms in filamentous fungi. In this study, a fungal secretory protein (1,2-α-D-mannosidase; MsdS) with a mutation that decreases its thermostability was expressed at different levels in Aspergillus oryzae. We found that, at moderate expression levels, wild-type MsdS was secreted to the medium, while the mutant was not. In the strain with a deletion for the hrdA gene, which is involved in the endoplasmic reticulum-associated degradation pathway, mutant MsdS had specifically increased levels in the intracellular fraction but was not secreted. When overexpressed, the mutant protein was secreted to the medium to a similar extent as the wild-type protein; however, the mutant underwent hyperglycosylation and induced the UPR. Deletion of α-amylase (the most abundant secretory protein in A. oryzae) alleviated the UPR induction by mutant MsdS overexpression. These findings suggest that misfolded MsdS and unfolded species of α-amylase might act synergistically for UPR induction.

  9. Proteomic analysis of plasma membrane and secretory vesicles from human neutrophils

    Directory of Open Access Journals (Sweden)

    Campbell Kevin P

    2007-08-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils (PMN constitute an essential cellular component of innate host defense against microbial invasion and exhibit a wide array of responses both to particulate and soluble stimuli. As the cells recruited earliest during acute inflammation, PMN respond rapidly and release a variety of potent cytotoxic agents within minutes of exposure to microbes or their products. PMN rely on the redistribution of functionally important proteins, from intracellular compartments to the plasma membrane and phagosome, as the means by which to respond quickly. To determine the range of membrane proteins available for rapid recruitment during PMN activation, we analyzed the proteins in subcellular fractions enriched for plasma membrane and secretory vesicles recovered from the light membrane fraction of resting PMN after Percoll gradient centrifugation and free-flow electrophoresis purification using mass spectrometry-based proteomics methods. Results To identify the proteins light membrane fractions enriched for plasma membrane vesicles and secretory vesicles, we employed a proteomic approach, first using MALDI-TOF (peptide mass fingerprinting and then by HPLC-MS/MS using a 3D ion trap mass spectrometer to analyze the two vesicle populations from resting PMN. We identified several proteins that are functionally important but had not previously been recovered in PMN secretory vesicles. Two such proteins, 5-lipoxygenase-activating protein (FLAP and dysferlin were further validated by immunoblot analysis. Conclusion Our data demonstrate the broad array of proteins present in secretory vesicles that provides the PMN with the capacity for remarkable and rapid reorganization of its plasma membrane after exposure to proinflammatory agents or stimuli.

  10. Clinicopathologic and molecular characterization of mammary analogue secretory carcinoma of salivary gland origin.

    Science.gov (United States)

    Baghai, F; Yazdani, F; Etebarian, A; Garajei, A; Skalova, A

    2017-09-01

    Mammary analogue secretory carcinoma (MASC) is a newly recognized salivary gland tumor that harbors a characteristic balanced chromosomal translocation t (12; 15) (p13; q25) resulting in an ETV6-NTRK3 fusion gene. Retrospective study of 111 salivary gland carcinomas revealed 37 cases with secretory features and growth patterns resembling secretory carcinoma of breast. These 37 cases were originally diagnosed as acinic cell carcinoma, adenocarcinoma not otherwise specified and cystadenocarcinoma. Positive immunostaining for S-100 protein and mammaglobin, followed by detection of ETV6 gene rearrangement by FISH and/or ETV6-NTRK3 fusion transcript by RT-PCR were used to identify MASCs. In the cohort of 37 salivary carcinomas with secretory features we have identified 10 cases of MASC. All 10 MASCs were positive for mammaglobin, S-100 protein and SOX10, while staining for DOG1 and p63 protein were mostly absent. In 7/10 cases, both FISH and RT-PCR were positive while three remaining cases showed break of ETV6 gene by FISH analysis and the RT-PCR was negative. Clinical follow-up data were obtained in 6 out of 10 patients with MASC. In 3 patients cervical lymph node metastases developed, one patient with high grade transformed MASC died with multiple distant bone metastases, and local recurrence was observed in three patients. Our clinicopathological data are in keeping with previous studies; in most cases, MASC is a low-grade malignancy with overall favorable prognosis. In rare cases, however, MASC with high-grade transformation may behave aggressively, and these patients could benefit from targeted biological treatment using tyrosine kinase inhibitors. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. Protein modifications in the plant secretory pathway: current status and practical implications in molecular pharming.

    Science.gov (United States)

    Faye, Loïc; Boulaflous, Aurelia; Benchabane, Meriem; Gomord, Véronique; Michaud, Dominique

    2005-03-01

    Plants have become, over the last ten years, a suitable alternative to microbial and animal cell factories for the production of clinically-useful, therapeutic proteins. Besides the well known advantage of low-cost and large-scale production of safe and biologically active mammalian proteins, plants also are able to perform most post-translational maturations required for biological activity and suitable pharmacokinetics of recombinant therapeutic proteins. In this short review we focus on glycosylation and proteolytic processing of plant-made pharmaceuticals during their transport through the plant cell's secretory pathway. We also address the practical implications of these important processes on the effectiveness of plant molecular pharming systems.

  12. Identification of CTLA2A, DEFB29, WFDC15B, SERPINA1F and MUP19 as Novel Tissue-Specific Secretory Factors in Mouse.

    Directory of Open Access Journals (Sweden)

    Jibin Zhang

    Full Text Available Secretory factors in animals play an important role in communication between different cells, tissues and organs. Especially, the secretory factors with specific expression in one tissue may reflect important functions and unique status of that tissue in an organism. In this study, we identified potential tissue-specific secretory factors in the fat, muscle, heart, lung, kidney and liver in the mouse by analyzing microarray data from NCBI's Gene Expression Omnibus (GEO public repository and searching and predicting their subcellular location in GeneCards and WoLF PSORT, and then confirmed tissue-specific expression of the genes using semi-quantitative PCR reactions. With this approach, we confirmed 11 lung, 7 liver, 2 heart, 1 heart and muscle, 7 kidney and 2 adipose and liver-specific secretory factors. Among these genes, 1 lung-specific gene--CTLA2A (cytotoxic T lymphocyte-associated protein 2 alpha, 3 kidney-specific genes--SERPINA1F (serpin peptidase inhibitor, Clade A, member 1F, WFDC15B (WAP four-disulfide core domain 15B and DEFB29 (defensin beta 29 and 1 liver-specific gene--MUP19 (major urinary protein 19 have not been reported as secretory factors. These genes were tagged with hemagglutinin at the 3'end and then transiently transfected to HEK293 cells. Through protein detection in cell lysate and media using Western blotting, we verified secretion of the 5 genes and predicted the potential pathways in which they may participate in the specific tissue through data analysis of GEO profiles. In addition, alternative splicing was detected in transcripts of CTLA2A and SERPINA1F and the corresponding proteins were found not to be secreted in cell culture media. Identification of novel secretory factors through the current study provides a new platform to explore novel secretory factors and a general direction for further study of these genes in the future.

  13. Caracterización de la mortalidad fetal tardía en Villa Clara. Characterization of Late Fetal Mortality in Villa Clara.

    Directory of Open Access Journals (Sweden)

    Juan Antonio Suárez González

    2011-10-01

    Full Text Available

    Fundamento: Eventos como la mortalidad fetal tardía agreden la evolución normal esperada en el embarazo, con una connotación en la mujer, la pareja y la comunidad. Objetivo: Caracterizar la mortalidad fetal tardía según factores asociados. Métodos: Se realizó un estudio descriptivo de las 74 muertes fetales registradas en el Hospital Universitario Ginecoobstétrico Mariana Grajales de Santa Clara, durante los años 2009 y 2010. Se analizaron las variables: edad materna, antecedentes patológicos personales maternos, edad gestacional al momento de la muerte fetal, lugar y momento de ocurrencia y causas de la muerte. Resultados: El 67,6 % de las gestantes tenían entre 20 y 35 años. La hipertensión arterial crónica y el asma bronquial fueron los antecedentes patológicos personales de mayor incidencia entre las gestantes. Ocurrieron los óbitos fetales en una edad gestacional entre 28 y 36,6 semanas fundamentalmente. El 52,7 % de las muertes ocurrieron fuera del hospital y antes del parto en 55 casos (74,3 %. Resultaron las causas más frecuentes las idiopáticas y los trastornos hipertensivos de la gestación. Conclusiones: Es necesario intensificar el control del riesgo reproductivo preconcepcional y la atención prenatal, pues sin dudas, aunque mucho se ha logrado en este sentido, los resultados del estudio muestran que en alguna medida las causas de los óbitos fetales fueron prevenibles.

    Background: Events like late fetal mortality alter the regular, expected course of pregnancy. This carries a negative connotation for the woman, the couple and the community. Objective: To characterize late fetal mortality according to associated factors. Methods: A descriptive study of the 74 fetal deaths registered in the ’Mariana Grajales’ Gynecological and Obstetric University Hospital of Santa

  14. Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV.

    Science.gov (United States)

    Park, Soonhong; Ahuja, Malini; Kim, Min Seuk; Brailoiu, G Cristina; Jha, Archana; Zeng, Mei; Baydyuk, Maryna; Wu, Ling-Gang; Wassif, Christopher A; Porter, Forbes D; Zerfas, Patricia M; Eckhaus, Michael A; Brailoiu, Eugen; Shin, Dong Min; Muallem, Shmuel

    2016-02-01

    Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood. Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explain impaired neuromuscular and secretory cells' functions that mediate regulated exocytosis. Here, we analyzed several forms of regulated exocytosis in a mouse model of MLIV and, opposite to expectations, we found enhanced exocytosis in secretory glands due to enlargement of secretory granules in part due to fusion with lysosomes. Preliminary exploration of synaptic vesicle size, spontaneous mEPSCs, and glutamate secretion in neurons provided further evidence for enhanced exocytosis that was rescued by re-expression of TRPML1 in neurons. These features were not observed in Niemann-Pick type C1. These findings suggest that TRPML1 may guard against pathological fusion of lysosomes with secretory organelles and suggest a new approach toward developing treatment for MLIV.

  15. Modeling Nitrogen Deposition for the Santa Clara County Habitat Conservation Plan

    Science.gov (United States)

    Weiss, S. B.; Meyers, T.; Held, T.; Zippen, D.

    2009-12-01

    Nutrient-poor serpentine soils in Santa Clara County, CA, support numerous rare, threatened, and endangered species such as the Bay checkerspot butterfly. Serpentine grasslands are particularly vulnerable to atmospheric nitrogen deposition, which provides a competitive advantage to invasive annual grasses which overrun the flower-filled grasslands and degrade habitat for the protected species. The effects of N-deposition on these grasslands was first scientifically documented in 1999, and led to a series of mitigation projects for powerplants and road improvements that include habitat acquisition, monitoring, and grazing management. In 2005, a Habitat Conservation Plan/Natural Communities Conservation Plan (HCP/NCCP) was initiated to consolidate project-by-project mitigation into a regional plan covering impacts, especially indirect impacts on N-deposition, from development within the 209,500 ha study area (62% of Santa Clara County) and the cities therein. This HCP/NCCP is the first to address N-deposition effects on biodiversity. To understand the origins of the nitrogen being deposited in Santa Clara grasslands, IFC Jones & Stokes used multiple air quality modeling approaches including Gaussian line-source modeling of major highways and regional Community Multiscale Air Quality (CMAQ) modeling. Line-source modeling allowed for the estimation of N-deposition resulting from increased traffic. Gaussian modeling results indicate that the major highways closest to serpentine habitats result in the greatest environmental impact. The CMAQ modeling used the Particle and Precursor Tagging Methodology (PPTM) source apportionment technique to partition sources. In the base period (Dec 2000- Jan 2001), the CMAQ PPTM simulation estimates that 30% of the total nitrogen deposition is associated with mobile sources operating within the study area; an additional 16% emanates from stationary sources in the study area. Therefore, 46% of nitrogen deposition on the habitat areas

  16. Migration, Memory and Hong Kong as a 'Space of Transit' in Clara Law's Autumn Moon

    Directory of Open Access Journals (Sweden)

    Tony Mitchell

    2013-09-01

    Full Text Available Macau-born and Melbourne-based film maker Clara Law and her screenwriter-producer-director husband Eddie Fong have produced a transnational output of films which are beginning to receive critical recognition as major contributions to contemporary cinema. These ‘films of migration’ explore what Gina Marchetti has encapsulated as ‘the Chinese experience of dislocation, relocation, emigration, immigration, cultural hybridity, migrancy, exile, and nomadism—together termed the “Chinese diaspora”’. The self-imposed ‘relocation’ of Law and Fong to Australia in 1994 was the result of increasing frustration with the rampantly commercial imperatives of Hong Kong cinema and its lack of appreciation for the auteur cinema they wanted to pursue.

