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Sample records for soluble activin type

  1. Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

    PubMed Central

    Rahimov, Fedik; King, Oliver D.; Warsing, Leigh C.; Powell, Rachel E.; Emerson, Charles P.; Kunkel, Louis M.

    2011-01-01

    Inhibition of the myostatin signaling pathway is emerging as a promising therapeutic means to treat muscle wasting and degenerative disorders. Activin type IIB receptor (ActRIIB) is the putative myostatin receptor, and a soluble activin receptor (ActRIIB-Fc) has been demonstrated to potently inhibit a subset of transforming growth factor (TGF)-? family members including myostatin. To determine reliable and valid biomarkers for ActRIIB-Fc treatment, we assessed gene expression profiles for quadriceps muscles from mice treated with ActRIIB-Fc compared with mice genetically lacking myostatin and control mice. Expression of 134 genes was significantly altered in mice treated with ActRIIB-Fc over a 2-wk period relative to control mice (fold change > 1.5, P < 0.001), whereas the number of significantly altered genes in mice treated for 2 days was 38, demonstrating a time-dependent response to ActRIIB-Fc in overall muscle gene expression. The number of significantly altered genes in Mstn?/? mice relative to control mice was substantially higher (360), but for most of these genes the expression levels in the 2-wk treated mice were closer to the levels in the Mstn?/? mice than in control mice (P < 10?30). Expression levels of 30 selected genes were further validated with quantitative real-time polymerase chain reaction (qPCR), and a correlation of ?0.89 was observed between the fold changes from the microarray analysis and the qPCR analysis. These data suggest that treatment with ActRIIB-Fc results in overlapping but distinct gene expression signatures compared with myostatin genetic mutation. Differentially expressed genes identified in this study can be used as potential biomarkers for ActRIIB-Fc treatment, which is currently in clinical trials as a therapeutic agent for muscle wasting and degenerative disorders. PMID:21266502

  2. Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

    PubMed Central

    DiGirolamo, Douglas J.; Singhal, Vandana; Chang, Xiaoli; Lee, Se-Jin; Germain-Lee, Emily L.

    2015-01-01

    Osteogenesis imperfecta (OI) comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI, many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B (ACVR2B) in a mouse model of type III OI (oim). Treatment of 12-week-old oim mice with ACVR2B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy, wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system. PMID:26161291

  3. The structure of the follistatin:activin complex reveals antagonism of both type I and type II receptor binding

    SciTech Connect

    Thompson, T.B.; Lerch, T.F.; Cook, R.W.; Woodruff, T.K.; Jardetzky, T.S.

    2010-03-08

    TGF-{beta} ligands stimulate diverse cellular differentiation and growth responses by signaling through type I and II receptors. Ligand antagonists, such as follistatin, block signaling and are essential regulators of physiological responses. Here we report the structure of activin A, a TGF-{beta} ligand, bound to the high-affinity antagonist follistatin. Two follistatin molecules encircle activin, neutralizing the ligand by burying one-third of its residues and its receptor binding sites. Previous studies have suggested that type I receptor binding would not be blocked by follistatin, but the crystal structure reveals that the follistatin N-terminal domain has an unexpected fold that mimics a universal type I receptor motif and occupies this receptor binding site. The formation of follistatin:BMP:type I receptor complexes can be explained by the stoichiometric and geometric arrangement of the activin:follistatin complex. The mode of ligand binding by follistatin has important implications for its ability to neutralize homo- and heterodimeric ligands of this growth factor family.

  4. The Structure of FSTL3·Activin A Complex: Differential Binding of N-Terminal Domains Influences Follistatin-Type Antagonist Specificity

    SciTech Connect

    Stamler, Robin; Keutmann, Henry T.; Sidis, Yisrael; Kattamuri, Chandramohan; Schneyer, Alan; Thompson, Thomas B.

    2009-03-06

    Transforming growth factor beta family ligands are neutralized by a number of structurally divergent antagonists. Follistatin-type antagonists, which include splice variants of follistatin (FS288 and FS315) and follistatin-like 3 (FSTL3), have high affinity for activin A but differ in their affinity for other ligands, particularly bone morphogenetic proteins. To understand the structural basis for ligand specificity within FS-type antagonists, we determined the x-ray structure of activin A in complex with FSTL3 to a resolution of 2.5 A. Similar to the previously resolved FS.activin A structures, the ligand is encircled by two antagonist molecules blocking all ligand receptor-binding sites. Recently, the significance of the FS N-terminal domain interaction at the ligand type I receptor site has been questioned; however, our data show that for FSTL3, the N-terminal domain forms a more intimate contact with activin A, implying that this interaction is stronger than that for FS. Furthermore, binding studies revealed that replacing the FSTL3 N-terminal domain with the corresponding FS domain considerably lowers activin A affinity. Therefore, both structural and biochemical evidence support a significant interaction of the N-terminal domain of FSTL3 with activin A. In addition, structural comparisons with bone morphogenetic proteins suggest that the interface where the N-terminal domain binds may be the key site for determining FS-type antagonist specificity.

  5. Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model

    SciTech Connect

    Nomura, Masatoshi; Tanaka, Kimitaka; Wang, Lixiang; Goto, Yutaka; Mukasa, Chizu; Ashida, Kenji; Takayanagi, Ryoichi

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer ActRIB signaling induces Snail and S100A4 expressions in prostate cancer cells. Black-Right-Pointing-Pointer The prostate cancer cell lines expressing an active form of ActRIB were established. Black-Right-Pointing-Pointer ActRIB signaling promotes EMT and lymph node metastasis in xenograft model. -- Abstract: Activin, a member of the transforming growth factor-{beta} family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.

  6. Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors.

    PubMed

    Fujimoto, Mai; Ohte, Satoshi; Osawa, Kenji; Miyamoto, Arei; Tsukamoto, Sho; Mizuta, Takato; Kokabu, Shoichiro; Suda, Naoto; Katagiri, Takenobu

    2015-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder characterized by progressive heterotopic ossification in soft tissues, such as the skeletal muscles. FOP has been shown to be caused by gain-of-function mutations in activin receptor-like kinase (ALK)-2, which is a type I receptor for bone morphogenetic proteins (BMPs). In the present study, we examined the molecular mechanisms that underlie the activation of intracellular signaling by mutant ALK2. Mutant ALK2 from FOP patients enhanced the activation of intracellular signaling by type II BMP receptors, such as BMPR-II and activin receptor, type II B, whereas that from heart disease patients did not. This enhancement was dependent on the kinase activity of the type II receptors. Substitution mutations at all nine serine and threonine residues in the ALK2 glycine- and serine-rich domain simultaneously inhibited this enhancement by the type II receptors. Of the nine serine and threonine residues in ALK2, T203 was found to be critical for the enhancement by type II receptors. The T203 residue was conserved in all of the BMP type I receptors, and these residues were essential for intracellular signal transduction in response to ligand stimulation. The phosphorylation levels of the mutant ALK2 related to FOP were higher than those of wild-type ALK2 and were further increased by the presence of type II receptors. The phosphorylation levels of ALK2 were greatly reduced in mutants carrying a mutation at T203, even in the presence of type II receptors. These findings suggest that the mutant ALK2 related to FOP is enhanced by BMP type II receptors via the T203-regulated phosphorylation of ALK2. PMID:25354296

  7. Mutation Detection in Activin A Receptor, Type I (ACVR1) Gene in Fibrodysplasia Ossificans Progressiva in An Iranian Family

    PubMed Central

    Morovvati, Ziba; Morovvati, Saeid; Alishiri, Gholamhossein Alishiri; Moosavi, Seyed Hossein; Ranjbar, Reza; Bolouki Moghaddam, Yaser

    2014-01-01

    Fibrodysplasia Ossificans Progressiva (FOP, MIM 135100) is a rare genetic disease that is often inherited sporadically in an autosomal dominant pattern. The disease manifests in early life with malformed great toes and, its episodic and progressive bone formation in skeletal muscle after trauma is led to extra-articular ankylosis. In this study, a 17 year-old affected girl born to a father with chemical injury due to exposure to Mustard gas during the Iran-Iraq war, and her first degree relatives were examined to find the genetic cause of the disease. The mutation c.617G>A in the Activin A receptor, type I (ACVR1) gene was found in all previously reported patients with FOP. Therefore, peripheral blood samples were taken from the patient and her first-degree relatives. DNA was extracted and PCR amplification for ACVR1 was performed. The sequencing of ACVR1 showed the existence of the heterozygous c.617G>A mutation in the patient and the lack of it in her relatives. Normal result of genetic evaluation in relatives of the patient, ruled out the possibility of the mutation being inherited from parents. Therefore, the mutation causing disease in the child, whether is a new mutation with no relation to the father’s exposure to chemical gas, or in case of somatic mutation due to exposure to chemical gas, the mutant cells were created in father’s germ cells and were not detectable in his blood sample. PMID:24518978

  8. Mutation Detection in Activin A Receptor, Type I (ACVR1) Gene in Fibrodysplasia Ossificans Progressiva in An Iranian Family.

    PubMed

    Morovvati, Ziba; Morovvati, Saeid; Alishiri, Gholamhossein; Moosavi, Seyed Hossein; Ranjbar, Reza; Bolouki Moghaddam, Yaser

    2014-02-01

    Fibrodysplasia Ossificans Progressiva (FOP, MIM 135100) is a rare genetic disease that is often inherited sporadically in an autosomal dominant pattern. The disease manifests in early life with malformed great toes and, its episodic and progressive bone formation in skeletal muscle after trauma is led to extra-articular ankylosis. In this study, a 17 year-old affected girl born to a father with chemical injury due to exposure to Mustard gas during the Iran-Iraq war, and her first degree relatives were examined to find the genetic cause of the disease. The mutation c.617G>A in the Activin A receptor, type I (ACVR1) gene was found in all previously reported patients with FOP. Therefore, peripheral blood samples were taken from the patient and her first-degree relatives. DNA was extracted and PCR amplification for ACVR1 was performed. The sequencing of ACVR1 showed the existence of the heterozygous c.617G>A mutation in the patient and the lack of it in her relatives. Normal result of genetic evaluation in relatives of the patient, ruled out the possibility of the mutation being inherited from parents. Therefore, the mutation causing disease in the child, whether is a new mutation with no relation to the father's exposure to chemical gas, or in case of somatic mutation due to exposure to chemical gas, the mutant cells were created in father's germ cells and were not detectable in his blood sample. PMID:24518978

  9. FOXL2-induced follistatin attenuates activin A-stimulated cell proliferation in human granulosa cell tumors

    SciTech Connect

    Cheng, Jung-Chien; Chang, Hsun-Ming; Qiu, Xin; Fang, Lanlan; Leung, Peter C.K.

    2014-01-10

    Highlights: •Activin A stimulates cell proliferation in KGN human granulosa cell tumor-derived cell line. •Cyclin D2 mediates activin A-induced KGN cell proliferation. •FOXL2 induces follistatin expression in KGN cells. •FOXL2-induced follistatin attenuates activin A-stimulated KGN cell proliferation. -- Abstract: Human granulosa cell tumors (GCTs) are rare, and their etiology remains largely unknown. Recently, the FOXL2 402C > G (C134W) mutation was found to be specifically expressed in human adult-type GCTs; however, its function in the development of human GCTs is not fully understood. Activins are members of the transforming growth factor-beta superfamily, which has been shown to stimulate normal granulosa cell proliferation; however, little is known regarding the function of activins in human GCTs. In this study, we examined the effect of activin A on cell proliferation in the human GCT-derived cell line KGN. We show that activin A treatment stimulates KGN cell proliferation. Treatment with the activin type I receptor inhibitor SB431542 blocks activin A-stimulated cell proliferation. In addition, our results show that cyclin D2 is induced by treatment with activin A and is involved in activin A-stimulated cell proliferation. Moreover, the activation of Smad signaling is required for activin A-induced cyclin D2 expression. Finally, we show that the overexpression of the wild-type FOXL2 but not the C134W mutant FOXL2 induced follistatin production. Treatment with exogenous follistatin blocks activin A-stimulated cell proliferation, and the overexpression of wild-type FOXL2 attenuates activin A-stimulated cell proliferation. These results suggest that FOXL2 may act as a tumor suppressor in human adult-type GCTs by inducing follistatin expression, which subsequently inhibits activin-stimulated cell proliferation.

  10. Overexpression of activin A in stage IV colorectal cancer

    PubMed Central

    Wildi, S; Kleeff, J; Maruyama, H; Maurer, C; Buchler, M; Korc, M

    2001-01-01

    BACKGROUND AND AIMS—Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-?) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII).?METHODS—Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin ?A and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin ?A localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation.?RESULTS—Inhibin ?A mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin ?B and inhibin ? were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin ?A mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin ?A mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers.?CONCLUSIONS—Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.???Keywords: colorectal cancer; activin ?A; northern blot analysis PMID:11511564

  11. Xnrs and Activin Regulate Distinct Genes during Xenopus Development: Activin Regulates Cell Division

    PubMed Central

    Ramis, Joana M.; Collart, Clara; Smith, James C.

    2007-01-01

    Background The mesoderm of the amphibian embryo is formed through an inductive interaction in which vegetal cells of the blastula-staged embryo act on overlying equatorial cells. Candidate mesoderm-inducing factors include members of the transforming growth factor type ? family such as Vg1, activin B, the nodal-related proteins and derrière. Methodology and Principle Findings Microarray analysis reveals different functions for activin B and the nodal-related proteins during early Xenopus development. Inhibition of nodal-related protein function causes the down-regulation of regionally expressed genes such as chordin, dickkopf and XSox17?/?, while genes that are mis-regulated in the absence of activin B tend to be more widely expressed and, interestingly, include several that are involved in cell cycle regulation. Consistent with the latter observation, cells of the involuting dorsal axial mesoderm, which normally undergo cell cycle arrest, continue to proliferate when the function of activin B is inhibited. Conclusions/Significance These observations reveal distinct functions for these two classes of the TGF-? family during early Xenopus development, and in doing so identify a new role for activin B during gastrulation. PMID:17299593

  12. Activin C Antagonizes Activin A in Vitro and Overexpression Leads to Pathologies in Vivo

    PubMed Central

    Gold, Elspeth; Jetly, Niti; O'Bryan, Moira K.; Meachem, Sarah; Srinivasan, Deepa; Behuria, Supreeti; Sanchez-Partida, L. Gabriel; Woodruff, Teresa; Hedwards, Shelley; Wang, Hong; McDougall, Helen; Casey, Victoria; Niranjan, Birunthi; Patella, Shane; Risbridger, Gail

    2009-01-01

    Activin A is a potent growth and differentiation factor whose synthesis and bioactivity are tightly regulated. Both follistatin binding and inhibin subunit heterodimerization block access to the activin receptor and/or receptor activation. We postulated that the activin-?C subunit provides another mechanism regulating activin bioactivity. To test our hypothesis, we examined the biological effects of activin C and produced mice that overexpress activin-?C. Activin C reduced activin A bioactivity in vitro; in LNCaP cells, activin C abrogated both activin A-induced Smad signaling and growth inhibition, and in L?T2 cells, activin C antagonized activin A-mediated activity of an follicle-stimulating hormone-? promoter. Transgenic mice that overexpress activin-?C exhibited disease in testis, liver, and prostate. Male infertility was caused by both reduced sperm production and impaired sperm motility. The livers of the transgenic mice were enlarged because of an imbalance between hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased evidence of nuclear Smad-2 localization in the testis, liver, and prostate, indicating that overexpression of activin-?C antagonized Smad signaling in vivo. Underlying the significance of these findings, human testis, liver, and prostate cancers expressed increased activin-?C immunoreactivity. This study provides evidence that activin-?C is an antagonist of activin A and supplies an impetus to examine its role in development and disease. PMID:19095948

  13. Activins and inhibins: Novel regulators of thymocyte development

    SciTech Connect

    Licona-Limon, Paula; Aleman-Muench, German; Macias-Silva, Marina; Garcia-Zepeda, Eduardo A.; Fortoul, Teresa I.; Soldevila, Gloria

    2009-04-03

    Activins and inhibins are members of the transforming growth factor-{beta} superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We demonstrate that both activin A and inhibin A promote the DN3-DN4 transition in vitro, although they differentially control the transition to the DP stage. Whereas activin A induces the accumulation of a CD8{sup +}CD24{sup hi}TCR{beta}{sup lo} intermediate subpopulation, inhibin A promotes the differentiation of DN4 to DP. In addition, both activin A and inhibin A appear to promote CD8{sup +}SP differentiation. Moreover, inhibin {alpha} null mice have delayed in vitro T cell development, showing both a decrease in the DN-DP transition and reduced thymocyte numbers, further supporting a role for inhibins in the control of developmental signals taking place during T cell differentiation in vivo.

  14. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response

    PubMed Central

    Antsiferova, Maria; Huber, Marcel; Meyer, Michael; Piwko-Czuchra, Aleksandra; Ramadan, Tamara; MacLeod, Amanda S.; Havran, Wendy L.; Dummer, Reinhard; Hohl, Daniel; Werner, Sabine

    2011-01-01

    Activin is an important orchestrator of wound repair, but its potential role in skin carcinogenesis has not been addressed. Here we show using different types of genetically modified mice that enhanced levels of activin in the skin promote skin tumour formation and their malignant progression through induction of a pro-tumourigenic microenvironment. This includes accumulation of tumour-promoting Langerhans cells and regulatory T cells in the epidermis. Furthermore, activin inhibits proliferation of tumour-suppressive epidermal ?? T cells, resulting in their progressive loss during tumour promotion. An increase in activin expression was also found in human cutaneous basal and squamous cell carcinomas when compared with control tissue. These findings highlight the parallels between wound healing and cancer, and suggest inhibition of activin action as a promising strategy for the treatment of cancers overexpressing this factor. PMID:22146395

  15. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin {beta}E subunit

    SciTech Connect

    Hashimoto, Osamu . E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-03-10

    Activins, TGF-{beta} superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin {beta} subunit genes, {beta}C and {beta}E, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin {beta}E subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells.

  16. Activin inhibits telomerase activity in cancer

    SciTech Connect

    Katik, Indzi; Mackenzie-Kludas, Charley; Nicholls, Craig; Jiang, Fang-Xu; Zhou, Shufeng; Li, He; Liu, Jun-Ping

    2009-11-27

    Activin is a pleiotropic cytokine with broad tissue distributions. Recent studies demonstrate that activin-A inhibits cancer cell proliferation with unknown mechanisms. In this report, we demonstrate that recombinant activin-A induces telomerase inhibition in cancer cells. In breast and cervical cancer cells, activin-A resulted in telomerase activity in a concentration-dependent manner. Significant inhibition was observed at 10 ng/ml of activin-A, with a near complete inhibition at 80 ng/ml. Consistently, activin-A induced repression of the telomerase reverse transcriptase (hTERT) gene, with the hTERT gene to be suppressed by 60-80% within 24 h. In addition, activin-A induced a concomitant increase in Smad3 signaling and decrease of the hTERT gene promoter activity in a concentration-dependent fashion. These data suggest that activin-A triggered telomerase inhibition by down-regulating hTERT gene expression is involved in activin-A-induced inhibition of cancer cell proliferation.

  17. Mutual effects of melatonin and activin on induction of aldosterone production by human adrenocortical cells.

    PubMed

    Hara, Takayuki; Otsuka, Fumio; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Hosoya, Takeshi; Nakamura, Eri; Terasaka, Tomohiro; Komatsubara, Motoshi; Makino, Hirofumi

    2015-08-01

    Melatonin has been reported to suppress adrenocorticotropin (ACTH) secretion in the anterior pituitary and cortisol production in the adrenal by different mechanisms. However, the effect of melatonin on aldosterone production has remained unknown. In this study, we investigated the role of melatonin in the regulation of aldosterone production using human adrenocortical H295R cells by focusing on the activin system expressed in the adrenal. Melatonin receptor MT1 mRNA and protein were expressed in H295R cells and the expression levels of MT1 were increased by activin treatment. Activin increased ACTH-induced, but not angiotensin II (Ang II)-induced, aldosterone production. Melatonin alone did not affect basal synthesis of either aldosterone or cortisol. However, melatonin effectively enhanced aldosterone production induced by co-treatment with ACTH and activin, although melatonin had no effect on aldosterone production induced by Ang II in combination with activin. These changes in steroidogenesis became apparent when the steroid production was evaluated by the ratio of aldosterone/cortisol. Melatonin also enhanced dibutyryl-AMP-induced aldosterone/cortisol levels in the presence of activin, suggesting a functional link to the cAMP-PKA pathway for induction of aldosterone production by melatonin and activin. In accordance with the data for steroids, ACTH-induced, but not Ang II-induced, cAMP synthesis was also amplified by co-treatment with melatonin and activin. Furthermore, the ratio of ACTH-induced mRNA level of CYP11B2 compared with that of CYP17 was amplified in the condition of treatment with both melatonin and activin. In addition, melatonin increased expression of the activin type-I receptor ALK-4 but suppressed expression of inhibitory Smads6/7, leading to the enhancement of Smad2 phosphorylation. Collectively, the results showed that melatonin facilitated aldosterone production induced by ACTH and activin via the cAMP-PKA pathway. The results also suggested that mutual enhancement of melatonin and activin receptor signaling is involved in the induction of aldosterone output by adrenocortical cells. PMID:25889901

  18. RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice.

    PubMed

    Langdon, Jacqueline M; Barkataki, Sangjucta; Berger, Alan E; Cheadle, Chris; Xue, Qian-Li; Sung, Victoria; Roy, Cindy N

    2015-01-01

    Over expression of hepcidin antimicrobial peptide is a common feature of iron-restricted anemia in humans. We investigated the erythroid response to either erythropoietin or RAP-011, a "murinized" ortholog of sotatercept, in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. Sotatercept, a soluble, activin receptor type IIA ligand trap, is currently being evaluated for the treatment of anemias associated with chronic renal disease, myelodysplastic syndrome, ?-thalassemia, and Diamond Blackfan anemia and acts by inhibiting signaling downstream of activin and other Transforming Growth Factor-? superfamily members. We found that erythropoietin and RAP-011 increased hemoglobin concentration in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. While erythropoietin treatment depleted splenic iron stores in C57BL/6 mice, RAP-011 treatment did not deplete splenic iron stores in mice of either genotype. Bone marrow erythroid progenitors from erythropoietin-treated mice exhibited iron-restricted erythropoiesis, as indicated by increased median fluorescence intensity of transferrin receptor immunostaining by flow cytometry. In contrast, RAP-011-treated mice did not exhibit the same degree of iron-restricted erythropoiesis. In conclusion, we have demonstrated that RAP-011 can improve hemoglobin concentration in hepcidin antimicrobial peptide 1 transgenic mice. Our data support the hypothesis that RAP-011 has unique biologic effects which prevent or circumvent depletion of mouse splenic iron stores. RAP-011 may, therefore, be an appropriate therapeutic for trials in human anemias characterized by increased expression of hepcidin antimicrobial peptide and iron-restricted erythropoiesis. PMID:25236856

  19. Activin is a nerve cell survival molecule.

    PubMed

    Schubert, D; Kimura, H; LaCorbiere, M; Vaughan, J; Karr, D; Fischer, W H

    1990-04-26

    The structures of five neurotrophic molecules have so far been published. Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules. More recently, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been cloned and sequenced. As all these proteins stimulate the survival of ciliary or sensory neurons, a new cell survival assay is required if novel neurotrophic molecules are to be discovered. P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10(-7) M retinoic acid (RA). But when P19 cells are plated in N2 synthetic medium without being exposed to RA, they die within 48 h. In an attempt to identify a molecule(s) that can substitute for RA in promoting P19 survival, we assayed serum-free growth-conditioned media for their ability to promote P19 survival. One cell line from the rat eye secreted a molecule that promoted the survival of P19 cells and some types of nerve cell. We identified this molecule as activin, better known for its role in hormone secretion. PMID:2330043

  20. Activin B receptor ALK7 is a negative regulator of pancreatic -cell function

    E-print Network

    Ibáñez, Carlos

    Activin B receptor ALK7 is a negative regulator of pancreatic -cell function Philippe Bertolino cell types in pancreatic islets express the transforming growth factor (TGF)- superfamily receptor ALK7 the specifi- cation and function of pancreatic endocrine cells is of major importance for understanding

  1. Vascular Endothelial Growth Factor-A (VEGF-A) Mediates Activin A-Induced Human Trophoblast Endothelial-Like Tube Formation.

    PubMed

    Li, Yan; Zhu, Hua; Klausen, Christian; Peng, Bo; Leung, Peter C K

    2015-11-01

    Remodeling of maternal spiral arteries during pregnancy requires a subpopulation of extravillous cytotrophoblasts (EVTs) to differentiate into endovascular EVTs. Activin A, which is abundantly expressed at the maternal-fetal interface, has been shown to promote trophoblast invasion, but its role in endovascular differentiation remains unknown. Vascular endothelial growth factor-A (VEGF-A) is well recognized as a key regulator in trophoblast endovascular differentiation. Whether and how activin A might regulate VEGF-A production in human trophoblasts and its relationship to endovascular differentiation have yet to be determined. In the present study, we found that activin A increased VEGF-A production in primary and immortalized (HTR8/SVneo) human EVT cells. In addition, activin A enhanced HTR8/SVneo endothelial-like tube formation, and these effects were attenuated by pretreatment with small interfering RNA targeting VEGF-A or the VEGF receptor 1/2 inhibitor SU4312. Pretreatment with the activin/TGF-? type 1 receptor (ALK4/5/7) inhibitor SB431542 abolished the stimulatory effects of activin A on phosphorylated mothers against decapentaplegic (SMAD)-2/3 phosphorylation, VEGF-A production, and endothelial-like tube formation. Moreover, small interfering RNA-mediated down-regulation of SMAD2, SMAD3, or common SMAD4 abolished the effects of activin A on VEGF-A production and endothelial-like tube formation. In conclusion, activin A may promote human trophoblast cell endothelial-like tube formation by up-regulating VEGF-A production in an SMAD2/3-SMAD4-dependent manner. These findings provide insight into the cellular and molecular events regulated by activin A during human implantation. PMID:26327470

  2. Virtual High-Throughput Screening To Identify Novel Activin Antagonists

    PubMed Central

    Zhu, Jie; Mishra, Rama K.; Schiltz, Gary E.; Makanji, Yogeshwar; Scheidt, Karl A.; Mazar, Andrew P.; Woodruff, Teresa K.

    2015-01-01

    Activin belongs to the TGF? superfamily, which is associated with several disease conditions, including cancer-related cachexia, preterm labor with delivery, and osteoporosis. Targeting activin and its related signaling pathways holds promise as a therapeutic approach to these diseases. A small-molecule ligand-binding groove was identified in the interface between the two activin ?A subunits and was used for a virtual high-throughput in silico screening of the ZINC database to identify hits. Thirty-nine compounds without significant toxicity were tested in two well-established activin assays: FSH? transcription and HepG2 cell apoptosis. This screening workflow resulted in two lead compounds: NUCC-474 and NUCC-555. These potential activin antagonists were then shown to inhibit activin A-mediated cell proliferation in ex vivo ovary cultures. In vivo testing showed that our most potent compound (NUCC-555) caused a dose-dependent decrease in FSH levels in ovariectomized mice. The Blitz competition binding assay confirmed target binding of NUCC-555 to the activin A:ActRII that disrupts the activin A:ActRII complex’s binding with ALK4-ECD-Fc in a dose-dependent manner. The NUCC-555 also specifically binds to activin A compared with other TGF? superfamily member myostatin (GDF8). These data demonstrate a new in silico-based strategy for identifying small-molecule activin antagonists. Our approach is the first to identify a first-in-class small-molecule antagonist of activin binding to ALK4, which opens a completely new approach to inhibiting the activity of TGF? receptor superfamily members. in addition, the lead compound can serve as a starting point for lead optimization toward the goal of a compound that may be effective in activin-mediated diseases. PMID:26098096

  3. Role of Activin-A and Myostatin and Their Signaling Pathway in Human Myometrial and Leiomyoma Cell Function

    PubMed Central

    Islam, Md Soriful; Catherino, William H.; Protic, Olga; Janjusevic, Milijana; Gray, Peter Clarke; Giannubilo, Stefano Raffaele; Ciavattini, Andrea; Lamanna, Pasquale; Tranquilli, Andrea Luigi; Petraglia, Felice

    2014-01-01

    Context: Uterine leiomyomas are highly prevalent benign tumors of premenopausal women and the most common indication for hysterectomy. However, the exact etiology of this tumor is not fully understood. Objective: The objective of the study was to evaluate the role of activin-A and myostatin and their signaling pathways in human myometrial and leiomyoma cells. Design: This was a laboratory study. Setting: Myometrial and leiomyoma cells (primary and cell lines) were cultured in vitro. Patients: The study included premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. Interventions: Primary myometrial and leiomyoma cells and/or cell lines were treated with activin-A (4 nM) and myostatin (4 nM) for different days of interval (to measure proliferation rate) or 30 minutes (to measure signaling molecules) or 48 hours to measure proliferating markers, extracellular matrix mRNA, and/or protein expression by real-time PCR, Western blot, and/or immunocytochemistry. Results: We found that activin-A and myostatin significantly reduce cell proliferation in primary myometrial cells but not in leiomyoma cells as measured by a CyQUANT cell proliferation assay kit. Reduced expression of proliferating cell nuclear antigen and Ki-67 were also observed in myometrial cells in response to activin-A and myostatin treatment. Activin-A also significantly increased mRNA expression of fibronectin, collagen1A1, and versican in primary leiomyoma cells. Finally, we found that activin-A and myostatin activate Smad-2/3 signaling but do not affect ERK or p38 signaling in both myometrial and leiomyoma cells. Conclusions: This study results suggest that activin-A and myostatin can exert antiproliferative and/or fibrotic effects on these cell types via Smad-2/3 signaling. PMID:24606069

  4. Human Umbilical Cord-Derived Mesenchymal Stem Cells Utilize Activin-A to Suppress Interferon-? Production by Natural Killer Cells

    PubMed Central

    Chatterjee, Debanjana; Marquardt, Nicole; Tufa, Dejene Milkessa; Hatlapatka, Tim; Hass, Ralf; Kasper, Cornelia; von Kaisenberg, Constantin; Schmidt, Reinhold Ernst; Jacobs, Roland

    2014-01-01

    Following allogeneic hematopoietic stem cell transplantation (HSCT), interferon (IFN)-? levels in the recipient’s body can strongly influence the clinical outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are lucrative as biological tolerance-inducers in HSCT settings. Hence, we studied the molecular mechanism of how UC-MSCs influence natural killer (NK) cell-mediated IFN-? production. Allogeneic NK cells were cultured in direct contact with UC-MSCs or cell-free supernatants from mesenchymal stem cell (MSC) cultures (MSC-conditioned media). We found that soluble factors secreted by UC-MSCs strongly suppressed interleukin (IL)-12/IL-18-induced IFN-? production by NK cells by reducing phosphorylation of STAT4, NF-?B, as well as T-bet activity. UC-MSCs secreted considerable amounts of activin-A, which could suppress IFN-? production by NK cells. Neutralization of activin-A in MSC-conditioned media significantly abrogated their suppressive abilities. Till date, multiple groups have reported that prostaglandin (PG)-E2 produced by MSCs can suppress NK cell functions. Indeed, we found that inhibition of PGE2 production by MSCs could also significantly restore IFN-? production. However, the effects of activin-A and PGE2 were not cumulative. To the best of our knowledge, we are first to report the role of activin-A in MSC-mediated suppression of IFN-? production by NK cells. PMID:25584044

  5. Activin A-Induced HepG2 Liver Cell Apoptosis: Involvement of Activin Receptors and Smad Proteins*

    E-print Network

    Mayo, Kelly E.

    Activin A-Induced HepG2 Liver Cell Apoptosis: Involvement of Activin Receptors and Smad Proteins and apoptosis is important for regulating normal liver function. Proteins of the transforming growth factor- superfamily are known to be important mediators of apopto- sis in the liver. In this study we demonstrate

  6. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A.

    PubMed

    Hatsell, Sarah J; Idone, Vincent; Wolken, Dana M Alessi; Huang, Lily; Kim, Hyon J; Wang, Lili; Wen, Xialing; Nannuru, Kalyan C; Jimenez, Johanna; Xie, Liqin; Das, Nanditha; Makhoul, Genevieve; Chernomorsky, Rostislav; D'Ambrosio, David; Corpina, Richard A; Schoenherr, Christopher J; Feeley, Kieran; Yu, Paul B; Yancopoulos, George D; Murphy, Andrew J; Economides, Aris N

    2015-09-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodically exuberant heterotopic ossification (HO), whereby skeletal muscle is abnormally converted into misplaced, but histologically normal bone. This HO leads to progressive immobility with catastrophic consequences, including death by asphyxiation. FOP results from mutations in the intracellular domain of the type I BMP (bone morphogenetic protein) receptor ACVR1; the most common mutation alters arginine 206 to histidine (ACVR1(R206H)) and has been thought to drive inappropriate bone formation as a result of receptor hyperactivity. We unexpectedly found that this mutation rendered ACVR1 responsive to the activin family of ligands, which generally antagonize BMP signaling through ACVR1 but cannot normally induce bone formation. To test the implications of this finding in vivo, we engineered mice to carry the Acvr1(R206H) mutation. Because mice that constitutively express Acvr1[R206H] die perinatally, we generated a genetically humanized conditional-on knock-in model for this mutation. When Acvr1[R206H] expression was induced, mice developed HO resembling that of FOP; HO could also be triggered by activin A administration in this mouse model of FOP but not in wild-type controls. Finally, HO was blocked by broad-acting BMP blockers, as well as by a fully human antibody specific to activin A. Our results suggest that ACVR1(R206H) causes FOP by gaining responsiveness to the normally antagonistic ligand activin A, demonstrating that this ligand is necessary and sufficient for driving HO in a genetically accurate model of FOP; hence, our human antibody to activin A represents a potential therapeutic approach for FOP. PMID:26333933

  7. Adipose Stromal Cell Contact with Endothelial Cells Results in Loss of Complementary Vasculogenic Activity Mediated by Induction of Activin A.