  17. Nutrient contributions to the Santa Barbara Channel, California, from the ephemeral Santa Clara River

    Science.gov (United States)

    Warrick, J.A.; Washburn, L.; Brzezinski, Mark A.; Siegel, D.A.

    2005-01-01

    The Santa Clara River delivers nutrient rich runoff to the eastern Santa Barbara Channel during brief (???1-3 day) episodic events. Using both river and oceanographic measurements, we evaluate river loading and dispersal of dissolved macronutrients (silicate, inorganic N and P) and comment on the biological implications of these nutrient contributions. Both river and ocean observations suggest that river nutrient concentrations are inversely related to river flow rates. Land use is suggested to influence these concentrations, since runoff from a subwatershed with substantial agriculture and urban areas had much higher nitrate than runoff from a wooded subwatershed. During runoff events, river nutrients were observed to conservatively mix into the buoyant, surface plume immediately seaward of the Santa Clara River mouth. Dispersal of these river nutrients extended 10s of km into the channel. Growth of phytoplankton and nutrient uptake was low during our observations (1-3 days following runoff), presumably due to the very low light levels resulting from high turbidity. However, nutrient quality of runoff (Si:N:P = 16:5:1) was found to be significantly different than upwelling inputs (13:10:1), which may influence different algal responses once sediments settle. Evaluation of total river nitrate loads suggests that most of the annual river nutrient fluxes to the ocean occur during the brief winter flooding events. Wet winters (such as El Nin??o) contribute nutrients at rates approximately an order-of-magnitude greater than "average" winters. Although total river nitrate delivery is considerably less than that supplied by upwelling, the timing and location of these types of events are very different, with river discharge (upwelling) occurring predominantly in the winter (summer) and in the eastern (western) channel. ?? 2004 Elsevier Ltd. All rights reserved.

  18. Comportamento do camarão em diferentes substratos nas fases clara e escura do dia

    Directory of Open Access Journals (Sweden)

    Daniele Bezerra dos Santos

    2013-08-01

    Full Text Available O objetivo deste trabalho foi avaliar o efeito do tipo de substrato sobre a preferência, o enterramento e a atividade natatória de camarões (Litopenaeus vannamei. Juvenis (0,93±0,29 g e adultos machos e fêmeas (10,05±1,18 g foram observados durante 24 horas, por meio do método animal focal, com registros instantâneos. Foram testadas as seguintes granulometrias (tratamentos dos substratos: I, 100% C; II, 50% C + 50% B; III, 50% A + 50% C; IV, 100% B; V, 50% B + 50% A; e VI, 100% A, em que as letras referemse ao diâmetro médio das partículas, A = 0,25-2,0 mm; B = 0,0625-0,25 mm; e C = <0,0625 mm. Foram aplicados seis tratamentos com 18 repetições para cada categoria: camarões juvenis, machos e fêmeas. Cada indivíduo foi exposto por 24 horas aos seis tipos de substrato, simultaneamente, e o seu comportamento foi observado nas fases clara e escura do dia. A natação ocorreu principalmente na fase escura e o enterramento, na fase clara, no substrato IV. Os camarões juvenis e adultos (machos ou fêmeas preferem o substrato composto de areia fina e muito fina (0,0625-0,25 mm, tanto para permanência quanto para enterramento.

  19. Mapping Typha Domingensis in the Cienega de Santa Clara Using Satellite Images, Global Positioning System, and Spectrometry

    Science.gov (United States)

    Sanchez, Richard D.; Burnett, Earl E.; Croxen, Fred

    2000-01-01

    The Cienega de Santa Clara, Sonora, Mexico, a brackish wetland area created near the delta of the Colorado River from drainage effluent flowing from the United States since 1977, may undergo changes owing to the operation of the Yuma Desalting Plant in the United States. This has become the largest wetland in the delta region containing rare and endangered species, yet little is known about the environmental impact of these changes. The water quality of the marsh is of growing concern to the Bureau of Reclamation (BOR) which operates the Desalting Plant. Consequently, the BOR solicited the U.S. Geological Survey to investigate the limits and usefulness of satellite, global positioning system (GPS), and spectra data to map the Typha domingensis (cattail) of the Cienega de Santa Clara. Typha domingensis was selected by the BOR as the Cienega de Santa Clara indicator species to best predict the environmental effects of effl uent from the Yuma Desalting Plant. The successful base mapping of Typha domingensis will provide a viable tool for long-term monitoring and stress detection in the Cienega de Santa Clara.

  20. 76 FR 68784 - Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA

    Science.gov (United States)

    2011-11-07

    ....EU0000; CACA 50168 12] Notice of Realty Action: Direct Sale of Public Land in Santa Clara County, CA....html . SUPPLEMENTARY INFORMATION: The following parcel of public land is being proposed for direct sale... legal access. The BLM is proposing a direct sale to Mariposa Peak, LLC. Mariposa Peak, LLC, owns...

  1. Map showing locations of damaging landslides in Santa Clara County, California, resulting from 1997-98 El Nino rainstorms

    Science.gov (United States)

    Ellis, William L.; Harp, Edwin L.; Arnal, Caroline H.; Godt, Jonathan W.

    1999-01-01

    Heavy rainfall associated with a strong El Nino caused over $150 million in landslide damage in the 10-county San Francisco Bay region during the winter and spring of 1998. A team of USGS scientists collected information on landslide locations and damage costs. About $7.6 million in damages were assessed in Santa Clara County.

  2. N-Glycans on secretory component: mediators of the interaction between secretory IgA and gram-positive commensals sustaining intestinal homeostasis.

    Science.gov (United States)

    Mathias, Amandine; Corthésy, Blaise

    2011-09-01

    Human beings live in symbiosis with billions of microorganisms colonizing mucosal surfaces. The understanding of the mechanisms underlying this fine-tuned intestinal balance has made significant processes during the last decades. We have recently demonstrated that the interaction of SIgA with Gram-positive bacteria is essentially based on Fab-independent, glycan-mediated recognition. Results obtained using mouse hybridoma- and colostrum-derived secretory IgA (SIgA) consistently show that N-glycans present on secretory component (SC) play a crucial role in the process. Natural coating may involve specific Gram-positive cell wall components, which may explain selective recognition at the molecular level. More widely, the existence of these complexes is involved in the modulation of intestinal epithelial cell (IEC) responses in vitro and the formation of intestinal biofilms. Thus, SIgA may act as one of the pillars in homeostatic maintenance of the microbiota in the gut, adding yet another facet to its multiple roles in the mucosal environment.

  3. Secretory component delays the conversion of secretory IgA into antigen-binding competent F(ab')2: a possible implication for mucosal defense.

    Science.gov (United States)

    Crottet, P; Corthésy, B

    1998-11-15

    Secretory component (SC) represents the soluble ectodomain of the polymeric Ig receptor, a membrane protein that transports mucosal Abs across epithelial cells. In the protease-rich environment of the intestine, SC is thought to stabilize the associated IgA by unestablished molecular mechanisms. To address this question, we reconstituted SC-IgA complexes in vitro by incubating dimeric IgA (IgAd) with either recombinant human SC (rSC) or SC isolated from human colostral milk (SCm). Both complexes exhibited an identical degree of covalency when exposed to redox agents, peptidyl disulfide isomerase, and temperature changes. In cross-competition experiments, 50% inhibition of binding to IgAd was achieved at approximately 10 nM SC competitor. Western blot analysis of IgAd digested with intestinal washes indicated that the alpha-chain in IgAd was primarily split into a 40-kDa species, a phenomenon delayed in rSC- or SCm-IgAd complexes. In the same assay, either of the SCs was resistant to degradation only if complexed with IgAd. In contrast, the kappa light chain was not digested at all, suggesting that the F(ab')2 region was left intact. Accordingly, IgAd and SC-IgAd digestion products retained functionality as indicated by Ag reactivity in ELISA. Size exclusion chromatography under native conditions of digested IgAd and rSC-IgAd demonstrates that SC exerts its protective role in secretory IgA by delaying cleavage in the hinge/Fc region of the alpha-chain, not by holding together degraded fragments. The function of integral secretory IgA and F(ab')2 is discussed in terms of mucosal immune defenses.

  4. A Comparison of the Beneficial Effects of Live and Heat-Inactivated Baker's Yeast on Nile Tilapia: Suggestions on the Role and Function of the Secretory Metabolites Released from the Yeast

    National Research Council Canada - National Science Library

    Ran, Chao; Huang, Lu; Liu, Zhi; Xu, Li; Yang, Yalin; Tacon, Philippe; Auclair, Eric; Zhou, Zhigang

    2015-01-01

    .... In this study, the involvement and extent to which the viability of yeast cells and thus the secretory metabolites released from the yeast contribute to effects of baker's yeast was investigated in Nile tilapia...

  5. A Comparison of the Beneficial Effects of Live and Heat-Inactivated Baker's Yeast on Nile Tilapia: Suggestions on the Role and Function of the Secretory Metabolites Released from the Yeast: e0145448

    National Research Council Canada - National Science Library

    Chao Ran; Lu Huang; Zhi Liu; Li Xu; Yalin Yang; Philippe Tacon; Eric Auclair; Zhigang Zhou

    2015-01-01

    .... In this study, the involvement and extent to which the viability of yeast cells and thus the secretory metabolites released from the yeast contribute to effects of baker's yeast was investigated in Nile tilapia...

  6. Normal Levels of Urinary CC16 Protein. Comments on Beamer et al. Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. Int. J. Environ. Res. Public Health 2016, 13, 521.

    Directory of Open Access Journals (Sweden)

    Víctor García-Nieto

    2016-10-01

    Full Text Available In 1937, Max Clara described a new type of cell in the human lung, which was later determined to be an exocrine secretory cell type containing granules composed of proteins [1].[...

  7. Mass Spectrometry-Based Neuropeptidomics of Secretory Vesicles from Human Adrenal Medullary Pheochromocytoma Reveals Novel Peptide Products of Prohormone Processing

    OpenAIRE

    Gupta, Nitin; Bark, Steven J.; Lu, Weiya D.; Taupenot, Laurent; O’Connor, Daniel T.; Pevzner, Pavel; Hook, Vivian

    2010-01-01

    Neuropeptides are required for cell-cell communication for the regulation of physiological and pathological processes. While selected neuropeptides of known biological activities have been studied, global analyses of the endogenous profile of human peptide products derived from prohormones by proteolytic processing in vivo is largely unknown. Therefore, this study utilized the global, unbiased approach of mass spectrometry-based neuropeptidomics to define peptide profiles in secretory vesicle...

  8. Diagnostic dilemma of FNA diagnosis of secretory carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Archana C Buch

    2014-01-01

    Full Text Available Secretory carcinoma (SC is one of the least common types of breast carcinoma. The tumor has distinctive histologic features with prominent secretory activity similar to lactational change and minimal nuclear atypia. As the cytomorphologic features of SC overlaps benign breast lesions with lactational change and apocrine change, the initial diagnosis of SC may be missed on cytology in some cases. A 29-year-old woman presented with a lump in the left breast since 9 months. The fine needle aspiration cytology (FNAC suggested proliferative breast disease without atypia. Excision biopsy showed secretory carcinoma. The case is presented to highlight the cytologic features of SC, which may overlap with lactational change and apocrine change.

  9. In silico identification of specialized secretory-organelle proteins in apicomplexan parasites and in vivo validation in Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Zhongqiang Chen

    Full Text Available Apicomplexan parasites, including the human pathogens Toxoplasma gondii and Plasmodium falciparum, employ specialized secretory organelles (micronemes, rhoptries, dense granules to invade and survive within host cells. Because molecules secreted from these organelles function at the host/parasite interface, their identification is important for understanding invasion mechanisms, and central to the development of therapeutic strategies. Using a computational approach based on predicted functional domains, we have identified more than 600 candidate secretory organelle proteins in twelve apicomplexan parasites. Expression in transgenic T. gondii of eight proteins identified in silico confirms that all enter into the secretory pathway, and seven target to apical organelles associated with invasion. An in silico approach intended to identify possible host interacting proteins yields a dataset enriched in secretory/transmembrane proteins, including most of the antigens known to be engaged by apicomplexan parasites during infection. These domain pattern and projected interactome approaches significantly expand the repertoire of proteins that may be involved in host parasite interactions.

  10. Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses

    Directory of Open Access Journals (Sweden)

    Sharp Tyler M

    2012-09-01

    Full Text Available Abstract Background Our previous report that the Norwalk virus nonstructural protein p22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus protein, we examined the effects of p22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. Findings All human noroviruses examined induced Golgi disruption and inhibited protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES motif that is highly conserved in human norovirus homologues of p22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of protein secretion. p22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular protein secretion. Conclusions These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of p22, which may affect viral replication and/or cellular pathogenesis.

  11. Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses.

    Science.gov (United States)

    Sharp, Tyler M; Crawford, Sue E; Ajami, Nadim J; Neill, Frederick H; Atmar, Robert L; Katayama, Kazuhiko; Utama, Budi; Estes, Mary K

    2012-09-03

    Our previous report that the Norwalk virus nonstructural protein p22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. To explore conservation of function of this highly divergent calicivirus protein, we examined the effects of p22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. All human noroviruses examined induced Golgi disruption and inhibited protein secretion, with the genogroup II.4 Houston virus being the most potent antagonist. Genogroup II.6 viruses have a conserved mutation in the mimic of an Endoplasmic Reticulum export signal (MERES) motif that is highly conserved in human norovirus homologues of p22 and is critical for secretory pathway antagonism, and these viruses had reduced levels of Golgi disruption and inhibition of protein secretion. p22 homologues from both persistent and nonpersistent strains of murine norovirus induced Golgi disruption, but only mildly inhibited cellular protein secretion. Feline calicivirus p30 did not induce Golgi disruption or inhibit cellular protein secretion. These differences confirm a norovirus-specific effect on host cell secretory pathway antagonism by homologues of p22, which may affect viral replication and/or cellular pathogenesis.

  12. Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Bao-qiang; YANG Quan-hui; XU Rong-kun; XU Jian-ning

    2013-01-01

    Background Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats.Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells.This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma.Methods In the in vivo study,mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin-and 17-β-estradiol (E2)-treated male rats.In the in vitro study,prolactinoma cells mitochondria were harvested.Activities of the four mitochondrial respiratory complexes were assayed using fluorometer.ATP production of prolactinoma cells was estimated using bioluminescent methods.Results Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells.Moreover,in both in vivo and in vitro studies,melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells.Conclusions There is a link between mitochondrial function increase and tumorigenesis.Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

  13. Identification and cloning of a novel isoform of mouse secretory leukocyte protease inhibitor, mSLPI-beta, overexpressed in murine leukemias and a highly liver metastatic tumor, IMC-HA1 cells.

    Science.gov (United States)

    Morita, M; Arakawa, H; Nishimura, S

    1999-01-01

    Several genes showing transcriptional alteration in a highly liver metastatic murine carcinoma cell line, IMC-HA1, were identified by mRNA differential display system. Among them, a gene identical to mSLPI was isolated as mSLPI-alpha and -beta. They were produced through an alternative splicing. Their full-length cDNA sequences were determined, and their expression in various murine tumors and normal tissues was analysed. The deduced translation product of mSLPI-alpha showed 59% identity to hSLPI. Although mSLPI-beta had the same 103-amino-acid sequence from the carboxyl terminus, the amino terminus showed hydrophilicity opposite mSLPI-alpha or hSLPI. The mSLPI-alpha was expressed ubiquitously in various tumor cell lines. Interestingly, however, mSLPI-beta expression was only observed in P388 and L1210 leukemias and IMC-HA1 cells, and in lower amounts in three normal tissues (thymus, lung and spleen), suggesting that mSLPI, and in particular the unusual splicing product, mSLPI-beta, plays a specific role in these cells, including malignant processes of tumor cells.

  14. Defensins, lectins, mucins, and secretory immunoglobulin A: microbe-binding biomolecules that contribute to mucosal immunity in the human gut.

    Science.gov (United States)

    Chairatana, Phoom; Nolan, Elizabeth M

    2017-02-01

    In the intestine, the mucosal immune system plays essential roles in maintaining homeostasis between the host and microorganisms, and protecting the host from pathogenic invaders. Epithelial cells produce and release a variety of biomolecules into the mucosa and lumen that contribute to immunity. In this review, we focus on a subset of these remarkable host-defense factors - enteric α-defensins, select lectins, mucins, and secretory immunoglobulin A - that have the capacity to bind microbes and thereby contribute to barrier function in the human gut. We provide an overview of the intestinal epithelium, describe specialized secretory cells named Paneth cells, and summarize our current understanding of the biophysical and functional properties of these select microbe-binding biomolecules. We intend for this compilation to complement prior reviews on intestinal host-defense factors, highlight recent advances in the field, and motivate investigations that further illuminate molecular mechanisms as well as the interplay between these molecules and microbes.

  15. Evaluación de la satisfacción del cliente de la Drogueria Villa Clara, 2008-2009 Assessment of the client satisfaction in Villa Clara Drugstore, 2008-2009

    Directory of Open Access Journals (Sweden)

    Geidy Lorezo Monteagudo

    2012-03-01

    Full Text Available Introducción: la Droguería Villa Clara es la encargada de la distribución de medicamentos, reactivos y otros insumos médicos en esta provincia de Cuba. Mantiene relaciones comerciales con gran variedad de clientes, pero los más importantes son los pertenecientes al Sistema de Salud. Objetivo: evaluar la calidad del servicio brindado por esta entidad a los hospitales, policlínicos y farmacias de la provincia durante el 2008 y el 2009. Métodos: se conformó una muestra representativa de estas instituciones en todos los municipios de Villa Clara y se aplicaron encuestas al personal responsable de medicamentos en cada tipo unidad. Se determinó el índice de satisfacción para cada cliente encuestado en particular, así como para policlínicos, hospitales y farmacias en sentido general. Por otra parte, se determinó el índice de satisfacción alcanzado de forma global por la droguería en cada año evaluado. Resultados: el servicio brindado por la Droguería Villa Clara durante el 2008 y el 2009 fue calificado como bueno, con una mejora palpable al obtenerse índices de satisfacción que variaron de 84,2 % en el 2008 a 88,3 % en el 2009. Conclusiones: los clientes del proceso de distribución de medicamentos, perciben la disponibilidad de medicamentos como el problema fundamental de la distribución en la provincia.Introduction: Villa Clara Drugstore is in charge of the distribution of drugs, reagents, and other medical inputs in this Cuban province. It has commercial relations with a wide variety of clients, but the most important ones are those within the health system. Objective: to evaluate the quality of service rendered by this entity to hospitals, polyclinics and pharmacies in the province in 2008 and 2009. Methods: a representative sample from these institutions in all Villa Clara municipalities was selected and the personnel in charge of medications in each unit was surveyed. Satisfaction index for each surveyed client was

  16. Extended High Frequency Audiometry in Secretory Otitis Media

    OpenAIRE

    Sharma, Deepika; Munjal, Sanjay K.; Panda, Naresh K.

    2012-01-01

    The objective of the present study was to determine the status of extended high frequencies in subjects with secretory otitis media. The study evaluated 30 ears of 20 subjects with secretory otitis media in the age group of 15–30 years. This data was compared with 20 ears of 10 volunteers of the same age group with clinically normal hearing. Pure tone air conduction thresholds were analyzed in three frequency groups: low frequency (LF: 0.25, 0.5, and 1 kHz), high frequency (HF: 2, 4, and 8 kH...

  17. A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis

    Directory of Open Access Journals (Sweden)

    Howells David W

    2009-09-01

    Full Text Available Abstract Background Phospholipase A2 liberates free fatty acids and lysophospholipids upon hydrolysis of phospholipids and these products are often associated with detrimental effects such as inflammation and cerebral ischemia. The neuroprotective effect of neutral phospholipase from snake venom has been investigated. Results A neutral anticoagulant secretory phospholipase A2 (nPLA from the venom of Naja sputatrix (Malayan spitting cobra has been found to reduce infarct volume in rats subjected to focal transient cerebral ischemia and to alleviate the neuronal damage in organotypic hippocampal slices subjected to oxygen-glucose deprivation (OGD. Real-time PCR based gene expression analysis showed that anti-apoptotic and pro-survival genes have been up-regulated in both in vivo and in vitro models. Staurosporine or OGD mediated apoptotic cell death in astrocytoma cells has also been found to be reduced by nPLA with a corresponding reduction in caspase 3 activity. Conclusion We have found that a secretory phospholipase (nPLA purified from snake venom could reduce infarct volume in rodent stroke model. nPLA, has also been found to reduce neuronal cell death, apoptosis and promote cell survival in vitro ischemic conditions. In all conditions, the protective effects could be seen at sub-lethal concentrations of the protein.

  18. Early secretory antigenic target protein-6/culture filtrate protein-10 fusion protein-specific Th1 and Th2 response and its diagnostic value in tuberculous pleural effusion

    Institute of Scientific and Technical Information of China (English)

    戈启萍

    2013-01-01

    Objective To detect the Th1 and Th2 cell percentage in pleural effusion mononuclear cells (PEMCs) stimulated by early secretory antigenic target protein-6 (ESAT-6) /culture filtrate protein-10 (CFP-10) fusion protein (E/C) with flow cytometry (FCM) ,and to explore the local antigen specific Th1 and Th2 response and

  19. [Ultrastructure of the "rudimentary secretory photoreceptors" (RSP) of the embryonic pineal body of Lacerta vivipara J. (Reptilia, Lacertilia) and the origin of the RSP of Sauropsida].

    Science.gov (United States)

    Meiniel, A

    1975-10-20

    The "secretory rudimentary photoreceptor-cells" of Lacerta vivipara J., during embryonic stages, exhibit photosensory differentiations (disks). Our ontogenetic observations agree with the phylogenetic studies and support the concept of a "sensory cell line" (Colin, 1969) in the pineal organ of vertebrates.

  20. IL-1β expression in the distal lung epithelium disrupts lung morphogenesis and epithelial cell differentiation in fetal mice.

    Science.gov (United States)

    Hogmalm, Anna; Bry, Maija; Strandvik, Birgitta; Bry, Kristina

    2014-01-01

    Perinatal inflammation and the inflammatory cytokine IL-1 can modify lung morphogenesis. To examine the effects of antenatal expression of IL-1β in the distal airway epithelium on fetal lung morphogenesis, we studied lung development and surfactant expression in fetal mice expressing human IL-1β under the control of the surfactant protein (SP)-C promoter. IL-1β-expressing pups suffered respiratory failure and died shortly after birth. IL-1β caused fetal lung inflammation and enhanced the expression of keratinocyte-derived chemokine (KC/CXCL1) and monocyte chemoattractant protein 3 (MCP-3/CCL7), the calgranulins S100A8 and S100A9, the acute-phase protein serum amyloid A3, the chitinase-like proteins Ym1 and Ym2, and pendrin. IL-1β decreased the percentage of the total distal lung area made up of air saccules and the number of air saccules in the lungs of fetal mice. IL-1β inhibited the expression of VEGF-A and its receptors VEGFR-1 and VEGFR-2. The percentage of the cellular area of the distal lung made up of capillaries was decreased in IL-1β-expressing fetal mice. IL-1β suppressed the production of SP-B and pro-SP-C and decreased the amount of phosphatidylcholine and the percentage of palmitic acid in the phosphatidylcholine fraction of lung phospholipids, indicating that IL-1β prevented the differentiation of type II epithelial cells. The production of Clara cell secretory protein in the nonciliated bronchiolar (Clara) cells was likewise suppressed by IL-1β. In conclusion, expression of IL-1β in the epithelium of the distal airways disrupted the development of the airspaces and capillaries in the fetal lung and caused fatal respiratory failure at birth.

  1. Secretory Carcinoma of the Breast: Report of Two Cases and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Vivekanand Sharma

    2015-01-01

    Full Text Available Secretory carcinoma of the breast is an extremely rare subtype of breast cancer characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. The disease which was considered to be predominant in younger age group has been recognized in adult population too and tends to show slow growth and indolent behavior. The disease occurs preferentially in females and only 27 cases have been reported amongst males. An optimal treatment for the disease subtype has been debated because of the paucity of data. We report two cases (one female and one male of this rare disease that underwent treatment at our institution.