    PubMed

    Merfeld-Clauss, Stephanie; Lupov, Ivan P; Lu, Hongyan; March, Keith L; Traktuev, Dmitry O

    2015-10-01

    Adipose stem/stromal cells (ASCs) after isolation produce numerous angiogenic growth factors. This justifies their use to promote angiogenesis per transplantation. In parallel, local coimplantation of ASC with endothelial cells (ECs) leading to formation of functional vessels by the donor cells suggests the existence of a mechanism responsible for fine-tuning ASC paracrine activity essential for vasculogenesis. As expected, conditioned media (CM) from ASC promoted ECs survival, proliferation, migration, and vasculogenesis. In contrast, media from EC-ASC cocultures had neutral effects upon EC responses. Media from cocultures exhibited lower levels of vascular endothelial growth factor (VEGF), hepatic growth factor, angiopoietin-1, and stromal cell-derived factor-1 compared with those in ASC CM. Activin A was induced in ASC in response to EC exposure and was responsible for overall antivasculogenic activity of EC-ASC CM. Except for VEGF, activin A diminished secretion of all tested factors by ASC. Activin A mediated induction of VEGF expression in ASC, but also upregulated expression of VEGF scavenger receptor FLT-1 in EC in EC-ASC cocultures. Blocking the FLT-1 expression in EC led to an increase in VEGF concentration in CM. In vitro pre-exposure of ASC to low number of EC before subcutaneous coimplantation with EC resulted in decrease in vessel density in the implants. In vitro tests suggested that activin A was partially responsible for this diminished ASC activity. This study shows that neovessel formation is associated with induction of activin A expression in ASC; this factor, by affecting the bioactivity of both ASC and EC, directs the crosstalk between these complementary cell types to establish stable vessels. Stem Cells 2015;33:3039-3051. PMID:26037810

  8. Activin A and Follistatin Influence Expression of Somatostatin in the Ciliary Ganglion in Vivo

    E-print Network

    Nishi, Rae

    Activin A and Follistatin Influence Expression of Somatostatin in the Ciliary Ganglion in Vivo of activin A and its endogenous inhibitor follistatin in CG neuron target tissues are responsible for selective expression of somatostatin in choroid neurons. Intraocular injection of activin A or follistatin

  9. Activin-A in Myometrium: Characterization of the Actions on Myometrial Cells

    PubMed Central

    Ciarmela, Pasquapina; Wiater, Ezra; Vale, Wylie

    2008-01-01

    Activin is a pleiotropic growth factor with a broad pattern of tissue distribution that includes reproductive tissues. Although direct actions of activin have been described in gonadal and uterine tissues, actions in the myometrium have not been defined. In this study we have characterized the responsiveness of uterine tissue and myometrial cell lines to activin-A. Uterine tissue and two myometrial cell lines, PHM1 (pregnant human myometrial 1) and hTERT HM (telomerase reverse transcriptase-infected human myometrial) respond to activin-A as measured by phosphorylation of Smad-2. Those cell lines express a full complement of activin receptors, as well as activin ?A subunit and follistatin. Activin inhibited proliferation of PHM1 and human telomerase reverse transcriptase-infected human myometrial cell line cells, with more extensive growth inhibition observed in PHM1s. In PHM1s, activin-A decreased oxytocin receptor and HoxA-10 mRNA expression but did not alter total progesterone receptor, cyclooxygenase-2 (Cox-2), and connexin 43 mRNA expression levels. Furthermore, treatment of PHM1 myometrial cells with activin-A attenuated oxytocin and thromboxaneA2 induced intracellular Ca2+ accumulation. In conclusion, myometrial cells are activin sensitive, and activin-A can regulate myometrial cell functions. PMID:18239071

  10. Antiviral activities of the soluble extracellular domains of type I interferon receptors

    PubMed Central

    Han, Chun-Sheng; Chen, Yizhen; Ezashi, Toshihiko; Roberts, R. Michael

    2001-01-01

    Alternative splicing leads to the expression of multiple isoforms of the subunits (IFNAR1 and IFNAR2) of the type I IFN receptor. Here we describe two transcripts representing extracellular forms of ovine IFNAR1 and show that soluble extracellular forms of both IFNAR2 and IFNAR1, prepared in recombinant form in Escherichia coli, have antiviral (AV) activity in the absence of IFN. Exposure of Madin-Darby bovine kidney cells to the extracellular domain (R2E) of IFNAR2 at concentrations as low as 10 nM afforded complete protection against vesicular stomatitis virus and led to the rapid activation of the transcription factors ISGF3 and GAF. Although R2E can bind IFN (Kd ?70 nM), activity was observed irrespective of whether or not ligand was present. R2E was inactive on mouse L929 cells but active on L929 cells expressing a membraneanchored, ovine/human chimeric IFNAR2 with an ovine extracellular domain. The data suggest that AV activity is conferred by the ability of soluble R2E to associate with the transfected IFNAR2 subunit rather than resident murine IFNAR1. Soluble extracellular forms of IFNAR1 have lower AV activity than R2E on Madin-Darby bovine kidney cells but are less species-specific and protect wild-type L929 cells as efficiently as the transfected cell line, presumably by interacting with one of the murine receptor subunits. PMID:11344274

  11. X-ray structure of a soluble Rieske-type ferredoxin from Mus musculus

    SciTech Connect

    Levin, Elena J.; Elsen, Nathaniel L.; Seder, Kory D.; McCoy, Jason G.; Fox, Brian G; Phillips, Jr., George N.

    2009-03-11

    The 2.07 {angstrom} resolution X-ray crystal structure of a soluble Rieske-type ferredoxin from Mus musculus encoded by the gene Mm.266515 is reported. Although they are present as covalent domains in eukaryotic membrane oxidase complexes, soluble Rieske-type ferredoxins have not previously been observed in eukaryotes. The overall structure of the mouse Rieske-type ferredoxin is typical of this class of iron-sulfur proteins and consists of a larger partial {beta}-barrel domain and a smaller domain containing Cys57, His59, Cys80 and His83 that binds the [2Fe-2S] cluster. The S atoms of the cluster are hydrogen-bonded by six backbone amide N atoms in a pattern typical of membrane-bound high-potential eukaryotic respiratory Rieske ferredoxins. However, phylogenetic analysis suggested that the mouse Rieske-type ferredoxin was more closely related to bacterial Rieske-type ferredoxins. Correspondingly, the structure revealed an extended loop most similar to that seen in Rieske-type ferredoxin subunits of bacterial aromatic dioxygenases, including the positioning of an aromatic side chain (Tyr85) between this loop and the [2Fe-2S] cluster. The mouse Rieske-type ferredoxin was shown to be capable of accepting electrons from both eukaryotic and prokaryotic oxidoreductases, although it was unable to serve as an electron donor for a bacterial monooxygenase complex. The human homolog of mouse Rieske-type ferredoxin was also cloned and purified. It behaved identically to mouse Rieske-type ferredoxin in all biochemical characterizations but did not crystallize. Based on its high sequence identity, the structure of the human homolog is likely to be modeled well by the mouse Rieske-type ferredoxin structure.

  12. Activin stimulates CYP19A gene expression in human ovarian granulosa cell-like KGN cells via the Smad2 signaling pathway.

    PubMed

    Nomura, Masatoshi; Sakamoto, Ryuichi; Morinaga, Hidetaka; Wang, Lixiang; Mukasa, Chizu; Takayanagi, Ryoichi

    2013-07-01

    Activin, a transforming growth factor ? family member, has a wide range of physiological roles during embryonic development and organogenesis. In the ovary, activin, secreted from ovarian granulosa cells, not only acts on the pituitary gland to regulate the gonadotropin secretion from the pituitary gland in an endocrine manner but also acts on granulosa cells in a paracrine/autocrine manner to regulate folliculogenesis. Previously, we showed that activin signals through activin type IB receptor (ActRIB) and up-regulates follicle-stimulating hormone receptor expression and P450 aromatase activity in human ovarian granulose cell-like KGN cells. In the current study, we demonstrate the direct involvement of Smad2 as a downstream signal mediator of ActRIB in the transcriptional regulation of the P450 aromatase gene (CYP19A) in KGN cells. Upon activin stimulation, Smad2 activation and an increase in P450 aromatase messenger RNA (mRNA) were observed in KGN cells. Interestingly, Smad2 phosphorylation correlated well with the increase in P450 aromatase mRNA. Reciprocally, knockdown of Smad2 mRNA in KGN cells led to a decrease in the P450 aromatase mRNA expression, suggesting that Smad2 regulates CYP19A gene expression. Further analysis of CYP19A promoter activity revealed that the 5' upstream region between -2069 and -1271bp is required for the activation by Smad2. Finally, we provide compelling evidence that Smad2 shows follicular stage-specific expression, which is high in granulosa cells of preantral or early antral follicles in mice. Our results suggest that activin signaling through the ActRIB-Smad2 pathway plays a pivotal role in CYP19A expression and thus in follicular development. PMID:23747729

  13. X-ray structure of a soluble Rieske-type ferredoxin from Mus musculus

    SciTech Connect

    Levin, Elena J.; Elsen, Nathaniel L.; Seder, Kory D.; McCoy, Jason G.; Fox, Brian G.; Phillips Jr, George N.

    2008-09-01

    The X-ray crystal structure of a soluble Rieske ferredoxin from M. musculus was solved at 2.07 Å resolution, revealing an iron–sulfur cluster-binding domain with similar architecture to the Rieske-type domains of bacterial aromatic dioxygenases. The ferredoxin was also shown to be capable of accepting electrons from both eukaryotic and prokaryotic oxidoreductases. The 2.07 Å resolution X-ray crystal structure of a soluble Rieske-type ferredoxin from Mus musculus encoded by the gene Mm.266515 is reported. Although they are present as covalent domains in eukaryotic membrane oxidase complexes, soluble Rieske-type ferredoxins have not previously been observed in eukaryotes. The overall structure of the mouse Rieske-type ferredoxin is typical of this class of iron–sulfur proteins and consists of a larger partial ?-barrel domain and a smaller domain containing Cys57, His59, Cys80 and His83 that binds the [2Fe–2S] cluster. The S atoms of the cluster are hydrogen-bonded by six backbone amide N atoms in a pattern typical of membrane-bound high-potential eukaryotic respiratory Rieske ferredoxins. However, phylogenetic analysis suggested that the mouse Rieske-type ferredoxin was more closely related to bacterial Rieske-type ferredoxins. Correspondingly, the structure revealed an extended loop most similar to that seen in Rieske-type ferredoxin subunits of bacterial aromatic dioxygenases, including the positioning of an aromatic side chain (Tyr85) between this loop and the [2Fe–2S] cluster. The mouse Rieske-type ferredoxin was shown to be capable of accepting electrons from both eukaryotic and prokaryotic oxidoreductases, although it was unable to serve as an electron donor for a bacterial monooxygenase complex. The human homolog of mouse Rieske-type ferredoxin was also cloned and purified. It behaved identically to mouse Rieske-type ferredoxin in all biochemical characterizations but did not crystallize. Based on its high sequence identity, the structure of the human homolog is likely to be modeled well by the mouse Rieske-type ferredoxin structure.

  14. Activin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary*

    E-print Network

    Mayo, Kelly E.

    , inflammation, renal tubule morphogenesis, and neuroprotection. In the reproductive system, in addition to regActivin Regulates Estrogen Receptor Gene Expression in the Mouse Ovary* Received for publication of Obstetrics and Gynecology, and § Center for Reproductive Science, Northwestern University, Evanston, Illinois

  15. Action of T-activin on activity of human natural killer cells in vitro

    SciTech Connect

    Cheknev, S.B.; Saidov, M.Z.; Koval'chuk, L.V.; Pavlyuk, A.S.; Arion, V.Ya.

    1986-09-01

    This paper describes a study of the action of T-activin on activity of human natural killer cells (NKC) in vitro. The K-562 chronic human myeloid leukemia cells, cultured in vitro, used as targets were labeled with /sup 3/H-uridine. The experimental results indicate that T-activin can depress NKC activity but under certain conditions, it can also stimulate NKC. T-activin possesses immunoregulatory properties relative to NKC activity in vitro.

  16. The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology.

    PubMed

    Hardy, Charles L; King, Susannah J; Mifsud, Nicole A; Hedger, Mark P; Phillips, David J; Mackay, Fabienne; de Kretser, David M; Wilson, John W; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-07-01

    Cystic fibrosis (CF) is the most common life-limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (?-ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn ?-ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of ?-ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof-of-concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long-term management of lung disease in CF patients. PMID:25753271

  17. The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology

    PubMed Central

    Hardy, Charles L; King, Susannah J; Mifsud, Nicole A; Hedger, Mark P; Phillips, David J; Mackay, Fabienne; de Kretser, David M; Wilson, John W; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-01-01

    Cystic fibrosis (CF) is the most common life-limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (?-ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn ?-ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of ?-ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof-of-concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long-term management of lung disease in CF patients. PMID:25753271

  18. Acute modulation of synaptic plasticity of pyramidal neurons by activin in adult hippocampus

    PubMed Central

    Hasegawa, Yoshitaka; Mukai, Hideo; Asashima, Makoto; Hojo, Yasushi; Ikeda, Muneki; Komatsuzaki, Yoshimasa; Ooishi, Yuuki; Kawato, Suguru

    2014-01-01

    Activin A is known as a neuroprotective factor produced upon acute excitotoxic injury of the hippocampus (in pathological states). We attempt to reveal the role of activin as a neuromodulator in the adult male hippocampus under physiological conditions (in healthy states), which remains largely unknown. We showed endogenous/basal expression of activin in the hippocampal neurons. Localization of activin receptors in dendritic spines (=postsynapses) was demonstrated by immunoelectron microscopy. The incubation of hippocampal acute slices with activin A (10 ng/mL, 0.4 nM) for 2 h altered the density and morphology of spines in CA1 pyramidal neurons. The total spine density increased by 1.2-fold upon activin treatments. Activin selectively increased the density of large-head spines, without affecting middle-head and small-head spines. Blocking Erk/MAPK, PKA, or PKC prevented the activin-induced spinogenesis by reducing the density of large-head spines, independent of Smad-induced gene transcription which usually takes more than several hours. Incubation of acute slices with activin for 2 h induced the moderate early long-term potentiation (moderate LTP) upon weak theta burst stimuli. This moderate LTP induction was blocked by follistatin, MAPK inhibitor (PD98059) and inhibitor of NR2B subunit of NMDA receptors (Ro25-6981). It should be noted that the weak theta burst stimuli alone cannot induce moderate LTP. These results suggest that MAPK-induced phosphorylation of NMDA receptors (including NR2B) may play an important role for activin-induced moderate LTP. Taken together, the current results reveal interesting physiological roles of endogenous activin as a rapid synaptic modulator in the adult hippocampus. PMID:24917791

  19. Neonatal Exposure to Estrogens Suppresses Activin Expression and Signaling in the Mouse Ovary

    E-print Network

    Mayo, Kelly E.

    Neonatal Exposure to Estrogens Suppresses Activin Expression and Signaling in the Mouse Ovary of the key factors involved in activin signaling in the mouse ovary. CD-1 mouse pups were given daily of estrogen action in the early mouse ovary. (Endocrinology 148: 1968­1976, 2007) OVARIAN FOLLICLE DEVELOPMENT

  20. Activin A is anti-lymphangiogenic in a melanoma mouse model.

    PubMed

    Heinz, Magdalena; Niederleithner, Heide Leb; Puujalka, Emmi; Soler-Cardona, Ana; Grusch, Michael; Pehamberger, Hubert; Loewe, Robert; Petzelbauer, Peter

    2015-01-01

    Melanoma spreads primarily to the sentinel lymph nodes, and its risk correlates with lymphangiogenesis, which is mainly driven by vascular endothelial growth factor (VEGF)-C. However, anti-lymphangiogenic factors are poorly characterized. We have shown in a melanoma model that Wnt1 reduces lymphangiogenesis by reducing VEGF-C expression. Screening this model for additional potentially anti-lymphangiogenic factors identified increased activin A expression and reduced expression of the antagonist, follistatin (FST), in Wnt1(+) cells. Activin A is known to reduce blood vessel formation, but the effects on lymphangiogenesis are unknown. Here we show that human primary melanoma expresses significantly higher levels of activin A and lower levels of FST compared with nevi and melanoma metastasis. Using our mouse model with melanoma cells overexpressing Wnt1, FST, Wnt1/FST, or the inhibin ?A subunit (INHBA, resulting in activin A expression), we found both activin A and Wnt1 to reduce lymphangiogenesis. Whereas Wnt1 also reduced metastasis, this was not seen with activin A. In vitro, activin A phosphorylated SMAD2 in both melanoma and lymphatic endothelium but, although it reduced sprouting of lymphatic endothelium, it enhanced the migration of melanoma cells. In conclusion, activin A is an anti-lymphangiogenic factor, but because of its pleiotropic effects on cell mobility it appears not suitable as a pharmacological target. PMID:25084052

  1. Gram-Negative Bacterial Lipopolysaccharide Stimulates Activin A Secretion from Human Amniotic Epithelial Cells

    PubMed Central

    Marukawa, Risa; Tsuru, Nami; Sato, Maki; Matsuda, Hiroko; Sadakata, Hisanobu; Minegishi, Takashi

    2013-01-01

    Activin A is involved in inflammation. The present study was performed to clarify if lipopolysaccharide, a component of Gram-negative bacteria, stimulates activin A secretion from human amniotic epithelial cells and to determine if activin A plays a role in amnionitis. Fetal membranes were obtained during elective cesarean sections performed in full-term pregnancies of patients without systemic disease, signs of premature delivery, or fetal complications. Amniotic epithelial cells were isolated by trypsinization. The activin A concentrations in the culture media were measured by enzyme-linked immunosorbent assay, and cell proliferation was assessed by 5-bromo-2?-deoxyuridine incorporation. Amniotic epithelial cells secreted activin A in a cell density-dependent manner, and lipopolysaccharide (10??g/mL) enhanced the secretion at each cell density. Lipopolysaccharide (10–50??g/mL) also stimulated activin A secretion in a dose-dependent manner. Contrary to the effect of activin A secretion, lipopolysaccharide inhibited cell proliferation in amniotic epithelial cells. The present study suggests that lipopolysaccharide stimulation of activin A secretion may be a mechanism in the pathogenesis of amnionitis. PMID:23956746

  2. Activin-?C modulates cachexia by repressing the ubiquitin-proteasome and autophagic degradation pathways

    PubMed Central

    Marino, Francesco Elia; Risbridger, Gail; Gold, Elspeth

    2015-01-01

    Background Cancer-associated cachexia and muscle wasting are considered key determinants of cancer-related death and reduction in the quality of life of cancer patients. A crucial link has been established between activin signaling and skeletal muscle atrophy-hypertrophy. We previously showed that activin-?C, a novel activin-A antagonist, is a tumor modulator that abolishes the cancer-associated cachexia in a mouse genetic model of gonadal tumorigenesis, in which the normal balance of inhibin/activin signalling is disrupted by a targeted mutation in the Inha gene (inhibin ?-KO mouse). This study aimed to identify the molecular mechanism by which activin-?C increases survival and abolishes cancer-associated cachexia in ?-KO mice. We hypothesized that overexpression of activin-?C modulates the cachexia phenotype by antagonizing the activin signaling pathway and repressing muscle wasting via the ubiquitin-proteasome and the autophagic-lysosomal degradation pathways. Methods Male and female ActC++, ?-KO, and ?-KO/ActC++ mice and WT littermate controls were studied. Western blot analysis for the specific E3 ubiquitin ligases, atrogin-1 and MuRF1, markers of the autophagic-lysosomal pathway, Beclin-1, p62, and LC3A/B, effectors Smad-2, Smad-3 and myostatin was performed in the gastrocnemius of age-matched mice. Histopathology of the gastrocnemius and survival analysis were also conducted in animals from the same breeding cohort. Serum levels of activin-A, inflammatory cytokines, hormonal profile, and bone density were also assessed. Results Increased levels of atrogin-1, MuRF-1, Beclin-1, p62, LC3A/B-I, Smad-2 and serum levels of activin-A were noted in the ?-KO mice. These mice developed gonadal cancers followed by severe weight loss, and reduced survival. Overexpression of activin- ?C antagonized the activin signaling cascade, attenuating the ubiquitin-proteasome and the autophagic-lysosomal degradation pathways, and reduced serum levels of activin-A. ?-KO/ActC++ mice displayed a less aggressive cachectic phenotype, reduced tumor weight, and prolonged survival. Conclusion Our findings show for the first time a specific effect of activin-?C on muscle wasting and transcription factors involved in muscle protein degradation. The study indicates that activin-?C may be a novel therapy to abrogate cancer-associated weight loss and prolong survival.

  3. The immunoregulatory and fibrotic roles of activin A in allergic asthma

    PubMed Central

    Hardy, C L; Rolland, J M; O'Hehir, R E

    2015-01-01

    Activin A, a member of the TGF-? superfamily of cytokines, was originally identified as an inducer of follicle stimulating hormone release, but has since been ascribed roles in normal physiological processes, as an immunoregulatory cytokine and as a driver of fibrosis. In the last 10–15 years, it has also become abundantly clear that activin A plays an important role in the regulation of asthmatic inflammation and airway remodelling. This review provides a brief introduction to the activin A/TGF-? superfamily, focussing on the regulation of receptors and signalling pathways. We examine the contradictory evidence for generalized pro- vs. anti-inflammatory effects of activin A in inflammation, before appraising its role in asthmatic inflammation and airway remodelling specifically by evaluating data from both murine models and clinical studies. We identify key issues to be addressed, paving the way for safe exploitation of modulation of activin A function for treatment of allergic asthma and other inflammatory lung diseases. PMID:25962695

  4. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

    PubMed

    Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

    2015-03-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24?h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  5. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

    PubMed Central

    Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

    2014-01-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  6. Activin signaling disruption in the cochlea does not influence hearing in adult mice.

    PubMed

    Horvath, Lukas; Bodmer, Daniel; Radojevic, Vesna; Monge Naldi, Arianne

    2015-01-01

    Activin, a member of the TGF-F superfamily, was found to play an important role in the development, repair and apoptosis of different tissues and organs. Accordingly, activin signaling is involved in the development of the cochlea. Activin binds to its receptor ActRII, then dimerizes with ActRI and induces a signaling pathway resulting in gene expression. A study reported a case of fibrodysplasia ossificans progressiva with an unusual mutation in the ActRI gene leading to sensorineural hearing loss. This draws attention to the role of activin and its receptors in the developed cochlea. To date, only the expression of ActRII is known in the adult mammalian cochlea. In this study, we present for the first time the presence of activin A and ActRIB in the adult cochlea. Transgenic mice with postnatal dominant-negative ActRIB expression causing disruption of activin signaling in vivo were used for assessing cochlear morphology and hearing ability through the auditory brainstem response (ABR) threshold. Nonfunctioning ActRIB did not affect the ABR thresholds and did not alter the microscopic anatomy of the cochlea. We conclude, therefore, that activin signaling is not necessary for hearing in adult mice under physiological conditions but may be important during and after damaging events in the inner ear. PMID:25428170

  7. The potential role of activin and follistatin in lung transplant dysfunction.

    PubMed

    Snell, James N; Westall, Glen P; Snell, Gregory I

    2015-12-01

    Activin A, a member of the transforming growth factor ? super-family, is a key regulator of multiple biological pathways including the physiological processes of organ development and homeostasis; as well as the pathological processes of inflammation, remodelling and fibrosis. Dysregulation of activin A and its naturally occurring antagonist follistatin, contribute to the development of disease in multiple organ systems. In this review, we summarize the regulation of activin A, its dysregulated expression in a number of respiratory diseases and postulate its potential role in contributing to allograft dysfunction following lung transplantation. PMID:26465827

  8. An Activin Receptor IA/Activin-Like Kinase-2 (R206H) Mutation in Fibrodysplasia Ossificans Progressiva.

    PubMed

    Herrera-Esparza, Rafael; Pacheco-Tovar, Deyanira; Bollain-Y-Goytia, Juan José; Torres Del Muro, Felipe; Ramírez-Sandoval, Roxana; Pacheco-Tovar, María Guadalupe; Castañeda-Ureña, María; Avalos-Díaz, Esperanza

    2013-01-01

    Fibrodysplasia ossificans progressiva (FOP) is an exceptionally rare genetic disease that is characterised by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomical areas. This disease is caused by a mutation in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2). A Mexican family with one member affected by FOP was studied. The patient is a 19-year-old female who first presented with symptoms of FOP at 8 years old; she developed spontaneous and painful swelling of the right scapular area accompanied by functional limitation of movement. Mutation analysis was performed in which genomic DNA as PCR amplified using primers flanking exons 4 and 6, and PCR products were digested with Cac8I and HphI restriction enzymes. The most informative results were obtained with the exon 4 flanking primers and the Cac8I restriction enzyme, which generated a 253 bp product that carries the ACVR1 617G>A mutation, which causes an amino acid substitution of histidine for arginine at position 206 of the glycine-serine (GS) domain, and its mutation results in the dysregulation of bone morphogenetic protein (BMP) signalling that causes FOP. PMID:23653868

  9. Humidity effects on soluble core mechanical and thermal properties (polyvinyl alcohol/microballoon composite) type CG extendospheres, volume 2

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This document constitutes the final report for the study of humidity effects and loading rate on soluble core (PVA/MB composite material) mechanical and thermal properties under Contract No. 100345. This report describes test results procedures employed, and any unusual occurrences or specific observations associated with this test program. The primary objective of this work was to determine if cured soluble core filler material regains its tensile and compressive strength after exposure to high humidity conditions and following a drying cycle. Secondary objectives include measurements of tensile and compressive modulus, and Poisson's ratio, and coefficient of thermal expansion (CTE) for various moisture exposure states. A third objective was to compare the mechanical and thermal properties of the composite using 'SG' and 'CG' type extendospheres. The proposed facility for the manufacture of soluble cores at the Yellow Creek site incorporates no capability for the control of humidity. Recent physical property tests performed with the soluble core filler material showed that prolonged exposure to high humidity significantly degradates in strength. The purpose of these tests is to determine if the product, process or facility designs require modification to avoid imparting a high risk condition to the ASRM.

  10. Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome.

    PubMed

    Pruitt, J H; Welborn, M B; Edwards, P D; Harward, T R; Seeger, J W; Martin, T D; Smith, C; Kenney, J A; Wesdorp, R I; Meijer, S; Cuesta, M A; Abouhanze, A; Copeland, E M; Giri, J; Sims, J E; Moldawer, L L; Oldenburg, H S

    1996-04-15

    Plasma interleukin-1 (IL-1) activity is modulated in part through the simultaneous appearance of several inhibitors of IL-1 action, including interleukin-1 receptor antagonist (IL-1ra) and the soluble IL-1 type II receptor (IL-1RII). However, little is known concerning the plasma appearance of these inhibitors in patients following operative trauma or those with sepsis syndrome. In the present report, plasma IL-1beta, IL-1ra, and soluble IL-1RI and IL-1RII concentrations were evaluated in 118 patients with sepsis syndrome or after elective operative trauma. Plasma concentrations of IL-1ra increased significantly following elective operative repair of thoraco-abdominal and abdominal aortic aneurysms, and after bowel resection for inflammatory bowel disease, but did not increase after laparoscopic cholecystectomy. Plasma IL-1ra levels were also elevated in patients with sepsis syndrome. In contrast, soluble IL-1RII levels were only increased in patients after operative repair of thoraco-abdominal aortic aneurysms and in sepsis syndrome, whereas concentrations were unaffected by the other more modest surgical procedures. Plasma IL-1RI concentrations decreased in all postoperative patients in the first 24 hours after surgery. We conclude that both plasma IL-1ra and soluble IL-1RII concentrations often increase in sepsis and following some operative trauma. Less severe operative trauma increases the plasma concentration of only IL-1ra, whereas both IL-1ra and soluble IL-1RII are increased in patients with sepsis syndrome or following thoraco-abdominal aneurysm repair. PMID:8605344

  11. Minireview: Activin Signaling in Gonadotropes: What Does the FOX say… to the SMAD?

    PubMed

    Fortin, Jérôme; Ongaro, Luisina; Li, Yining; Tran, Stella; Lamba, Pankaj; Wang, Ying; Zhou, Xiang; Bernard, Daniel J

    2015-07-01

    The activins were discovered and named based on their abilities to stimulate FSH secretion and FSH? (Fshb) subunit expression by pituitary gonadotrope cells. According to subsequent in vitro observations, activins also stimulate the transcription of the GnRH receptor (Gnrhr) and the activin antagonist, follistatin (Fst). Thus, not only do activins stimulate FSH directly, they have the potential to regulate both FSH and LH indirectly by modulating gonadotrope sensitivity to hypothalamic GnRH. Moreover, activins may negatively regulate their own actions by stimulating the production of one of their principal antagonists. Here, we describe our current understanding of the mechanisms through which activins regulate Fshb, Gnrhr, and Fst transcription in vitro. The activin signaling molecules SMAD3 and SMAD4 appear to partner with the winged-helix/forkhead transcription factor, forkhead box L2 (FOXL2), to regulate expression of all 3 genes. However, in vivo data paint a different picture. Although conditional deletion of Foxl2 and/or Smad4 in murine gonadotropes produces impairments in FSH synthesis and secretion as well as in pituitary Fst expression, Gnrhr mRNA levels are either unperturbed or increased in these animals. Surprisingly, gonadotrope-specific deletion of Smad3 alone or with Smad2 does not impair FSH production or fertility; however, mice harboring these mutations may express a DNA binding-deficient, but otherwise functional, SMAD3 protein. Collectively, the available data firmly establish roles for FOXL2 and SMAD4 in Fshb and Fst expression in gonadotrope cells, whereas SMAD3's role requires further investigation. Gnrhr expression, in contrast, appears to be FOXL2, SMAD4, and, perhaps, activin independent in vivo. PMID:25942106

  12. Expression changes of activin A in the development of hepatic fibrosis

    PubMed Central

    Huang, Xin; Li, Ding Guo; Wang, Zhi Rong; Wei, Hong Shan; Cheng, Ji Lin; Zhan, Yu Tao; Zhou, Xin; Xu, Qin Fang; Li, Xin; Lu, Han Ming

    2001-01-01

    AIM: To examine the expression of activin A, a member of the transforming growth factor (TGF-?) superfamily, recently has been reported to beoverexpressed in liver cirrhosis, in the course of carbon tetrachloride-induced rat hepatic fibrosis. METHODS: Hepatic fibrosis was induced in rats by subcutaneous injections of 40% carbon tetrachloride oily solution for a period of 1 to 7 weeks. At the end of 1, 2, 3, 4, 5, 6 and 7 weeks after carbon tetrachloride injections, the rats were killed in group (6-10 rats each time) for study. The activin A messenger RNA expression and its protein localization were assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The normal rat liver expressed activin A mRNA and protein, and its expression was transiently decreased and became undetectable after carbon tetrachloride injections for 2 or 3 weeks and then increased gradually. After injection of carbon tetrachloride for 6 and 7 weeks, activin A mRNA and protein expressions were significantly enchanced in rat liver. Compared with that of the normal rat liver. Activin A mRNA expression levels in rats receiving carbon tetrachloride injections for 6 and 7 weeks were 1.6 and 2.2 times that of those in normal rat liver respectively (0.456 ± 0.094 vs 0.286 ± 0.0670, P < 0.01; 0.620 ± 0.134 vs 0.286 ± 0.0670, P < 0.01). Immunohistochemistry showed that activin A expressed in hepatocytes of normal liver, and its expression was decreased in rats receiving carbon tetrachloride for 2 or 3 weeks. Compared with normal liver, activin A expression distribution mode changed in fibrotic liver, being increased significantly in hepatocytes around fibrotic areas. CONCLUSION: Activin A expression was increased in late stage of hepatic fibrosis, and this may be involved in hepatic fibrosis formation in this period. PMID:11819730

  13. Solubility of 238U radionuclide from various types of soil in synthetic gastrointestinal fluids using "US in vitro" digestion method

    NASA Astrophysics Data System (ADS)

    Rashid, Nur Shahidah Abdul; Sarmani, Sukiman; Majid, Amran Ab.; Mohamed, Faizal; Siong, Khoo Kok

    2015-04-01

    238U radionuclide is a naturally occuring radioactive material that can be found in soil. In this study, the solubility of 238U radionuclide obtained from various types of soil in synthetic gastrointestinal fluids was analysed by "US P in vitro" digestion method. The synthetic gastrointestinal fluids were added to the samples with well-ordered, mixed throughly and incubated according to the human physiology digestive system. The concentration of 238U radionuclide in the solutions extracted from the soil was measured using Induced Coupling Plasma Mass Spectrometer (ICP-MS). The concentration of 238U radionuclide from the soil samples in synthetic gastrointestinal fluids showed different values due to different homogenity of soil types and chemical reaction of 238U radionuclide. In general, the solubility of 238U radionuclide in gastric fluid was higher (0.050 - 0.209 ppm) than gastrointestinal fluids (0.024 - 0.050 ppm). It could be concluded that the US P in vitro digestion method is practicle for estimating the solubility of 238U radionuclide from soil materials and could be useful for monitoring and risk assessment purposes applying to environmental, health and contaminated soil samples.