  2. Secretory Carcinoma of the Breast: Report of Two Cases and Review of the Literature

    Science.gov (United States)

    Sharma, Vivekanand; Anuragi, Gajendra; Singh, Suresh; Patel, Pinakin; Jindal, Arpita; Sharma, Raj Govind

    2015-01-01

    Secretory carcinoma of the breast is an extremely rare subtype of breast cancer characterized by intracellular or extracellular secretion and granular eosinophilic cytoplasm of the neoplastic cells. The disease which was considered to be predominant in younger age group has been recognized in adult population too and tends to show slow growth and indolent behavior. The disease occurs preferentially in females and only 27 cases have been reported amongst males. An optimal treatment for the disease subtype has been debated because of the paucity of data. We report two cases (one female and one male) of this rare disease that underwent treatment at our institution. PMID:26236516

  3. E-cadherin can replace N-cadherin during secretory-stage enamel development.

    Science.gov (United States)

    Guan, Xiaomu; Bidlack, Felicitas B; Stokes, Nicole; Bartlett, John D

    2014-01-01

    N-cadherin is a cell-cell adhesion molecule and deletion of N-cadherin in mice is embryonic lethal. During the secretory stage of enamel development, E-cadherin is down-regulated and N-cadherin is specifically up-regulated in ameloblasts when groups of ameloblasts slide by one another to form the rodent decussating enamel rod pattern. Since N-cadherin promotes cell migration, we asked if N-cadherin is essential for ameloblast cell movement during enamel development. The enamel organ, including its ameloblasts, is an epithelial tissue and for this study a mouse strain with N-cadherin ablated from epithelium was generated. Enamel from wild-type (WT) and N-cadherin conditional knockout (cKO) mice was analyzed. μCT and scanning electron microscopy showed that thickness, surface structure, and prism pattern of the cKO enamel looked identical to WT. No significant difference in hardness was observed between WT and cKO enamel. Interestingly, immunohistochemistry revealed the WT and N-cadherin cKO secretory stage ameloblasts expressed approximately equal amounts of total cadherins. Strikingly, E-cadherin was not normally down-regulated during the secretory stage in the cKO mice suggesting that E-cadherin can compensate for the loss of N-cadherin. Previously it was demonstrated that bone morphogenetic protein-2 (BMP2) induces E- and N-cadherin expression in human calvaria osteoblasts and we show that the N-cadherin cKO enamel organ expressed significantly more BMP2 and significantly less of the BMP antagonist Noggin than did WT enamel organ. The E- to N-cadherin switch at the secretory stage is not essential for enamel development or for forming the decussating enamel rod pattern. E-cadherin can substitute for N-cadherin during these developmental processes. Bmp2 expression may compensate for the loss of N-cadherin by inducing or maintaining E-cadherin expression when E-cadherin is normally down-regulated. Notably, this is the first demonstration of a natural endogenous

  4. E-cadherin can replace N-cadherin during secretory-stage enamel development.

    Directory of Open Access Journals (Sweden)

    Xiaomu Guan

    Full Text Available BACKGROUND: N-cadherin is a cell-cell adhesion molecule and deletion of N-cadherin in mice is embryonic lethal. During the secretory stage of enamel development, E-cadherin is down-regulated and N-cadherin is specifically up-regulated in ameloblasts when groups of ameloblasts slide by one another to form the rodent decussating enamel rod pattern. Since N-cadherin promotes cell migration, we asked if N-cadherin is essential for ameloblast cell movement during enamel development. METHODOLOGY/PRINCIPAL FINDINGS: The enamel organ, including its ameloblasts, is an epithelial tissue and for this study a mouse strain with N-cadherin ablated from epithelium was generated. Enamel from wild-type (WT and N-cadherin conditional knockout (cKO mice was analyzed. μCT and scanning electron microscopy showed that thickness, surface structure, and prism pattern of the cKO enamel looked identical to WT. No significant difference in hardness was observed between WT and cKO enamel. Interestingly, immunohistochemistry revealed the WT and N-cadherin cKO secretory stage ameloblasts expressed approximately equal amounts of total cadherins. Strikingly, E-cadherin was not normally down-regulated during the secretory stage in the cKO mice suggesting that E-cadherin can compensate for the loss of N-cadherin. Previously it was demonstrated that bone morphogenetic protein-2 (BMP2 induces E- and N-cadherin expression in human calvaria osteoblasts and we show that the N-cadherin cKO enamel organ expressed significantly more BMP2 and significantly less of the BMP antagonist Noggin than did WT enamel organ. CONCLUSIONS/SIGNIFICANCE: The E- to N-cadherin switch at the secretory stage is not essential for enamel development or for forming the decussating enamel rod pattern. E-cadherin can substitute for N-cadherin during these developmental processes. Bmp2 expression may compensate for the loss of N-cadherin by inducing or maintaining E-cadherin expression when E-cadherin is

  5. Subsurface and petroleum geology of the southwestern Santa Clara Valley ("Silicon Valley"), California

    Science.gov (United States)

    Stanley, Richard G.; Jachens, Robert C.; Lillis, Paul G.; McLaughlin, Robert J.; Kvenvolden, Keith A.; Hostettler, Frances D.; McDougall, Kristin A.; Magoon, Leslie B.

    2002-01-01

    Gravity anomalies, historical records of exploratory oil wells and oil seeps, new organic-geochemical results, and new stratigraphic and structural data indicate the presence of a concealed, oil-bearing sedimentary basin beneath a highly urbanized part of the Santa Clara Valley, Calif. A conspicuous isostatic-gravity low that extends about 35 km from Palo Alto southeastward to near Los Gatos reflects an asymmetric, northwest-trending sedimentary basin comprising low-density strata, principally of Miocene age, that rest on higher-density rocks of Mesozoic and Paleogene(?) age. Both gravity and well data show that the low-density rocks thin gradually to the northeast over a distance of about 10 km. The thickest (approx 4 km thick) accumulation of low-density material occurs along the basin's steep southwestern margin, which may be controlled by buried, northeast-dipping normal faults that were active during the Miocene. Movement along these hypothetical normal faults may been contemporaneous (approx 17–14 Ma) with sedimentation and local dacitic and basaltic volcanism, possibly in response to crustal extension related to passage of the northwestward-migrating Mendocino triple junction. During the Pliocene and Quaternary, the normal faults and Miocene strata were overridden by Mesozoic rocks, including the Franciscan Complex, along northeastward-vergent reverse and thrust faults of the Berrocal, Shannon, and Monte Vista Fault zones. Movement along these fault zones was accompanied by folding and tilting of strata as young as Quaternary and by uplift of the modern Santa Cruz Mountains; the fault zones remain seismically active. We attribute the Pliocene and Quaternary reverse and thrust faulting, folding, and uplift to compression caused by local San Andreas Fault tectonics and regional transpression along the Pacific-North American Plate boundary. Near the southwestern margin of the Santa Clara Valley, as many as 20 exploratory oil wells were drilled between 1891

  6. SRTM Perspective View with Landsat Overlay: Santa Paula, and Santa Clara River Valley, California

    Science.gov (United States)

    2000-01-01

    Rectangular fields of the agriculturally rich Santa Clara River Valley are visible in this perspective view generated using data from the Shuttle Radar Topography Mission and an enhanced Landsat image. The Santa Clara River, which lends its name to this valley, flows from headwaters near Acton, California, 160 km (100 miles) to the Pacific Ocean, and is one of only two natural river systems remaining in southern California. In the foreground of this image, the largely dry riverbed can be seen as a bright feature as it winds its way along the base of South Mountain. The bright region at the right end of this portion of the valley is the city of Santa Paula, California. Founded in 1902, this small, picturesque town at the geographic center of Ventura County is referred to as the 'Citrus Capital of the World.' The city is surrounded by orange, lemon, and avocado groves and is a major distribution point for citrus fruits in the United States. The bright, linear feature in the center of the valley is State Highway 126, the valley's 'main drag.' For visualization purposes, topographic heights displayed in this image are exaggerated two times. Colors, from Landsat data, approximate natural color.The elevation data used in this image was acquired by SRTM aboard the Space Shuttle Endeavour, launched on February 11, 2000. SRTM used the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) that flew twice on Endeavour in 1994. SRTM was designed to collect three-dimensional measurements of Earth's land surface. To collect the 3-D SRTM data, engineers added a mast 60 meters (about 200 feet)long, installed additional C-band and X-band antennas, and improved tracking and navigation devices. The mission is a cooperative project between the NASA, the National Imagery and Mapping Agency (NIMA) of the U.S. Department of Defense, and the German and Italian space agencies. It is managed by NASA's Jet Propulsion Laboratory

  7. Genome-scale modeling of the protein secretory machinery in yeast.

    Science.gov (United States)

    Feizi, Amir; Österlund, Tobias; Petranovic, Dina; Bordel, Sergio; Nielsen, Jens

    2013-01-01

    The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lacking. Here, we present the first genome-scale model for the yeast secretory machinery which captures the knowledge generated through more than 50 years of research. The model is based on the concept of a Protein Specific Information Matrix (PSIM: characterized by seven PTMs features). An algorithm was developed which mimics secretory machinery and assigns each secretory protein to a particular secretory class that determines the set of PTMs and transport steps specific to each protein. Protein abundances were integrated with the model in order to gain system level estimation of the metabolic demands associated with the processing of each specific protein as well as a quantitative estimation of the activity of each component of the secretory machinery.

  8. Secretory glands and microvascular systems imaged in aqueous solution by atmospheric scanning electron microscopy (ASEM).

    Science.gov (United States)

    Yamazawa, Toshiko; Nakamura, Naotoshi; Sato, Mari; Sato, Chikara

    2016-12-01

    Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.g., pancreatic islets, secrete hormones that regulate blood glucose levels. The dysfunction of these secretory organs immediately leads to various diseases, such as diabetes or Sjögren's syndrome, by poorly understood mechanisms. Gland-related diseases have been studied by optical microscopy (OM), and at higher resolution by transmission electron microscopy (TEM) of Epon embedded samples, which necessitates hydrophobic sample pretreatment. Here, we report the direct observation of tissue in aqueous solution by atmospheric scanning electron microscopy (ASEM). Salivary glands, lacrimal glands, and pancreas were fixed, sectioned into slabs, stained with phosphotungstic acid (PTA), and inspected in radical scavenger d-glucose solution from below by an inverted scanning electron microscopy (SEM), guided by optical microscopy from above to target the tissue substructures. A 2- to 3-µm specimen thickness was visualized by the SEM. In secretory cells, cytoplasmic vesicles and other organelles were clearly imaged at high resolution, and the former could be classified according to the degree of PTA staining. In islets of Langerhans, the microvascular system used as an outlet by the secretory cells was also clearly observed. Microvascular system is also critically involved in the onset of diabetic complications and was clearly visible in subcutaneous tissue imaged by ASEM. The results suggest the use of in-solution ASEM for histology and to study vesicle secretion systems. Further, the high-throughput of ASEM makes it a potential tool for the diagnosis of exocrine and endocrine-related diseases.

  9. Mechanism of action of magnesium on acetylcholine-evoked secretory responses in isolated rat pancreas.

    Science.gov (United States)

    Francis, L P; Lennard, R; Singh, J

    1990-09-01

    This study investigates the effects of magnesium (Mg2+) on acetylcholine (ACh)-evoked secretory responses and calcium (Ca2+) mobilization in the isolated rat pancreas. ACh induced marked dose-dependent increases in total protein output and amylase release from superfused pancreatic segments in zero, normal (1 x 1 mM) and elevated (10 mM) extracellular Mg2+. Elevated Mg2+ attenuated the ACh-evoked secretory responses compared to zero and normal Mg2+. In the absence of extracellular Ca2+, but presence of 1 mM-EGTA (ethylene glycol bis(beta-aminoethylether)-N,N,N',N''-tetraacetic acid), ACh elicited a small transient release of protein from pancreatic segments compared to a larger and more sustained secretion in the absence of both Ca2+ and Mg2+. Incubation of pancreatic segments with 45Ca2+ resulted in time-dependent uptake with maximum influx of 45Ca2+ occurring after 20 min of incubation period. ACh stimulated markedly the 45Ca2+ uptake compared to control tissues. In elevated extracellular Mg2+ the ACh-induced 45Ca2+ influx was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. ACh also evoked dose-dependent increases in cytosolic free Ca2+ concentrations ([Ca2+]i) in pancreatic acinar cells loaded with the fluorescent dye Fura-2 AM. In elevated Mg2+ the ACh-induced cytosolic [Ca2+]i was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. These results indicate that Mg2+ can influence ACh-evoked secretory responses possibly by controlling both Ca2+ influx and release in pancreatic acinar cells.

  10. Generic sorting of raft lipids into secretory vesicles in yeast

    DEFF Research Database (Denmark)

    Surma, Michal A; Klose, Christian; Klemm, Robin W;

    2011-01-01

    a complete lipid overview of the yeast late secretory pathway. We could show that vesicles captured with different baits carry the same cargo and have almost identical lipid compositions; being highly enriched in ergosterol and sphingolipids. This finding indicates that lipid raft sorting is a generic...... feature of vesicles carrying PM cargo and suggests a common lipid-based mechanism for their formation....

  11. Plant expression of chicken secretory antibodies derived from combinatorial libraries

    NARCIS (Netherlands)

    Wieland, W.H.; Lammers, A.; Schots, A.; Orzaéz, D.V.

    2006-01-01

    Delivery of secretory IgA antibodies (sIgA) to mucosal surfaces is a promising strategy to passively prevent infectious diseases. Plants have been proposed as biofactories for such complex immunoglobulin molecules. Recently, the molecular characterization of all four monomers of chicken sIgA (IgA im

  12. Plant expression of chicken secretory antibodies derived from combinatorial libraries

    NARCIS (Netherlands)

    Wieland, W.H.; Lammers, A.; Schots, A.; Orzaéz, D.V.

    2006-01-01

    Delivery of secretory IgA antibodies (sIgA) to mucosal surfaces is a promising strategy to passively prevent infectious diseases. Plants have been proposed as biofactories for such complex immunoglobulin molecules. Recently, the molecular characterization of all four monomers of chicken sIgA (IgA

  13. Proteolytic processing in the secretory pathway of Aspergillus niger

    NARCIS (Netherlands)

    Jalving, R.

    2005-01-01

    A number of filamentous fungi are saprophytes and they secrete a wide spectrum of enzymes to degrade their complex substrates. Many secreted proteins enter the secretory pathway as proproteins and need some form of proteolytic processing before they obtain their mature active state. As described in

  14. Proteolytic processing in the secretory pathway of Aspergillus niger

    NARCIS (Netherlands)

    Jalving, R.

    2005-01-01

    A number of filamentous fungi are saprophytes and they secrete a wide spectrum of enzymes to degrade their complex substrates. Many secreted proteins enter the secretory pathway as proproteins and need some form of proteolytic processing before they obtain their mature active state. As described in

  15. Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clea

  16. Secretory ribonucleases in the primitive ruminant chevrotain (Tragulus javanicus)

    NARCIS (Netherlands)

    Breukelman, HJ; Jekel, PA; Dubois, JYF; Mulder, PPMFA; Warmels, HW; Beintema, JJ

    2001-01-01

    Phylogenetic analyses of secretory ribonucleases or RNases 1 have shown that gene duplication events, giving rise to three paralogous genes (pancreatic, seminal and brain RNase), occurred during the evolution of ancestral ruminants. A higher number of paralogous sequences are present in chevrotain (

  17. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2012-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +\\/- 2.6 and 38.8 +\\/- 6.7% (n=16; P<\\/=0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  18. Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.

    LENUS (Irish Health Repository)

    Ward, Joseph B J

    2011-02-01

    Hydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 ± 2.6 and 38.8 ± 6.7% (n=16; P≤0.001) of those in control cells, respectively. Antisecretory actions of DMOG were time and concentration dependent, being maximal after 18 h of DMOG (1 mM) treatment. DMOG specifically inhibited Na(+)\\/K(+)-ATPase pump activity without altering its expression or membrane localization. In mice, DMOG inhibited agonist-induced secretory responses ex vivo and prevented allergic diarrhea in vivo. In conclusion, hydroxylases are important regulators of epithelial Cl(-) and fluid secretion and present a promising target for development of new drugs to treat transport disorders.

  19. Neuronal porosome - The secretory portal at the nerve terminal: Its structure-function, composition, and reconstitution

    Science.gov (United States)

    Jena, Bhanu P.

    2014-09-01

    Cup-shaped secretory portals at the cell plasma membrane called porosomes mediate secretion from cells. Membrane bound secretory vesicles transiently dock and fuse at the cytosolic compartment of the porosome base to expel intravesicular contents to the outside during cell secretion. In the past decade, the structure, isolation, composition, and functional reconstitution of the neuronal porosome complex has been accomplished providing a molecular understanding of its structure-function. Neuronal porosomes are 15 nm cup-shaped lipoprotein structures composed of nearly 40 proteins; compared to the 120 nm nuclear pore complex comprised of over 500 protein molecules composed of 30 different proteins. Being a membrane-associated supramolecular complex has precluded determination of the atomic structure of the porosome. However recent studies using small-angle X-ray solution scattering (SAXS), provide at sub-nanometer resolution, the native 3D structure of the neuronal porosome complex associated with docked synaptic vesicle at the nerve terminal. Additionally, results from the SAXS study and earlier studies using atomic force microscopy, provide the possible molecular mechanism involved in porosome-mediated neurotransmitter release at the nerve terminal.

  20. Mass spectrometry-based neuropeptidomics of secretory vesicles from human adrenal medullary pheochromocytoma reveals novel peptide products of prohormone processing.

    Science.gov (United States)

    Gupta, Nitin; Bark, Steven J; Lu, Weiya D; Taupenot, Laurent; O'Connor, Daniel T; Pevzner, Pavel; Hook, Vivian

    2010-10-01

    Neuropeptides are required for cell-cell communication in the regulation of physiological and pathological processes. While selected neuropeptides of known biological activities have been studied, global analyses of the endogenous profile of human peptide products derived from prohormones by proteolytic processing in vivo are largely unknown. Therefore, this study utilized the global, unbiased approach of mass spectrometry-based neuropeptidomics to define peptide profiles in secretory vesicles, isolated from human adrenal medullary pheochromocytoma of the sympathetic nervous system. The low molecular weight pool of secretory vesicle peptides was subjected to nano-LC-MS/MS with ion trap and QTOF mass spectrometry analyzed by different database search tools (InsPecT and Spectrum Mill). Peptides were generated by processing of prohormones at dibasic cleavage sites as well as at nonbasic residues. Significantly, peptide profiling provided novel insight into newly identified peptide products derived from proenkephalin, pro-NPY, proSAAS, CgA, CgB, and SCG2 prohormones. Previously unidentified intervening peptide domains of prohormones were observed, thus providing new knowledge of human neuropeptidomes generated from precursors. The global peptidomic approach of this study demonstrates the complexity of diverse neuropeptides present in human secretory vesicles for cell-cell communication.

  1. Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.

    Science.gov (United States)

    Hood, Brian L; Liu, Baoquan; Alkhas, Addie; Shoji, Yutaka; Challa, Rusheeswar; Wang, Guisong; Ferguson, Susan; Oliver, Julie; Mitchell, Dave; Bateman, Nicholas W; Zahn, Christopher M; Hamilton, Chad A; Payson, Mark; Lessey, Bruce; Fazleabas, Asgerally T; Maxwell, G Larry; Conrads, Thomas P; Risinger, John I

    2015-04-01

    Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

  2. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma.

    Science.gov (United States)

    Bishop, Justin A; Yonescu, Raluca; Batista, Denise; Begum, Shahnaz; Eisele, David W; Westra, William H

    2013-10-01

    Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.

  3. Genome-scale modeling of the protein secretory machinery in yeast

    DEFF Research Database (Denmark)

    Feizi, Amir; Österlund, Tobias; Petranovic, Dina;

    2013-01-01

    The protein secretory machinery in Eukarya is involved in post-translational modification (PTMs) and sorting of the secretory and many transmembrane proteins. While the secretory machinery has been well-studied using classic reductionist approaches, a holistic view of its complex nature is lackin...

  4. Land subsidence in the Santa Clara Valley, California as of 1980

    Science.gov (United States)

    Poland, J.F.; Ireland, R.L.

    1984-01-01

    From 1916 to 1966 in the San Jose area of Santa Clara Valley, California, deficient rainfall and runoff was accompanied by a fourfold increase in groundwater withdrawals. In response the artesian head declined 180-240 ft. The land surface subsided 12.7 ft in San Jose, due to compaction of the fine-grained compressible beds. The subsidence resulted in flooding of lands, and the compaction of the sediments caused compressional failure of many well casings. From 1967 to 1975, the artesian head recovered 70 to 100 feet due to a fivefold increase in surface water imports, favorable local water supply, decreased withdrawal, and increased recharge. In 1960, the Geological Survey installed extensometers in core holes 1,000 ft deep in San Jose and Sunnyvale. Measurements of compaction of the confined aquifer system obtained from these extensometers demonstrate the marked decrease in rate of compaction in response to the major head recovery since 1967. In San Jose the rate decreased from about 1 ft/yr in 1961 to 0.1 ft/yr in 1973. The subsidence has been stopped by raising the artesian head in the aquifers until it equaled or exceeded the maximum pore pressures in the fine-grained beds. However, the subsidence will recommence if the artesian head is drawn down appreciably below the levels of 1971-73. (USGS)

  5. Osmotic Effect of Conditioning on Seeds of Tomato (Solanum Lycopersicum L. Santa Clara Variety

    Directory of Open Access Journals (Sweden)

    Brigitte Liliana Moreno Medina

    2013-12-01

    Full Text Available The tomato (Solanum lycopersicum L. is one of the most important vegetables in the world, taking into account its nutritional potential and high economic value. In this crop the quality of seed depends on various factors, one of which is its physiology, which is determined by a germination and viability test. Osmotic seed conditioning is reported to be a technique for improving the physiological quality through the uniformity of the germination percentage. For this reason, the objective of this research was to evaluate the osmotic conditioning on tomato seeds of the Santa Clara variety. Using treatments of four doses of potassium nitrate (0, 100, 200 and 400 mg L-1 , the seeds were imbibitioned for 24 hours in solution and then washed with distilled water. They were placed in petri dishes in random order with three replications for a total of 12 experimental units, consisting of 35 seeds. The method seeks to hydrate the seeds with a solution of given concentration and for a period of time, in order to activate the seed metabolism. The best result was obtained with the treatment of 200 mg L-1 of potassium nitrate, followed by 400 mg L-1 , represented by a lower TMG , lower and higher PG VMG.

  6. Chromium geochemistry of serpentinous sediment in the Willow core, Santa Clara County, California

    Science.gov (United States)

    Oze, Christopher J.; LaForce, Matthew J.; Wentworth, Carl M.; Hanson, Randall T.; Bird, Dennis K.; Coleman, Robert G.

    2003-01-01

    A preliminary investigation of Cr geochemistry in serpentinous sediment completed for a multiple-aquifer ground-water monitoring well (Willow core of Santa Clara County, CA) determined sediment at depths >225 meters contains Cr concentrations ranging from 195 to 1155 mg/kg. Serpentinous sediment from this site is a potential source of non-anthropogenic Cr contamination. Chromium-bearing minerals such as Cr-spinel appear to be the main source of Cr in the sediment; however, Cr-bearing silicates and clay minerals are additional Cr sources. Aqueous Cr concentrations in the sediment are <4.6 mg/L; however, the valence of Cr was not identified in the solutions or in the sediment. Although there is no indication of Cr(VI) contamination derived from the serpentinous sediment, elevated Cr concentrations in the sediment, the observed ‘dissolution’ textures of the Cr-bearing minerals, the estimated redox environment, and water chemistry indicate the formation of Cr(VI) is potentially favorable.

  7. Seasonal trends of atmospheric nitrogen dioxide and sulfur dioxide over North Santa Clara, Cuba.

    Science.gov (United States)

    Alejo, Daniellys; Morales, Mayra C; de la Torre, Jorge B; Grau, Ricardo; Bencs, László; Van Grieken, René; Van Espen, Piet; Sosa, Dismey; Nuñez, Vladimir

    2013-07-01

    Atmospheric nitrogen dioxide (NO2) and sulfur dioxide (SO2) levels were monitored simultaneously by means of Radiello passive samplers at six sites of Santa Clara city, Cuba, in the cold and the warm seasons in 2010. The dissolved ionic forms of NO2 and SO2 as nitrate and sulfite plus sulfate, respectively, were determined by means of ion chromatography. Analysis of NO2 as nitrite was also performed by UV-Vis spectrophotometry. For NO2, significant t tests show good agreement between the results of IC and UV-Vis methods. The NO2 and SO2 concentrations peaked in the cold season, while their minimum levels were experienced in the warm season. The pollutant levels do not exceed the maximum allowable limit of the Cuban Standard 39:1999, i.e., 40 μg/m(3) and 50 μg/m(3) for NO2 and SO2, respectively. The lowest pollutant concentrations obtained in the warm season can be attributed to an increase in their removal via precipitation (scavenging) while to the decreased traffic density and industrial emission during the summer holidays (e.g., July and August).

  8. The Ecological Footprint of the Agrarian Sector in Villa Clara. A qualitative approximation

    Directory of Open Access Journals (Sweden)

    Mario Reinoso Pérez

    2015-01-01

    Full Text Available This research deals with the environmental impacts and aspects and their relationship to the ecological footprint of the agrarian sector in Villa Clara. In order to achieve this goal, 23 enterprises were used as study cases, which were clustered according to the main land use: (i succession planting (17 and (ii livestock and animal production (6. The information collected was used to develop the environmental aspects and impacts matrixes associated to the productive processes in each enterprise. The environmental aspects with higher relative frequencies (> 0.60 were water and energy consumption, the existence of invasive plants, the soil use, the greenhouse gas emissions, the use of forest resources, the generation of solid wastes and the use of agro-chemicals. Such aspects are causing negative impacts on the environment, and consequently they are increasing the ecological print of the sector in this province. The use of heavy machineries, the generation of liquid and dangerous residues, the continuous grazing and the use of alien species had a significant impact with a relative frequency below 0.55. However, these environmental aspects should be under control. It is concluded that, in all of the studied cases, the environmental aspects had a negative incidence on the environment. And they contribute in many ways to increase the ecological footprint of the agrarian sector in the territory. The implementation of the Environmental Management System, according to the international standards, is recommended.