  14. Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes.

    PubMed

    Bamberger, Casimir; Schärer, Agnes; Antsiferova, Maria; Tychsen, Birte; Pankow, Sandra; Müller, Mischa; Rülicke, Thomas; Paus, Ralf; Werner, Sabine

    2005-09-01

    The transforming growth factor-beta family member activin is a potent regulator of skin morphogenesis and repair. Transgenic mice overexpressing activin in keratinocytes display epidermal hyper-thickening and dermal fibrosis in normal skin and enhanced granulation tissue formation after wounding. Mice overexpressing the secreted activin antagonist follistatin, however, have the opposite wound-healing phenotype. To determine whether activin affects skin morphogenesis and repair via activation of keratinocytes and/or stromal cells, we generated transgenic mice expressing a dominant-negative activin receptor IB mutant (dnActRIB) in keratinocytes. The architecture of adult skin was unaltered in these mice, but delays were observed in postnatal pelage hair follicle morphogenesis and in the first catagen-telogen transformation of hair follicles. Although dnActRIB-transgenic mice showed slightly delayed wound re-epithelialization after skin injury, the strong inhibition of granulation tissue formation seen in follistatin-transgenic mice was not observed. Therefore, although endogenous activin appeared to affect skin morphogenesis and repair predominantly via stromal cells, overexpressed activin strongly affected the epidermis. The epidermal phenotype of activin-overexpressing mice was partially rescued by breeding these animals with dnActRIB-transgenic mice. These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo. PMID:16127153

  15. Serum immunoreactive activin A levels in normal subjects and patients with various diseases.

    PubMed

    Harada, K; Shintani, Y; Sakamoto, Y; Wakatsuki, M; Shitsukawa, K; Saito, S

    1996-06-01

    We developed and validated a RIA for measuring serum activin A. The least detectable value of this assay was 0.1 micrograms/L, and the antibody used cross-reacted slightly with bovine inhibin (3.2%) and porcine activin AB (10.0%) but not with porcine activin B (< 0.5%). Serum activin A was extracted with acetonitrile and trifluoroacetic acid to get rid of the interaction with possible binding proteins in serum. As a result of this extraction procedure, the dose-response curve of serum extract was parallel to the standard curve and a single immunoreactive (ir-) peak was demonstrated on gel chromatographic analysis with constant recovery rates over 80%. Serum ir-activin A level in healthy adults was 1.27 +/- 0.03 micrograms/L (mean +/- SEM, n = 180); being 1.38 +/- 0.05 micrograms/L (n = 90) in male, and 1.16 +/- 0.05 micrograms/L (n = 90) in female subjects, with a tendency to increase with age. Serum ir-activin A level during pregnancy showed a marked increase with the advance of gestation; 1.65 +/- 0.41 micrograms/L (n = 7) in the early, 4.50 +/- 1.13 micrograms/L (n = 21) in the middle, and 16.32 +/- 2.25 micrograms/L (n = 26) in the late trimester, with a rapid decline after delivery. On the other hand, serum ir-activin A level was elevated in patients with hyperthyroidism (1.91 +/- 0.37 micrograms/L, n = 31), liver cirrhosis (2.03 +/- 0.71 micrograms/L, n = 10), chronic renal failure (3.41 +/- 0.34 micrograms/L, n = 41), and advanced solid cancer (2.24 +/- 0.52 micrograms/L, n = 67). These findings indicate that serum ir-activin A level varies with physiological conditions such as aging and pregnancy, and that it may reflect the altered production and metabolism of activin A in certain diseased conditions. PMID:8964839

  16. Activin A Protects Midbrain Neurons in the 6-Hydroxydopamine Mouse Model of Parkinson’s Disease

    PubMed Central

    Li, Kong M.; Vissel, Bryce

    2015-01-01

    Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) and a subsequent loss of dopamine (DA) within the striatum. Despite advances in the development of pharmacological therapies that are effective at alleviating the symptoms of PD, the search for therapeutic treatments that halt or slow the underlying nigral degeneration remains a particular challenge. Activin A, a member of the transforming growth factor ? superfamily, has been shown to play a role in the neuroprotection of midbrain neurons against 6-hydroxydopamine (6-OHDA) in vitro, suggesting that activin A may offer similar neuroprotective effects in in vivo models of PD. Using robust stereological methods, we found that intrastriatal injections of 6-OHDA results in a significant loss of both TH positive and NeuN positive populations in the SNpc at 1, 2, and 3 weeks post-lesioning in drug naïve mice. Exogenous application of activin A for 7 days, beginning the day prior to 6-OHDA administration, resulted in a significant survival of both dopaminergic and total neuron numbers in the SNpc against 6-OHDA-induced toxicity. However, we found no corresponding protection of striatal DA or dopamine transporter (DAT) expression levels in animals receiving activin A compared to vehicle controls. These results provide the first evidence that activin A exerts potent neuroprotection in a mouse model of PD, however this neuroprotection may be localized to the midbrain. PMID:25902062

  17. Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis

    PubMed Central

    Bufalino, Andreia; Cervigne, Nilva K.; de Oliveira, Carine Ervolino; Fonseca, Felipe Paiva; Rodrigues, Priscila Campioni; Macedo, Carolina Carneiro Soares; Sobral, Lays Martin; Miguel, Marcia Costa; Lopes, Marcio Ajudarte; Leme, Adriana Franco Paes; Lambert, Daniel W.; Salo, Tuula A.; Kowalski, Luiz Paulo; Graner, Edgard; Coletta, Ricardo D.

    2015-01-01

    Deregulated expression of activin A is reported in several tumors, but its biological functions in oral squamous cell carcinoma (OSCC) are unknown. Here, we investigate whether activin A can play a causal role in OSCCs. Activin A expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low activin A-expressing cells were treated with recombinant activin A and assessed for apoptosis, proliferation, adhesion, migration, invasion and epithelial-mesenchymal transition (EMT). Those phenotypes were also evaluated in high activin A-expressing cells treated with follistatin (an activin A antagonist) or stably expressing shRNA targeting activin A. Transfections of microRNA mimics were performed to determine whether the overexpression of activin A is regulated by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison with normal oral mucosa, and high activin A levels were significantly associated with lymph node metastasis, tumor differentiation and poor survival. High activin A levels promoted multiple properties associated with malignant transformation, including decreased apoptosis and increased proliferation, migration, invasion and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines and in clinical specimens, and inversely correlated to activin A levels. Forced expression of miR-143 and miR-145 in OSCC cells significantly decreased the expression of activin A. Overexpression of activin A in OSCCs, which is controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis, proliferation and invasiveness, and it is clinically correlated with lymph node metastasis and poor survival. PMID:26317418

  18. Antidiabetic Rosiglitazone Reduces Soluble Intercellular Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Coronary Artery Disease

    PubMed Central

    Wang, Guang; Zhang, Zhe; Yu, Jie; Zhang, Fuchun; He, Liyun; Wei, Jinru; Mao, Jieming; Wang, Xian

    2008-01-01

    Background. We investigated the level of soluble adhesion molecules in diabetic patients and the effect of the peroxisome proliferator-activated receptor-? (PPAR-?) agonist rosiglitazone on plasma levels of adhesion molecules and an inflammation marker in type 2 diabetic patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods. A total of 116 diabetic patients with CAD who had undergone PCI were randomized to receive rosiglitazone (4 mg/d) or not for 6 months. Plasma levels of soluble intercellular adhesion molecules (sICAM-1) and P-selectin (sP-selectin) were measured on ELISA. Results. After 6-month rosiglitazone treatment, plasma levels of sICAM-1 were lower than baseline and control group levels (370.4 (332.4–421.9) pg/mL versus 423.5 (327.4–500.3) pg/mL and 404.6 (345.2–483.4) pg/mL, P < .001). In addition, plasma levels of C-reactive protein were significantly reduced from baseline levels. However, plasma level of sP-selectin was not significantly lowered with rosiglitazone treatment than with control treatment after 6-month follow-up. Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-? agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI. PMID:19107216

  19. Brugia malayi soluble and excretory-secretory proteins attenuate development of streptozotocin-induced type 1 diabetes in mice.

    PubMed

    Amdare, N; Khatri, V; Yadav, R S P; Tarnekar, A; Goswami, K; Reddy, M V R

    2015-12-01

    Understanding the modulation of the host-immune system by pathogens-like filarial parasites offers an alternate approach to prevent autoimmune diseases. In this study, we have shown that treatment with filarial proteins prior to or after the clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of fasting blood glucose levels with as many as 57·5-62·5% of mice remaining nondiabetic. These proteins were more effective when they were used to treat the mice with established T1D as 62·5-71·5% of the mice turned to be nondiabetic. Histopathological examination of pancreas of treated mice showed minor inflammatory changes in pancreatic islet cell architecture. The therapeutic effect was found to be associated with the decreased production of cytokines TNF-? & IFN-? and increased production of IL-10 in the culture supernatants of splenocytes of treated mice. A switch in the production of anti-insulin antibodies from IgG2a to IgG1 isotype was also seen. Together these results provide a proof towards utilizing the filarial derived proteins as novel anti-diabetic therapeutics. PMID:26434489

  20. Activin/Nodal signalling before implantation: setting the stage for embryo patterning

    PubMed Central

    Papanayotou, Costis; Collignon, Jérôme

    2014-01-01

    Activins and Nodal are members of the transforming growth factor beta (TGF-?) family of growth factors. Their Smad2/3-dependent signalling pathway is well known for its implication in the patterning of the embryo after implantation. Although this pathway is active early on at preimplantation stages, embryonic phenotypes for loss-of-function mutations of prominent components of the pathway are not detected before implantation. It is only fairly recently that an understanding of the role of the Activin/Nodal signalling pathway at these stages has started to emerge, notably from studies detailing how it controls the expression of target genes in embryonic stem cells. We review here what is currently known of the TGF-?-related ligands that determine the activity of Activin/Nodal signalling at preimplantation stages, and recent advances in the elucidation of the Smad2/3-dependent mechanisms underlying developmental progression. PMID:25349448

  1. Uterine Activin-Like Kinase 4 Regulates Trophoblast Development During Mouse Placentation.

    PubMed

    Peng, Jia; Fullerton, Paul T; Monsivais, Diana; Clementi, Caterina; Su, Gloria H; Matzuk, Martin M

    2015-12-01

    The placenta is the first organ to develop after fertilization. It forms an interface between the maternal uterus and growing fetus to allow nutrient uptake, waste elimination, and gas exchange for a successful pregnancy in both mice and humans. In the past 2 decades, in vivo and in vitro approaches have been used to show that several members of the TGF-? superfamily regulate embryo implantation and placental development. Nodal, a TGF-? superfamily ligand, is essential for mesendoderm formation and left-right axis patterning during embryogenesis, and Nodal null mutants exhibit abnormal placental organization with expansion of trophoblast giant cells and a decrease of spongiotrophoblast and labyrinth. To better understand the importance of Nodal signaling in the uterus, we established a mouse model to conditionally ablate activin-like kinase 4 (ALK4; the Nodal type 1 receptor) using Cre recombinase driven by the progesterone receptor promoter sequences (Pgr-Cre). Alk4 conditional knockout females are subfertile due to placental abnormalities and fetal loss in pregnancy, with a placental disorganization phenotype similar to what is observed in Nodal null mice. Thus, Nodal likely functions as an indirect regulator of placental development by binding to type 1 and type 2 receptors on maternal decidual cells to stimulate expression of unknown regulators of placental development. Our findings not only describe the generation of a mouse model that enables study of Nodal signaling in placentation but also provides insights into the pathogenesis of pregnancy complications in humans, including spontaneous abortion, preeclampsia, intrauterine growth restriction, and preterm birth. PMID:26484579

  2. Bioinformatic Analysis of Pathogenic Missense Mutations of Activin Receptor Like Kinase 1 Ectodomain

    PubMed Central

    Scotti, Claudia; Olivieri, Carla; Boeri, Laura; Canzonieri, Cecilia; Ornati, Federica; Buscarini, Elisabetta; Pagella, Fabio; Danesino, Cesare

    2011-01-01

    Activin A receptor, type II-like kinase 1 (also called ALK1), is a serine-threonine kinase predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. The study of the structural effects of mutations is crucial to understand their pathogenic mechanism. However, while an X-ray structure of ALK1 intracellular domain has recently become available (PDB ID: 3MY0), structure determination of ALK1 ectodomain (ALK1EC) has been elusive so far. We here describe the building of a homology model for ALK1EC, followed by an extensive bioinformatic analysis, based on a set of 38 methods, of the effect of missense mutations at the sequence and structural level. ALK1EC potential interaction mode with its ligand BMP9 was then predicted combining modelling and docking data. The calculated model of the ALK1EC allowed mapping and a preliminary characterization of HHT2 associated mutations. Major structural changes and loss of stability of the protein were predicted for several mutations, while others were found to interfere mainly with binding to BMP9 or other interactors, like Endoglin (CD105), whose encoding ENG gene (9q34) mutations are known to cause type 1 HHT. This study gives a preliminary insight into the potential structure of ALK1EC and into the structural effects of HHT2 associated mutations, which can be useful to predict the potential effect of each single mutation, to devise new biological experiments and to interpret the biological significance of new mutations, private mutations, or non-synonymous polymorphisms. PMID:22028876

  3. Pegylated Interferon-? Modulates Liver Concentrations of Activin-A and Its Related Proteins in Normal Wistar Rat

    PubMed Central

    Refaat, Bassem; El-Shemi, Adel Galal; Ashshi, Ahmed Mohamed; Mahamid, Elaf Wael; Al-Qadi, Noha Mohammed

    2015-01-01

    Aims. To measure the expression of activin ?A-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-? (Peg-INF-?) and ribavirin (RBV). Materials and Methods. 40 male Wistar rats were divided equally into 4 groups: “control,” “Peg-only” receiving 4 injections of Peg-INF-? (6?µg/rat/week), “RBV-only” receiving ribavirin (4?mg/rat/day) orally, and “Peg & RBV” group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA. Results. Peg-INF-???± RBV altered the expression of all candidate molecules in the liver at the gene and protein levels (P < 0.05) and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groups (P < 0.05). There were also significant correlations between serum and liver activin-A and follistatin. Conclusion. Peg-INF-? modulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-? on the production of activins and follistatin by the liver and immune cells. PMID:26236109

  4. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament.

    PubMed Central

    Yonemori, K.; Imamura, T.; Ishidou, Y.; Okano, T.; Matsunaga, S.; Yoshida, H.; Kato, M.; Sampath, T. K.; Miyazono, K.; ten Dijke, P.; Sakou, T.

    1997-01-01

    Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9094990

  5. Differential regulation of mouse pancreatic islet insulin secretion and Smad proteins by activin ligands

    E-print Network

    Ibáñez, Carlos

    ARTICLE Differential regulation of mouse pancreatic islet insulin secretion and Smad proteins-stimulated insulin secretion (GSIS) from pancreatic beta cells is regulated by paracrine factors, the identity and mechanisms of action of which are incompletely understood. Activins are expressed in pancreatic islets

  6. Activin-Like Kinase 2 Functions in Peri-implantation Uterine Signaling in Mice and Humans

    PubMed Central

    Clementi, Caterina; Tripurani, Swamy K.; Large, Michael J.; Edson, Mark A.; Creighton, Chad J.; Hawkins, Shannon M.; Kovanci, Ertug; Kaartinen, Vesa; Lydon, John P.; Pangas, Stephanie A.; DeMayo, Francesco J.; Matzuk, Martin M.

    2013-01-01

    Implantation of a blastocyst in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the uterus of pregnant mice, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing mice carrying a conditional ablation of Alk2 in the uterus (Alk2 cKO mice). In the absence of ALK2, embryos demonstrate delayed invasion into the uterine epithelium and stroma, and upon implantation, stromal cells fail to undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein ? (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of CEBPB in the stroma to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (hESC) and discovered that ablation of ALK2 alters hESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing hESC confirmed that BMP signaling proteins, SMAD1/5, directly regulate expression of CEBPB by binding a distinct regulatory sequence in the 3? UTR of this gene; CEBPB, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate peri-implantation in rodents and primates and, for the first time, uncovers a linear pathway of BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization. PMID:24244176

  7. Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development.

    PubMed

    Peng, Jia; Monsivais, Diana; You, Ran; Zhong, Hua; Pangas, Stephanie A; Matzuk, Martin M

    2015-09-01

    Members of the transforming growth factor ? (TGF-?) superfamily are key regulators in most developmental and physiological processes. However, the in vivo roles of TGF-? signaling in female reproduction remain uncertain. Activin receptor-like kinase 5 (ALK5) is the major type 1 receptor for the TGF-? subfamily. Absence of ALK5 leads to early embryonic lethality because of severe defects in vascular development. In this study, we conditionally ablated uterine ALK5 using progesterone receptor-cre mice to define the physiological roles of ALK5 in female reproduction. Despite normal ovarian functions and artificial decidualization in conditional knockout (cKO) mice, absence of uterine ALK5 resulted in substantially reduced female reproduction due to abnormalities observed at different stages of pregnancy, including implantation defects, disorganization of trophoblast cells, fewer uterine natural killer (uNK) cells, and impairment of spiral artery remodeling. In our microarray analysis, genes encoding proteins involved in cytokine-cytokine receptor interactions and NK cell-mediated cytotoxicity were down-regulated in cKO decidua compared with control decidua. Flow cytometry confirmed a 10-fold decrease in uNK cells in cKO versus control decidua. According to these data, we hypothesize that TGF-? acts on decidual cells via ALK5 to induce expression of other growth factors and cytokines, which are key regulators in luminal epithelium proliferation, trophoblast development, and uNK maturation during pregnancy. Our findings not only generate a mouse model to study TGF-? signaling in female reproduction but also shed light on the pathogenesis of many pregnancy complications in human, such as recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction. PMID:26305969

  8. Hydrothermal synthesis of brookite-type titanium dioxide with snowflake-like nanostructures using a water-soluble citratoperoxotitanate complex

    NASA Astrophysics Data System (ADS)

    Kobayashi, Makoto; Petrykin, Valery; Tomita, Koji; Kakihana, Masato

    2011-12-01

    Hydrothermal synthesis of brookite-type titanium dioxide was performed with excellent reproducibility using an aqueous NH 3 solution of a water-soluble citratoperoxotitanate (CPT) complex. X-ray diffraction confirmed that the brookite phase was formed by hydrothermal treatment of the CPT complex in NH 3 solution with a concentration of more than 6.5 wt%, whereas single phase anatase was obtained when distilled water without any additives was applied as the solvent. The aspect ratios of the obtained rod-like brookite particles increased from 5 up to 20 with an increase of the NH 3 concentration. Transmission electron microscopy and selected area electron diffraction measurements provided evidence that the growth of the brookite particles is along the c-axis. Hydrothermal treatment of the CPT complex at high NH 3 concentrations resulted in the formation of agglomerated brookite particles with unusual shapes, where many rod-like particles were branched around a somewhat longer central particle, and the side view of the agglomerated particles revealed two-dimensional crystal growth within a given restricted plane. The multi-needle agglomerate of particles was snowflake shaped. The reason for the formation of brookite with this unique morphology may be attributed to an intrinsic character of the CPT complex itself, although the mechanism is yet to be clarified.

  9. Differential Expression and Release of Activin A and Follistatin in Chronic Rhinosinusitis with and without Nasal Polyps

    PubMed Central

    Lan, Feng; Hu, Guohua; Hong, Suling; Bachert, Claus

    2015-01-01

    Background Chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP) should be regarded as distinct clinical entities based on differential inflammatory mediator and remodeling profiles. Activin A, a member of the TGF-? superfamily, plays an important role in inflammation and remodeling in the lower airways, although its expression and release in the upper airways remain undescribed. Objective To investigate the expression of activin A and its inhibitor follistatin in nasal tissue samples from CRSsNP and CRSwNP patients, and to monitor the spontaneous release of these molecules in a human mucosal model. Methods Protein levels were determined using ELISA for activin A, follistatin, TGF-?1 and indicator proteins (IL-5, ECP, IFN?) in 13 CRSsNP, 23 CRSwNP, and 10 control samples. The spontaneous release rate and the release ratios of activin A, follistatin and TGF-?1 were determined in 9 CRSsNP and 7 CRSwNP tissue fragments cultured ex-vivo. The induction of activin A and TGF-?1 by one another was studied in 7 CRSsNP tissue fragments cultured ex-vivo. Results Significantly higher concentrations of activin A, follistatin, TGF-?1, and IFN? were observed in CRSsNP compared with CRSwNP samples, whereas the concentrations of IL-5 and ECP were significantly lower. Follistatin was positively and linearly correlated with activin A in CRSsNP and CRSwNP. Activin A, follistatin and TGF-?1 were all spontaneously released by the samples, although the relative ratios released by tissue fragments from CRSsNP and CRSwNP samples were significantly different, with a higher follistatin/activin A-ratio and a follistatin/TGFß1-ratio (with less overall TGF-?1) in CRSwNP than in CRSsNP. Furthermore, TGF-?1 enhanced activin A secretion in CRSsNP tissue fragments cultured ex-vivo. Conclusion The differences in tissue concentrations and spontaneous release rates for activin A and follistatin in different CRS samples support the hypothesis that CRSsNP and CRSwNP are two distinct disease entities with respect to remodeling patterns. PMID:26030615

  10. [Molecular cloning of activin betaA subunit mature peptide from peafowl and its application in taxonomy and phylogeny].

    PubMed

    Zou, Fang-Dong; Tong, Xin-Xin; Yue, Bi-Song

    2005-03-01

    The sequences of activin gene betaA subunit mature peptide have been amplified from white peafowl, blue peafowl (pavo cristatus) and green peafowl (pavo muticus) genomic DNA by polymerase chain reaction (PCR) with a pair of degenerate primers. The target fragments were cloned into the vector pMD18-T and sequenced. The length of activin gene betaA subunit mature peptide is 345bp, which encoded a peptide of 115 amino acid residues. Sequence analysis of activin gene betaA subunit mature peptide demonstrated that the identity of nucleotide is 98.0% between blue peaflowl and green peafowl, and the identity of that is 98.8% between blue peaflowl and white peafow. Sequences comparison in NCBI revealed that the sequences of activin gene betaA subunit mature peptides of different species are highly conserved during evolution process. In addition, the restriction enzyme map of activins is high similar between white peafowl and blue peafowl. Phylogenetic tree was constructed with Mega 2 and Clustalxldx software. The result showed that white peafowl has a closer relationship to blue peafowl than to green peafowl. Considered the nucleotide differences of peafowls' activin gene betaA subunit mature peptides, a highly conserved region, we supported that white peafowl was derived from blue peafowl, and it is more possible the hybrid but just the product of color mutation, or maybe as a subspecies of Pavo genus. PMID:15843351

  11. Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes.

    PubMed

    Goulopoulou, Styliani; Hannan, Johanna L; Matsumoto, Takayuki; Ogbi, Safia; Ergul, Adviye; Webb, R Clinton

    2015-07-15

    Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (activators). In this study, we hypothesized that resistance arteries from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats, GK) would have reduced vasodilatory responses to heme-dependent sGC activation and increased responses to heme-independent sGC activation compared with control rats (Wistar). Endothelium-dependent and -independent relaxation was assessed in isolated segments from mesenteric resistance arteries (MA) mounted in a wire myograph. GK MA had reduced responses to acetylcholine (pEC50: 7.96 ± 0.06 vs. 7.66 ± 0.05, P < 0.05) and sodium nitroprusside (pEC50: 8.34 ± 0.05 vs. 7.77 ± 0.04, P < 0.05). There were no group differences in 8-bromoguanosine cGMP-induced relaxation and protein kinase G1 expression (P > 0.05). GK MA had attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56 ± 0.05 vs. 6.93 ± 0.06, P < 0.05) and BAY 58-2667 (heme-independent sGC activator; pEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, P < 0.05) and increased sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, P < 0.05]. Isolated resistance arteries from female rats of reproductive age that spontaneously develop type 2 diabetes have increased sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and stimulators. PMID:25957216

  12. Activin A Accelerates the Progression of Fetal Oocytes Throughout Meiosis and Early Oogenesis in the Mouse.

    PubMed

    Liang, Gui-Jin; Zhang, Xi-Feng; Wang, Jun-Jie; Sun, Yuan-Chao; Sun, Xiao-Feng; Cheng, Shun-Feng; Li, Lan; De Felici, Massimo; Shen, Wei

    2015-10-15

    Activins can exert several roles in ovary development. However, little is known about their involvement in early mammalian oogenesis. In this study, we reported that activin receptors (including ActRIA, ActRIB, ActRIIA, and ActRIIB) are expressed throughout the development of the mouse ovaries from 12.5 days postcoitum (dpc) to 21 days postparturition (dpp). Moreover, we found that in vitro, the addition of activin A (ActA) to the culture medium of 12.5?dpc ovarian tissues accelerated the progression of oocytes throughout meiotic prophase I stages. This result was reproduced in vivo following administration of ActA to pregnant mice. The in vitro effect of ActA was associated with increased expression of premeiotic and meiotic genes (including Dazl, Spo11, Stra8, Scp3, and Rec8) in the ovarian tissues. Mechanistically, ActA-dependent SMAD3 signaling modulated the expression of members of the retinoic acid (RA) system, including the RA degradation CYP26B1 enzyme and the RA receptors. Finally, ActA promoted the survival and growth of fetal and early postnatal oocytes and primordial follicle assembly both in vitro and in vivo. In conclusion, the present study identifies new roles of ActA in early oogenesis and suggested that ActA and RA might cooperate in promoting meiosis in female germ cells. PMID:26083127

  13. Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

    PubMed Central

    Lee, Alan C. H.; Lam, Joanne K. Y.; Shiu, Sammy W. M.; Wong, Ying; Betteridge, D. John; Tan, Kathryn C. B.

    2015-01-01

    Background The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE. PMID:26325204

  14. A truncated, activin-induced Smad3 isoform acts as a transcriptional repressor of FSH? expression in mouse pituitary.

    PubMed

    Kim, So-Youn; Zhu, Jie; Woodruff, Teresa K

    2011-08-01

    The receptor-regulated protein Smad3 is key player in the signaling cascade stimulated by the binding of activin to its cell surface receptor. Upon phosphorylation, Smad3 forms a heterocomplex with Smad2 and Smad4, translocates to the nucleus and acts as a transcriptional co-activator. We have identified a unique isoform of Smad3 that is expressed in mature pituitary gonadotropes. 5' RACE revealed that this truncated Smad3 isoform is transcribed from an ATG site within exon 4 and consists of 7 exons encoding half of the linker region and the MH2 region. In pituitary cells, the truncated Smad3 isoform was phosphorylated upon activin treatment, in a manner that was temporally distinct from the phosphorylation of full-length Smad3. Activin-induced phosphorylation of Smad3 and the truncated Smad3 isoform was blocked by both follistatin and siRNA-mediated knockdown of Smad3. The truncated Smad3 isoform antagonized Smad3-mediated, activin-responsive promoter activity. We propose that the pituitary gonadotrope contains an ultra-short, activin-responsive feedback loop utilizing two different isoforms of Smad3, one which acts as an agonist (Smad3) and another that acts as an intracrine antagonist (truncated Smad3 isoform) to regulate FSH? production. PMID:21664424

  15. Solubility of {sup 238}U radionuclide from various types of soil in synthetic gastrointestinal fluids using “US in vitro” digestion method

    SciTech Connect

    Rashid, Nur Shahidah Abdul; Sarmani, Sukiman; Majid, Amran Ab.; Mohamed, Faizal; Siong, Khoo Kok

    2015-04-29

    238U radionuclide is a naturally occuring radioactive material that can be found in soil. In this study, the solubility of 238U radionuclide obtained from various types of soil in synthetic gastrointestinal fluids was analysed by “US P in vitro” digestion method. The synthetic gastrointestinal fluids were added to the samples with well-ordered, mixed throughly and incubated according to the human physiology digestive system. The concentration of 238U radionuclide in the solutions extracted from the soil was measured using Induced Coupling Plasma Mass Spectrometer (ICP-MS). The concentration of 238U radionuclide from the soil samples in synthetic gastrointestinal fluids showed different values due to different homogenity of soil types and chemical reaction of 238U radionuclide. In general, the solubility of 238U radionuclide in gastric fluid was higher (0.050 – 0.209?ppm) than gastrointestinal fluids (0.024 – 0.050?ppm). It could be concluded that the US P in vitro digestion method is practicle for estimating the solubility of 238U radionuclide from soil materials and could be useful for monitoring and risk assessment purposes applying to environmental, health and contaminated soil samples.

  16. Solubility Database

    National Institute of Standards and Technology Data Gateway

    SRD 106 IUPAC-NIST Solubility Database (Web, free access)   These solubilities are compiled from 18 volumes (Click here for List) of the International Union for Pure and Applied Chemistry(IUPAC)-NIST Solubility Data Series. The database includes liquid-liquid, solid-liquid, and gas-liquid systems. Typical solvents and solutes include water, seawater, heavy water, inorganic compounds, and a variety of organic compounds such as hydrocarbons, halogenated hydrocarbons, alcohols, acids, esters and nitrogen compounds. There are over 67,500 solubility measurements and over 1800 references.

  17. Differential regulation of cellular tropism and sensitivity to soluble CD4 neutralization by the envelope gp120 of human immunodeficiency virus type 1.

    PubMed Central

    Stamatatos, L; Werner, A; Cheng-Mayer, C

    1994-01-01

    Using recombinant and mutant viruses generated between two human immunodeficiency virus type 1 isolates that display differences in cell tropism and sensitivity to soluble CD4 neutralization, we show that these two properties of the virus are regulated by different mechanisms. Whereas there is an association between V3 loop conformation and a particular cellular tropism, soluble CD4 neutralization sensitivity appears to be determined by amino acid differences in the C2 domain of the envelope gp120 that modulate the stability of gp120-gp41 association. Our findings further illustrate the importance of functional interactions among different regions of the envelope gp120 in regulating the biological phenotypes of human immunodeficiency virus and suggest that additional probing of the V3 loop with monoclonal antibodies may identify specific structural features of this loop that determine cell tropism. Images PMID:8035496

  18. Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin in treatment naïve patients and their correlations with interleukin-6, tumour necrosis factor-?, viral load and liver damage.

    PubMed

    Refaat, Bassem; Ashshi, Ahmed Mohammed; El-Shemi, Adel Galal; AlZanbagi, Adnan

    2015-08-01

    The importance of activins and follistatin in liver diseases has recently emerged. The aim of the present study was to measure the influence of chronic infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-?. Sera samples collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (ten males and ten females for each genotype), and 40 gender- and age-matched healthy participants were analysed for activin-A, activin-B and follistatin using enzyme-linked immunosorbent assay and their levels were correlated with IL-6, TNF-?, viral load and AST platelet ratio index (APRI). Serum activin-A, activin-B, IL-6 and TNF-? were significantly increased, while serum follistatin was significantly decreased, in both genders of CHC patients compared with control subjects, In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-?, and negatively with albumin (P < 0.01). Activin-B showed the same correlations of activin-A only in CHC genotype 1 patients, but it was weaker than activin-A. No correlation was detected with follistatin. Serum activins, particularly activin-A, and follistatin are significantly altered by CHC genotype 1 and 4. This dysregulation of activins/follistatin axis may be associated with viral replication, host immune response and liver injury. Further studies are needed to illustrate the definite role(s) and clinical value of activins and follistatin in CHC. PMID:24925642

  19. Efficient retina formation requires suppression of both Activin and BMP signaling pathways in pluripotent cells

    PubMed Central

    Wong, Kimberly A.; Trembley, Michael; Abd Wahab, Syafiq; Viczian, Andrea S.