  9. The role of cysteine-rich secretory proteins in male fertility

    Institute of Scientific and Technical Information of China (English)

    Adam J Koppers; Thulasimala Reddy; Moira K O'Bryan

    2011-01-01

    The cysteine-rich secretory proteins(CRISPs)are a subgroup of the CRISP,antigen 5 and Pr-1(CAP)protein superfamily,and are found only in vertebrates.They show a strong expression bias to the mammalian male reproductive tract and the venom of poisonous reptiles.Within the male reproductive tract CRISPs have been implicated in many aspects of male germ cell biology spanning haploid germ cell development,epididymal maturation,capacitation,motility and the actual processes of fertilization.At a structural level,CRISPs are composed of two domains,a CAP domain,which has been implicated in cell-cell adhesion,and a CRISP domain,which has been shown to regulate several classes of ion channels across multiple species.Herein,we will review the current literature on the role of CRISPs in male fertility,and by inference to related non-mammalian protein,infer potential biochemical functions.

  10. Field-trip guide to the southeastern foothills of the Santa Cruz Mountains in Santa Clara County, California

    Science.gov (United States)

    Stoffer, Philip W.; Messina, Paula

    2002-01-01

    This field trip is an introduction to the geology of the southeastern foothills of the Santa Cruz Mountains in southern Santa Clara County. Seven stops include four short hikes to access rock exposures and views of the foothills east of Loma Prieta Peak between Gilroy and San José. Field-trip destinations highlight the dominant rock types of the "Franciscan assemblage" including outcrops of serpentinite, basalt, limestone, ribbon chert, graywacke sandstone, and shale. General discussions include how the rocks formed, and how tectonism and stream erosion have changed the landscape through time. All field trip stops are on public land; most are near reservoir dams of the Santa Clara Valley Water District. In addition, stops include examination of an Ohlone Indian heritage site and the New Almaden Mining Museum.

  11. The primitives of Santa Clara of Ubeda: stylistic and iconographic study, critical appraisals and vicissitudes of a dispersed heritage

    Directory of Open Access Journals (Sweden)

    Clara Beltrán Catalán

    2016-12-01

    Full Text Available The authors study the stylistic and iconographic aspects of a collection of paintings on wood dating from the 15th and 16th centuries, originally in the Royal Monastery of Santa Clara at Úbeda. This collection was sold in the 1920s with the participation of the antique dealer Celestino Dupont. The research is complemented by an analysis of the critical appraisals given to these works and their history since their introduction into the art market.

  12. Modeling and validation of a 3D velocity structure for the Santa Clara Valley, California, for seismic-wave simulations

    Science.gov (United States)

    Hartzell, S.; Harmsen, S.; Williams, R.A.; Carver, D.; Frankel, A.; Choy, G.; Liu, P.-C.; Jachens, R.C.; Brocher, T.M.; Wentworth, C.M.

    2006-01-01

    A 3D seismic velocity and attenuation model is developed for Santa Clara Valley, California, and its surrounding uplands to predict ground motions from scenario earthquakes. The model is developed using a variety of geologic and geophysical data. Our starting point is a 3D geologic model developed primarily from geologic mapping and gravity and magnetic surveys. An initial velocity model is constructed by using seismic velocities from boreholes, reflection/refraction lines, and spatial autocorrelation microtremor surveys. This model is further refined and the seismic attenuation is estimated through waveform modeling of weak motions from small local events and strong-ground motion from the 1989 Loma Prieta earthquake. Waveforms are calculated to an upper frequency of 1 Hz using a parallelized finite-difference code that utilizes two regions with a factor of 3 difference in grid spacing to reduce memory requirements. Cenozoic basins trap and strongly amplify ground motions. This effect is particularly strong in the Evergreen Basin on the northeastern side of the Santa Clara Valley, where the steeply dipping Silver Creek fault forms the southwestern boundary of the basin. In comparison, the Cupertino Basin on the southwestern side of the valley has a more moderate response, which is attributed to a greater age and velocity of the Cenozoic fill. Surface waves play a major role in the ground motion of sedimentary basins, and they are seen to strongly develop along the western margins of the Santa Clara Valley for our simulation of the Loma Prieta earthquake.

  13. SLAH3-type anion channel expressed in poplar secretory epithelia operates in calcium kinase CPK-autonomous manner.

    Science.gov (United States)

    Jaborsky, Mario; Maierhofer, Tobias; Olbrich, Andrea; Escalante-Pérez, María; Müller, Heike M; Simon, Judy; Krol, Elzbieta; Cuin, Tracey Ann; Fromm, Jörg; Ache, Peter; Geiger, Dietmar; Hedrich, Rainer

    2016-05-01

    Extrafloral nectaries secrete a sweet sugar cocktail that lures predator insects for protection from foraging herbivores. Apart from sugars and amino acids, the nectar contains the anions chloride and nitrate. Recent studies with Populus have identified a type of nectary covered by apical bipolar epidermal cells, reminiscent of the secretory brush border epithelium in animals. Border epithelia operate transepithelial anion transport, which is required for membrane potential and/or osmotic adjustment of the secretory cells. In search of anion transporters expressed in extrafloral nectaries, we identified PttSLAH3 (Populus tremula × Populus tremuloides SLAC1 Homologue3), an anion channel of the SLAC/SLAH family. When expressed in Xenopus oocytes, PttSLAH3 displayed the features of a voltage-dependent anion channel, permeable to both nitrate and chloride. In contrast to the Arabidopsis SLAC/SLAH family members, the poplar isoform PttSLAH3 is independent of phosphorylation activation by protein kinases. To understand the basis for the autonomous activity of the poplar SLAH3, we generated and expressed chimera between kinase-independent PttSLAH3 and kinase-dependent Arabidopsis AtSLAH3. We identified the N-terminal tail and, to a lesser extent, the C-terminal tail as responsible for PttSLAH3 kinase-(in)dependent action. This feature of PttSLAH3 may provide the secretory cell with a channel probably controlling long-term nectar secretion.

  14. Caracterización de las farmacias comunitarias de Santa Clara para la implementación de la Dispensación de Medicamentos Characterization of community pharmacies in Santa Clara city for the implementation of drug dispensing

    Directory of Open Access Journals (Sweden)

    Liset Jaramillo Hernández

    2012-03-01

    Full Text Available Introducción: la inclusión del Servicio de Dispensación de Medicamentos en la Atención Farmacéutica, busca evidenciar la participación del farmacéutico en el logro de resultados positivos en los tratamientos, basado en los conocimientos farmacoterapéuticos y principios éticos que identifican esta profesión. La caracterización de las farmacias comunitarias resulta elemental para trazar acciones que permitan implementar dicho servicio. Objetivo: caracterizar las farmacias comunitarias de Santa Clara para la implementación del Servicio de Dispensación de Medicamentos. Métodos: se realizó una investigación en sistemas y servicios de salud con un enfoque sistémico (evaluación de la estructura, el proceso y los resultados. El estudio fue observacional, descriptivo y transversal. El contexto espacial lo constituyeron las farmacias comunitarias del municipio de Santa Clara, en el período comprendido entre enero y mayo de 2010. Se seleccionó el 30 % del total de farmacias comunitarias del municipio de Santa Clara. Resultados: la disponibilidad de los recursos humanos fue limitada y no existieron suficientes recursos materiales para sustentar el servicio. El 95,2 % de los farmacéuticos comunitarios presentaron altas necesidades de aprendizaje sobre Dispensación y no existieron Procedimientos Normalizados de Trabajo. A través de la observación directa se determinó que el servicio no se ejecutó, lo cual se corroboró con la encuesta realizada a los usuarios. Conclusiones: las farmacias comunitarias del municipio de Santa Clara se caracterizan por tener una estructura parcialmente adecuada y por ser el proceso y los resultados no adecuados para la ejecución del Servicio de Dispensación de Medicamentos.Introduction: the drug dispensing service as part of the pharmaceutical care is aimed at showing the involvement of the pharmacist in attaining positive results of therapies, based on the pharmaco-therapeutic knowledge and the

  15. Enhanced and Secretory Expression of Human Granulocyte Colony Stimulating Factor by Bacillus subtilis SCK6

    Directory of Open Access Journals (Sweden)

    Shaista Bashir

    2015-01-01

    Full Text Available This study describes a simplified approach for enhanced expression and secretion of a pharmaceutically important human cytokine, that is, granulocyte colony stimulating factor (GCSF, in the culture supernatant of Bacillus subtilis SCK6 cells. Codon optimized GCSF and pNWPH vector containing SpymwC signal sequence were amplified by prolonged overlap extension PCR to generate multimeric plasmid DNA, which was used directly to transform B. subtilis SCK6 supercompetent cells. Expression of GCSF was monitored in the culture supernatant for 120 hours. The highest expression, which corresponded to 17% of the total secretory protein, was observed at 72 hours of growth. Following ammonium sulphate precipitation, GCSF was purified to near homogeneity by fast protein liquid chromatography on a QFF anion exchange column. Circular dichroism spectroscopic analysis showed that the secondary structure contents of the purified GCSF are similar to the commercially available GCSF. Biological activity, as revealed by the regeneration of neutrophils in mice treated with ifosfamine, was also similar to the commercial preparation of GCSF. This, to our knowledge, is the first study that reports secretory expression of human GCSF in B. subtilis SCK6 with final recovery of up to 96 mg/L of the culture supernatant, without involvement of any chemical inducer.

  16. Effects of ozone on the cholinergic secretory responsiveness of ferret tracheal glands

    Energy Technology Data Exchange (ETDEWEB)

    McBride, R.K.; Oberdoerster, G.; Marin, M.G. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

    1991-06-01

    Oxidant air pollutants exacerbate several pulmonary diseases. Inhalation of ozone has been shown to induce airway smooth muscle hyperresponsiveness. Oxidant injury could also affect airway secretory mechanisms. The authors postulated that oxidant exposure would alter the glycoconjugate secretory function of airway submucosal glands. To test this hypothesis they examined the effects of in vivo ozone exposure on the in vitro secretory responsiveness of ferret tracheal glands. Ferrets were exposed to 1 ppm ozone, 24 hr/day for 3 or 7 days. Following exposure, glandular explants, denuded of surface epithelial cells, were prepared and incubated in medium containing 3H-glucosamine for 18 hr. Basal secretion of labeled glycoconjugates was significantly increased 31% following 3 days of ozone exposure (P less than or equal to 0.05) and remained elevated 11% after 7 days of exposure compared to the air-exposed group. After 3 or 7 days of exposure to ozone, tracheal gland responsiveness to carbachol was increased as indicated by significantly lower EC50 values (log molar concentration) of -6.43 {plus minus} 0.04 (n = 6) and -6.50 {plus minus} 0.11 (n = 5), respectively; compared to -6.20 {plus minus} 0.08 (n = 6) for the air-exposed group. There was no difference in carbachol EC50 values for air and 7-day ozone-exposed animals treated with dexamethasone. Dexamethasone did not attenuate the ozone-induced increase in basal secretion. Tracheal gland responsiveness to {alpha}- or {beta}-adrenergic agonists was not changed by oxidant exposure. These experiments suggest that oxidant injury not only increases basal secretion of respiratory glycoconjugates but also increases tracheal gland sensitivity to a cholinergic agonist.

  17. A change in the number of CCSP(pos)/SPC(pos) cells in mouse lung during development, growth, and repair.

    Science.gov (United States)

    Sun, Ruowen; Zhou, Qiliang; Ye, Xulu; Takahata, Takenori; Ishiguro, Atsushi; Kijima, Hiroshi; Nukiwa, Toshihiro; Saijo, Yasuo

    2013-12-01

    Putative resident stem/progenitor cells have been identified in the bronchoalveolar duct junction (BADJ) of the murine lung. However, the contribution of stem cells expressing both Clara cell secretory protein (CCSP) and pro-surfactant protein C (SP-C) to the repair and maintenance of normal homeostasis is still unclear. In this study, we identified and then quantified CD45(neg)/CCSP(pos)/SP-C(pos) cell numbers in normal and lung-injured mice. Normal lung tissues of fetal, newborn, and adult mice were used to evaluate lung progenitor cells during development and growth. Mice treated with naphthalene were used for the bronchiolar epithelium injury model, and mice treated with bleomycin were used for the alveolar epithelium injury model. These lung tissues were stained with CD45, CCSP, and SP-C antibodies by immunofluorescence. The number of lung progenitor cells was counted as CD45(neg)/CCSP(pos)/SP-C(pos) cells by flow cytometry. CCSP(pos)/SP-C(pos) epithelial cells in the BADJ were identified from E18 to 7 months after birth. The percentage of CD45(neg)/CCSP(pos)/SP-C(pos) cells was relatively stable to 7 months (between 0.3±0.04% and 1.28±0.11%). When lungs were treated with naphthalene, the proliferation of CCSP(pos)/SP-C(pos) cells was observed as patches of double-positive cells and preceded the recovery of bronchioles. In contrast, when lungs were treated with bleomycin, the proliferation of CCSP(pos)/SP-C(pos) cells was observed, but the type II alveolar epithelial cells never recovered to baseline. CCSP(pos)/SP-C(pos) lung cells were stable until 7 months after birth. These cells in the BADJ primarily regenerate bronchiolar epithelial cells and not alveolar epithelial cells. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  18. Non-secretory immunoglobulin E myeloma associated with immunoglobulin G monoclonal gammopathy of undetermined significance

    Directory of Open Access Journals (Sweden)

    Masako Yasuyama

    2012-07-01

    Full Text Available A 68-year old woman came to our hospital with a severe case of anemia. Serum immunoelectropheresis identified a monoclonal immunoglobulin (Ig G and κ protein. The serum IgE level was within the nomal range and the amounts of remaining immuno - globlins were low. On bone marrow aspirate, plasma cells made up 55.5% of nucleated cells and the plasma cells showed positive readings for IgE κ and IgG by immunohistochemistry. Serum immunofixation did not reveal the IgE monoclonal band. She was diagnosed as having non-secretory IgE myeloma with IgG monoclonal gammopathy of undetermined significance. The nature of this rare myeloma will be discussed.