    2015-01-01

    Retina formation requires the correct spatiotemporal patterning of key regulatory factors. While it is known that repression of several signaling pathways lead to specification of retinal fates, addition of only Noggin, a known BMP antagonist, can convert pluripotent Xenopus laevis animal cap cells to functional retinal cells. The aim of this study is to determine the intracellular molecular events that occur during this conversion. Surprisingly, blocking BMP signaling alone failed to mimic Noggin treatment. Overexpressing Noggin in pluripotent cells resulted in a concentration-dependent suppression of both Smad1 and Smad2 phosphorylation, which act downstream of BMP and Activin signaling, respectively. This caused a decrease in downstream targets: endothelial marker, xk81, and mesodermal marker, xbra. We treated pluripotent cells with dominant-negative receptors or the chemical inhibitors, dorsomorphin and SB431542, which each target either the BMP or Activin signaling pathway. We determined the effect of these treatments on retina formation using the Animal Cap Transplant (ACT) assay; in which treated pluripotent cells were transplanted into the eye field of host embryos. We found that inhibition of Activin signaling, in the presence of BMP signaling inhibition, promotes efficient retinal specification in Xenopus tissue, mimicking the affect of adding Noggin alone. In whole embryos, we found that the eye field marker, rax, expanded when adding both dominant-negative Smad1 and Smad2, as did treating the cells with both dorsomorphin and SB431542. Future studies could translate these findings to a mammalian culture assay, in order to more efficiently produce retinal cells in culture. PMID:25750435

  20. Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats

    PubMed Central

    2014-01-01

    Background Dietary fibre-induced satiety offers a physiological approach to body weight regulation, yet there is lack of scientific evidence. This experiment quantified food intake, body weight and body composition responses to three different soluble fermentable dietary fibres in an animal model and explored underlying mechanisms of satiety signalling and hindgut fermentation. Methods Young adult male rats were fed ad libitum purified control diet (CONT) containing 5% w/w cellulose (insoluble fibre), or diet containing 10% w/w cellulose (CELL), fructo-oligosaccharide (FOS), oat beta-glucan (GLUC) or apple pectin (PECT) (4 weeks; n = 10/group). Food intake, body weight, and body composition (MRI) were recorded, final blood samples analysed for gut satiety hormones, hindgut contents for fermentation products (including short-chain fatty acids, SCFA) and intestinal tissues for SCFA receptor gene expression. Results GLUC, FOS and PECT groups had, respectively, 10% (P < 0.05), 17% (P < 0.001) and 19% (P < 0.001) lower food intake and 37% (P < 0.01), 37% (P < 0.01) and 45% (P < 0.001) lower body weight gain than CONT during the four-week experiment. At the end they had 26% (P < 0.05), 35% (P < 0.01) and 42% (P < 0.001) less total body fat, respectively, while plasma total glucagon-like peptide-1 (GLP-1) was 2.2-, 3.2- and 2.6-fold higher (P < 0.001) and peptide tyrosine tyrosine (PYY) was 2.3-, 3.1- and 3.0-fold higher (P < 0.001). There were no differences in these parameters between CONT and CELL. Compared with CONT and CELL, caecal concentrations of fermentation products increased 1.4- to 2.2-fold in GLUC, FOS and PECT (P < 0.05) and colonic concentrations increased 1.9- to 2.5-fold in GLUC and FOS (P < 0.05), with no consistent changes in SCFA receptor gene expression detected. Conclusions This provides animal model evidence that sustained intake of three different soluble dietary fibres decreases food intake, weight gain and adiposity, increases circulating satiety hormones GLP-1 and PYY, and increases hindgut fermentation. The presence of soluble fermentable fibre appears to be more important than its source. The results suggest that dietary fibre-induced satiety is worthy of further investigation towards natural body weight regulation in humans. PMID:25152765

  1. Crystallization and preliminary X-ray analysis of the complex between a Bacillus subtilis ?/?-type small acid-soluble spore protein and DNA

    SciTech Connect

    Bumbaca, Daniela; Kosman, Jeffrey; Setlow, Peter; Henderson, R. Keith; Jedrzejas, Mark J.

    2007-06-01

    An ?/?-type small, acid-soluble spore protein (SASP) from Bacillus subtilis, a major source of DNA protection against damaging effects in spores, was crystallized in a functionally relevant complex with a double-stranded DNA. This report provides insights into initial characterization of the complex and its structure elucidation. An engineered variant of an ?/?-type small acid-soluble spore protein (SASP) from Bacillus subtilis was crystallized in a complex with a ten-base-pair double-stranded DNA by the hanging-drop vapor-diffusion method using ammonium sulfate as a precipitating agent. Crystals grew at 281 K using sodium cacodylate buffer pH 5.5 and these crystals diffracted X-rays to beyond 2.4 Å resolution using synchrotron radiation. The crystallized complex contains two or three SASP molecules bound to one DNA molecule. The crystals belong to the hexagonal space group P6{sub 1}22 or P6{sub 5}22, with unit-cell parameters a = b = 87.0, c = 145.4 Å, ? = ? = 90.0, ? = 120.0°. Diffraction data were 96.6% complete to 2.4 Å resolution, with an R{sub sym} of 8.5%. Structure solution by the multiwavelength/single-wavelength anomalous dispersion method using isomorphous crystals of selenomethionine-labeled protein is in progress.

  2. Modulation of adenosine triphosphate-sensitive potassium channel and voltage-dependent calcium channel by activin A in HIT-T15 cells.

    PubMed

    Mogami, H; Kanzaki, M; Nobusawa, R; Zhang, Y Q; Furukawa, M; Kojima, I

    1995-07-01

    The ATP-sensitive potassium channel (KATP channel) determines the membrane potential of pancreatic beta-cells and plays a critical role in the regulation of insulin secretion. The present study was conducted to investigate the effect of activin A, a member of the transforming growth factor-beta supergene family, on the KATP channel in HIT-T15 clonal hamster insulinoma cells. In an excised inside-out patch, ATP-sensitive currents with a single channel conductance of approximately 20 picosiemens were observed. In an outside-out patch, currents with identical unitary conductance were also observed. In either case, the currents were augmented by diazoxide and blocked by glibenclamide, verifying that they were KATP channel currents. When KATP channel currents were monitored in an outside-out patch, activin A added to the bath solution inhibited KATP channel currents. Upon removal of activin A, the KATP channel currents were restored, suggesting that the inhibition was not due simply to spontaneous disappearance of channel activity (run-down). The KATP channel activity was markedly reduced after the addition of activin A and was reversed by diazoxide. Besides the inhibition of KATP channel, activin A increased, in a perforated patch, the amplitude of the inward Ba2+ current in response to a depolarizing pulse from -40 to +10 mV. Under the current clamp condition, activin A induced gradual depolarization, followed by a burst of action potentials. Activin-mediated action potentials were accompanied by an elevation of the cytoplasmic free calcium concentration. These results indicate that activin A causes depolarization of the plasma membrane by inhibiting the activity of the KATP channel. In addition, activin A directly modulates the voltage-dependent calcium channel and augments calcium entry. PMID:7789321

  3. Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-? Based Therapy

    PubMed Central

    Refaat, Bassem; Ashshi, Ahmed Mohamed; El-Shemi, Adel Galal

    2015-01-01

    Pegylated-interferon-? based therapy for the treatment of chronic hepatitis C (CHC) is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC. PMID:25969625

  4. Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-? Based Therapy.

    PubMed

    Refaat, Bassem; Ashshi, Ahmed Mohamed; El-Shemi, Adel Galal; Azhar, Esam

    2015-01-01

    Pegylated-interferon-? based therapy for the treatment of chronic hepatitis C (CHC) is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC. PMID:25969625

  5. Activin Plays a Key Role in the Maintenance of Long-Term Memory and Late-LTP

    ERIC Educational Resources Information Center

    Ageta, Hiroshi; Ikegami, Shiro; Miura, Masami; Masuda, Masao; Migishima, Rika; Hino, Toshiaki; Takashima, Noriko; Murayama, Akiko; Sugino, Hiromu; Setou, Mitsutoshi; Kida, Satoshi; Yokoyama, Minesuke; Hasegawa, Yoshihisa; Tsuchida, Kunihiro; Aosaki, Toshihiko; Inokuchi, Kaoru

    2010-01-01

    A recent study has revealed that fear memory may be vulnerable following retrieval, and is then reconsolidated in a protein synthesis-dependent manner. However, little is known about the molecular mechanisms of these processes. Activin [beta]A, a member of the TGF-[beta] superfamily, is increased in activated neuronal circuits and regulates…

  6. Identification and expression of Smads associated with TGF-beta/activin/nodal signaling pathways in the rainbow trout (Oncorhynuchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Smad proteins are essential components of the TGF-beta/activin/nodal family signaling pathway. We report the identification and characterization of transcripts representing 3 receptor Smads (Smad2a, Smad2b, Smad3), 2 common Smads (Smad4a, Smad4b) and one inhibitory Smad (Smad7). Phylogenetic an...

  7. Effects of thyroxin (T4) and activin A on in vitro growth of preantral follicles in domestic cats.

    PubMed

    Wongbandue, Grisnarong; Jewgenow, Katarina; Chatdarong, Kaywalee

    2013-03-15

    Preantral follicle culture is a promising technique for rescuing gametes from endangered animals that die abruptly. The objective was to determine effects of thyroxin (T(4)) and activin A on in vitro growth and morphology of preantral feline ovarian follicles. Preantral follicles (86.3 ± 18.7 ?m) were isolated from fresh ovaries of domestic cats. Healthy follicles were cultured individually for 14 days in 20-?L microdrops of M199 supplemented with 0.23 mmol/L sodium pyruvate, 2 mmol/L L-glutamine, 12.5 mmol/L HEPES, 0.3% (wt/vol) BSA, 1% (vol/vol) insulin-transferrin-selenite solution, 100 IU/mL penicillin, 0.1 mg/mL streptomycin, 1.0 mIU/mL growth hormone, 2.13 ?g/mL FSH, and 10 ng/mL insulin-like growth factor I. The effect of various concentrations of T(4) (0.5, 1.0, or 2.0 ?g/mL) or activin A (10, 100, or 200 ng/mL) on follicle growth and follicular integrity were assessed. Follicle diameter was measured on Days 0, 3, 7, and 14 of culture. Follicle morphology was characterized based on granulosa cell proliferation, dissociation of somatic cells, and detachment of oocytes from follicles. On Day 14, follicles were assessed for viability using ethidium homodimer-1 staining. In the control sample, diameters of follicles increased from initial sizes on Day 3, and peaked on Day 7. This pattern was also observed in both T(4)- and activin A-treated follicles. On Day 7, diameters and diameter gains of follicles treated with 10 ng/mL (mean ± SEM; 170.8 ± 7.6 and 35.9 ± 5.1 ?m, respectively) and 200 ng/mL activin A (165.2 ± 10.4 and 32.8 ± 5.5 ?m, respectively) were larger than those of the control follicles (P < 0.05). Furthermore, 10 ng/mL activin A increased percentage of viable follicles on Day 14 (46.9% viable; P < 0.05). Follicles treated with activin A had rapid granulosa cell proliferation until Day 7. In conclusion, activin A promoted growth of preantral feline follicles and supported follicle viability during a 14-day culture, whereas T(4) supplementation had no beneficial effects. PMID:23439008

  8. Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease*

    PubMed Central

    Wieczór, Rados?aw; Gadomska, Gra?yna; Ruszkowska-Ciastek, Barbara; Stankowska, Katarzyna; Budzy?ski, Jacek; Fabisiak, Jacek; Suppan, Karol; Pulkowski, Grzegorz; Ro??, Danuta

    2015-01-01

    Objective: Type 2 diabetes coexistent with lower extremity artery disease (peripheral arterial disease (PAD)) can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis—the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor (vascular endothelial growth factor A (VEGF-A)) and angiogenesis inhibitors (soluble VEGF receptors type 1 and type 2 (sVEGFR-1 and sVEGFR-2)) in patients with PAD. Methods: Among 46 patients with PAD under pharmacological therapy (non-invasive), we identified, based on medical history, a subgroup with coexistent type 2 diabetes (PAD-DM2+, n=15) and without diabetes (PAD-DM2?, n=31). The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Results: The subgroups of PAD-DM2+ and PAD-DM2? revealed significantly higher concentrations of VEGF-A (P=0.000 007 and P=0.000 000 1, respectively) and significantly lower sVEGFR-2 levels (P=0.02 and P=0.000 01, respectively), when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions: The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor (VEGF-A) and higher levels of angiogenesis inhibitors (sVEGFR-1 and sVEGFR-2) at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs. PMID:26537213

  9. Fibrodysplasia ossificans progressiva-related activated activin-like kinase signaling enhances osteoclast formation during heterotopic ossification in muscle tissues.

    PubMed

    Yano, Masato; Kawao, Naoyuki; Okumoto, Katsumi; Tamura, Yukinori; Okada, Kiyotaka; Kaji, Hiroshi

    2014-06-13

    Fibrodysplasia ossificans progressiva is characterized by extensive ossification within muscle tissues, and its molecular pathogenesis is responsible for the constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2). In this study, we investigated the effects of implanting ALK2 (R206H)-transfected myoblastic C2C12 cells into nude mice on osteoclast formation during heterotopic ossification in muscle and subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells with BMP-2 in nude mice induced robust heterotopic ossification with an increase in the formation of osteoclasts in muscle tissues but not in subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells in muscle induced heterotopic ossification more effectively than that of empty vector-transfected cells. A co-culture of ALK2 (R206H)-transfected C2C12 cells as well as the conditioned medium from ALK2 (R206H)-transfected C2C12 cells enhanced osteoclast formation in Raw264.7 cells more effectively than those with empty vector-transfected cells. The transfection of ALK2 (R206H) into C2C12 cells elevated the expression of transforming growth factor (TGF)-?, whereas the inhibition of TGF-? signaling suppressed the enhanced formation of osteoclasts in the co-culture with ALK2 (R206H)-transfected C2C12 cells and their conditioned medium. In conclusion, this study demonstrated that the causal mutation transfection of fibrodysplasia ossificans progressiva in myoblasts enhanced the formation of osteoclasts from its precursor through TGF-? in muscle tissues. PMID:24798338

  10. Fibrodysplasia Ossificans Progressiva-related Activated Activin-like Kinase Signaling Enhances Osteoclast Formation during Heterotopic Ossification in Muscle Tissues*

    PubMed Central

    Yano, Masato; Kawao, Naoyuki; Okumoto, Katsumi; Tamura, Yukinori; Okada, Kiyotaka; Kaji, Hiroshi

    2014-01-01

    Fibrodysplasia ossificans progressiva is characterized by extensive ossification within muscle tissues, and its molecular pathogenesis is responsible for the constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2). In this study, we investigated the effects of implanting ALK2 (R206H)-transfected myoblastic C2C12 cells into nude mice on osteoclast formation during heterotopic ossification in muscle and subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells with BMP-2 in nude mice induced robust heterotopic ossification with an increase in the formation of osteoclasts in muscle tissues but not in subcutaneous tissues. The implantation of ALK2 (R206H)-transfected C2C12 cells in muscle induced heterotopic ossification more effectively than that of empty vector-transfected cells. A co-culture of ALK2 (R206H)-transfected C2C12 cells as well as the conditioned medium from ALK2 (R206H)-transfected C2C12 cells enhanced osteoclast formation in Raw264.7 cells more effectively than those with empty vector-transfected cells. The transfection of ALK2 (R206H) into C2C12 cells elevated the expression of transforming growth factor (TGF)-?, whereas the inhibition of TGF-? signaling suppressed the enhanced formation of osteoclasts in the co-culture with ALK2 (R206H)-transfected C2C12 cells and their conditioned medium. In conclusion, this study demonstrated that the causal mutation transfection of fibrodysplasia ossificans progressiva in myoblasts enhanced the formation of osteoclasts from its precursor through TGF-? in muscle tissues. PMID:24798338

  11. Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice

    PubMed Central

    González-Núñez, María; Riolobos, Adela S.; Castellano, Orlando; Fuentes-Calvo, Isabel; de los Ángeles Sevilla, María; Oujo, Bárbara; Pericacho, Miguel; Cruz-Gonzalez, Ignacio; Pérez-Barriocanal, Fernando; ten Dijke, Peter; López-Novoa, Jose M.

    2015-01-01

    ABSTRACT The activin receptor-like kinase 1 (ALK-1) is a type I cell-surface receptor for the transforming growth factor-? (TGF-?) family of proteins. Hypertension is related to TGF-?1, because increased TGF-?1 expression is correlated with an elevation in arterial pressure (AP) and TGF-? expression is upregulated by the renin-angiotensin-aldosterone system. The purpose of this study was to assess the role of ALK-1 in regulation of AP using Alk1 haploinsufficient mice (Alk1+/?). We observed that systolic and diastolic AP were significantly higher in Alk1+/? than in Alk1+/+ mice, and all functional and structural cardiac parameters (echocardiography and electrocardiography) were similar in both groups. Alk1+/? mice showed alterations in the circadian rhythm of AP, with higher AP than Alk1+/+ mice during most of the light period. Higher AP in Alk1+/? mice is not a result of a reduction in the NO-dependent vasodilator response or of overactivation of the peripheral renin-angiotensin system. However, intracerebroventricular administration of losartan had a hypotensive effect in Alk1+/? and not in Alk1+/+ mice. Alk1+/? mice showed a greater hypotensive response to the ?-adrenergic antagonist atenolol and higher concentrations of epinephrine and norepinephrine in plasma than Alk1+/+ mice. The number of brain cholinergic neurons in the anterior basal forebrain was reduced in Alk1+/? mice. Thus, we concluded that the ALK-1 receptor is involved in the control of AP, and the high AP of Alk1+/? mice is explained mainly by the sympathetic overactivation shown by these animals, which is probably related to the decreased number of cholinergic neurons. PMID:26398936

  12. Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice.

    PubMed

    González-Núñez, María; Riolobos, Adela S; Castellano, Orlando; Fuentes-Calvo, Isabel; de Los Ángeles Sevilla, María; Oujo, Bárbara; Pericacho, Miguel; Cruz-Gonzalez, Ignacio; Pérez-Barriocanal, Fernando; Ten Dijke, Peter; López-Novoa, Jose M

    2015-11-01

    The activin receptor-like kinase 1 (ALK-1) is a type I cell-surface receptor for the transforming growth factor-? (TGF-?) family of proteins. Hypertension is related to TGF-?1, because increased TGF-?1 expression is correlated with an elevation in arterial pressure (AP) and TGF-? expression is upregulated by the renin-angiotensin-aldosterone system. The purpose of this study was to assess the role of ALK-1 in regulation of AP using Alk1 haploinsufficient mice (Alk1(+/-)). We observed that systolic and diastolic AP were significantly higher in Alk1(+/-) than in Alk1(+/+) mice, and all functional and structural cardiac parameters (echocardiography and electrocardiography) were similar in both groups. Alk1(+/-) mice showed alterations in the circadian rhythm of AP, with higher AP than Alk1(+/+) mice during most of the light period. Higher AP in Alk1(+/-) mice is not a result of a reduction in the NO-dependent vasodilator response or of overactivation of the peripheral renin-angiotensin system. However, intracerebroventricular administration of losartan had a hypotensive effect in Alk1(+/-) and not in Alk1(+/+) mice. Alk1(+/-) mice showed a greater hypotensive response to the ?-adrenergic antagonist atenolol and higher concentrations of epinephrine and norepinephrine in plasma than Alk1(+/+) mice. The number of brain cholinergic neurons in the anterior basal forebrain was reduced in Alk1(+/-) mice. Thus, we concluded that the ALK-1 receptor is involved in the control of AP, and the high AP of Alk1(+/-) mice is explained mainly by the sympathetic overactivation shown by these animals, which is probably related to the decreased number of cholinergic neurons. PMID:26398936

  13. Increased Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in Plasma of Suicide Attempters

    PubMed Central

    Ventorp, Filip; Gustafsson, Anna; Träskman-Bendz, Lil; Westrin, Åsa; Ljunggren, Lennart

    2015-01-01

    The soluble form of the urokinase receptor, suPAR, has been suggested as a novel biomarker of low-grade inflammation. Activation of the immune system has been proposed to contribute to the development of depression and suicidal behavior. In order to identify depressed and suicidal individuals who could benefit from an anti-inflammatory treatment, a reliable biomarker of low-grade inflammation is vital. This study evaluates plasma suPAR levels as a biomarker of low-grade inflammation in patients with major depressive disorder and in patients who recently attempted suicide. The plasma suPAR and an established biomarker, C reactive protein (CRP) of suicide attempters (n = 54), depressed patients (n = 19) and healthy controls (n = 19) was analyzed with enzyme-linked immunosorbent assays. The biomarker attributes of sensitivity and sensibility were evaluated using ROC curve analysis. Both the depressed patients and suicide attempters had increased plasma suPAR. The levels of suPAR discriminated better between controls and suicide attempters than did CRP. In the future, plasma suPAR might be a superior prognosticator regarding outcome of treatment applying conventional antidepressants in conjunction with anti-inflammatory drugs. PMID:26451727

  14. Detection on immunoblot of new proteins from the soluble fraction of the cell recognized either by anti-liver-kidney microsome antibodies type 1 or by anti-liver cytosol antibodies type 1--relationship with hepatitis C virus infection.

    PubMed

    Ballot, E; Desbos, A; Monier, J C

    1996-09-01

    Antibodies directed against liver cytosol protein, called anti-liver cytosol type 1 (LC1 Ab), have been described by both immunofluorescence (IF) and immunodiffusion techniques in sera from patients with autoimmune hepatitis (AIH). They have never been found in association with antibodies directed against the hepatitis C virus (HCV), unlike the anti-liver-kidney microsome antibodies type 1 (LKM1 Ab), the serological marker of AIH type 2. This suggests that there are two subgroups of AIH type 2, i.e., HCV-related and non-HCV-related. In this study, immunoblotting experiments were performed using proteins from the soluble phase of the rat liver cell; 141 sera which tested positive for LKM1 Ab by IF, 24 identified as having LC1 Ab by IF, and 50 from blood donors as controls were analyzed. Three bands were stained by LC1 Ab sera more often than by the control sera, and with a statistically significant frequency. These 3 proteins were located at apparent Mr 50,000, 55,000, and 60,000. The LKM1 Ab-positive sera as defined by IF stained six bands with a statistically significant frequency compared to the controls. Their apparent Mr were 35,000, 39,000, 47,000, 50,000, 55,000, and 60,000. LKM1 Ab-positive sera which were anti-HCV negative recognized a 60,000 protein belonging to the soluble phase of the cell, with a statistically significant frequency compared to LKM1 Ab-positive sera which were anti-HCV positive. This 60,000 protein was also recognized by LC1 Ab-positive sera, which were almost always anti-HCV negative. The presence of antibodies against a 60,000 protein from the soluble phase of the cell is discussed in terms of the anti-HCV serological markers found in the sera from patients with AIH. PMID:8811044

  15. IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production

    E-print Network

    Maier, Lisa M.

    Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex ...

  16. Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

    PubMed Central

    Lear, Calli; Chen, Li; Yantosca, L. Michael; Scully, Corinne; Sarraju, Ashish; Sokolovska, Anna; Zariffard, M. Reza; Eisen, Damon P.; Mungall, Bruce A.; Kotton, Darrell N.; Omari, Amel; Huang, I-Chueh; Farzan, Michael; Takahashi, Kazue; Stuart, Lynda; Stahl, Gregory L.; Ezekowitz, Alan B.; Spear, Gregory T.; Olinger, Gene G.; Schmidt, Emmett V.; Michelow, Ian C.

    2013-01-01

    Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes. PMID:23573288

  17. Parasite-Specific IL-17-Type Cytokine Responses and Soluble IL-17 Receptor Levels in Alveolar Echinococcosis Patients

    PubMed Central

    Lechner, Christian J.; Grüner, Beate; Huang, Xiangsheng; Hoffmann, Wolfgang H.; Kern, Peter; Soboslay, Peter T.

    2012-01-01

    Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host. PMID:22969818

  18. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells.

    PubMed

    Sharkey, David J; Schjenken, John E; Mottershead, David G; Robertson, Sarah A

    2015-12-01

    Seminal fluid induces pro-inflammatory cytokines and elicits an inflammation-like response in the cervix. Here, Affymetrix microarray and qPCR was utilised to identify activin A (INHBA) and its inhibitor follistatin (FST) amongst the cytokines induced by seminal plasma in Ect1 ectocervical epithelial cells, and a similar response was confirmed in primary ectocervical epithelial cells. TGFB is abundant in seminal plasma and all three TGFB isoforms induced INHBA in Ect1 and primary cells, and neutralisation of TGFB in seminal plasma suppressed the INHBA response. Bacterial lipopolysaccharide in seminal plasma also elicited INHBA, but potently suppressed FST production. There was moderate reciprocal inhibition between FST and INHBA, and cross-attenuating effects were seen. These data identify TGFB and potentially LPS as factors mediating seminal plasma-induced INHBA synthesis in cervical cells. INHBA and FST induced by seminal fluid in cervical tissues may thus contribute to regulation of the post-coital response in women. PMID:26415587

  19. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

    SciTech Connect

    Sandhu, Hardip; Xu, Cang Bao; Edvinsson, Lars

    2010-11-15

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke particles (DSP) induces upregulation of contractile endothelin type B (ET{sub B}) receptors in rat cerebral arteries and if activation of mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-{kappa}B) mediate the upregulation of contractile endothelin receptors in the cerebral arteries. Rat middle cerebral arteries were isolated and organ cultured in serum free medium for 24 h in the presence of DSP with or without specific inhibitors: MEK specific (U0126), p38 specific (SB202190), JNK specific (SP600125), NF-{kappa}B specific (BMS-345541) or (IMD-0354), transcription inhibitor (actinomycin D), or translation blocker (cycloheximide). Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c were investigated by a sensitive myograph. The expression of the ET{sub B} receptors were studied at mRNA and protein levels using quantitative real time PCR and immunohistochemistry, respectively. Results show that organ culture per se induced transcriptional upregulation of contractile ET{sub B} receptors in the cerebral vascular smooth muscle cells. This upregulation was further increased at the translational level by addition of DSP to the organ culture, but this increase was not seen by addition of nicotine or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET{sub B} receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK and JNK MAPK-mediated transcription and translation of new contractile ET{sub B} receptors. Thus, the MAPK-mediated upregulation of contractile ET{sub B} receptors in cerebral arteries might be a pharmacological target for the treatment of smoke-associated cerebral vascular disease like stroke.

  20. Human Lipocalin-Type Prostaglandin D Synthase-Based Drug Delivery System for Poorly Water-Soluble Anti-Cancer Drug SN-38

    PubMed Central

    Nakatsuji, Masatoshi; Inoue, Haruka; Kohno, Masaki; Saito, Mayu; Tsuge, Syogo; Shimizu, Shota; Ishida, Atsuko; Ishibashi, Osamu; Inui, Takashi

    2015-01-01

    Lipocalin-type prostaglandin D synthase (L-PGDS) is a member of the lipocalin superfamily, which is composed of secretory transporter proteins, and binds a wide variety of small hydrophobic molecules. Using this function, we have reported the feasibility of using L-PGDS as a novel drug delivery vehicle for poorly water-soluble drugs. In this study, we show the development of a drug delivery system using L-PGDS, one that enables the direct clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), a poorly water-soluble anti-cancer drug. In the presence of 2 mM L-PGDS, the concentration of SN-38 in PBS increased 1,130-fold as compared with that in PBS. Calorimetric experiments revealed that L-PGDS bound SN-38 at a molecular ratio of 1:3 with a dissociation constant value of 60 ?M. The results of an in vitro growth inhibition assay revealed that the SN-38/L-PGDS complexes showed high anti-tumor activity against 3 human cancer cell lines, i.e., Colo201, MDA-MB-231, and PC-3 with a potency similar to that of SN-38 used alone. The intravenous administration of SN-38/L-PGDS complexes to mice bearing Colo201 tumors showed a pronounced anti-tumor effect. Intestinal mucositis, which is one of the side effects of this drug, was not observed in mice administered SN-38/L-PGDS complexes. Taken together, L-PGDS enables the direct usage of SN-38 with reduced side effects. PMID:26529243

  1. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    PubMed Central

    Bertacchi, Michele; Lupo, Giuseppe; Pandolfini, Luca; Casarosa, Simona; D’Onofrio, Mara; Pedersen, Roger A.; Harris, William A.; Cremisi, Federico

    2015-01-01

    Summary Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs) toward eye field fates. Inhibition of Wnt/?-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine. PMID:26388287

  2. Simultaneous enhancement of electron injection and air stability in N-type organic field-effect transistors by water-soluble polyfluorene interlayers.

    PubMed

    Kim, Jihong; Khim, Dongyoon; Kang, Rira; Lee, Seung-Hoon; Baeg, Kang-Jun; Kang, Minji; Noh, Yong-Young; Kim, Dong-Yu

    2014-06-11

    Here, we report the simultaneous attainment of efficient electron injection and enhanced stability under ambient conditions for top-gate/bottom-contact (TG/BC), n-type, organic field-effect transistors (OFETs) using water-soluble polyfluorene derivatives (WPFs). When inserting the WPF interlayers between a semiconductor and the BC Au electrodes, initially the ambipolar (6,6)-phenyl-C61butyric acid methyl ester (PCBM) OFETs were fully converted to unipolar charge transport characteristics that were exclusively n-type with significantly increased electron mobilities as high as 0.12 cm(2)/(V s) and a decreased threshold voltage. These improvements were mostly attributed to the interfacial dipoles of WPF layers that aligned to form a favorable energy band structure for efficient electron injection and to effectively block counter charge carriers. These were confirmed when values for the reduced work function of metal electrodes with WPFs and their correlated contact resistance were measured via the ultraviolet photoemission spectroscopy and the transmission-line method, respectively. Moreover, the WPF interlayers played an important role in air stability of PCBM OFETs that exhibited higher and appreciably enhanced by increasing the ethylene-oxide side chain lengths of WPFs, which presumably was due to the water/oxygen/ion capturing effects in the hydrophilic interlayers. PMID:24840007

  3. Activins regulate 17b-hydroxysteroid dehydrogenase type I transcription in murine gonadotrope cells

    E-print Network

    Mayo, Kelly E.

    and in different physiological and pathophysiological processes in adulthood (Matzuk et al. 1996, Reis et al. 2004 gonadotropin synthesis and secretion indirectly, in addition to their direct effects on the Fshb subunit

  4. Comparable generation of activin-induced definitive endoderm via additive Wnt or BMP signaling in absence of serum.

    PubMed

    Teo, Adrian Kee Keong; Valdez, Ivan Achel; Dirice, Ercument; Kulkarni, Rohit N

    2014-07-01

    There is considerable interest in differentiating human pluripotent stem cells (hPSCs) into definitive endoderm (DE) and pancreatic cells for in vitro disease modeling and cell replacement therapy. Numerous protocols use fetal bovine serum, which contains poorly defined factors to induce DE formation. Here, we compared Wnt and BMP in their ability to cooperate with Activin signaling to promote DE formation in a chemically defined medium. Varying concentrations of WNT3A, glycogen synthase kinase (GSK)-3 inhibitors CHIR99021 and 6-bromoindirubin-3'-oxime (BIO), and BMP4 could independently co-operate with Activin to effectively induce DE formation even in the absence of serum. Overall, CHIR99021 is favored due to its cost effectiveness. Surprisingly, WNT3A was ineffective in suppressing E-CADHERIN/CDH1 and pluripotency factor gene expression unlike GSK-3 inhibitors or BMP4. Our findings indicate that both Wnt and BMP effectively synergize with Activin signaling to generate DE from hPSCs, although WNT3A requires additional factors to suppress the pluripotency program inherent in hPSCs. PMID:25068117

  5. A novel factor, Tmem176b, induced by activin-like kinase 2 signal promotes the differentiation of myoblasts into osteoblasts.

    PubMed

    Yano, M; Kawao, N; Tamura, Y; Okada, K; Kaji, H

    2014-01-01

    Previous studies have suggested some interactions between muscle tissues and bone metabolism. The constitutively activating mutation (R206H) of the BMP type I receptor, activin-like-kinase 2 (ALK2), causes fibrodysplasia ossificans progressiva (FOP), which is characterized by extensive ossifications within muscle tissues. In the present study, we revealed that Tmem176b mRNA levels were upregulated by stable transfection of ALK2 (R206H) in mouse myoblastic C2C12 cells. Transient Tmem176b overexpression elevated levels of osteoblast differentiation markers, such as Osterix and alkaline phosphatase, as well as mineralization in C2C12 cells. In addition, Tmem176b overexpression elevated the levels of these markers in mouse osteoblastic MC3T3-E1 cells. On the other hand, Tmem176b overexpression suppressed the levels of myogenic markers, such as MyoD and myogenin in C2C12 cells, although it did not affect the levels of chondrogenic markers, such as type II and X collagens. In conclusion, the present study is the first to demonstrate that Tmem176b induces the differentiation of myoblasts into an osteoblast lineage. PMID:24085390

  6. Total Soluble and Endogenous Secretory Receptor for Advanced Glycation End Products as Predictive Biomarkers of Coronary Heart Disease Risk in Patients With Type 2 Diabetes

    PubMed Central

    Colhoun, Helen M.; Betteridge, D. John; Durrington, Paul; Hitman, Graham; Neil, Andrew; Livingstone, Shona; Charlton-Menys, Valentine; Bao, Weihang; DeMicco, David A.; Preston, Gregory M.; Deshmukh, Harshal; Tan, Kathryn; Fuller, John H.

    2011-01-01

    OBJECTIVE Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoform (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS). RESEARCH DESIGN AND METHODS We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates. RESULTS sRAGE and esRAGE were strongly correlated (? = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25–2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11–1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38–1.14). Atorvastatin, 10 mg daily, did not alter sRAGE. CONCLUSIONS Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes. PMID:21771973

  7. Beneficial effect of the soluble guanylyl cyclase stimulator BAY 41-2272 on impaired penile erection in db/db-/- type II diabetic and obese mice.

    PubMed

    Nunes, Kenia Pedrosa; Teixeira, Cleber E; Priviero, Fernanda B M; Toque, Haroldo A; Webb, R Clinton

    2015-05-01

    Type 2 diabetes mellitus (DM2) and obesity are major risk factors for erectile dysfunction (ED). In diabetes, increased oxidative stress leads to decreased nitric oxide (NO) bioavailability, and diabetic patients appear to be less responsive to conventional therapy with phosphodiesterase type 5 inhibitors. We investigated whether the soluble guanylyl cyclase stimulator BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4ylamine) is effective in improving impaired corpus cavernosum (CC) relaxation in obese DM2 mice by reducing oxidative stress. Adult db/db(-/-) mice or their lean db(/+) littermates were used to assess vascular function, cGMP levels, antioxidant status, NADPH oxidase expression, and superoxide formation in the absence or presence of BAY 41-2272. Results showed that BAY 41-2272 (10(-8) to 10(-5) M) potently relaxed CC from db(/+) or db/db(-/-) mice in a similar manner. BAY 41-2272 significantly enhanced both endothelium-dependent and nitrergic relaxation induced by electrical field stimulation (EFS), and improved the impaired relaxation to acetylcholine and EFS in the diabetic animals in a concentration-dependent manner (10(-8) to 10(-7) M). BAY 41-2272 increased cGMP levels and potentiated relaxation responses to exogenous NO in CC. Total antioxidant status was reduced in plasma and urine whereas expression of vascular NADPH oxidase subunits (gp91phox, p22phox, and p47phox) was increased in the CC of db/db(-/-) mice, suggesting a state of oxidative stress. These effects were prevented by BAY 41-2272 in a concentration-dependent manner. These results suggest that BAY 41-2272 improves CC relaxation in db/db(-/-) mice by increasing cGMP and augmenting antioxidant status, making this drug is a potential novel candidate to treat ED. PMID:25740897

  8. Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva.

    PubMed

    Shi, Songting; Cai, Jie; de Gorter, David J J; Sanchez-Duffhues, Gonzalo; Kemaladewi, Dwi U; Hoogaars, Willem M H; Aartsma-Rus, Annemieke; 't Hoen, Peter A C; ten Dijke, Peter

    2013-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disease characterized by progressive heterotopic ossification of connective tissues, for which there is presently no definite treatment. A recurrent activating mutation (c.617G?A; R206H) of activin receptor-like kinase 2 (ACVR1/ALK2), a BMP type I receptor, has been shown as the main cause of FOP. This mutation constitutively activates the BMP signaling pathway and initiates the formation of heterotopic bone. In this study, we have designed antisense oligonucleotides (AONs) to knockdown mouse ALK2 expression by means of exon skipping. The ALK2 AON could induce exon skipping in cells, which was accompanied by decreased ALK2 mRNA levels and impaired BMP signaling. In addition, the ALK2 AON potentiated muscle differentiation and repressed BMP6-induced osteoblast differentiation. Our results therefore provide a potential therapeutic approach for the treatment of FOP disease by reducing the excessive ALK2 activity in FOP patients. PMID:23861958

  9. Identification of BMP and activin membrane-bound inhibitor (BAMBI) as a potent negative regulator of adipogenesis and modulator of autocrine/paracrine adipogenic factors.

    PubMed

    Luo, Xiao; Hutley, Louise J; Webster, Julie A; Kim, Yu-Hee; Liu, Dong-Fang; Newell, Felicity S; Widberg, Charlotte H; Bachmann, Anthony; Turner, Nigel; Schmitz-Peiffer, Carsten; Prins, Johannes B; Yang, Gong-She; Whitehead, Jonathan P

    2012-01-01

    Adipose tissue dysfunction underpins the association of obesity with type 2 diabetes. Adipogenesis is required for the maintenance of adipose tissue function. It involves the commitment and subsequent differentiation of preadipocytes and is coordinated by autocrine, paracrine, and endocrine factors. We previously reported that fibroblast growth factor-1 (FGF-1) primes primary human preadipocytes and Simpson Golabi Behmel syndrome (SGBS) preadipocytes and increases adipogenesis through a cascade involving extracellular signal-related kinase 1/2 (ERK1/2). Here, we aimed to use the FGF-1 system to identify novel adipogenic regulators. Expression profiling revealed bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) as a putative FGF-1 effector. BAMBI is a transmembrane protein and modulator of paracrine factors that regulate adipogenesis, including transforming growth factor (TGF) superfamily members (TGF-? and BMP) and Wnt. Functional investigations established BAMBI as a negative regulator of adipogenesis and modulator of the anti- and proadipogenic effects of Wnt3a, TGF-?1, and BMP-4. Further studies showed that BAMBI expression levels are decreased in a mouse model of diet-induced obesity. Collectively, these findings establish BAMBI as a novel, negative regulator of adipogenesis that can act as a nexus to integrate multiple paracrine signals to coordinate adipogenesis. Alterations in BAMBI may play a role in the (patho)physiology of obesity, and manipulation of BAMBI may present a novel therapeutic approach to improve adipose tissue function. PMID:22187378

  10. The ActR-I activin receptor protein is expressed in notochord, lens placode and pituitary primordium cells in the mouse embryo.

    PubMed

    Yoshikawa, S I; Aota, S; Shirayoshi, Y; Okazaki, K

    2000-03-01

    ActR-I is a type I serine/threonine kinase receptor which has been shown to bind activin and bone morphogenetic proteins (BMPs). To study the function of ActR-I, we have generated novel monoclonal antibodies that specifically recognize the extracellular domain of mouse ActR-I. We examined the level of ActR-I protein during mouse development by immunohistochemistry. We found that in the embryonic body, ActR-I protein first appears in a restricted part of the primitive streak region and is present throughout the length of notochord. Furthermore, ActR-I protein is expressed in the facial sensory organ primordia, including eye area, otic vesicle and olfactory placode, which all contain invaginating ectoderm. In addition, ActR-I is produced in pituitary primordium (Rathke's pouch), mammary buds and the epithelial layer of branchial arches. Interestingly, in the lens placodes and in early Rathke's pouch, ActR-I protein is transiently localized at the apical surface of the epithelial cells, indicating the presence of an apical-basal asymmetry in these cells. PMID:10704880

  11. The Notch ligand Delta-like 1 integrates inputs from TGFbeta/Activin and Wnt pathways

    SciTech Connect

    Bordonaro, Michael Tewari, Shruti Atamna, Wafa Lazarova, Darina L.

    2011-06-10

    Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promoter sequences containing a Smad binding element. The indirect upregulation of CTGF expression by Dll1 is likely due to the ability of Dll1icd to increase Wnt signaling, a pathway that targets CTGF. CTGF expression is induced in butyrate-treated CC cells and results from clonal growth assays support a role for CTGF in the cell growth-suppressive role of butyrate. In conclusion, integration of the Notch, Wnt, and TGFbeta/Activin signaling pathways is in part mediated by the interactions of Dll1 with Smad2/3 and Tcf4.

  12. Attenuation of corneal myofibroblast development through nanoparticle-mediated soluble transforming growth factor-? type II receptor (sTGF?RII) gene transfer

    E-print Network

    Sharma, Ajay

    Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of ...

  13. Soluble vs. insoluble fiber

    MedlinePLUS

    ... soluble and insoluble. Both are important for health, digestion, and preventing diseases. Soluble fiber attracts water and turns to gel during digestion. This slows digestion. Soluble fiber is found in ...

  14. Activin, BMP and FGF pathways cooperate to promote endoderm and pancreatic lineage cell differentiation from human embryonic stem cells

    PubMed Central

    Xu, Xiaofang; Browning, Victoria; Odorico, Jon

    2011-01-01

    The study of how human embryonic stem cells (hESCs) differentiate into insulin-producing beta cells has two-fold significance: first, it provides an in vitro model system for the study of human pancreatic development, and second, it serves as a platform for the ultimate production of beta cells for transplantation into patients with diabetes. The delineation of growth factor interactions regulating pancreas specification from hESCs in vitro is critical to achieving these goals. In this study, we describe the roles of growth factors bFGF, BMP4 and Activin A in early hESC fate determination. The entire differentiation process is carried out in serum-free chemically defined media (CDM) and results in reliable and robust induction of pancreatic endoderm cells, marked by PDX1, and cell clusters co-expressing markers characteristic of beta cells, including PDX1 and insulin/C-peptide. Varying the combinations of growth factors, we found that treatment of hESCs with bFGF, Activin A and BMP4 (FAB) together for 3 to 4 days resulted in strong induction of primitive-streak and definitive endoderm-associated genes, including MIXL1, GSC, SOX17 and FOXA2. Early proliferative foregut endoderm and pancreatic lineage cells marked by PDX1, FOXA2 and SOX9 expression are specified in EBs made from FAB-treated hESCs, but not from Activin A alone treated cells. Our results suggest that important tissue interactions occur in EB-based suspension culture that contribute to the complete induction of definitive endoderm and pancreas progenitors. Further differentiation occurs after EBs are embedded in Matrigel and cultured in serum-free media containing insulin, transferrin, selenium, FGF7, nicotinamide, islet neogenesis associated peptide (INGAP) and exendin-4, a long acting GLP-1 agonist. 21–28 days after embedding, PDX1 gene expression levels are comparable to those of human islets used for transplantation, and many PDX1+ clusters are formed. Almost all cells in PDX1+ clusters co-express FOXA2, HNF1ß, HNF6 and SOX9 proteins, and many cells also express CPA1, NKX6.1 and PTF1a. If cells are then switched to medium containing B27 and nicotinamide for 7 to 14 days, then the number of insulin+ cells increases markedly. Our study identifies a new chemically defined culture protocol for inducing endoderm- and pancreas-committed cells from hESCs and reveals an interplay between FGF, Activin A and BMP signaling in early hESC fate determination. PMID:21855631

  15. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin.

    PubMed

    Gilson, Hélène; Schakman, Olivier; Kalista, Stéphanie; Lause, Pascale; Tsuchida, Kunihiro; Thissen, Jean-Paul

    2009-07-01

    Follistatin (FS) inhibits several members of the TGF-beta superfamily, including myostatin (Mstn), a negative regulator of muscle growth. Mstn inhibition by FS represents a potential therapeutic approach of muscle atrophy. The aim of our study was to investigate the mechanisms of the FS-induced muscle hypertrophy. To test the role of satellite cells in the FS effect, we used irradiation to destroy their proliferative capacity. FS overexpression increased the muscle weight by about 37% in control animals, but the increase reached only 20% in irradiated muscle, supporting the role of cell proliferation in the FS-induced hypertrophy. Surprisingly, the muscle hypertrophy caused by FS reached the same magnitude in Mstn-KO as in WT mice, suggesting that Mstn might not be the only ligand of FS involved in the regulation of muscle mass. To assess the role of activin (Act), another FS ligand, in the FS-induced hypertrophy, we electroporated FSI-I, a FS mutant that does not bind Act with high affinity. Whereas FS electroporation increased muscle weight by 32%, the muscle weight gain induced by FSI-I reached only 14%. Furthermore, in Mstn-KO mice, FSI-I overexpression failed to induce hypertrophy, in contrast to FS. Therefore, these results suggest that Act inhibition may contribute to FS-induced hypertrophy. Finally, the role of Act as a regulator of muscle mass was supported by the observation that ActA overexpression induced muscle weight loss (-15%). In conclusion, our results show that satellite cell proliferation and both Mstn and Act inhibition are involved in the FS-induced muscle hypertrophy. PMID:19435857

  16. Differential Expression and Regulation by Activin of the Neurotrophins BDNF and NT4 During Human and Mouse Ovarian Development

    PubMed Central

    Childs, Andrew J; Bayne, Rosemary AL; Murray, Alison A; Martins Da Silva, Sarah J; Collins, Craig S; Spears, Norah; Anderson, Richard A

    2010-01-01

    The tropomyosin-related kinase (Trk) B neurotrophin receptor is essential for ovarian germ cell survival and primordial follicle formation, but the contributions of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), are unknown. We have investigated their expression and regulation in developing human and mouse ovaries. BDNF expression increased with increasing gestation, expression of human NTF4 and of both Ntf5 and Bdnf in the mouse was unchanged. Bdnf expression was dramatically lower than Ntf5 in the mouse, but levels were comparable in the human. Human fetal ovarian somatic cells expressed BDNF. Activin A selectively regulated BDNF and Ntf5 expression in human and mouse, respectively, identifying an oocyte/somatic signaling pathway which might mediate the pro-survival effects of activin. These data reveal that expression and regulation of the TrkB ligands are differentially controlled in the developing ovaries of humans and mice, and identify BDNF as a potential regulator of germ cell fate in the human fetal ovary. Developmental Dynamics 239:1211–1219, 2010. © 2010 Wiley-Liss, Inc. PMID:20175187

  17. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    SciTech Connect

    Sui, Lina; Mfopou, Josue K.; Geens, Mieke; Sermon, Karen; Bouwens, Luc

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  18. Bioactivity of water soluble extracts and some characteristics of white cheese during the ripening period as effected by packaging type and probiotic adjunct cultures.

    PubMed

    Erkaya, Tuba; ?engul, Mustafa

    2015-02-01

    In this study, the chemical composition, proteolysis and in vitro angiotensin-converting enzyme-(ACE)-inhibitory and antioxidant activities of white cheeses made using probiotic adjunct cultures (Bifidobacterium bifidum DSMZ 20456 and Lactobacillus acidophilus DSMZ 20079) were investigated. The cheeses were ripened in a vacuum package or brine for 120 d at 4 °C. The cheese samples maintained the probiotic characteristics of the viable cells as >106 cfu/g even after ripening for 120 d. The proteolysis degrees in terms of water-soluble nitrogen/total nitrogen (WSN/TN), trichloroacetic acid-soluble nitrogen/total nitrogen (TCA-SN/TN) and phosphotungstic acid-soluble nitrogen/total nitrogen (PTA-SN/TN) values in the cheeses increased throughout the ripening. The highest levels of proteolysis were found in cheese made using Lb. acidophilus DSMZ 20079 and ripened in a vacuum package. ACE-inhibitory activity of the water soluble extracts (WSEs) of the cheeses increased significantly (P < 0·05) throughout the ripening (IC50 values 82·78-140·99 ?g/ml). Use of Lb. acidophilus DSMZ 20079 and packaging under vacuum significantly increased the percentage of ACE inhibiting activity. WSEs had DPPH scavenging activity (the IC50 values were 2·41-5·39 mg/ml and the inhibition values were 5·10-10·38%), increasing up to 60 d ripening. In the present study, it was observed that Lb. acidophilus DSMZ 20079 was more effective than Bifido. bifidum DSMZ 20456 in terms of the cheese characteristics investigated. PMID:25592630

  19. Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case of cobalt oxide on human lung cells

    PubMed Central

    2014-01-01

    Background The mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4). Methods This study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry. Results Our study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity. Conclusions Cobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity. PMID:24669904

  20. Production of bioactive chicken (Gallus gallus) follistatin-type proteins in E. coli.

    PubMed

    Lee, Sang Beum; Park, Sung Kwon; Kim, Yong Soo

    2015-12-01

    Follistatin (FST) is a cysteine-rich autocrine glycoprotein and plays an important role in mammalian prenatal and postnatal development. FST binds to and inhibit myostatin (MSTN), a potent negative regulator of skeletal muscle growth, and FST abundance enhances muscle growth in animals via inhibition of MSTN activity. The objective of this study was to produce biologically active, four chicken FST-type proteins in an Escherichia coli expression system. Gibson assembly cloning method was used to insert the DNA fragments of four FST-type proteins, designated as FST288, NDFSD1/2, NDFSD1, and NDFSD1/1, into pMALc5x vector downstream of the maltose-binding protein (MBP) gene, and the plasmids containing the inserts were eventually transformed into Shuffle E. coli strain for protein expression. We observed a soluble expression of the four MBP-fused FST-type proteins, and the proteins could be easily purified by the combination of amylose and heparin resin affinity chromatography. MBP-fused FST-type proteins demonstrated their affinity to anti-FST antibody. In an in vitro reporter gene assay to examine their potencies and selectivities to different ligands (MSTN, GDF11, and activin A), the four FST-type proteins (MBP-FST288, MBP-NDFSD1/2, MBP-NDFSD1, and MBP-NDFSD1/1) showed different potency and selectivity against the three ligands from each other. Ligand selectivity of each FST-type proteins was similar to its counterpart FST-type protein of eukaryotic origin. In conclusion, we could produce four FST-type proteins having different ligand selectivity in E. coli, and the results imply that economic production of a large amount of FST-type proteins with different ligand selectivity is possible to examine their potential use in meat-producing animals. PMID:26302688

  1. Amyloid Fibril Solubility

    E-print Network

    Rizzi, L G

    2015-01-01

    It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain side-chain interactions, backbone hydrogen bonding and temperature affect amyloid fibril solubility, which might prove a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.

  2. Small-molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells.

    PubMed

    Morizane, Asuka; Doi, Daisuke; Kikuchi, Tetsuhiro; Nishimura, Kaneyasu; Takahashi, Jun

    2011-02-01

    The balance of bone morphogenic protein (BMP), transforming growth factor-? (TGF?)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small-molecule inhibitors of BMP (Dorsomorphin) and TGF?/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder-free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine. PMID:21162120

  3. Transcriptional activation of mouse mast cell Protease-7 by activin and transforming growth factor-beta is inhibited by microphthalmia-associated transcription factor.

    PubMed

    Funaba, Masayuki; Ikeda, Teruo; Murakami, Masaru; Ogawa, Kenji; Tsuchida, Kunihiro; Sugino, Hiromu; Abe, Matanobu

    2003-12-26

    Previous studies have revealed that activin A and transforming growth factor-beta1 (TGF-beta1) induced migration and morphological changes toward differentiation in bone marrow-derived cultured mast cell progenitors (BMCMCs). Here we show up-regulation of mouse mast cell protease-7 (mMCP-7), which is expressed in differentiated mast cells, by activin A and TGF-beta1 in BMCMCs, and the molecular mechanism of the gene induction of mmcp-7. Smad3, a signal mediator of the activin/TGF-beta pathway, transcriptionally activated mmcp-7. Microphthalmia-associated transcription factor (MITF), a tissue-specific transcription factor predominantly expressed in mast cells, melanocytes, and heart and skeletal muscle, inhibited Smad3-mediated mmcp-7 transcription. MITF associated with Smad3, and the C terminus of MITF and the MH1 and linker region of Smad3 were required for this association. Complex formation between Smad3 and MITF was neither necessary nor sufficient for the inhibition of Smad3 signaling by MITF. MITF inhibited the transcriptional activation induced by the MH2 domain of Smad3. In addition, MITF-truncated N-terminal amino acids could associate with Smad3 but did not inhibit Smad3-mediated transcription. The level of Smad3 was decreased by co-expression of MITF but not of dominant-negative MITF, which resulted from proteasomal protein degradation. The changes in the level of Smad3 protein were paralleled by those in Smad3-mediated signaling activity. These findings suggest that MITF negatively regulates Smad-dependent activin/TGF-beta signaling in a tissue-specific manner. PMID:14527958

  4. Signaling via the transcriptionally regulated activin receptor 2B is a novel mediator of neuronal cell death during chicken ciliary ganglion development.

    PubMed

    Koszinowski, S; Buss, K; Kaehlcke, K; Krieglstein, K

    2015-04-01

    The TGF-? ligand superfamily members activin A and BMP control important aspects of embryonic neuronal development and differentiation. Both are known to bind to activin receptor subtypes IIA (ActRIIA) and IIB, while in the avian ciliary ganglion (CG), so far only ActRIIA-expression has been described. We show that the expression of ACVR2B, coding for the ActRIIB, is tightly regulated during CG development and the knockdown of ACVR2B expression leads to a deregulation in the execution of neuronal apoptosis and therefore affects ontogenetic programmed cell death in vivo. While the differentiation of choroid neurons was impeded in the knockdown, pointing toward a reduction in activin A-mediated neural differentiation signaling, naturally occurring neuronal cell death in the CG was not prevented by follistatin treatment. Systemic injections of the BMP antagonist noggin, on the other hand, reduced the number of apoptotic neurons to a similar extent as ACVR2B knockdown. We therefore propose a novel pathway in the regulation of CG neuron ontogenetic programmed cell death, which could be mediated by BMP and signals via the ActRIIB. PMID:25660516

  5. Activin A in combination with OP9 cells facilitates development of Flk-1(+) PDGFR?(-) and Flk-1(+) PDGFR?(+) hematopoietic mesodermal cells from murine embryonic stem cells.

    PubMed

    Hirota, Saeka; Ogawa, Minetaro

    2015-11-20

    Lateral mesoderm-derived hemogenic endothelial cells are known to originate the definitive hematopoietic lineage in mouse embryogenesis. The developmental process of the definitive hematopoietic lineage can be recapitulated by inducing differentiation of mouse embryonic stem (ES) cells in a co-culture system with OP9 stromal cells. However, the signaling molecules that can modulate the development of the definitive hematopoietic lineage in the OP9 co-culture system have yet to be identified. Here we report that activin A enhanced the hematopoietic potential of endothelial cells derived from ES cells in the OP9 co-culture system. Activin A in combination with OP9 cells augmented development of Flk-1(+) PDGFR?(+) early mesodermal cells and Flk-1(+) PDGFR?(-) lateral mesodermal cells from ES cells. These Flk-1(+) mesodermal cells further differentiated into CD41(+) endothelial cells, which preferentially possessed high hematopoietic potential. Furthermore, Flk-1(+) PDGFR?(+) cells but not Flk-1(+) PDGFR?(-) cells produced hematopoietic progenitors with a bimodal pattern when cultured as an aggregate with OP9 cells. Our results suggest that activin A in combination with OP9 cells facilitates differentiation of ES cells to Flk-1(+) mesodermal cells, which encompass various precursors that separately contribute to the development of hematopoietic lineages. PMID:26417686

  6. Concentration of activin A and follistatin in follicular fluid from human small antral follicles associated to gene expression of the corresponding granulosa cells.

    PubMed

    Jeppesen, J V; Nielsen, M E; Kristensen, S G; Yding Andersen, C

    2012-06-01

    The present study correlated concentrations of activin A and follistatin in follicular fluid (FF) from human small antral follicles to FF concentrations of AMH, inhibin B, progesterone, and oestradiol and to the mRNA expression of FSH-receptor (FSHR), LH-receptor (LHR), AMH-receptor2 (AMHR2), CYP19a, and androgen-receptor (AR) in the corresponding granulosa cells (GC). FF from 144 follicles (3-12 mm in diameter) was included whereas mRNA expression profiles were established in GC from 66 of the 144 follicles. Levels of follistatin remained constant in relation to follicular diameter, whereas activin A levels increased in follicles exceeding 10 mm in diameter. Levels of activin A and inhibin B showed a highly significant inverse association. Follistatin showed highly significant positive associations with AMH and inhibin B levels and with FSHR and AR gene expression in GC. This study revealed unexpected associations that probably reflect the complicated regulatory mechanisms governing human folliculogenesis. PMID:21846490

  7. Serum erythropoietin and its relation with soluble transferrin receptor in patients with different types of anaemia in a locally defined reference population.

    PubMed

    Roque, M E; Sandoval, M J; Aggio, M C

    2001-10-01

    Serum erythropoietin (Epo) and soluble transferrin receptor (sTR) were measured in a locally defined reference population (n=100): healthy volunteers (n=50); iron- deficiency anaemia (n=41) and haemolytic anaemia (n=9) (beta-thalassaemia, n = 4; autoimmune, n=5). Our data demonstrated an inverse relationship between erythroid activity and Epo levels. The regression line between Ln Epo and haemoglobin (Hb) was highly significant: P < 0.0001, r2=0.8275, Ln Epo=8.5346-0.04275 Hb, confidence limit 95%. The mean observed/predicted (O/P) ratio of Ln (Epo) was 1.01 +/- 0.11. We demonstrated that the serum Epo concentration in this particular population correlated consistently with clinical measures of erythropoietic activity. sTR, a new index of erythropoiesis, varied from 16.1 to 148 nmol/l, mean 62.0 nmol/l in the anaemic patients' group. The relationship between Ln Epo and Ln sTR was highly significant: P < 0.0001. We conclude that locally defined regression analyses are crucial for correct data interpretation and can indicate whether or not Epo production is appropriate or inappropriate. Serial determinations of sTR could help in the assessment of response to therapeutic doses of Epo. PMID:11703410

  8. Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization.

    PubMed Central

    Koito, A; Harrowe, G; Levy, J A; Cheng-Mayer, C

    1994-01-01

    We have examined the influence of the V1/V2 region of the human immunodeficiency virus type 1 (HIV-1) gp120 on certain biologic properties of the virus. We observed that on the genomic background of the T-cell-line-tropic strain, HIV-1SF2mc, both the V1 and V2 domains of the macrophage-tropic strain, HIV-1SF162mc, in addition to the required V3 domain, are necessary to attain full macrophage tropism. Furthermore, the V2 domain modulates the sensitivity of HIV-1 to soluble CD4 neutralization. Structural studies of recombinant and mutant envelope glycoproteins suggest that the function of the V1/V2 region is to interact with the V3 domain and confer on the envelope gp120 of HIV-1SF2mc a conformation more similar to that of the macrophage-tropic strain HIV-1SF162mc. The conformation of the envelope gp120 appears to be strain specific and plays an important role in determining HIV-1 tissue tropism and sensitivity to soluble CD4 neutralization. Images PMID:8139010

  9. Quality of soluble organic C, N, and P produced by different types and species of litter: root litter versus leaf litter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In forested ecosystems, the quality of dissolved organic matter (DOM) produced by freshly senesced litter may differ by litter type and species, and these differences may influence the amount of DOM that is respired versus that which may either contribute to soil organic matter accumulation or be le...

  10. EFFECTS OF SOLUBLE FRACTIONS OF USED LIGHT-WEIGHT LIGNOSULFONATE TYPE MUD AND HEXAVALENT CHROMIUM ON THE COMPLETE LARVAL DEVELOPMENT OF THE CRABS, 'RHITHROPANOPEUS HARRISII' AND 'CALLINECTES SAPIDUS'

    EPA Science Inventory

    The mud aqueous fractions (MAF) and suspended particulate phase (SPP) of lignosulfonate type mud were nontoxic to the complete larval development of Rhithropanopeus harrisii. Five percent MAF and SPP were not toxic to Callinectes sapidus. Differential survival of C. sapidus larva...

  11. Peptide length and folding state govern the capacity of staphylococcal ?-type phenol-soluble modulins to activate human formyl-peptide receptors 1 or 2.

    PubMed

    Kretschmer, Dorothee; Rautenberg, Maren; Linke, Dirk; Peschel, Andreas

    2015-04-01

    Most staphylococci produce short ?-type PSMs and about twice as long ?-type PSMs that are potent leukocyte attractants and toxins. PSMs are usually secreted with the N-terminal formyl group but are only weak agonists for the leukocyte FPR1. Instead, the FPR1-related FPR2 senses PSMs efficiently and is crucial for leukocyte recruitment in infection. Which structural features distinguish FPR1 from FPR2 ligands has remained elusive. To analyze which peptide properties may govern the capacities of ?-type PSMs to activate FPRs, full-length and truncated variants of such peptides from Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis were synthesized. FPR2 activation was observed even for short N- or C-terminal ?-type PSM variants once they were longer than 18 aa, and this activity increased with length. In contrast, the shortest tested peptides were potent FPR1 agonists, and this property declined with increasing peptide length. Whereas full-length ?-type PSMs formed ?-helices and exhibited no FPR1-specific activity, the truncated peptides had less-stable secondary structures, were weak agonists for FPR1, and required N-terminal formyl-methionine residues to be FPR2 agonists. Together, these data suggest that FPR1 and FPR2 have opposed ligand preferences. Short, flexible PSM structures may favor FPR1 but not FPR2 activation, whereas longer peptides with ?-helical, amphipathic properties are strong FPR2 but only weak FPR1 agonists. These findings should help to unravel the ligand specificities of 2 critical human PRRs, and they may be important for new, anti-infective and anti-inflammatory strategies. PMID:25724390

  12. Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain

    PubMed Central

    Xuan, Meiyan; Okazaki, Mari; Iwata, Naohiro; Asano, Satoshi; Kamiuchi, Shinya; Matsuzaki, Hirokazu; Sakamoto, Takeshi; Miyano, Yoshiyuki; Iizuka, Hiroshi; Hibino, Yasuhide

    2015-01-01

    Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20?min) and subsequent reoxygenation. Pretreatment with MAK (1?g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24?h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice. PMID:25945116

  13. Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

    PubMed

    Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

    2015-11-15

    The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ? fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ? fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility. PMID:25977056

  14. Development of a small-molecule screening method for inhibitors of cellular response to myostatin and activin A.

    PubMed

    Cash, Jennifer N; Angerman, Elizabeth B; Kirby, R Jason; Merck, Lisa; Seibel, William L; Wortman, Matthew D; Papoian, Ruben; Nelson, Sandra; Thompson, Thomas B

    2013-08-01

    Myostatin, a member of the transforming growth factor (TGF)-? family of secreted ligands, is a strong negative regulator of muscle growth. As such, therapeutic inhibitors of myostatin are actively being investigated for their potential in the treatment of muscle-wasting diseases such as muscular dystrophy and sarcopenia. Here, we sought to develop a high-throughput screening (HTS) method for small-molecule inhibitors that target myostatin. We created a HEK293 stable cell line that expresses the (CAGA)12-luciferase reporter construct and robustly responds to signaling of certain classes of TGF-? family ligands. After optimization and miniaturization of the assay to a 384-well format, we successfully screened a library of compounds for inhibition of myostatin and the closely related activin A. Selection of some of the tested compounds was directed by in silico screening against myostatin, which led to an enrichment of target hits as compared with random selection. Altogether, we present an HTS method that will be useful for screening potential inhibitors of not only myostatin but also many other ligands of the TGF-? family. PMID:23543431

  15. Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes

    PubMed Central

    Jiménez, G.; López-Ruiz, E.; Kwiatkowski, W.; Montañez, E.; Arrebola, F.; Carrillo, E.; Gray, P. C.; Belmonte, J. C. Izpisua; Choe, S.; Perán, M.; Marchal, J. A.

    2015-01-01

    Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo. PMID:26563344

  16. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

    PubMed Central

    Yoshimatsu, Yasuhiro; Lee, Yulia G.; Akatsu, Yuichi; Taguchi, Luna; Suzuki, Hiroshi I.; Cunha, Sara I.; Maruyama, Kazuichi; Suzuki, Yuka; Yamazaki, Tomoko; Katsura, Akihiro; Oh, S. Paul; Zimmers, Teresa A.; Lee, Se-Jin; Pietras, Kristian; Koh, Gou Young; Miyazono, Kohei; Watabe, Tetsuro

    2013-01-01

    Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-?/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1 (ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation. PMID:24133138

  17. Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes.

    PubMed

    Jiménez, G; López-Ruiz, E; Kwiatkowski, W; Montañez, E; Arrebola, F; Carrillo, E; Gray, P C; Belmonte, J C Izpisua; Choe, S; Perán, M; Marchal, J A

    2015-01-01

    Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological, histological and immunological analysis together with a RT-PCR detection of collagen I and collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of patients and subjected to long-term culture undergo dedifferentiation and that these cells can be redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets also integrated into the surrounding subcutaneous tissue following transplantation in mice as demonstrated by their dramatic increase in size while non-treated control pellets disintegrated upon transplantation. Thus, our findings describe an effective protocol for the promotion of redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a cartilage-like ECM that can integrate into the surrounding tissue in vivo. PMID:26563344

  18. Protein solubility modeling.

    PubMed

    Agena, S M; Pusey, M L; Bogle, I D

    1999-07-20

    A thermodynamic framework (UNIQUAC model with temperature dependent parameters) is applied to model the salt-induced protein crystallization equilibrium, i.e., protein solubility. The framework introduces a term for the solubility product describing protein transfer between the liquid and solid phase and a term for the solution behavior describing deviation from ideal solution. Protein solubility is modeled as a function of salt concentration and temperature for a four-component system consisting of a protein, pseudo solvent (water and buffer), cation, and anion (salt). Two different systems, lysozyme with sodium chloride and concanavalin A with ammonium sulfate, are investigated. Comparison of the modeled and experimental protein solubility data results in an average root mean square deviation of 5.8%, demonstrating that the model closely follows the experimental behavior. Model calculations and model parameters are reviewed to examine the model and protein crystallization process. PMID:10397850

  19. Learning about Solubility

    ERIC Educational Resources Information Center

    Salinas, Dino G.; Reyes, Juan G.

    2015-01-01

    Qualitative questions are proposed to assess the understanding of solubility and some of its applications. To improve those results, a simple quantitative problem on the precipitation of proteins is proposed.

  20. Protein solubility modeling

    NASA Technical Reports Server (NTRS)

    Agena, S. M.; Pusey, M. L.; Bogle, I. D.