  19. Comparison of ion transport by cultured secretory and absorptive canine airway epithelia

    DEFF Research Database (Denmark)

    Boucher, R C; Larsen, Erik Hviid

    1988-01-01

    The use of primary cell culture techniques to predict the function of native respiratory epithelia was tested in studies of dog airway epithelia. Epithelial cells from Cl- secretory (tracheal) and Na+ absorptive (bronchial) airway regions were isolated by enzymatic digestion, plated on collagen...... sensitive to amiloride but insensitive to bumetanide. As compared with the trachea, the bronchial (absorptive) epithelium is characterized by 1) a large amiloride-sensitive cellular conductance and 2) a relatively depolarized basolateral membrane. We conclude that this primary cell culture technique...... matrices, and maintained in serum-free, hormone-supplemented media. Transepithelial and intracellular studies showed that both the tracheal and bronchial culture preparations exhibited bioelectric parameters quantitatively similar to those of intact tissues. Similar to the native tissue, the tracheal...

  20. 不同毒力株弓形虫速殖子排泄分泌抗原(ESA)对小鼠自然杀伤细胞(NK)作用的比较%EFFECTS OF DIFFERENT VIRULENT STRAINS OF TOXOPLASMA GONDII EXCRETORY-SECRETORY ANTIGENS (ESA) ON MURINE NK CELLS

    Institute of Scientific and Technical Information of China (English)

    毛雯倩; 张洁; 陈金铃; 李冉; 王勇; 吴江平

    2012-01-01

    In order to observe the effects of different virulent strains of Toxoplasma gondii excretory-secretory antigens ( ESA ) on murine NK cells, 18 C57BL/6J mice were used and treated with 200 jxL different strains of T. gondii ESA ( containing ESA 0. 002 nig) or PBS, respectively. The numbers of splenic NK cells in splenocytes were measured by flow cytometry. Cytotoxicity of NK cells on YAC-1 cells were detected by LDH method. The IFN-7 levels in serum were also tested by ELISA. The result showed that the numbers of NK cells in either RH ESA or PRU ESA treated groups were increased significantly compared with that of PBS control ( 3. 08 ±0. 39 )% ( P < 0. 001 ). In addition, the increasement in RH ESA treated group ( 5. 97 ±0. 26 )% was higher than that in PRU ESA treated group ( 3. 32 ± 0. 29 )% , and the difference is of statistic significance ( P < 0. 001 ). The cytotoxic effects of NK cells on YAC-1 cells in both RH ESA and PRU ESA treated groups were increased obviously compared with that of PBS control ( P < 0. 01 ). The levels of sera IFN-7 in both RH ESA and PRU ESA treated groups were increased significantly compared with that of PBS control ( P < 0. 01 ). Also, the increasement in RH ESA treated group was higher than that in PRU ESA treated group, and the difference is of statistic significance ( P < 0. 05 ). The results suggested that T. gondii ESA could activate NK cells and the efficiency of RH ESA was higher than that of PRU ESA.%为观察不同毒力株弓形虫排泄分泌抗原(Excretory-Secretory antigen,ESA)对小鼠NK细胞的作用,将18只雌性C57BL/6J小鼠随机分为3组,各组每鼠分别腹腔注射刚地弓形虫RH株ESA 200 μL(含ESA 0.002 mg),PRU株ESA 200 μL(含ESA 0.002 mg)和PBS 200 μL.于注射后6天取脾,流式细胞仪检测脾脏NK细胞的比例,并用乳酸脱氢酶(Lactate dehydrogenase,LDH )法检测各组NK细胞的杀伤活性,ELISA检测血清IFN-γ水平.结果显示,RH株ESA处理组NK细胞比例(5.97±0.26)%,PRU

  1. Caracterización de la mortalidad fetal tardía en Villa Clara.

    Directory of Open Access Journals (Sweden)

    Juan Antonio Suárez González

    2011-10-01

    Full Text Available Fundamento: Eventos como la mortalidad fetal tardía agreden la evolución normal esperada en el embarazo, con una connotación en la mujer, la pareja y la comunidad. Objetivo: Caracterizar la mortalidad fetal tardía según factores asociados. Métodos: Se realizó un estudio descriptivo de las 74 muertes fetales registradas en el Hospital Universitario Ginecoobstétrico Mariana Grajales de Santa Clara, durante los años 2009 y 2010. Se analizaron las variables: edad materna, antecedentes patológicos personales maternos, edad gestacional al momento de la muerte fetal, lugar y momento de ocurrencia y causas de la muerte. Resultados: El 67,6 % de las gestantes tenían entre 20 y 35 años. La hipertensión arterial crónica y el asma bronquial fueron los antecedentes patológicos personales de mayor incidencia entre las gestantes. Ocurrieron los óbitos fetales en una edad gestacional entre 28 y 36,6 semanas fundamentalmente. El 52,7 % de las muertes ocurrieron fuera del hospital y antes del parto en 55 casos (74,3 %. Resultaron las causas más frecuentes las idiopáticas y los trastornos hipertensivos de la gestación. Conclusiones: Es necesario intensificar el control del riesgo reproductivo preconcepcional y la atención prenatal, pues sin dudas, aunque mucho se ha logrado en este sentido, los resultados del estudio muestran que en alguna medida las causas de los óbitos fetales fueron prevenibles.

  2. A case history study on causation of the landslide in Santa Clara, California, USA

    Institute of Scientific and Technical Information of China (English)

    Yun Liao; Sadek M. Derrega; Craig A. Hall

    2015-01-01

    This paper presents a case history study on the geologic investigation and numerical modeling of a reactivated landslide in the County of Santa Clara, California to identify the failure mechanism. The landslide occurred on an approximately 18.3-m high, north-facing slope during March 2011. The land-slide measured about 33.5 m in width and about 51.8 m in length. Along the toe of the slope, a residential structure with a swimming pool was built on a cut and fill pad and there are several other structures present along the western side of the pad. The landslide occurred immediately to the south of the residential building and moved northward between the County Road A and the house’s side yard. The movement of the landslide resulted in damaging the west-bound traffic lane of County Road A and encroached onto the paved driveway for the residential property. An investigation was performed to identify the failure mechanism of the landslide to conclude whether Road A re-alignment by the County or prominent cutting performed along the lower portion of the slope by the homeowner during 2000 through 2004 contributed to the reactivation of the old landslide deposit. The investigation included site reconnaissance, reviewing available published geologic information, reviewing site-specific geologic and geotechnical data developed by other consultants, and performing numerical modeling. The outcomes of the investigation indicate that the primary causation for the reactivation and failure of the subject pre-existing landslide is the prominent cutting performed along the lower portion of the slope during 2000 through 2004 and water tank cut bench. The Road A re-alignment did not contribute to the reactivation of the old landslide deposit.

  3. A case history study on causation of the landslide in Santa Clara, California, USA

    Directory of Open Access Journals (Sweden)

    Yun Liao

    2015-04-01

    Full Text Available This paper presents a case history study on the geologic investigation and numerical modeling of a reactivated landslide in the County of Santa Clara, California to identify the failure mechanism. The landslide occurred on an approximately 18.3-m high, north-facing slope during March 2011. The landslide measured about 33.5 m in width and about 51.8 m in length. Along the toe of the slope, a residential structure with a swimming pool was built on a cut and fill pad and there are several other structures present along the western side of the pad. The landslide occurred immediately to the south of the residential building and moved northward between the County Road A and the house's side yard. The movement of the landslide resulted in damaging the west-bound traffic lane of County Road A and encroached onto the paved driveway for the residential property. An investigation was performed to identify the failure mechanism of the landslide to conclude whether Road A re-alignment by the County or prominent cutting performed along the lower portion of the slope by the homeowner during 2000 through 2004 contributed to the reactivation of the old landslide deposit. The investigation included site reconnaissance, reviewing available published geologic information, reviewing site-specific geologic and geotechnical data developed by other consultants, and performing numerical modeling. The outcomes of the investigation indicate that the primary causation for the reactivation and failure of the subject pre-existing landslide is the prominent cutting performed along the lower portion of the slope during 2000 through 2004 and water tank cut bench. The Road A re-alignment did not contribute to the reactivation of the old landslide deposit.

  4. Shaded relief aeromagnetic map of the Santa Clara Valley and vicinity, California

    Science.gov (United States)

    Roberts, Carter W.; Jachens, Robert C.

    2003-01-01

    This aeromagnetic map covers the southern portion of San Francisco Bay, the Santa Clara Valley and surrounding mountains, part of which has been modelled in threedimensions (Jachens and other, 2001). The magnetic anomaly map has been compiled from existing digital data. Data was obtained from six aeromagnetic surveys that were flown at different times, spacings and elevations. The International Geomagnetic Reference Field (IGRF) for the date of each survey had been removed in the initial processing. The resulting residual magnetic anomalies were analytically continued onto a common surface 305 m (1000 ft) above terrain. Portions of each survey were substantially above the specified flight height listed in the table. The surveys were then merged together using a commercial software package called Oasis Montage. The gray lines on the map indicate the extent of each survey. The program used these regions of overlap to determine the best fit between surveys. Black dots show probable edges of magnetic bodies defined by the maximum horizontal gradient determined using a computer program by Blakely (1995). Crystalline rocks generally contain sufficient magnetic minerals to cause variations in the Earth’s magnetic field that can be mapped by aeromagnetic surveys. Sedimentary rocks are generally weakly magnetized and consequently have a small effect on the magnetic field: thus a magnetic anomaly map can be used to “see through” the sedimentary rock cover and can convey information on lithologic contrasts and structural trends related to the underlying crystalline basement (see Nettleton,1971; Blakely, 1995). Faults often cut magnetic bodies and offset magnetic anomalies can thus be used to help determine fault motion. Serpentinite, which is highly magnetic, is often found along faults. On this map areas of low magnetic anomalies are shown in blues and green while highs are shown in reds and magentas. Faults are from Brabb and others, 1998a,1998b, Graymer and others

  5. 活性氧清除剂 NAC 抑制阴道毛滴虫排泄分泌物诱导的 SiHa 细胞凋亡%REACTIVE OXYGEN SPECIES SCAVENGER PROTECTS SIHA CELL APOPTOSIS INDUCED BY TRICHOMONAS VAGINALIS EXCRETORY-SECRETORY PRODUCTS

    Institute of Scientific and Technical Information of China (English)

    全娟花; 李鹏; 黄瑞; 楚佳奇

    2015-01-01

    本研究旨在探讨活性氧( ROS)清除剂N-乙酰-L-半胱氨酸( NAC)能否抑制滴虫排泄分泌物( Tv ESP)诱导的人子宫颈癌SiHa细胞凋亡。体外培养阴道毛滴虫并制备Tv ESP,分别用100μg/mL Tv ESP和PBS处理SiHa细胞, Tv ESP处理SiHa细胞30 min前加入NAC,进行预处理。使用CellTiter 96 AQueous单溶液细胞增殖检测试剂盒检测细胞存活率;利用2′,7′-二氯荧光黄双乙酸盐( DCFH-DA)进行荧光探针标记测定胞内ROS水平;免疫印迹法检测cleaved caspase-3和PARP-1蛋白表达。结果显示, NAC预处理可降低Tv ESP的细胞毒性作用。 Tv ESP作用SiHa细胞16 h后,细胞内ROS水平升高,但经过NAC预处理后胞内ROS生成显著降低。此外, NAC预处理后能显著下调Tv ESP诱导的cleaved caspase-3和cleaved PARP-1的表达水平。%This study intends to investigate whether the reactive oxygen species ( ROS ) scavenger N-aeetyl-L-cysteine ( NAC ) can inhibit Trichomonas vaginalis excretory-secretory products ( Tv ESP ) induced apoptosis of human cervical cancer ( SiHa) cells.T.vaginalis were in vitro cultured and Tv ESP were prepared.SiHa cells were treated with 100 μg/mL Tv ESP, PBS and NAC was pretreated with SiHa cells 30 min prior to exposure to 100 μg/mL Tv ESP.The cell viability was evaluated using CellTiter 96 AQueous One Solution Cell Proliferation Assay kit, and the intercellular ROS level was measured by fluorescent probe 2′, 7′-dichlorfluorescein-diacetate ( DCFH-DA ) .Cleaved caspase-3 and PARP-1 protein levels were detected by Western blot.Our results demonstrate that pretreatment of NAC reduced Tv ESP induced SiHa cell cytotoxicity.Intracellular ROS levels were highly induced after exposure to 100 μg/mL Tv ESP for 16 h, however, intracellular ROS levels were significantly reduced by pretreatment of NAC.In addition, pretreatment of NAC, significantly reduced cleaved caspase-3 and cleaved PARP-1

  6. Deficiency of ATP2C1, a golgi ion pump, induces secretory pathway defects in endoplasmic reticulum ( ER)-associated degradation and sensitivity to ER stress

    NARCIS (Netherlands)

    Ramos-Castaneda, J; Park, YN; Liu, M; Hauser, K; Rudolph, H; Shull, GE; Jonkman, MF; Mori, K; Ikeda, S; Ogawa, H; Arvan, P

    2005-01-01

    Relatively few clues have been uncovered to elucidate the cell biological role(s) of mammalian ATP2C1 encoding an inwardly directed secretory pathway Ca2+/Mn2+ pump that is ubiquitously expressed. Deficiency of ATP2C1 results in a human disease ( Hailey-Hailey), which primarily affects keratinocytes

  7. The murine cytomegalovirus immunoevasin gp40 binds MHC class I molecules to retain them in the early secretory pathway.