    1999-01-01

    A thermodynamic framework (UNIQUAC model with temperature dependent parameters) is applied to model the salt-induced protein crystallization equilibrium, i.e., protein solubility. The framework introduces a term for the solubility product describing protein transfer between the liquid and solid phase and a term for the solution behavior describing deviation from ideal solution. Protein solubility is modeled as a function of salt concentration and temperature for a four-component system consisting of a protein, pseudo solvent (water and buffer), cation, and anion (salt). Two different systems, lysozyme with sodium chloride and concanavalin A with ammonium sulfate, are investigated. Comparison of the modeled and experimental protein solubility data results in an average root mean square deviation of 5.8%, demonstrating that the model closely follows the experimental behavior. Model calculations and model parameters are reviewed to examine the model and protein crystallization process. Copyright 1999 John Wiley & Sons, Inc.

  1. DEVELOPMENT OF SOLUBILITY PRODUCT VISUALIZATION TOOLS

    SciTech Connect

    T.F. Turner; A.T. Pauli; J.F. Schabron

    2004-05-01

    Western Research Institute (WRI) has developed software for the visualization of data acquired from solubility tests. The work was performed in conjunction with AB Nynas Petroleum, Nynashamn, Sweden who participated as the corporate cosponsor for this Jointly Sponsored Research (JSR) task. Efforts in this project were split between software development and solubility test development. The Microsoft Windows-compatible software developed inputs up to three solubility data sets, calculates the parameters for six solid body types to fit the data, and interactively displays the results in three dimensions. Several infrared spectroscopy techniques have been examined for potential use in determining bitumen solubility in various solvents. Reflectance, time-averaged absorbance, and transmittance techniques were applied to bitumen samples in single and binary solvent systems. None of the techniques were found to have wide applicability.

  2. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

    SciTech Connect

    Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P. . E-mail: jpm2003@med.cornell.edu

    2007-04-10

    The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1{sub JR-FL}. Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140{sub UNC}), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1{sub JR-FL}. All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1{sub JR-FL} were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes.

  3. Gonadotropin-induced changes in oviducal mRNA expression levels of sex steroid hormone receptors and activin-related signaling factors in the alligator

    PubMed Central

    Moore, Brandon C.; Forouhar, Sara; Kohno, Satomi; Botteri, Nicole L.; Hamlin, Heather J.; Guillette, Louis J.

    2011-01-01

    Oviducts respond to hormonal cues from ovaries with tissue proliferation and differentiation in preparation of transporting and fostering gametes. These responses produce oviducal microenvironments conducive to reproductive success. Here we investigated changes in circulating plasma sex steroid hormones concentrations and ovarian and oviducal mRNA expression to an in vivo gonadotropin (FSH) challenge in sexually immature, five-month-old alligators. Further, we investigated differences in these observed responses between alligators hatched from eggs collected at a heavily-polluted (Lake Apopka, FL) and minimally-polluted (Lake Woodruff, FL) site. In oviducts, we measured mRNA expression of estrogen, progesterone, and androgen receptors and also beta A and B subunits which homo- or heterodimerize to produce the transforming growth factor activin. In comparison, minimal inhibin alpha subunit mRNA expression suggests that these oviducts produce a primarily activin-dominated signaling milieu. Ovaries responded to a five-day FSH challenge with increased expression of steroidogenic enzyme mRNA which was concomitant with increased circulating sex steroid hormone concentrations. Oviducts in the FSH-challenged Lake Woodruff alligators increased mRNA expression of progesterone and androgen receptors, proliferating cell nuclear antigen, and the activin signaling antagonist follistatin. In contrast, Lake Apopka alligators displayed a diminished increase in ovarian CYP19A1 aromatase expression and no increase in oviducal AR expression, as compared to those observed in Lake Woodruff alligators. These results demonstrate that five-month-old female alligators display an endocrine-responsive ovarian-oviducal axis and environmental pollution exposure may alter these physiological responses. PMID:22154572

  4. Autoantibody From Women With Preeclampsia Induces Soluble Fms-Like Tyrosine Kinase-1 Production via Angiotensin Type 1 Receptor and Calcineurin/Nuclear Factor of Activated T-Cells Signaling

    PubMed Central

    Zhou, Cissy Chenyi; Ahmad, Shakil; Mi, Tiejuan; Abbasi, Shahrzad; Xia, Lingwei; Day, Mary-Clare; Ramin, Susan M.; Ahmed, Asif; Kellems, Rodney E.; Xia, Yang

    2012-01-01

    Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention. PMID:18259044

  5. Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling.

    PubMed

    Zhou, Cissy Chenyi; Ahmad, Shakil; Mi, Tiejuan; Abbasi, Shahrzad; Xia, Lingwei; Day, Mary-Clare; Ramin, Susan M; Ahmed, Asif; Kellems, Rodney E; Xia, Yang

    2008-04-01

    Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT(1)) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT(1) receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT(1) receptor to induce sFlt-1 synthesis and secretion by AT(1)-receptor activating autoantibodies. AT(1)-receptor activating autoantibody-induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention. PMID:18259044

  6. Elimination of soluble sup 123 I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1

    SciTech Connect

    Halma, C.; Breedveld, F.C.; Daha, M.R.; Blok, D.; Evers-Schouten, J.H.; Hermans, J.; Pauwels, E.K.; van Es, L.A. )

    1991-04-01

    Using soluble {sup 123}I-labeled aggregates of human IgG ({sup 123}I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of {sup 123}I-AHIgG to erythrocytes and a faster initial rate of elimination of {sup 123}I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of {sup 123}I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE.

  7. Angiomodulin is required for cardiogenesis of embryonic stem cells and is maintained by a feedback loop network of p63 and Activin-A.

    PubMed

    Wolchinsky, Zohar; Shivtiel, Shoham; Kouwenhoven, Evelyn Nathalie; Putin, Daria; Sprecher, Eli; Zhou, Huiqing; Rouleau, Matthieu; Aberdam, Daniel

    2014-01-01

    The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ?Np63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis and heart development in vivo. TAp63 is expressed by embryonic endoderm and acts on cardiac progenitors by a cell-non-autonomous manner. In the present study, we search for cardiogenic secreted factors that could be regulated by TAp63 and, by ChIP-seq analysis, identified Angiomodulin (AGM), also named IGFBP7 or IGFBP-rP1. We demonstrate that AGM is necessary for cardiac commitment of embryonic stem cells (ESCs) and its regulation depends on TAp63 isoform. TAp63 directly activates both AGM and Activin-A during ESC cardiogenesis while these secreted factors modulate TAp63 gene expression by a feedback loop mechanism. The molecular circuitry controlled by TAp63 on AGM/Activin-A signaling pathway and thus on cardiogenesis emphasizes the importance of p63 during early cardiac development. PMID:24145187

  8. Soluble Tetraaminotriptycene Precursors.

    PubMed

    White, Nicholas G; MacLachlan, Mark J

    2015-08-21

    An efficient route to soluble triptycene tetraamines, shape-persistent molecules containing two ortho-phenylenediamine motifs, is reported. These tetraamines are stable, prepared in good yields, easily purified by column chromatography, and can be readily condensed to give a range of imidazole and pyrazine derivatives. PMID:26241485

  9. Fluorine (soluble fluoride)

    Integrated Risk Information System (IRIS)

    Fluorine ( soluble fluoride ) ; CASRN 7782 - 41 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for No

  10. Nickel, soluble salts

    Integrated Risk Information System (IRIS)

    Nickel , soluble salts ; CASRN Various Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  11. Uranium, soluble salts

    Integrated Risk Information System (IRIS)

    Uranium , soluble salts ; no CASRN Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Eff

  12. Acyclic cucurbit[n]uril molecular containers enhance the solubility and bioactivity of poorly soluble pharmaceuticals

    NASA Astrophysics Data System (ADS)

    Ma, Da; Hettiarachchi, Gaya; Nguyen, Duc; Zhang, Ben; Wittenberg, James B.; Zavalij, Peter Y.; Briken, Volker; Isaacs, Lyle

    2012-06-01

    The solubility characteristics of 40-70% of new drug candidates are so poor that they cannot be formulated on their own, so new methods for increasing drug solubility are highly prized. Here, we describe a new class of general-purpose solubilizing agents—acyclic cucurbituril-type containers—which increase the solubility of ten insoluble drugs by a factor of between 23 and 2,750 by forming container-drug complexes. The containers exhibit low in vitro toxicity in human liver, kidney and monocyte cell lines, and outbred Swiss Webster mice tolerate high doses of the container without sickness or weight loss. Paclitaxel solubilized by the acyclic cucurbituril-type containers kills cervical and ovarian cancer cells more efficiently than paclitaxel alone. The acyclic cucurbituril-type containers preferentially bind cationic and aromatic drugs, but also solubilize neutral drugs such as paclitaxel, and represent an attractive extension of cyclodextrin-based technology for drug solubilization and delivery.

  13. Down-regulation of transforming growth factor ?1/activin receptor-like kinase 1 pathway gene expression by herbal compound 861 is related to deactivation of LX-2 cells

    PubMed Central

    Li, Li; Zhao, Xin-Yan; Wang, Bao-En

    2008-01-01

    AIM: To investigate the effect of herbal compound 861 (Cpd861) on the transforming growth factor-?1 (TGF?1)/activin receptor-like kinase 1 (ALK1, type I receptor) signaling-pathway-related gene expression in the LX-2 cell line, and the inhibitory mechanism of Cpd861 on the activation of LX-2 cells. METHODS: LX-2 cells were treated with TGF?1 (5 ng/mL) Cpd861 (0.1 mg/mL), TGF?1 (5 ng/mL) plus Cpd861 (5 ng/mL) for 24 h to investigate the effect of Cpd861 on the TGF?1/ALK1 pathway. Real-time PCR was performed to examine the expression of ?-SMA (?-smooth muscle actin), ALK1, Id1 (inhibitor of differentiation 1). Western blotting was carried out to measure the levels of ?-SMA and phosphorylated Smad1, and immunocytochemical analysis for the expression of ?-SMA. RESULTS: In LX-2 cells, TGF?1/ALK1-pathway-related gene expression could be stimulated by TGF?1, which led to excessive activation of the cells. Cpd861 decreased the activation of LX-2 cells by reducing the expression of ?-SMA mRNA and protein expression. This effect was related to inhibition of the above TGF?1/ALK1-pathway-related expression of genes such as Id1 and ALK1, and phosphorylation of Smad1 in LX-2 cells, even with TGF?1 co-treatment for 24 h. CONCLUSION: Cpd861 can restrain the activation of LX-2 cells by inhibiting the TGF?1/ALK1/Smad1 pathway. PMID:18473417

  14. The solubility of uranium hexafluoride in perfluoroethers

    SciTech Connect

    Barber, E.J.

    1984-07-15

    The polyperfluoroethers are compatible with uranium hexafluoride (UF/sub 6/) and are suitable for use in diffusion pumps and in mechanical vacuum pumps which rely on oil as both the lubricant and the seal. The UF/sub 6/ is soluble in all fluids with which it is compatible. Because a number of vacuum pumps in the BOP facilities of the GCEP plant employ these perfluoroether oils as the working fluid and have oil chambers which are large, questions have been raised as to the relationships governing the solubility of UF/sub 6/ in these materials and the maximum quantities of UF/sub 6/ which could be dissolved in these oils under credible accident conditions. This report summarizes these solubility relations and the interaction of the UF/sub 6/ solubility and the pumping capability of this type of vacuum pump. It will be shown that, whereas the solubility of UF/sub 6/ in Fomblin Y25 fluoroether fluid under a UF/sub 6/ pressure of 760 torr and at the pump operating temperature of 160/sup 0/F is about 500 g of UF/sub 6/ per liter of oil, the system controls are such as to isolate the system from the pumps before the quantity of UF/sub 6/ dissolved in the perfluoroether exceeds about 10 g of UF/sub 6/ per liter of oil. 13 refs., 7 figs.

  15. The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells*

    PubMed Central

    Nishii, Keigo; Nakaseko, Chiaki; Jiang, Meizi; Shimizu, Naomi; Takeuchi, Masahiro; Schneider, Wolfgang J.; Bujo, Hideaki

    2013-01-01

    A key property of hematopoietic stem and progenitor cells (HSPCs) regarding differentiation from the self-renewing quiescent to the proliferating stage is their adhesion to the bone marrow (BM) niche. An important molecule involved in proliferation and pool size of HSPCs in the BM is the hypoxia-induced urokinase-type plasminogen activator receptor (uPAR). Here, we show that the soluble form (sLR11) of LR11 (also called SorLA or SORL1) modulates the uPAR-mediated attachment of HSPCs under hypoxic conditions. Immunohistochemical and mRNA expression analyses revealed that hypoxia increased LR11 expression in hematological c-Kit+ Lin? cells. In U937 cells, hypoxia induced a transient rise in LR11 transcription, production of cellular protein, and release of sLR11. Attachment to stromal cells of c-Kit+ Lin? cells of lr11?/? mice was reduced by hypoxia much more than of lr11+/+ animals. sLR11 induced the adhesion of U937 and c-Kit+ Lin? cells to stromal cells. Cell attachment was increased by sLR11 and reduced in the presence of anti-uPAR antibodies. Furthermore, the fraction of uPAR co-immunoprecipitated with LR11 in membrane extracts of U937 cells was increased by hypoxia. CoCl2, a chemical inducer of HIF-1?, enhanced the levels of LR11 and sLR11 in U937 cells. The decrease in hypoxia-induced attachment of HIF-1?-knockdown cells was largely prevented by exogenously added sLR11. Finally, hypoxia induced HIF-1? binding to a consensus binding site in the LR11 promoter. Thus, we conclude that sLR11 regulates the hypoxia-enhanced adhesion of HSPCs via an uPAR-mediated pathway that stabilizes the hematological pool size by controlling cell attachment to the BM niche. PMID:23486467

  16. The soluble form of LR11 protein is a regulator of hypoxia-induced, urokinase-type plasminogen activator receptor (uPAR)-mediated adhesion of immature hematological cells.

    PubMed

    Nishii, Keigo; Nakaseko, Chiaki; Jiang, Meizi; Shimizu, Naomi; Takeuchi, Masahiro; Schneider, Wolfgang J; Bujo, Hideaki

    2013-04-26

    A key property of hematopoietic stem and progenitor cells (HSPCs) regarding differentiation from the self-renewing quiescent to the proliferating stage is their adhesion to the bone marrow (BM) niche. An important molecule involved in proliferation and pool size of HSPCs in the BM is the hypoxia-induced urokinase-type plasminogen activator receptor (uPAR). Here, we show that the soluble form (sLR11) of LR11 (also called SorLA or SORL1) modulates the uPAR-mediated attachment of HSPCs under hypoxic conditions. Immunohistochemical and mRNA expression analyses revealed that hypoxia increased LR11 expression in hematological c-Kit(+) Lin(-) cells. In U937 cells, hypoxia induced a transient rise in LR11 transcription, production of cellular protein, and release of sLR11. Attachment to stromal cells of c-Kit(+) Lin(-) cells of lr11(-/-) mice was reduced by hypoxia much more than of lr11(+/+) animals. sLR11 induced the adhesion of U937 and c-Kit(+) Lin(-) cells to stromal cells. Cell attachment was increased by sLR11 and reduced in the presence of anti-uPAR antibodies. Furthermore, the fraction of uPAR co-immunoprecipitated with LR11 in membrane extracts of U937 cells was increased by hypoxia. CoCl2, a chemical inducer of HIF-1?, enhanced the levels of LR11 and sLR11 in U937 cells. The decrease in hypoxia-induced attachment of HIF-1?-knockdown cells was largely prevented by exogenously added sLR11. Finally, hypoxia induced HIF-1? binding to a consensus binding site in the LR11 promoter. Thus, we conclude that sLR11 regulates the hypoxia-enhanced adhesion of HSPCs via an uPAR-mediated pathway that stabilizes the hematological pool size by controlling cell attachment to the BM niche. PMID:23486467

  17. Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer.

    PubMed

    Ozkan, Cigdem; Akturk, Mujde; Altinova, Alev Eroglu; Cerit, Ethem Turgay; Gulbahar, Ozlem; Yalcin, Mehmet Muhittin; Cakir, Nuri; Balos Toruner, Fusun

    2015-12-27

    The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAI) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels. PMID:26490048

  18. Two mechanisms of soluble CD4 (sCD4)-mediated inhibition of human immunodeficiency virus type 1 (HIV-1) infectivity and their relation to primary HIV-1 isolates with reduced sensitivity to sCD4.

    PubMed Central

    Orloff, S L; Kennedy, M S; Belperron, A A; Maddon, P J; McDougal, J S

    1993-01-01

    Two assays for measuring inhibition of human immunodeficiency virus type 1 (HIV-1) infection by soluble CD4 (sCD4) are described. Experiments in which sCD4, HIV-1, and cell concentrations and sequence of combination, noninfectious/infectious particle ratio, and temperature were varied produced results that support the conclusion that sCD4 inhibits HIV-1 infection by two mechanisms: reversible blockage of receptor binding and irreversible inactivation of infectivity. Fresh isolates obtained from HIV-1-infected persons were tested in both assays and found to be more resistant to both mechanisms of sCD4-mediated inhibition than multiply passaged laboratory strains. Binding studies revealed similar affinities for sCD4 in detergent lysates of sensitive and resistant strains at both 4 and 37 degrees C. The avidity of intact virions for sCD4 was lower at 4 than at 37 degrees C, and in the presence of excess sCD4, less sCD4 was bound at 4 than at 37 degrees C. The avidity differences were similar for fresh isolates and laboratory strains. However, fresh isolates were more resistant to sCD4-induced shedding of envelope glycoprotein gp120 from intact virions than was the laboratory strain. Relative resistance to sCD4 by certain isolates does not represent a lower intrinsic affinity of their envelope for sCD4 or a lower capacity for sCD4 binding. Rather, an event that occurs after binding may account for the differences. This postbinding event or feature may be determined by regions of the envelope outside the CD4 binding site. Images PMID:8437224

  19. Randomized pilot trial of bariatric surgery vs. intensive medical weight management on diabetes remission in type 2 diabetic patients who do NOT meet NIH criteria for surgery and the role of soluble RAGE as a novel biomarker of success

    PubMed Central

    Parikh, Manish; Chung, Mimi; Sheth, Sheetal; McMacken, Michelle; Zahra, Tasneem; Saunders, John K; Ude-Welcome, Aku; Ogedegbe, Gbenga; Schmidt, Ann Marie; Pachter, H Leon

    2015-01-01

    Structured Abstract Objective To compare bariatric surgery vs. intensive medical weight management (MWM) in patients with type 2 diabetes (T2DM) who do not meet current NIH criteria for bariatric surgery. To assess whether the soluble form of receptor for advanced glycation endproducts (sRAGE) is a biomarker to identify patients most likely to benefit from surgery. Summary Background Data There are few studies comparing surgery to MWM for patients with T2DM and BMI < 35. Methods 57 patients with T2DM and BMI 30–35 who otherwise met criteria for bariatric surgery were randomized to MWM vs. surgery (bypass, sleeve or band, based on patient preference). The primary outcomes assessed at 6 months were change in insulin resistance (HOMA-IR) and diabetes remission. Secondary outcomes included changes in HbA1c, weight, and sRAGE. Results The surgery group had improved HOMA-IR (?4.6 vs. +1.6; p=0.0004) and higher diabetes remission (65% vs. 0%, p<0.0001) than the MWM group at 6 months. Compared to MWM, the surgery group had lower HbA1c (6.2 vs. 7.8, p=0.002), lower fasting glucose (99.5 vs. 157; p=0.0068) and fewer T2DM medication requirements (20% vs. 88%; p<0.0001) at 6 months. The surgery group lost more weight (7.0 BMI decrease vs. 1.0 BMI decrease, p<0.0001). Higher baseline sRAGE was associated with better weight loss outcomes (r=?0.641; p=0.046). There were no mortalities. Conclusions Surgery was very effective short-term in patients with T2DM and BMI 30–35. Baseline sRAGE may predict patients most likely to benefit from surgery. These findings need to be confirmed with larger studies. ClinicalTrials.gov ID: NCT01423877 PMID:25203878

  20. Solubility and Solubility Product Determination of a Sparingly Soluble Salt: A First-Level Laboratory Experiment

    ERIC Educational Resources Information Center

    Bonomo, Raffaele P.; Tabbi, Giovanni; Vagliasindi, Laura I.

    2012-01-01

    A simple experiment was devised to let students determine the solubility and solubility product, "K"[subscript sp], of calcium sulfate dihydrate in a first-level laboratory. The students experimentally work on an intriguing equilibrium law: the constancy of the product of the ion concentrations of a sparingly soluble salt. The determination of…

  1. Solubility of commercial milk protein concentrates and milk protein isolates.

    PubMed

    Sikand, V; Tong, P S; Roy, S; Rodriguez-Saona, L E; Murray, B A

    2011-12-01

    High-protein milk protein concentrate (MPC) and milk protein isolate (MPI) powders may have lower solubility than low-protein MPC powders, but information is limited on MPC solubility. Our objectives in this study were to (1) characterize the solubility of commercially available powder types with differing protein contents such as MPC40, MPC80, and MPI obtained from various manufacturers (sources), and (2) determine if such differences could be associated with differences in mineral, protein composition, and conformational changes of the powders. To examine possible predictors of solubility as measured by percent suspension stability (%SS), mineral analysis, Fourier transform infrared (FTIR) spectroscopy, and quantitative protein analysis by HPLC was performed. After accounting for overall differences between powder types, %SS was found to be strongly associated with the calcium, magnesium, phosphorus, and sodium content of the powders. The FTIR score plots were in agreement with %SS results. A principal component analysis of FTIR spectra clustered the highly soluble MPC40 separately from the rest of samples. Furthermore, 2 highly soluble MPI samples were clustered separately from the rest of the MPC80 and MPI samples. We found that the 900 to 1,200 cm?¹ region exhibited the highest discriminating power, with dominant bands at 1,173 and 968 cm?¹, associated with phosphate vibrations. The 2 highly soluble MPI powders were observed to have lower ?-casein and ?-(S1)-casein contents and slightly higher whey protein contents than the other powders. The differences in the solubility of MPC and MPI were associated with a difference in mineral composition, which may be attributed to differences in processing conditions. Additional studies on the role of minerals composition on MPC80 solubility are warranted. Such a study would provide a greater understanding of factors associated with differences in solubility and can provide insight on methods to improve solubility of high-protein milk protein concentrates. PMID:22118108

  2. Soluble porphyrin polymers

    DOEpatents

    Gust, Jr., John Devens; Liddell, Paul Anthony

    2015-07-07

    Porphyrin polymers of Structure 1, where n is an integer (e.g., 1, 2, 3, 4, 5, or greater) ##STR00001## are synthesized by the method shown in FIGS. 2A and 2B. The porphyrin polymers of Structure 1 are soluble in organic solvents such as 2-MeTHF and the like, and can be synthesized in bulk (i.e., in processes other than electropolymerization). These porphyrin polymers have long excited state lifetimes, making the material suitable as an organic semiconductor for organic electronic devices including transistors and memories, as well as solar cells, sensors, light-emitting devices, and other opto-electronic devices.

  3. Selective Deletion of Leptin Receptors in Gonadotropes Reveals Activin and GnRH-Binding Sites as Leptin Targets in Support of Fertility

    PubMed Central

    Akhter, Noor; CarlLee, Tyler; Syed, Mohsin M.; Odle, Angela K.; Cozart, Michael A.; Haney, Anessa C.; Allensworth-James, Melody L.; Beneš, Helen

    2014-01-01

    The adipokine, leptin (LEP), is a hormonal gateway, signaling energy stores to appetite-regulatory neurons, permitting reproduction when stores are sufficient. Dual-labeling for LEP receptors (LEPRs) and gonadotropins or GH revealed a 2-fold increase in LEPR during proestrus, some of which was seen in LH gonadotropes. We therefore investigated LEPR functions in gonadotropes with Cre-LoxP technology, deleting the signaling domain of the LEPR (Lepr-exon 17) with Cre-recombinase driven by the rat LH-? promoter (Lh?-cre). Selectivity of the deletion was validated by organ genotyping and lack of LEPR and responses to LEP by mutant gonadotropes. The mutation had no impact on growth, body weight, the timing of puberty, or pregnancy. Mutant females took 36% longer to produce their first litter and had 50% fewer pups/litter. When the broad impact of the loss of gonadotrope LEPR on all pituitary hormones was studied, mutant diestrous females had reduced serum levels of LH (40%), FSH (70%), and GH (54%) and mRNA levels of Fsh? (59%) and inhibin/activin ? A and ? B (25%). Mutant males had reduced serum levels of GH (74%), TSH (31%), and prolactin (69%) and mRNA levels of Gh (31%), Ghrhr (30%), Fsh? (22%), and glycoprotein ?-subunit (Cga) (22%). Serum levels of LEP and ACTH and mRNA levels of Gnrhr were unchanged. However, binding to GnRH receptors was reduced in LEPR-null LH or FSH gonadotropes by 82% or 89%, respectively, in females (P < .0001) and 27% or 53%, respectively, in males (P < .03). This correlated with reductions in GnRH receptor protein immunolabeling, suggesting that LEP's actions may be posttranscriptional. Collectively, these studies highlight the importance of LEP to gonadotropes with GnRH-binding sites and activin as potential targets. LEP may modulate population growth, adjusting the number of offspring to the availability of food supplies. PMID:25057790

  4. Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

    PubMed Central

    Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Muniandy, Sekaran

    2015-01-01

    Background A soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy. Methods We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome). Results Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels. Conclusion Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c. PMID:26474470

  5. Surface state of carbon nanotubes and Hansen solubility parameters.

    PubMed

    Detriche, S; Nagy, J B; Mekhalif, Z; Delhalle, J

    2009-10-01

    Carbon nanotubes (CNTs) are often described as insoluble or poorly soluble in organic solvents. In a recent study, we have reported that nonfunctionalized CNTs can be solubilized in suitably chosen organic solvents. Furthermore, their solubility could be understood in terms of the Hansen Solubility Parameters (HSPs). The present work addresses further the question of the CNTs solubility by considering a larger range of solvents. A second part is devoted to the application of the HSPs to two types of functionalized CNTs: oxidized and silanized. These results stress the critical role played by the surface state of the CNTs, on the one hand, and the interest in using the HSPs to guide solubility investigations, on the other hand. PMID:19908489

  6. Water soluble laser dyes

    DOEpatents

    Hammond, Peter R. (Livermore, CA); Feeman, James F. (Wyomissing, PA); Field, George F. (Santa Ana, CA)

    1998-01-01

    Novel water soluble dyes of the formula I are provided ##STR1## wherein R.sup.1 and R.sup.4 are alkyl of 1 to 4 carbon atoms or hydrogen; or R.sup.1 -R.sup.2 or R.sup.2 -R.sup.4 form part of aliphatic heterocyclic rings; R.sup.2 is hydrogen or joined with R.sup.1 or R.sup.4 as described above; R.sup.3 is --(CH.sub.2).sub.m --SO.sub.3.sup.-, where m is 1 to 6; X is N, CH or ##STR2## where Y is 2 --SO.sub.3.sup.- ; Z is 3, 4, 5 or 6 --SO.sub.3.sup.-. The novel dyes are particularly useful as the active media in water solution dye lasers.

  7. Water soluble laser dyes

    DOEpatents

    Hammond, P.R.; Feeman, J.F.; Field, G.F.

    1998-08-11

    Novel water soluble dyes of the formula 1 are provided by the formula described in the paper wherein R{sup 1} and R{sup 4} are alkyl of 1 to 4 carbon atoms or hydrogen; or R{sup 1}--R{sup 2} or R{sup 2}--R{sup 4} form part of aliphatic heterocyclic rings; R{sup 2} is hydrogen or joined with R{sup 1} or R{sup 4} as described above; R{sup 3} is --(CH{sub 2}){sub m}--SO{sub 3}{sup {minus}}, where m is 1 to 6; X is N, CH or formula 2 given in paper where Y is 2 --SO{sub 3}{sup {minus}} ; Z is 3, 4, 5 or 6 --SO{sub 3}{sup {minus}}. The novel dyes are particularly useful as the active media in water solution dye lasers.

  8. Water-soluble dietary fibers and cardiovascular disease.

    PubMed

    Theuwissen, Elke; Mensink, Ronald P

    2008-05-23

    One well-established way to reduce the risk of developing cardiovascular disease (CVD) is to lower serum LDL cholesterol levels by reducing saturated fat intake. However, the importance of other dietary approaches, such as increasing the intake of water-soluble dietary fibers is increasingly recognized. Well-controlled intervention studies have now shown that four major water-soluble fiber types-beta-glucan, psyllium, pectin and guar gum-effectively lower serum LDL cholesterol concentrations, without affecting HDL cholesterol or triacylglycerol concentrations. It is estimated that for each additional gram of water-soluble fiber in the diet serum total and LDL cholesterol concentrations decrease by -0.028 mmol/L and -0.029 mmol/L, respectively. Despite large differences in molecular structure, no major differences existed between the different types of water-soluble fiber, suggesting a common underlying mechanism. In this respect, it is most likely that water-soluble fibers lower the (re)absorption of in particular bile acids. As a result hepatic conversion of cholesterol into bile acids increases, which will ultimately lead to increased LDL uptake by the liver. Additionally, epidemiological studies suggest that a diet high in water-soluble fiber is inversely associated with the risk of CVD. These findings underlie current dietary recommendations to increase water-soluble fiber intake. PMID:18302966

  9. Pure Phase Solubility Limits: LANL

    SciTech Connect

    C. Stockman

    2001-01-26

    The natural and engineered system at Yucca Mountain (YM) defines the site-specific conditions under which one must determine to what extent the engineered and the natural geochemical barriers will prevent the release of radioactive material from the repository. Most important mechanisms for retention or enhancement of radionuclide transport include precipitation or co-precipitation of radionuclide-bearing solid phases (solubility limits), complexation in solution, sorption onto surfaces, colloid formation, and diffusion. There may be many scenarios that could affect the near-field environment, creating chemical conditions more aggressive than the conditions presented by the unperturbed system (such as pH changes beyond the range of 6 to 9 or significant changes in the ionic strength of infiltrated waters). For an extended period of time, the near-field water composition may be quite different and more extreme in pH, ionic strength, and CO{sub 2} partial pressure (or carbonate concentration) than waters at some distance from the repository. Reducing conditions, high pH (up to 11), and low carbonate concentration may be present in the near-field after reaction of infiltrating groundwater with engineered barrier systems, such as cementitious materials. In the far-field, conditions are controlled by the rock-mass buffer providing a near-neutral, oxidizing, low-ionic-strength environment that controls radionuclide solubility limits and sorption capacities. There is the need for characterization of variable chemical conditions that affect solubility, speciation, and sorption reactions. Modeling of the groundwater chemistry is required and leads to an understanding of solubility and speciation of the important radionuclides. Because experimental studies cannot be performed under the numerous potential chemical conditions, solubility limitations must rely on geochemical modeling of the radionuclide's chemistry. Fundamental thermodynamic properties, such as solubility products, complex stability constants, and redox potentials for radionuclides in different oxidation states, form the underlying database to be used for those calculations. The potentially low solubilities of many radionuclides in natural waters constitute the first barrier for their migration from the repository into the environment. Evaluation of this effect requires a knowledge of the site-specific water chemistry and the expected spatial and temporal ranges of its variability. Quantitative determinations of radionuclide solubility in waters within the range of chemistry must be made. Speciation and molecular complexation must be ascertained to interpret and apply solubility results. The solubilities thus determined can be used to assess the effectiveness of solubility in limiting radionuclide migration. These solubilities can also be used to evaluate the effectiveness of other retardation processes expected to occur once dissolution of the source material and migration begin. Understanding the solubility behavior of radionuclides will assist in designing valuable sorption experiments that must be conducted below the solubility limit since only soluble species participate in surface reactions and sorption processes. The present strategy for radionuclide solubility tasks has been to provide a solubility model from bulk-experiments that attempt to bracket the estimate made for this Analysis and Modeling Report (AMR) of water conditions on site. The long-term goal must be to develop a thermodynamic database for solution speciation and solid-state determination as a prerequisite for transport calculations and interpretation of empirical solubility data. The model has to be self-consistent and tested against known solubility studies in order to predict radionuclide solubilities over the continuous distribution ranges of potential water compositions for performance assessment of the site. Solubility studies upper limits for radionuclide concentrations in natural waters. The concentration in the aqueous phase is controlled by the radionuclide-bearing solid phase and by

  10. Scoring function to predict solubility mutagenesis

    PubMed Central

    2010-01-01

    Background Mutagenesis is commonly used to engineer proteins with desirable properties not present in the wild type (WT) protein, such as increased or decreased stability, reactivity, or solubility. Experimentalists often have to choose a small subset of mutations from a large number of candidates to obtain the desired change, and computational techniques are invaluable to make the choices. While several such methods have been proposed to predict stability and reactivity mutagenesis, solubility has not received much attention. Results We use concepts from computational geometry to define a three body scoring function that predicts the change in protein solubility due to mutations. The scoring function captures both sequence and structure information. By exploring the literature, we have assembled a substantial database of 137 single- and multiple-point solubility mutations. Our database is the largest such collection with structural information known so far. We optimize the scoring function using linear programming (LP) methods to derive its weights based on training. Starting with default values of 1, we find weights in the range [0,2] so that predictions of increase or decrease in solubility are optimized. We compare the LP method to the standard machine learning techniques of support vector machines (SVM) and the Lasso. Using statistics for leave-one-out (LOO), 10-fold, and 3-fold cross validations (CV) for training and prediction, we demonstrate that the LP method performs the best overall. For the LOOCV, the LP method has an overall accuracy of 81%. Availability Executables of programs, tables of weights, and datasets of mutants are available from the following web page: http://www.wsu.edu/~kbala/OptSolMut.html. PMID:20929563

  11. Recombinant soluble adenovirus receptor

    DOEpatents

    Freimuth, Paul I. (East Setauket, NY)

    2002-01-01

    Disclosed are isolated polypeptides from human CAR (coxsackievirus and adenovirus receptor) protein which bind adenovirus. Specifically disclosed are amino acid sequences which corresponds to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2. In other aspects, the disclosure relates to nucleic acid sequences encoding these domains as well as expression vectors which encode the domains and bacterial cells containing such vectors. Also disclosed is an isolated fusion protein comprised of the D1 polypeptide sequence fused to a polypeptide sequence which facilitates folding of D1 into a functional, soluble domain when expressed in bacteria. The functional D1 domain finds application for example in a therapeutic method for treating a patient infected with a virus which binds to D1, and also in a method for identifying an antiviral compound which interferes with viral attachment. Also included is a method for specifically targeting a cell for infection by a virus which binds to D1.

  12. Method for enhancing the solubility of boron and indium in silicon

    DOEpatents

    Sadigh, Babak (Oakland, CA); Lenosky, Thomas J. (Pleasanton, CA); Diaz de la Rubia, Tomas (Danville, CA); Giles, Martin (Hillsborough, OR); Caturla, Maria-Jose (Livermore, CA); Ozolins, Vidvuds (Pleasanton, CA); Asta, Mark (Evanston, IL); Theiss, Silva (St. Paul, MN); Foad, Majeed (Santa Clara, CA); Quong, Andrew (Livermore, CA)

    2002-01-01

    A method for enhancing the equilibrium solubility of boron and indium in silicon. The method involves first-principles quantum mechanical calculations to determine the temperature dependence of the equilibrium solubility of two important p-type dopants in silicon, namely boron and indium, under various strain conditions. The equilibrium thermodynamic solubility of size-mismatched impurities, such as boron and indium in silicon, can be raised significantly if the silicon substrate is strained appropriately. For example, for boron, a 1% compressive strain raises the equilibrium solubility by 100% at 1100.degree. C.; and for indium, a 1% tensile strain at 1100.degree. C., corresponds to an enhancement of the solubility by 200%.

  13. A Semiconductor Material And Method For Enhancing Solubility Of A Dopant Therein

    DOEpatents

    Sadigh, Babak (Oakland, CA); Lenosky, Thomas J. (Pleasanton, CA); Diaz de la Rubia, Tomas (Danville, CA); Giles, Martin (Hillsborough, OR); Caturla, Maria-Jose (Livermore, CA); Ozolins, Vidvuds (Pleasanton, CA); Asta, Mark (Evanston, IL); Theiss, Silva (St. Paul, MN); Foad, Majeed (Santa Clara, CA); Quong, Andrew (Livermore, CA)

    2005-03-29

    A method for enhancing the equilibrium solubility of boron ad indium in silicon. The method involves first-principles quantum mechanical calculations to determine the temperature dependence of the equilibrium solubility of two important p-type dopants in silicon, namely boron and indium, under various strain conditions. The equilibrium thermodynamic solubility of size-mismatched impurities, such as boron and indium in silicon, can be raised significantly if the silicon substrate is strained appropriately. For example, for boron, a 1% compressive strain raises the equilibrium solubility by 100% at 1100.degree. C.; and for indium, a 1% tensile strain at 1100.degree. C., corresponds to an enhancement of the solubility by 200%.

  14. Semiconductor material and method for enhancing solubility of a dopant therein

    DOEpatents

    Sadigh, Babak; Lenosky, Thomas J.; Rubia, Tomas Diaz; Giles, Martin; Caturla, Maria-Jose; Ozolins, Vidvuds; Asta, Mark; Theiss, Silva; Foad, Majeed; Quong, Andrew

    2003-09-09

    A method for enhancing the equilibrium solubility of boron and indium in silicon. The method involves first-principles quantum mechanical calculations to determine the temperature dependence of the equilibrium solubility of two important p-type dopants in silicon, namely boron and indium, under various strain conditions. The equilibrium thermodynamic solubility of size-mismatched impurities, such as boron and indium in silicon, can be raised significantly if the silicon substrate is strained appropriately. For example, for boron, a 1% compressive strain raises the equilibrium solubility by 100% at 1100.degree. C.; and for indium, a 1% tensile strain at 1100.degree. C., corresponds to an enhancement of the solubility by 200%.

  15. THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS

    PubMed Central

    Heidelberger, Michael; Avery, Oswald T.

    1924-01-01

    1. The method for the concentration and purification of the soluble specific substance of Pneumococcus has been improved. 2. Highly purified specific substance of Type II pneumococcus of polysaccharide nature is shown to be recovered essentially unchanged after precipitation by immune serum, by uranyl nitrate, by basic lead acetate, or by safranine. 3. Marked chemical differences are shown to exist between the specific substances of Type II and Type III pneumococcus, although both react as polysaccharides. 4. The weight of evidence is considered to be in favor of the view that the specific substances of Pneumococcus Types II and III are actually polysaccharide derivatives. 5. The immunological significance of the foregoing view is discussed. PMID:19868919

  16. Method for enhancing the solubility of dopants in silicon

    DOEpatents

    Sadigh, Babak; Lenosky, Thomas J.; De La Rubia, Tomas Diaz

    2003-09-30

    A method for enhancing the equilibrium solid solubility of dopants in silicon, germanium and silicon-germanium alloys. The method involves subjecting silicon-based substrate to biaxial or compression strain. It has been determined that boron solubility was largely enhanced (more than 100%) by a compressive bi-axial strain, based on a size-mismatch theory since the boron atoms are smaller than the silicon atoms. It has been found that the large enhancement or mixing properties of dopants in silicon and germanium substrates is primarily governed by their, and to second order by their size-mismatch with the substrate. Further, it has been determined that the dopant solubility enhancement with strain is most effective when the charge and the size-mismatch of the impurity favor the same type of strain. Thus, the solid solubility of small p-type (e.g., boron) as well as large n-type (e.g., arsenic) dopants can be raised most dramatically by appropriate bi-axial (compressive) strain, and that solubility of a large p-type dopant (e.g, indium) in silicon will be raised due to size-mismatch with silicon, which favors tensile strain, while its negative charge prefers compressive strain, and thus the two effects counteract each other.

  17. Tough, Soluble, Aromatic, Thermoplastic Copolyimides

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    1998-01-01

    Tough, soluble, aromatic, thermoplastic copolyimides were prepared by reacting 4,4'-oxydiphthalic anhydride, 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydianiline. These copolyimides were found to be soluble in common amide solvents such as N,N'-dimethyl acetamide, N-methylpyrrolidinone, and dimethylformamide allowing them to be applied as the fully imidized copolymer and to be used to prepare a wide range of articles.

  18. PI3K/mTORC2 regulates TGF-?/Activin signalling by modulating Smad2/3 activity via linker phosphorylation

    PubMed Central

    Yu, Jason S. L.; Ramasamy, Thamil Selvee; Murphy, Nick; Holt, Marie K.; Czapiewski, Rafal; Wei, Shi-Khai; Cui, Wei

    2015-01-01

    Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-? signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator. PMID:25998442

  19. High Density Lipoproteins Affect Endothelial BMP-Signaling by Modulating Expression of the Activin-Like Kinase Receptor 1 and 2

    PubMed Central

    Yao, Yucheng; Shao, Esther S.; Jumabay, Medet; Shahbazian, Ani; Ji, Sheng; Boström, Kristina I.

    2009-01-01

    Objective High-density lipoproteins (HDL) have antiinflammatory effects on the vascular endothelium. Because bone morphogenetic proteins (BMP) are known to be inflammatory mediators, we examined the effect of HDL on BMP signaling. Methods and Results Increasing concentrations of HDL progressively enhanced expression of the activin-like kinase receptor (ALK)1 and ALK2 in human aortic endothelial cells as determined by real-time PCR and immunoblotting. Induction of ALK1 was a result of enhanced ALK2 expression as determined by siRNA interference, and was associated with increased levels of vascular endothelial growth factor (VEGF) and matrix Gla protein (MGP). The HDL-induction of ALK2 was dependent on BMP-signaling, and affected co-regulation of the ALK2 gene by the homeodomain proteins MSX2, DLX3 and DLX5, as determined by reporter gene assays, siRNA interference and chromatin immunoprecipitation. Apolipoprotein A-I transgenic mice, known to have high HDL and inhibition of atherogenesis, exhibited similar changes in aortic gene expression as seen in endothelial cells treated with HDL in vitro. Conclusions We conclude that HDL benefits the arterial wall by allowing for enhanced ALK1 and ALK2 signaling, resulting in an increase of VEGF and MGP, essential for endothelial cell survival and prevention of vascular calcification, respectively. PMID:18948634

  20. Macrophage uptake and accumulation of folates are polarization-dependent in vitro and in vivo and are regulated by activin A.

    PubMed

    Samaniego, Rafael; Palacios, Blanca Soler; Domiguez-Soto, Angeles; Vidal, Carlos; Salas, Azucena; Matsuyama, Takami; Sánchez-Torres, Carmen; de la Torre, Inmaculada; Miranda-Carús, Maria Eugenia; Sánchez-Mateos, Paloma; Puig-Kröger, Amaya

    2014-01-01

    Vitamin B9, commonly known as folate, is an essential cofactor for one-carbon metabolism that enters cells through three major specialized transporter molecules (RFC, FR, and PCFT), which differ in expression pattern, affinity for substrate, and ligand-binding pH dependency. We now report that the expression of the folate transporters differs between macrophage subtypes and explains the higher accumulation of 5-MTHF-the major folate form found in serum-in M2 macrophages in vitro and in vivo. M1 macrophages display a higher expression of RFC, whereas FR? and PCFT are preferentially expressed by anti-inflammatory and homeostatic M2 macrophages. These differences are also seen in macrophages from normal tissues involved in folate transit (placenta, liver, colon) and inflamed tissues (ulcerative colitis, RA), as M2-like macrophages from normal tissues express FR? and PCFT, whereas TNF-?-expressing M1 macrophages from inflamed tissues are RFC+. Besides, we provide evidences that activin A is a critical factor controlling the set of folate transporters in macrophages, as it down-regulates FR?, up-regulates RFC expression, and modulates 5-MTHF uptake. All of these experiments support the notion that folate handling is dependent on the stage of macrophage polarization. PMID:24399840

  1. How Important is Methodology to Estimates of Aerosol Solubility?

    NASA Astrophysics Data System (ADS)

    Buck, C. S.; Paytan, A.

    2009-12-01

    The atmospheric deposition of nutrients and trace elements, such as iron, has been shown to support primary productivity and is therefore important to the biogeochemical cycling of carbon in the ocean. Atmospheric deposition is particularly important in HNLC regions but may also contribute to productivity in coastal settings. Efforts have been made to better characterize the flux and solubility of atmospherically derived nutrients and trace elements in order to provide data that will better constrain models of the marine carbon cycle. The result has been numerous studies using various methods of aerosol collection and solubility treatments ultimately yielding a wide range of solubility estimates (e.g. iron solubility estimates range between <1% - 90%). Differences in aerosol solubility estimates may be the product of particular aerosol characteristics such as aerosol source, transport history, and atmospheric processing. These differences might also be caused by methodological factors such as collection method, storage conditions, and extraction technique. Given the complexity of the processes that may impact aerosol solubility, both in the atmosphere and within the water column, it is imperative that this variability be characterized in order that differences in aerosol solubility may be correctly attributed to the respective aerosol characteristics and not to some analytical artifact. The work presented in this study attempts to ascertain the relative impact of aerosol characteristics, aerosol collection filter type, and extraction procedure on measurements of aerosol solubility as well as on collection efficiency and blank levels. Aerosols were collected on four replicate filters at a coastal station in Eilat, Israel and stored frozen prior to extraction. Three extraction procedures were used, two with ultrapure deionized water and one using ammonium acetate buffer solution (only for soluble iron) serving as the extraction solution, to assess procedural variability. These procedures differed in such key areas as exposure time, solution pH, and particle to solution ratio. Different filter types were also deployed including polycarbonate, mixed cellulose ester, polyethersulfone, Whatman, quartz, and Teflon to determine differences inherent to the various substrates. Soluble nutrients and elements were measured using a combination of IC, ICP-MS, and GF-AAS analyses. Insoluble aerosol concentrations were measured by ICP-MS after strong acid digestion. Preliminary results suggest a good correlation in the solubility of aerosol iron and nutrients between samples extracted with different ultrapure deionized water methods.

  2. Development of Microemulsion for Solubility Enhancement of Clopidogrel

    PubMed Central

    Patel, Vandana; Kukadiya, Hirenkumar; Mashru, Rajshree; Surti, Naazneen; Mandal, Surjyanarayan

    2010-01-01

    Clopidogrel, an inhibitor of platelet aggregation, selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Oral bioavailability of clopidogrel is very low (less than 50%), due to its poor water solubility. The aim of this investigation was to design and develop a microemulsion formulation of clopidogrel for enhancing its solubility, and hence its oral bioavailability. For this purpose, initially, solubility of clopidogrel was determined in various vehicles. Next, pseudo-ternary phase diagrams were constructed to identify the microemulsion existing zone. Solubility study was also performed for optimization of formulation. The optimized microemulsion formulation was characterized for its transparency, droplet size, zeta potential, viscosity, conductivity, % assay, and phase separation study. Particle size and zeta potential of the optimized microemulsion formulation were found to be 12.3 nm, and -6.34 mV, respectively. The viscosity and conductivity data indicated that the microemulsion was of the o/w type. Solubility of clopidogrel was successfully enhanced by 80.66 times, via capmul microemulsion, compared with distilled water (pH = 7.4). 75.53% and 71.2 % of the drug content were found to be released within 9 h in the in-vitro and ex-vivo studies, respectively. Hence, by formulating into microemulsion, the solubility of clopidogrel was found to be significantly enhanced. PMID:24381597

  3. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy.

    PubMed

    Madan, Jyotsana R; Pawar, Kiran T; Dua, Kamal

    2015-01-01

    Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future for other poorly water-soluble drugs in which low bioavailability is a major concern. PMID:25838997

  4. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy

    PubMed Central

    Madan, Jyotsana R.; Pawar, Kiran T.; Dua, Kamal

    2015-01-01

    Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future for other poorly water-soluble drugs in which low bioavailability is a major concern. PMID:25838997

  5. Modulation of Th1/Th2 Immune Responses by Killed Propionibacterium acnes and Its Soluble Polysaccharide Fraction in a Type I Hypersensitivity Murine Model: Induction of Different Activation Status of Antigen-Presenting Cells

    PubMed Central

    Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugéri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  6. Modulation of Th1/Th2 immune responses by killed Propionibacterium acnes and its soluble polysaccharide fraction in a type I hypersensitivity murine model: induction of different activation status of antigen-presenting cells.

    PubMed

    Squaiella-Baptistão, Carla Cristina; Teixeira, Daniela; Mussalem, Juliana Sekeres; Ishimura, Mayari Eika; Longo-Maugéri, Ieda Maria

    2015-01-01

    Propionibacterium acnes (P. acnes) is a gram-positive anaerobic bacillus present in normal human skin microbiota, which exerts important immunomodulatory effects, when used as heat- or phenol-killed suspensions. We previously demonstrated that heat-killed P. acnes or its soluble polysaccharide (PS), extracted from the bacterium cell wall, suppressed or potentiated the Th2 response to ovalbumin (OVA) in an immediate hypersensitivity model, depending on the treatment protocol. Herein, we investigated the mechanisms responsible for these effects, using the same model and focusing on the activation status of antigen-presenting cells (APCs). We verified that higher numbers of APCs expressing costimulatory molecules and higher expression levels of these molecules are probably related to potentiation of the Th2 response to OVA induced by P. acnes or PS, while higher expression of toll-like receptors (TLRs) seems to be related to Th2 suppression. In vitro cytokines production in cocultures of dendritic cells and T lymphocytes indicated that P. acnes and PS seem to perform their effects by acting directly on APCs. Our data suggest that P. acnes and PS directly act on APCs, modulating the expression of costimulatory molecules and TLRs, and these differently activated APCs drive distinct T helper patterns to OVA in our model. PMID:25973430

  7. Solubility limits on radionuclide dissolution

    SciTech Connect

    Kerrisk, J.F.

    1984-12-31

    This paper examines the effects of solubility in limiting dissolution rates of a number of important radionuclides from spent fuel and high-level waste. Two simple dissolution models were used for calculations that would be characteristics of a Yucca Mountain repository. A saturation-limited dissolution model, in which the water flowing through the repository is assumed to be saturated with each waste element, is very conservative in that it overestimates dissolution rates. A diffusion-limited dissolution model, in which element-dissolution rates are limited by diffusion of waste elements into water flowing past the waste, is more realistic, but it is subject to some uncertainty at this time. Dissolution rates of some elements (Pu, Am, Sn, Th, Zr, Sm) are always limited by solubility. Dissolution rates of other elements (Cs, Tc, Np, Sr, C, I) are never solubility limited; their release would be limited by dissolution of the bulk waste form. Still other elements (U, Cm, Ni, Ra) show solubility-limited dissolution under some conditions. 9 references, 3 tables.

  8. Soluble cadherins as cancer biomarkers.

    PubMed

    De Wever, Olivier; Derycke, Lara; Hendrix, An; De Meerleer, Gert; Godeau, François; Depypere, Herman; Bracke, Marc

    2007-01-01

    Molecular activities, regulating a balanced tissue organisation, are frequently disturbed during cancer progression. These include protein ectodomain shedding, a post-translational process that substantially changes the functional properties of the substrate protein. In comparison with normal epithelia, cancer cells almost invariably show diminished cadherin-mediated intercellular adhesion. This review will address cadherin ectodomain shedding and its functional consequence in normal physiology and in the tumor environment. Soluble cadherin fragments may retain specific biological activities during cancer cell invasion, angiogenesis and perineural invasion. When diffusion barriers disappear, soluble cadherins are detected in sera from cancer patients. Soluble N-(neural) cadherin may represent a novel diagnosis/prognostic biomarker showing a correlation with PSA in sera of prostate cancer patients. Furthermore, therapeutic monitoring in pancreas adenomacarcinoma revealed a correlation between circulating soluble N-cadherin and CA 19-9. A better understanding of cadherin regulation in cancer progression will likely increase our awareness of the importance of the combinatorial signals that regulate tissue integrity and eventually result in the identification of new therapeutics targeting cadherins. PMID:17952616

  9. New ideas about the solubility of drugs.

    PubMed

    Box, Karl; Comer, John E; Gravestock, Tom; Stuart, Martin

    2009-11-01

    Methods are described for detecting precipitation of ionisable drugs under conditions of changing pH, estimating kinetic solubility from the onset of precipitation, and measuring solubility by chasing equilibrium. Definitions are presented for kinetic, equilibrium, and intrinsic solubility of ionisable drugs, supersaturation and subsaturation, and for chasers and non-chasers, which are two classes of ionisable drug with significantly different solubility properties. The use of Bjerrum Curves and Neutral-Species Concentration Profiles to depict solubility properties are described and illustrated with case studies showing super-dissolving behaviour, conversion between crystalline forms and enhancement of solubility through supersaturation, and the use of additives and simulated gastrointestinal fluids. PMID:19937815

  10. Measuring thermodynamically-interpretable solubilities at high pressures and temperatures

    NASA Astrophysics Data System (ADS)

    Barnes, H. L.

    Solubilities are useful only if measured in defined systems where at least the minimum number of intensive variables required by the Gibbs' phase rule for invariancy are either fixed, measured, or controlled in the experiment. The array of determined intensive variables and any necessary buffers should be selected also to provide maximum resolution in identifying stoichiometries of solute species and in evaluating equilibrium constants of solubility-controlling reactions. Simultaneous measurements of volumetric properties of solutions and gases present during solubility measurements are practical and simplify thermodynamic analysis of solubilities. Equilibration is best demonstrated by equal solubilities for the same conditions approached from opposite directions. In solubility experiments at high pressures and temperatures, continuous analyses are possible using spectra, cell potentials, or radioactive tracers but they are uncertain indicators of total solute concentration. Methods providing only a single data point per experiment, by nutrient weight-loss or by analysis of quenched fluids, are comparatively slow and are not reversible. Better are periodic sampling and analysis of quenched, filtered fluids from two types of experimental systems. Condensed fluids are investigated effectively with an external-fluid-supported flexible cell but vapor-containing or supercritical experiments are less complex in a fixed-volume, rocking vessel. In both systems the parent solution remains virtually isothermal and isobaric during sampling, replicate sampling is possible, and reversing of reactions is simple. The less-complicated, fixed-volume system also permits P- V- T measurements on liquids and gases together with sampling. The stoichiometry of the dominant solute species is given, commonly with satisfactory resolution, by the exponential dependence of the solubility on the concentration of each potential ligand. The exponent closely approximates the stoichiometric coefficient of the ligand in the solute species. From these ligand and solute concentrations and tabulated or calculated activity coefficients, activities are obtained for dominant solute species, ligands, and gases corresponding to each solubility measurement. These activities permit the calculation of an equilibrium constant for each principal reaction representing equilibration among the solute, its dissolved species, and reacting ligands. The resulting constants, based on individual solubility measurements may then be compared for consistency both isothermally and polythermally. Measurements of solubilities at high temperatures and pressures are now impeded primarily by the lack of (1) well-calibrated buffers of oxidation state and acidity with known reaction rates for hydrothermal use, and (2) inert high-strength alloys that are resistant to hydrogen embrittlement, nonreactive with acidic and other high temperature fluids, and with mechanical properties compatible with use in the bodies or liners of reaction vessels.

  11. Soluble adenylyl cyclase of sea urchin spermatozoa.

    PubMed

    Vacquier, Victor D; Loza-Huerta, Arlet; García-Rincón, Juan; Darszon, Alberto; Beltrán, Carmen

    2014-12-01

    Fertilization, a key step in sexual reproduction, requires orchestrated changes in cAMP concentrations. It is notable that spermatozoa (sperm) are among the cell types with extremely high adenylyl cyclase (AC) activity. As production and consumption of this second messenger need to be locally regulated, the discovery of soluble AC (sAC) has broadened our understanding of how such cells deal with these requirements. In addition, because sAC is directly regulated by HCO(3)(-) it is able to translate CO?/HCO(3)(-)/pH changes into cAMP levels. Fundamental sperm functions such as maturation, motility regulation and the acrosome reaction are influenced by cAMP; this is especially true for sperm of the sea urchin (SU), an organism that has been a model in the study of fertilization for more than 130 years. Here we summarize the discovery and properties of SU sperm sAC, and discuss its involvement in sperm physiology. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. PMID:25064590

  12. Towards a Molecular Understanding of Protein Solubility 

    E-print Network

    Kramer, Ryan 1984-

    2011-05-31

    Protein solubility is a problem for many protein chemists including structural biologists and those developing protein pharmaceuticals. Knowledge of how intrinsic factors influence solubility is limited due to the difficulty in obtaining...

  13. Characterization of Soluble Organics in Produced Water

    SciTech Connect

    Bostick, D.T.

    2002-01-16

    Soluble organics in produced water and refinery effluents represent treatment problems for the petroleum industry. Neither the chemistry involved in the production of soluble organics nor the impact of these chemicals on total effluent toxicity is well understood. The U.S. Department of Energy provides funding for Oak Ridge National Laboratory (ORNL) to support a collaborative project with Shell, Chevron, Phillips, and Statoil entitled ''Petroleum and Environmental Research Forum project (PERF 9844: Manage Water-Soluble Organics in Produced Water''). The goal of this project, which involves characterization and evaluation of these water-soluble compounds, is aimed at reducing the future production of such contaminants. To determine the effect that various drilling conditions might have on water-soluble organics (WSO) content in produced water, a simulated brine water containing the principal inorganic components normally found in Gulf of Mexico (GOM) brine sources was prepared. The GOM simulant was then contacted with as-received crude oil from a deep well site to study the effects of water cut, produced-water pH, salinity, pressure, temperature, and crude oil sources on the type and content of the WSO in produced water. The identities of individual semivolatile organic compounds (SVOCs) were determined in all as-received crude and actual produced water samples using standard USEPA Method (8270C) protocol. These analyses were supplemented with the more general measurements of total petroleum hydrocarbon (TPH) content in the gas (C{sub 6}-C{sub 10}), diesel (C{sub 10}-C{sub 20}), and oil (C{sub 20}-C{sub 28}) carbon ranges as determined by both gas chromatographic (GC) and infrared (IR) analyses. An open liquid chromatographic procedure was also used to differentiate the saturated hydrocarbon, aromatic hydrocarbon, and polar components within the extractable TPH. Inorganic constituents in the produced water were analyzed by ion-selective electrodes and inductively coupled plasma (ICP)-atomic emission spectrometry (AES). The WSO found in produced water samples was primarily polar in nature and distributed between the low and midrange carbon ranges. Typical levels of total extractable material (TEM) was about 20 mg/L; that associated with the aromatic fraction was present at 0.2 mg/L and that in the saturated hydrocarbon fraction was present at less than 0.02 mg/L. Formic, acetic, and propionic acids were also found in the produced water, occurring at a total concentration of 30 mg/L. It was estimated that the presence of 30 mg/L organic acids would artificially overstate TEM content by 2 mg/L. Of the five tested parameters, the factor that most controlled the total WSO in produced water was that of aqueous phase pH. Beyond a value of pH7 significant quantities of C{sub 10}-C{sub 20} range material become markedly soluble as they deprotonate in a basic aqueous phase. Both the absolute and relative volumes of GOM brine and crude additionally affected total WSO. Produced water appeared to reach a saturation level of WSO at a.50% water/oil ratio. Pressure slightly enhanced WSO by increasing the relative quantity of C{sub 6}-C{sub 10} range material. Temperature primarily altered the relative ratio of carbon ranges within the WSO without significantly elevating the total WSO in the GOM brine. Salinity had the least affect on the chemical character or the carbon size of WSO in produced water.

  14. Tough soluble aromatic thermoplastic copolyimides

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    2000-01-01

    Tough, soluble, aromatic, thermoplastic copolyimides were prepared by reacting 4,4'-oxydiphthalic anhydride, 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydianiline. Alternatively, these copolyimides may be prepared by reacting 4,4'-oxydiphthalic anhydride with 3,4,3',4'-biphenyltetracarboxylic dianhydride and 3,4'-oxydiisocyanate. Also, the copolyimide may be prepared by reacting the corresponding tetra acid and ester precursors of 4,4'-oxydiphthalic anhydride and 3,4,3',4'-biphenyltetracarboxylic dianhydride with 3,4'-oxydianiline. These copolyimides were found to be soluble in common amide solvents such as N,N'-dimethyl acetamide, N-methylpyrrolidinone, and dimethylformamide allowing them to be applied as the fully imidized copolymer and to be used to prepare a wide range of articles.

  15. [Soluble of Metals within TSP in Shanghai].

    PubMed

    Chang, Yan; Feng, Chong; Qu, Jian-guo; Zhang, Jing

    2015-04-01

    The dissolution of metals within aerosol particles is meaningful to evaluate the bioavailability and mobility of metals. Total suspended particles (TSP) samples were collected in Shanghai. We extracted the water soluble and acid soluble (pH = 2) metals by the mini-recirculation-leach-system and measured their concentrations by the high resolution inductively coupled plasma mass spectrometry. The dissolution kinetics were rapid, the maximum solubility of metals could be reached in a few minutes. Overall, the average water-soluble concentrations were low for Co, Cr, Cd, V and Ni, median for Cu, Pb and Mn and high for Fe, Al, Zn and Mg. Combine the soluble metal concentrations with the back trajectory, the original air mass had significant impacts on water soluble metal concentrations. The water solubility and acid solubility were different for various metals, the water solubility of Fe was the lowest (2.0%), others followed an order: Al, Cr, V, Pb, Co, Ni, Cu, Cd, Mn, Mg, Zn. The metals' solubility was increased with the decrease of the solvent pH value. While the chemical speciation of metals was the internal cause of metals' solubility, the metals' ionic potential and the water solubility was negatively correlated. PMID:26164886

  16. Hydrogen adsorption of ruthenium: Isosteres of solubility of adsorbed hydrogen

    SciTech Connect

    Zaginaichenko, S.Y.; Matysina, Z.A.; Schur, D.V.; Pishuk, V.K.

    1998-12-31

    The theoretical investigation of solubility isosteres of adsorbed hydrogen has been performed for free face (0001) of crystals with hexagonal close-packed lattice A3 of Mg type. The face free energy has been calculated and its dependence on temperature, pressure, hydrogen concentration and character of hydrogen atoms distribution over surface interstitial sites of different type has been defined. The equations of thermodynamic equilibrium and solubility of adsorbed hydrogen have been defined. The plots of isosteres in the region of phase transition from isotropic to anisotropic state have been constructed and it has been established that in anisotropic state the order in distribution of hydrogen atoms over interstitial sites of different type must become apparent. Comparison of the theoretical isosteres with experimental for ruthenium has been carried out, the isotropic-anisotropic state transition can stipulate a stepwise and break-like change in isosteres.

  17. The crucial role of Activin A on the formation of primordial germ cell-like cells from skin-derived stem cells in vitro.

    PubMed

    Sun, Rui; Sun, Yuan-Chao; Ge, Wei; Tan, Hui; Cheng, Shun-Feng; Yin, Shen; Sun, Xiao-Feng; Li, Lan; Dyce, Paul; Li, Julang; Yang, Xiao; Shi, Qing-Hua; Shen, Wei

    2015-10-01

    Primordial germ cells (PGCs) are founder cells of the germ cell lineage, and can be differentiated from stem cells in an induced system in vitro. However, the induction conditions need to be optimized in order to improve the differentiation efficiency. Activin A (ActA) is a member of the TGF-? super family and plays an important role in oogenesis and folliculogenesis. In the present study, we found that ActA promoted PGC-like cells (PGCLCs) formation from mouse skin-derived stem cells (SDSCs) in both embryoid body-like structure (EBLS) differentiation and the co-culture stage in a dose dependent manner. ActA treatment (100 ng/ml) during EBLS differentiation stage and further co-cultured for 6 days without ActA significantly increased PGCLCs from 53.2% to 82.8%, and as well as EBLS differentiation without ActA followed by co-cultured with 100 ng/ml ActA for 4 to 12 days with the percentage of PGCLCs increasing markedly in vitro. Moreover, mice treated with ActA at 100 ng/kg body weight from embryonic day (E) 5.5-12.5 led to more PGCs formation. However, the stimulating effects of ActA were interrupted by Smad3 RNAi, and in an in vitro cultured Smad3(-/-) mouse skin cells scenario. SMAD3 is thus likely a key effecter molecule in the ActA signaling pathway. In addition, we found that the expression of some epiblast cell markers, Fgf5, Dnmt3a, Dnmt3b and Wnt3, was increased in EBLSs cultured for 4 days or PGCLCs co-cultured for 12 days with ActA treatment. Interestingly, at 16 days of differentiation, the percentage of PGCLCs was decreased in the presence of ActA, but the expression of meiosis-relative genes, such as Stra8, Dmc1, Sycp3 and Sycp1, was increased. In conclusion, our data here demonstrated that ActA can promote PGCLC formation from SDSCs in vitro, at early stages of differentiation, and affect meiotic initiation of PGCLCs in later stages. PMID:26406115

  18. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling

    PubMed Central

    Hay, David C.; Fletcher, Judy; Payne, Catherine; Terrace, John D.; Gallagher, Ronald C. J.; Snoeys, Jan; Black, James R.; Wojtacha, Davina; Samuel, Kay; Hannoun, Zara; Pryde, Anne; Filippi, Celine; Currie, Ian S.; Forbes, Stuart J.; Ross, James A.; Newsome, Philip N.; Iredale, John P.

    2008-01-01

    Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. To date, however, their homogeneous cellular differentiation to specific cell types in vitro has proven difficult. Wnt signaling has been shown to play important roles in coordinating development, and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development in vivo. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our in vitro model, demonstrating the importance of a physiologic approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepatocellular function in vitro and in vivo. In addition, we demonstrate that Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation. These studies represent an important step toward the use of hESC-derived hepatocytes in high-throughput metabolic analysis of human liver function. PMID:18719101

  19. ~]~ERSPECTIVES Almost all of the studies to date in which growth

    E-print Network

    Stern, Claudio

    ~]~ERSPECTIVES Almost all of the studies to date in which growth factors have been assessed with soluble growth factors. Nanogram per ml concentrations of activin, TGF-]32 and the FGFs can all cause some recog- nizing different cell types, or by RNase protection using probes such as cardiac muscle actin

  20. Ice nucleation by water-soluble macromolecules

    NASA Astrophysics Data System (ADS)

    Pummer, B. G.; Budke, C.; Augustin-Bauditz, S.; Niedermeier, D.; Felgitsch, L.; Kampf, C. J.; Huber, R. G.; Liedl, K. R.; Loerting, T.; Moschen, T.; Schauperl, M.; Tollinger, M.; Morris, C. E.; Wex, H.; Grothe, H.; Pöschl, U.; Koop, T.; Fröhlich-Nowoisky, J.