    Science.gov (United States)

    Janßen, Linda; Ramnarayan, Venkat Raman; Aboelmagd, Mohamed; Iliopoulou, Maro; Hein, Zeynep; Majoul, Irina; Fritzsche, Susanne; Halenius, Anne; Springer, Sebastian

    2016-01-01

    In the presence of the murine cytomegalovirus (mCMV) gp40 (m152) protein, murine major histocompatibility complex (MHC) class I molecules do not reach the cell surface but are retained in an early compartment of the secretory pathway. We find that gp40 does not impair the folding or high-affinity peptide binding of the class I molecules but binds to them, leading to their retention in the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi, most likely by retrieval from the cis-Golgi to the ER. We identify a sequence in gp40 that is required for both its own retention in the early secretory pathway and for that of class I molecules.

  8. Secretory cavities and volatiles of Myrrhinium atropurpureum Schott var. atropurpureum (Myrtaceae): an endemic species collected in the restingas of Rio de Janeiro, Brazil.

    Science.gov (United States)

    Victório, Cristiane Pimentel; Moreira, Claudio B; Souza, Marcelo da Costa; Sato, Alice; Arruda, Rosani do Carmo de Oliveira

    2011-07-01

    In this study, we investigated the leaf anatomy and the composition of volatiles in Myrrhinium atropurpureum var. atropurpureum endemic to Rio de Janeiro restingas. Particularly, leaf secretory structures were described using light microscopy, and histochemical tests were performed from fresh leaves to localize the secondary metabolites. To observe secretory cavities, fixed leaf samples were free-hand sectioned. To evaluate lipophilic compounds and terpenoids the following reagents were employed: Sudans III and IV, Red oil O and Nile blue. Leaf volatiles were characterized by gas chromatography after hydrodistillation (HD) or simultaneous distillation-extraction (SDE). Leaf analysis showed several cavities in mesophyll that are the main sites of lipophilic and terpenoid production. Monoterpenes, which represented more than 80% of the major volatiles, were characterized mainly by alpha- and beta-pinene and 1,8-cineole. In order to provide tools for M. atropurpureum identification, the following distinguishing characteristics were revealed by the following data: 1) adaxial face clear and densely punctuated by the presence of round or ellipsoidal secretory cavities randomly distributed in the mesophyll; 2) the presence of cells overlying the upper neck cells of secretory cavities; 3) the presence of numerous paracytic stomata distributed on the abaxial leaf surface, but absent in vein regions and leaf margin; and 4) non-glandular trichomes on both leaf surfaces. Our study of the compounds produced by the secretory cavities of M. atropurpureum led us to conclude that volatile terpenoid class are the main secretory compounds and that they consist of a high concentration of monoterpenes, which may indicate the phytotherapeutic importance of this plant.

  9. Role of adaptor proteins in secretory granule biogenesis and maturation

    Directory of Open Access Journals (Sweden)

    Mathilde L Bonnemaison

    2013-08-01

    Full Text Available In the regulated secretory pathway, secretory granules (SGs store peptide hormones that are released on demand. SGs are formed at the trans-Golgi network (TGN and must undergo a maturation process to become responsive to secretagogues. The production of mature SGs requires concentrating newly synthesized soluble content proteins in granules whose membranes contain the appropriate integral membrane proteins. The mechanisms underlying the sorting of soluble and integral membrane proteins destined for SGs from other proteins are not yet well understood. For soluble proteins, luminal pH and divalent metals can affect aggregation and interaction with surrounding membranes. The trafficking of granule membrane proteins can be controlled by both luminal and cytosolic factors. Cytosolic adaptor proteins, which recognize the cytosolic domains of proteins that span the SG membrane, have been shown to play essential roles in the assembly of functional SGs. Adaptor protein 1A (AP-1A is known to interact with specific motifs in its cargo proteins and with the clathrin heavy chain, contributing to the formation of a clathrin coat. AP-1A is present in patches on immature SG membranes, where it removes cargo and facilitates SG maturation. AP-1A recruitment to membranes can be modulated by PACS-1 (Phosphofurin Acidic Cluster Sorting protein 1, a cytosolic protein which interacts with both AP-1A and cargo that has been phosphorylated by casein kinase II. A cargo/PACS-1/AP-1A complex is necessary to drive the appropriate transport of several cargo proteins within the regulated secretory pathway. The GGA (Golgi-localized, -ear containing, ADP-ribosylation factor binding family of adaptor proteins serve a similar role. We review the functions of AP-1A, PACS-1 and GGAs in facilitating the retrieval of proteins from immature SGs and review examples of cargo proteins whose trafficking within the regulated secretory pathway is governed by adaptor proteins.

  10. Extended high frequency audiometry in secretory otitis media.

    Science.gov (United States)

    Sharma, Deepika; Munjal, Sanjay K; Panda, Naresh K

    2012-06-01

    The objective of the present study was to determine the status of extended high frequencies in subjects with secretory otitis media. The study evaluated 30 ears of 20 subjects with secretory otitis media in the age group of 15-30 years. This data was compared with 20 ears of 10 volunteers of the same age group with clinically normal hearing. Pure tone air conduction thresholds were analyzed in three frequency groups: low frequency (LF: 0.25, 0.5, and 1 kHz), high frequency (HF: 2, 4, and 8 kHz) and extended high frequency (EHF: 10, 12, and 16 kHz). The results showed elevated extended high frequency thresholds (EHFG) as compared to control group and comparatively better thresholds at high frequencies(HFG)s as compared to low (LFG)and extended high frequencies(EHFG) in the study group. This validates the importance of including an extended high frequency audiometry in the test battery of patients with secretory otitis media.

  11. Souffle/Spastizin controls secretory vesicle maturation during zebrafish oogenesis.

    Directory of Open Access Journals (Sweden)

    Palsamy Kanagaraj

    2014-06-01

    Full Text Available During oogenesis, the egg prepares for fertilization and early embryogenesis. As a consequence, vesicle transport is very active during vitellogenesis, and oocytes are an outstanding system to study regulators of membrane trafficking. Here, we combine zebrafish genetics and the oocyte model to identify the molecular lesion underlying the zebrafish souffle (suf mutation. We demonstrate that suf encodes the homolog of the Hereditary Spastic Paraplegia (HSP gene SPASTIZIN (SPG15. We show that in zebrafish oocytes suf mutants accumulate Rab11b-positive vesicles, but trafficking of recycling endosomes is not affected. Instead, we detect Suf/Spastizin on cortical granules, which undergo regulated secretion. We demonstrate genetically that Suf is essential for granule maturation into secretion competent dense-core vesicles describing a novel role for Suf in vesicle maturation. Interestingly, in suf mutants immature, secretory precursors accumulate, because they fail to pinch-off Clathrin-coated buds. Moreover, pharmacological inhibition of the abscission regulator Dynamin leads to an accumulation of immature secretory granules and mimics the suf phenotype. Our results identify a novel regulator of secretory vesicle formation in the zebrafish oocyte. In addition, we describe an uncharacterized cellular mechanism for Suf/Spastizin activity during secretion, which raises the possibility of novel therapeutic avenues for HSP research.

  12. Política social para la atención a la vejez: una necesidad para. Villa Clara Social policy for old age care: a necessity for Villa Clara

    Directory of Open Access Journals (Sweden)

    Yamila Roque Doval

    2015-12-01

    Full Text Available Resumen Villa Clara es la provincia más envejecida del país y la atención a este proceso demográfico se declara como urgente para este territorio. El artículo que se presenta constituye un resultado parcial del estudio que viene realizando, en el área de Política Social, un grupo de investigadores del proyecto Estudios de Población, que coordina el Centro de Estudios Demográficos (CEDEM, en la Universidad Central “Marta Abreu” de Las Villas. El objetivo del estudio es destacar, a partir del análisis de datos estadísticos del Censo de Población y Viviendas del 2012 ofrecidos por la Oficina Nacional de Estadísticas e Información (ONEI, la urgencia de incorporar a la estrategia de desarrollo de la provincia de Villa Clara la necesidad de la atención al adulto mayor. La muestra seleccionada está compuesta por 8 municipios de la provincia (Quemado de Güines, Sagua la Grande, Encrucijada, Cifuentes, Santa Clara, Placetas, Camajuaní y Remedios, que son los más envejecidos, según datos de la ONEI. Como resultado se propone que: la política social que se diseñe tenga como objetivo general lograr una atención eficaz a las necesidades del adulto mayor de la provincia a partir de los rasgos esenciales que caracterizan ese proceso en el territorio, que se base en valores como la solidaridad, la cooperación, que los principios que la sustenten sean de descentralización, flexibilidad en el diseño de la política, prevención, equidad, valorando siempre las necesidades y las posibilidades reales de acceso a los servicios de este grupo poblacional. Villa Clara provinceis the oldest in the country and attention to this demographic processis declared a surgent for this territory. The present article is a partial result of the study being done in the area of Social Policy, a group of researchers at the Population Studies project, coordinated by CEDEM at the Central University “Marta Abreu” of Las Villas. The aim of the studyis to

  13. The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Stephen eSalton

    2013-08-01

    Full Text Available The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs, where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs, with neuropsychiatric, endocrine and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A of the human brain-derived neurotrophic factor (BDNF gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired.

  14. Divalent cations increase lipid order in erythrocytes and susceptibility to secretory phospholipase A2.

    Science.gov (United States)

    Vest, Rebekah S; Gonzales, Laurie J; Permann, Seth A; Spencer, Emily; Hansen, Lee D; Judd, Allan M; Bell, John D

    2004-04-01

    Elevated concentrations of intracellular calcium in erythrocytes increase membrane order and susceptibility to secretory phospholipase A2. We hypothesize that calcium aids the formation of domains of ordered lipids within erythrocyte membranes by interacting directly with the inner leaflet of the cell membrane. The interface of these domains with regions of more fluid lipids may create an environment with weakened neighbor-neighbor interactions that would facilitate phospholipid migration into the active site of bound secretory phospholipase A2. This hypothesis was investigated by determining the effects of seven other divalent ions on erythrocyte membrane properties. Changes in membrane order were assessed with steady-state fluorescence spectroscopy and two-photon microscopy with an environment-sensitive probe, laurdan. Each ion increased apparent membrane order in model membranes and in erythrocytes when introduced with an ionophore, suggesting that direct binding to the inner face of the membrane accounts for the effects of calcium on membrane fluidity. Furthermore, the degree to which ions affected membrane properties correlated with the ionic radius and electronegativity of the ions. Lastly, erythrocytes became more susceptible to enzyme hydrolysis in the presence of elevated intracellular levels of nickel and manganese, but not magnesium. These differences appeared related to the ability of the ions to induce a transition in erythrocyte shape.

  15. Bacterial mimetics of endocrine secretory granules as immobilized in vivo depots for functional protein drugs

    Science.gov (United States)

    Céspedes, María Virtudes; Fernández, Yolanda; Unzueta, Ugutz; Mendoza, Rosa; Seras-Franzoso, Joaquin; Sánchez-Chardi, Alejando; Álamo, Patricia; Toledo-Rubio, Verónica; Ferrer-Miralles, Neus; Vázquez, Esther; Schwartz, Simó; Abasolo, Ibane; Corchero, José Luis; Mangues, Ramon; Villaverde, Antonio

    2016-01-01

    In the human endocrine system many protein hormones including urotensin, glucagon, obestatin, bombesin and secretin, among others, are supplied from amyloidal secretory granules. These granules form part of the so called functional amyloids, whic