    2015-04-01

    Cloud glaciation is critically important for the global radiation budget (albedo) and for initiation of precipitation. But the freezing of pure water droplets requires cooling to temperatures as low as 235 K. Freezing at higher temperatures requires the presence of an ice nucleator, which serves as a template for arranging water molecules in an ice-like manner. It is often assumed that these ice nucleators have to be insoluble particles. We point out that also free macromolecules which are dissolved in water can efficiently induce ice nucleation: the size of such ice nucleating macromolecules (INMs) is in the range of nanometers, corresponding to the size of the critical ice embryo. As the latter is temperature-dependent, we see a correlation between the size of INMs and the ice nucleation temperature as predicted by classical nucleation theory. Different types of INMs have been found in a wide range of biological species and comprise a variety of chemical structures including proteins, saccharides, and lipids. Our investigation of the fungal species Acremonium implicatum, Isaria farinosa, and Mortierella alpina shows that their ice nucleation activity is caused by proteinaceous water-soluble INMs. We combine these new results and literature data on INMs from fungi, bacteria, and pollen with theoretical calculations to develop a chemical interpretation of ice nucleation and water-soluble INMs. This has atmospheric implications since many of these INMs can be released by fragmentation of the carrier cell and subsequently may be distributed independently. Up to now, this process has not been accounted for in atmospheric models.

  1. Drug Solubility: Importance and Enhancement Techniques

    PubMed Central

    Savjani, Ketan T.; Gajjar, Anuradha K.; Savjani, Jignasa K.

    2012-01-01

    Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics. PMID:22830056

  2. Thorium(IV) hydrous oxide solubility

    SciTech Connect

    Ryan, J.L.; Rai, D.

    1987-12-02

    The results of a study of the solubility of amorphous, hydrous ThO/sub 2/ over the pH range 3.5 - 14.2 are reported. The solubility is high at pH 3.5 and decreases rapidly at pH 4.5. The chemical modes of solubility over various pH ranges are discussed. No conclusive evidence for any amphoteric behavior of Th(IV) is reported. 22 references, 1 figure.

  3. Water soluble pentacene Chandrani Pramanik,a

    E-print Network

    Müller, Peter

    Water soluble pentacene Chandrani Pramanik,a Yushu Li,a Anup Singh,b Weimin Lin,a Jennifer L*a A water soluble pentacene, potassium 3,30 -(pentacene-6,13-diylbis(sulfanediyl))dipropanoate (4), has been HOMO­LUMO gap of approximately 1.91­1.97 eV. Water soluble pentacene 4 is long-lived in the solution

  4. Crosslinking of water-soluble polymers

    NASA Astrophysics Data System (ADS)

    Lei, Cuiyue

    The crosslinking of water-soluble polymers is important in many industrial processes. In the oil industry, minimizing the concentration of polymers is desirable for technical and economic reasons. This dissertation provides a link between measurable polymer properties and the minimum concentration necessary for crosslinking. The influences of polymer type and concentration, crosslinker type, salt and additives on the crosslinking process were studied by steady shear test, creep test, oscillatory test, Atomic Force Microscopy and other techniques. Solution properties, crosslinked gel properties and the relationship between them were investigated. Test results indicate that the rheological properties of guar solutions and its derivatives are quite different. The critical overlap concentrations increase in the order GW-3, CMG, CMHPG, guar and HPG. And, the intrinsic viscosity increases in the order of HPG, guar, CMHPG, GW-3 and CMG. At low concentrations, steady shear viscosity decreases in the order of CMG, CMHPG, GW-3, guar and HPG, while at high concentrations, the steady shear viscosities decrease in the order of GW-3, guar, CMG, CMHPG and HPG. Addition of urea and sugar reduces the viscosity of guar solutions. The influence of salts on the viscosity of CMG solutions varies with salt types and polymer concentrations. The strength of crosslinked gels increases with polymer concentration. At low polymer concentrations, gel strength of guar derivatives increases in the order of HPG, guar, GW-3, CMG and CMHPG, while at high concentrations, gel strength increases in the order of CMG, CMHPG, HPG, guar and GW-3. The critical crosslinking concentration increases in the order of GW-3, CMG, CMHPG, guar and HPG. A mathematical model is developed to relate critical crosslinking concentration and critical crosslinking concentration. The relationship between them is scaled as a power law. Models of the plateau modulus dependence on concentration are also developed. The modulus can be scaled as power law of the concentration with different exponents for different type of polymer gels.

  5. Solubility and speciation of atmospheric iron in buffer systems simulating cloud conditions

    NASA Astrophysics Data System (ADS)

    Upadhyay, Nabin; Majestic, Brian J.; Herckes, Pierre

    2011-04-01

    The solubility of iron (Fe) in atmospheric particulate matter (PM) is important to understand its chemistry and potential bioavailability to ocean phytoplankton. However, current studies on Fe solubility and its speciation are highly uncertain partly due to inconsistencies in analytical protocols. In this study, cloud-processing of atmospheric PM was simulated in acetate, formate, and oxalate buffers (pH = 4.30 ± 0.05) at 0.5, 1, 5, and 20 mM. Colorimetric analysis of Fe(II)-ferrozine complex showed that Fe solubility increased by an order of magnitude when acetate and formate concentrations increased from 0.5 mM to 5 mM, with a higher fraction of soluble Fe in acetate than in formate at lower buffer concentration (0.5 mM). Measured pH of sample extracts revealed that weak buffers are unable to maintain pH, presumably due to acidic or alkaline components of PM, requiring an optimum concentration (5 mM in this study) of acetate and formate for Fe solubility measurements. Similar extraction procedures revealed that oxalate buffer inhibits the formation of Fe(II)-ferrozine complex, especially with Fe(III)-containing solutions, rendering it unsuitable for Fe solubility measurements by Ferrozine method. Application of the optimized analytical method to PM samples from different environments showed quite variable Fe solubility, with the lowest (<1%) in dust-impacted samples and the highest (5%) in urban samples. The highest solubility (6.8%) was observed in ambient PM2.5 samples influenced by anthropogenic sources (car emissions) with more than 90% of soluble Fe in the form of Fe(II). Results from this study highlight the importance of the type and strength of buffer at a given pH for Fe solubility and provide further evidence of a higher Fe solubility in urban PM samples compared to desert dust.

  6. Filtrates & Residues: An Experiment on the Molar Solubility and Solubility Product of Barium Nitrate.

    ERIC Educational Resources Information Center

    Wruck, Betty; Reinstein, Jesse

    1989-01-01

    Provides a two hour experiment using direct gravimetric methods to determine solubility constants. Provides methodology and sample results. Discusses the effect of the common ion on the solubility constant. (MVL)

  7. WATER SOLUBLE VITAMIN REQUIREMENTS OF SILVER SALMON

    E-print Network

    WATER SOLUBLE VITAMIN REQUIREMENTS OF SILVER SALMON Marine Biological Laboratory FEB !) ~iy;)9, Commissioner WATER-SOLUBLE VITAMIN REQUIREMENTS OF SILVER SALMON By John A. Coates* and John E. Halver Western, John A Wiiti'i-sohilile vitamin ivcjuireineiits of silver sahnon, by John A. CoiUes and John E. Ilalver

  8. A Colorful Solubility Exercise for Organic Chemistry

    ERIC Educational Resources Information Center

    Shugrue, Christopher R.; Mentzen, Hans H., II; Linton, Brian R.

    2015-01-01

    A discovery chemistry laboratory has been developed for the introductory organic chemistry student to investigate the concepts of polarity, miscibility, solubility, and density. The simple procedure takes advantage of the solubility of two colored dyes in a series of solvents or solvent mixtures, and the diffusion of colors can be easily…

  9. Calculation of Drug Solubilities by Pharmacy Students.

    ERIC Educational Resources Information Center

    Cates, Lindley A.

    1981-01-01

    A method of estimating the solubilities of drugs in water is reported that is based on a principle applied in quantitative structure-activity relationships. This procedure involves correlation of partition coefficient values using the octanol/water system and aqueous solubility. (Author/MLW)

  10. Role of Hansen solubility parameters in solid phase extraction.

    PubMed

    Bielicka-Daszkiewicz, K; Voelkel, A; Pietrzy?ska, M; Héberger, K

    2010-08-27

    The sorbent-eluent systems combined from eight polymeric sorbents and seven solvents as eluents were used for the extraction of phenol and its oxidation products from water samples. The individual interactions between sorbents, eluents and analytes were characterized by Hansen solubility parameters. Principal components analysis (PCA) was used for revealing the dominant interactions (dispersive, polar, and hydrogen bonding type) in sorbent-analyte-eluent systems. The importance of solubility parameters was also determined by a novel procedure based on sum of ranking differences (SRD). Although PCA and ranking by SRD are based on different principles and calculations, they have provided very similar results. The recovery in a given system has been predicted from the magnitudes of mutual interactions (sorbent-analyte, sorbent-eluent, analyte-eluent) by multiple linear regression. PMID:20643412

  11. OZONE TREATMENT OF SOLUBLE ORGANICS IN PRODUCED WATER

    SciTech Connect

    Klasson, KT

    2002-03-14

    This project was an extension of previous research to improve the applicability of ozonation and will help address the petroleum-industry problem of treating produced water containing soluble organics. The goal of this project was to maximize oxidation of hexane-extractable organics during a single-pass operation. The project investigated: (1) oxidant production by electrochemical and sonochemical methods, (2) increasing the mass transfer rate in the reactor by forming microbubbles during ozone injection into the produced water, and (3) using ultraviolet irradiation to enhance the reaction if needed. Several types of methodologies for treatment of soluble organics in synthetic and actual produced waters have been performed. The technologies tested may be categorized as follows: (1) Destruction via sonochemical oxidation at different pH, salt concentration, ultraviolet irradiation, and ferrous iron concentrations. (2) Destruction via ozonation at different pH, salt concentration, hydrogen peroxide concentrations, ultraviolet irradiation, temperature, and reactor configurations.

  12. Soluble Adenylyl Cyclase of Sea Urchin Spermatozoa

    PubMed Central

    Vacquier, Victor D.; Loza-Huerta, Arlet; García-Rincón, Juan; Darszon, Alberto; Beltrán, Carmen

    2014-01-01

    Fertilization, a key step in sexual reproduction, requires orchestrated changes in cAMP concentrations. It is notable that spermatozoa (sperm) are amongst the cell types with extremely high adenylyl cyclase (AC) activity. As production and consumption of this second messenger need to be locally regulated, the discovery of soluble AC (sAC) has broadened our understanding of how such cells deal with these requirements. In addition, because sAC is directly regulated by HCO3- it is able to translate CO2/HCO3-/pH changes into cAMP levels. Fundamental sperm functions such as maturation, motility regulation and the acrosome reaction are influenced by cAMP; this is especially true for sperm of the sea urchin (SU), an organism that has been a model in the study of fertilization for more than 130 years. Here we summarize the discovery and properties of SU sperm sAC, and discuss its involvement in sperm physiology. PMID:25064590

  13. Water-soluble conductive polymers

    DOEpatents

    Aldissi, Mahmoud (Sante Fe, NM)

    1989-01-01

    Polymers which are soluble in water and are electrically conductive. The monomer repeat unit is a thiophene or pyrrole molecule having an alkyl group substituted for the hydrogen atom located in the beta position of the thiophene or pyrrole ring and having a surfactant molecule at the end of the alkyl chain. Polymers of this class having 8 or more carbon atoms in the alkyl chain exhibit liquid crystalline behavior, resulting in high electrical anisotropy. The monomer-to-monomer bonds are located between the carbon atoms which are adjacent to the sulfur or nitrogen atoms. The number of carbon atoms in the alkyl group may vary from 1 to 20 carbon atoms. The surfactant molecule consists of a sulfonate group, or a sulfate group, or a carboxylate group, and hydrogen or an alkali metal. Negative ions from a supporting electrolyte which may be used in the electrochemical synthesis of a polymer may be incorporated into the polymer during the synthesis and serve as a dopant to increase the conductivity.

  14. Water-soluble conductive polymers

    DOEpatents

    Aldissi, Mahmoud (Sante Fe, NM)

    1990-01-01

    Polymers which are soluble in water and are electrically conductive. The monomer repeat unit is a thiophene or pyrrole molecule having an alkyl group substituted for the hydrogen atom located in the beta position of the thiophene or pyrrole ring and having a surfactant molecule at the end of the alkyl chain. Polymers of this class having 8 or more carbon atoms in the alkyl chain exhibit liquid crystalline behavior, resulting in high electrical anisotropy. The monomer-to-monomer bonds are located between the carbon atoms which are adjacent to the sulfur or nitrogen atoms. The number of carbon atoms in the alkyl group may vary from 1 to 20 carbon atoms. The surfactant molecule consists of a sulfonate group, or a sulfate group, or a carboxylate group, and hydrogen or an alkali metal. Negative ions from a supporting electrolyte which may be used in the electrochemical synthesis of a polymer may be incorporated into the polymer during the synthesis and serve as a dopant to increase the conductivity.

  15. Water-soluble conductive polymers

    DOEpatents

    Aldissi, M.

    1988-02-12

    Polymers which are soluble in water and are electrically conductive. The monomer repeat unit is a thiophene or pyrrole molecule having an alkyl group substituted for the hydrogen atom located in the beta position of the thiophene or pyrrole ring and having a surfactant molecule at the end of the alkyl chain. Polymers of this class having 8 or more carbon atoms in the alkyl chain exhibit liquid crystalline behavior, resulting in high electrical anisotropy. The monomer-to-monomer bonds are located between the carbon atoms which are adjacent to the sulfur or nitrogen atoms. The number of carbon atoms in the alkyl group may vary from 1 to 20 carbon atoms. The surfactant molecule consists of a sulfonate group, or a sulfate group, or a carboxylate group, and hydrogen or an alkali metal. Negative ions from a supporting electrolyte which may be used in the electrochemical synthesis of a polymer may be incorporated into the polymer during the synthesis and serve as a dopant to increase the conductivity.

  16. Analysis of amino acid contributions to protein solubility using short peptide tags fused to a simplified BPTI variant.

    PubMed

    Islam, Mohammad Monirul; Khan, Monsur A; Kuroda, Yutaka

    2012-10-01

    Protein solubility is usually characterized in terms of a hydrophobicity scale, which refers to the free energy of transfer of a molecule from an aqueous to a nonpolar solution and is not a "solubility propensity scale" per se. Using a "host-guest" approach, we measured the effects of short poly-amino-acid tags (guests) on the solubility of a host protein, a simplified bovine pancreatic trypsin inhibitor (BPTI), to which they were fused at the C-terminus. We analyzed 10 amino acid types, representing the full range of biophysical properties (acidic, basic, polar, and hydrophobic). As anticipated, positively charged residues significantly increased the solubility of the model protein, at both pH 4.7 and 7.7, whereas very hydrophobic poly-Ile markedly reduced the solubility of BPTI. Poly-Asp and poly-Glu barely affected BPTI solubility at pH 4.7, but induced an eight to ten-fold increase at pH 7.7, attributable to the ionization of their side chains. Although Pro is the most soluble amino acid, poly-Pro did not affect the protein's solubility. The effects of the other tags on BPTI solubility ranged from none to an eight-fold increase. To ensure that the measured solubility values were context independent and could provide a "solubility propensity scale", we confirmed that the tags remained independent of the structure, thermal stability, and biochemical activity of the host protein. These observations suggest that this approach is valuable for measuring the solubility propensities of amino acids, which could eventually allow the calculation of a polypeptide's relative solubility from its amino acid sequence. PMID:22728531

  17. Dermal nanocrystals from medium soluble actives - physical stability and stability affecting parameters.

    PubMed

    Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

    2014-09-01

    Nanocrystals are meanwhile applied to increase the dermal penetration of drugs, but were applied by now only to poorly soluble drugs (e.g. 1-10 ?g/ml). As a new concept nanocrystals from medium soluble actives were produced, using caffeine as model compound (solubility 16 mg/ml at 20 °C). Penetration should be increased by (a) further increase in solubility and (b) mainly by increased hair follicle targeting of nanocrystals compared to pure solution. Caffeine nanocrystal production in water lead to pronounced crystal growth. Therefore the stability of nanocrystals in water-ethanol (1:9) and ethanol-propylene glycol (3:7) mixtures with lower dielectric constant D was investigated, using various stabilizers. Both mixtures in combination with Carbopol 981 (non-neutralized) yielded stable nanosuspensions over 2 months at 4 °C and room temperature. Storage at 40 °C lead to crystal growth, attributed to too strong solubility increase, supersaturation and Ostwald ripening effects. Stability of caffeine nanocrystals at lower temperatures could not only be attributed to lower solubility, because the solubilities of caffeine in mixtures and in water are not that much different. Other effects such as quantified by reduced dielectric constant D, and specific interactions between dispersion medium and crystal surface seem to play a role. With the 2 mixtures and Carbopol 981, a basic formulation composition for this type of nanocrystals has been established, to be used in the in vivo proof of principle of the new concept. PMID:25016978

  18. Calibrative approaches to protein solubility modeling of a mutant series using physicochemical descriptors

    PubMed Central

    Labute, P.

    2010-01-01

    A set of physicochemical properties describing a protein of known structure is employed for a calibrative approach to protein solubility. Common hydrodynamic and electrophoretic properties routinely measured in the bio-analytical laboratory such as zeta potential, dipole moment, the second osmotic virial coefficient are first estimated in silico as a function a pH and solution ionic strength starting with the protein crystal structure. The utility of these descriptors in understanding the solubility of a series of ribonuclease Sa mutants is investigated. A simple two parameter model was trained using solubility data of the wild type protein measured at a restricted number of solution pHs. Solubility estimates of the mutants demonstrate that zeta potential and dipole moment may be used to rationalize solubility trends over a wide pH range. Additionally a calibrative model based on the protein’s second osmotic virial coefficient, B22 was developed. A modified DVLO type potential along with a simplified representation of the protein allowed for efficient computation of the second viral coefficient. The standard error of prediction for both models was on the order of 0.3 log S units. These results are very encouraging and demonstrate that these models may be trained with a small number of samples and employed extrapolatively for estimating mutant solubilities. PMID:20842408

  19. Acid soluble, pepsin resistant platelet aggregating material

    SciTech Connect

    Schneider, M.D.

    1982-08-31

    Disclosed is an acid soluble, pepsin resistant, platelet aggregating material isolated from equine arterial tissue by extraction with dilute aqueous acid. The method of isolation and use to control bleeding are described. 4 figs.

  20. Organogel formation rationalized by Hansen solubility parameters.

    PubMed

    Raynal, Matthieu; Bouteiller, Laurent

    2011-08-01

    Some organic compounds gelate particular solvents by forming a network of anisotropic fibres. We show that Hansen solubility parameters can be used to predict the range of solvents that are likely to be gelled by any given gelator. PMID:21709882

  1. ANALYSIS OF WATER-SOLUBLE ORGANICS

    EPA Science Inventory

    The report gives results of several analytical procedures for separating and detecting non-extractable water-soluble organic material, including low molecular weight acids, alcohols, ketones, and other categories of compounds. (There are many ways to analyze hydrophobic extractab...

  2. Phase Selectively Soluble Polystyrene-Supported Organocatalysts 

    E-print Network

    Khamatnurova, Tatyana

    2014-08-10

    Alkane phase selectively soluble poly(4-alkylstyrene) supports have been developed. 4-Methyl-, 4-tert-butyl, 4-dodecyl-, and 4-octadecylstyrene were copolymerized with 5-10 mol % of 4-chloromethylstyrene to afford co- and terpolymers containing...

  3. Soluble endoglin, hypercholesterolemia and endothelial dysfunction.

    PubMed

    Rathouska, Jana; Jezkova, Katerina; Nemeckova, Ivana; Nachtigal, Petr

    2015-12-01

    A soluble form of endoglin (sEng) is known to be an extracellular domain of the full-length membrane endoglin, which is elevated during various pathological conditions related to vascular endothelium. In the current review, we tried to summarize a possible role of soluble endoglin in cardiovascular pathologies, focusing on its relation to endothelial dysfunction and cholesterol levels. We discussed sEng as a proposed biomarker of cardiovascular disease progression, cardiovascular disease treatment and endothelial dysfunction. We also addressed a potential interaction of sEng with TGF-?/eNOS or BMP-9 signaling. We suggest soluble endoglin levels to be monitored, because they reflect the progression/treatment efficacy of cardiovascular diseases related to endothelial dysfunction and hypercholesterolemia. A possible role of soluble endoglin as an inducer of endothelial dysfunction however remains to be elucidated. PMID:26520890

  4. Cu and Ni solubility in high-temperature aqueous fluids

    NASA Astrophysics Data System (ADS)

    Watenphul, A.; Scholten, L.; Beermann, O.; Kavner, A.; Alraun, P.; Falkenberg, G.; Newville, M.; Lanzirotti, A.; Schmidt, C.

    2013-12-01

    Copper and nickel are generally associated in magmatic sulfide ores formed by immiscibility in mafic and ultramafic magmas. In contrast, hydrothermal Cu-Ni deposits are uncommon and these elements usually occur in separate Cu-Fe-sulfide and Ni-Co-Ag-Bi-As-S mineralizations. Among the porphyry-type deposits formed at high temperatures to about 700 °C, there are many copper but no nickel deposits [1], pointing to a higher solubility of Cu relative to Ni in aqueous fluids at such conditions. The aim of this study is to measure the solubilities of Cu and Ni sulfides in high-temperature hydrothermal fluids in-situ using synchrotron-radiation micro-X-ray fluorescence spectrometry. Synthetic CuS or NiS crystals were partly dissolved in aqueous NaCl, NaCl+HCl, or CaCl2 solutions at temperatures of 400 to 600 °C and pressures between 70 and 900 MPa using a modified hydrothermal diamond-anvil cell with a recess in one diamond [2]. Consecutive XRF spectra of the fluid in the recess were collected in a confocal mode to exclude signal contributions from the crystals in the sample chamber [3]. Equilibrium was assumed if the determined concentrations of the dissolved metals indicated that a steady state was attained. The measured dissolved Cu concentrations ranged between 22 ppm at 70 MPa, 500 °C and 235 ppm at 306 MPa, 600 °C in 0.5 to 1.6 m NaCl solutions. We observed a decrease in Cu concentration with increasing pressure at constant temperature, and for 1.6 m NaCl an increase by a factor of two along an isochore from 120 MPa, 500 °C to 306 MPa, 600 °C. Higher Cu solubilities were determined in more concentrated solutions. A preliminary run with a more acidic NaCl+HCl solution (pH ~1) revealed a dramatic increase in the dissolved Cu concentration to 7898 ppm at 170 MPa, 500 °C. The measured dissolved Ni concentrations ranged between 3 ppm at 200 MPa, 500 °C in a 1 m NaCl solution and 33 ppm at 411 MPa, 500 °C in a 0.75 m CaCl2 solution. A solubility maximum at 500 °C along an isochore was observed for both solutions. The Ni solubility increased with pressure at constant temperature. Experiments with aqueous CaCl2 solutions resulted in higher dissolved Ni concentrations compared to NaCl solutions at similar pressure-temperature conditions. Our experiments suggest that the solubility of Cu and Ni in aqueous fluids is mainly governed by fluid composition. For both elements, solubility increased in more chlorine-rich fluids, which could reflect metal-chlorine complexation. Preliminary results for Cu indicate a strong dependence of the solubility on the pH of the fluid. A contrasting solubility behavior of Cu and Ni was observed with increasing pressure, which might be one reason for the difference in hydrothermal ore deposit formation. [1] Barnes (1979) Geochemistry of hydrothermal ore deposits, Wiley. [2] Schmidt and Rickers (2003) Am. Mineral. 88, 288-292. [3] Wilke el al. (2010) J. Synchrotron Rad. 17, 669-675.

  5. Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with Gelucire 50/13.

    PubMed

    Potluri, Raja Hemanth Kumar; Bandari, Suresh; Jukanti, Raju; Veerareddy, Prabhakar Reddy

    2011-01-01

    The objective of the study was enhancement of dissolution of poorly soluble carvedilol by solid dispersions (SDs) with Gelucire 50/13 using solvent evaporation method. The solubility of carvedilol showed linear increase with increasing concentrations of Gelucire indicating A(L) type solubility diagrams. SDs characterized for physicochemical characteristics using differential scanning calorimetry and X-ray diffractometry revealed transformation of crystalline form of drug to amorphous form which was confirmed by scanning electron micrographs. Further fourier transform infrared spectroscopy results suggested there is no drug carrier interaction. From the dissolution parameters such as mean dissolution time, dissolution efficiency and drug release rate, improved dissolution characteristics for SDs were observed compared with physical mixture and pure drug. Thus SDs of carvedilol in Gelucire 50/13 showed enhanced solubility and dissolution rate compared to pure drug. PMID:21468915

  6. Soluble proteins of chemical communication: an overview across arthropods

    PubMed Central

    Pelosi, Paolo; Iovinella, Immacolata; Felicioli, Antonio; Dani, Francesca R.

    2014-01-01

    Detection of chemical signals both in insects and in vertebrates is mediated by soluble proteins, highly concentrated in olfactory organs, which bind semiochemicals and activate, with still largely unknown mechanisms, specific chemoreceptors. The same proteins are often found in structures where pheromones are synthesized and released, where they likely perform a second role in solubilizing and delivering chemical messengers in the environment. A single class of soluble polypeptides, called Odorant-Binding Proteins (OBPs) is known in vertebrates, while two have been identified in insects, OBPs and CSPs (Chemosensory Proteins). Despite their common name, OBPs of vertebrates bear no structural similarity with those of insects. We observed that in arthropods OBPs are strictly limited to insects, while a few members of the CSP family have been found in crustacean and other arthropods, where however, based on their very limited numbers, a function in chemical communication seems unlikely. The question we address in this review is whether another class of soluble proteins may have been adopted by other arthropods to perform the role of OBPs and CSPs in insects. We propose that lipid-transporter proteins of the Niemann-Pick type C2 family could represent likely candidates and report the results of an analysis of their sequences in representative species of different arthropods. PMID:25221516

  7. Controlled porosity solubility modulated osmotic pump tablets of gliclazide.

    PubMed

    Banerjee, Arti; Verma, P R P; Gore, Subhash

    2015-06-01

    A system that can deliver drug at a controlled rate is very important for the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Poorly water-soluble drug with pH-dependent solubility such as gliclazide (GLZ) offers challenges in the controlled-release formulation because of low dissolution rate and poor bioavailability. Solid dispersion (SD) of GLZ consisted of hydroxypropyl cellulose (HPC-SSL) as a polymeric solubilizer was manufactured by hot melt extrusion (HME) technology. Then, controlled porosity osmotic pump (CPOP) tablet of gliclazide was designed to deliver drug in a controlled manner up to 16 h. The developed formulation was optimized for type and level of pore former and coating weight gain. The optimized formulation was found to exhibit zero order kinetics independent of pH and agitation speed but depends on osmotic pressure of dissolution media indicated that mechanism of drug release was osmotic pressure. The in vivo performance prediction of developed formulation using convolution approach revealed that the developed formulation was superior to the existing marketed extended-release formulation in terms of attaining steady state plasma levels and indicated adequate exposure in translating hypoglycemic response. The prototype solubilization method combined with controlled porosity osmotic pump based technique could provide a unique way to increase dissolution rate and bioavailability of many poorly water-soluble, narrow therapeutic index drugs used in diabetes, cardiovascular diseases, etc. PMID:25378281

  8. GADOLINIUM SOLUBILITY AND VOLATILITY DURING DWPF PROCESSING

    SciTech Connect

    Reboul, S

    2008-01-30

    Understanding of gadolinium behavior, as it relates to potential neutron poisoning applications at the DWPF, has increased over the past several years as process specific data have been generated. Of primary importance are phenomena related to gadolinium solubility and volatility, which introduce the potential for gadolinium to be separated from fissile materials during Chemical Process Cell (CPC) and Melter operations. Existing data indicate that gadolinium solubilities under moderately low pH conditions can vary over several orders of magnitude, depending on the quantities of other constituents that are present. With respect to sludge batching processes, the gadolinium solubility appears to be highly affected by iron. In cases where the mass ratio of Fe:Gd is 300 or more, the gadolinium solubility has been observed to be low, one milligram per liter or less. In contrast, when the ratio of Fe:Gd is 20 or less, the gadolinium solubility has been found to be relatively high, several thousands of milligrams per liter. For gadolinium to serve as an effective neutron poison in CPC operations, the solubility needs to be limited to approximately 100 mg/L. Unfortunately, the Fe:Gd ratio that corresponds to this solubility limit has not been identified. Existing data suggest gadolinium and plutonium are not volatile during melter operations. However, the data are subject to inherent uncertainties preventing definitive conclusions on this matter. In order to determine if gadolinium offers a practical means of poisoning waste in DWPF operations, generation of additional data is recommended. This includes: Gd solubility testing under conditions where the Fe:Gd ratio varies from 50 to 150; and Gd and Pu volatility studies tailored to quantifying high temperature partitioning. Additional tests focusing on crystal aging of Gd/Pu precipitates should be pursued if receipt of gadolinium-poisoned waste into the Tank Farm becomes routine.

  9. Correlation of Helium Solubility in Liquid Nitrogen

    NASA Technical Reports Server (NTRS)

    VanDresar, Neil T.; Zimmerli, Gregory A.

    2012-01-01

    A correlation has been developed for the equilibrium mole fraction of soluble gaseous helium in liquid nitrogen as a function of temperature and pressure. Experimental solubility data was compiled and provided by National Institute of Standards and Technology (NIST). Data from six sources was used to develop a correlation within the range of 0.5 to 9.9 MPa and 72.0 to 119.6 K. The relative standard deviation of the correlation is 6.9 percent.

  10. Solubility-excipient classification gradient maps.

    PubMed

    Avdeef, Alex; Bendels, Stefanie; Tsinman, Oksana; Tsinman, Konstantin; Kansy, Manfred

    2007-03-01

    This study assessed the effect of excipients (sodium taurocholate, 2-hydroxypropyl-f-cyclodextrin, potassium chloride, propylene glycol, 1-methyl-2-pyrrolidone, and polyethylene glycol 400) on the apparent intrinsic solubility properties of eight sparingly soluble drugs (four bases, two neutrals, and two acids): astemizole, butacaine, clotrimazole, dipyridamole, griseofulvin, progesterone, glibenclamide, and mefenemic acid. Over 1,200 UV-based solubility measurements (pH 3-10) were made with a high-throughput instrument. New equations, based on the "shift-in-pKa" method, were derived to interpret the complicated solubility-pH dependence observed, and poorly predicted by the Henderson-Hasselbalch equation. An intrinsic solubility-excipient classification gradient map visualization tool was developed to rank order the compounds and the excipients. In excipient-free solutions, all of the ionizable compounds formed either uncharged or mixed-charge aggregates. Mefenamic acid formed anionic dimers and trimers. Glibenclamide displayed a tendency to form monoanionic dimers. Dipyridamole and butacaine tended to form uncharged aggregates. With strong excipients, the tendency to form aggregates diminished, except in the case of glibenclamide. We conclude that a low-cost, compound-sparing, and reasonably accurate high-throughput assay which can be used in early screening to prioritize candidate molecules by their eventual developability via the excipient route is possible with the aid of the "self-organized" intrinsic solubility-excipient classification gradient maps. PMID:17245653

  11. Ammonia Solubility in High Concentration Salt Solutions

    SciTech Connect

    HEDENGREN, D.C.

    2000-02-01

    Solubility data for ammonia in water and various dilute solutions are abundant in the literature. However, there is a noticeable lack of ammonia solubility data for high salt, basic solutions of various mixtures of salts including those found in many of the Hanford Washington underground waste tanks. As a result, models based on solubility data for dilute salt solutions have been used to extrapolate to high salt solutions. These significant extrapolations need to be checked against actual laboratory data. Some indirect vapor measurements have been made. A more direct approach is to determine the ratio of solubility of ammonia in water to its solubility in high salt solutions. In various experiments, pairs of solutions, one of which is water and the other a high salt solution, are allowed to come to equilibrium with a common ammonia vapor pressure. The ratio of concentrations of ammonia in the two solutions is equal to the ratio of the respective ammonia solubilities (Henry's Law constants) at a given temperature. This information can then be used to refine the models that predict vapor space compositions of ammonia. Ammonia at Hanford is of concern because of its toxicity in the environment and its contribution to the flammability of vapor space gas mixtures in waste tanks.

  12. Solubility enhancement of desloratadine by solid dispersion in poloxamers.

    PubMed

    Kolašinac, Nemanja; Kachrimanis, Kyriakos; Homšek, Irena; Gruji?, Branka; Ðuri?, Zorica; Ibri?, Svetlana

    2012-10-15

    The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of the poorly water soluble drug substance desloratadine that can be used for the preparation of immediate release tablet formulation. Two commercially available poloxamer grades (poloxamer P 188 and poloxamer P 407) were selected, and solid dispersions (SDs) containing different weight ratio of poloxamers and desloratadine were prepared by a low temperature melting method. All SDs were subjected to basic physicochemical characterization by thermal and vibrational spectroscopy methods in order to evaluate the efficiency of poloxamers as solubility enhancers. Immediate release tablets were prepared by direct compression of powdered solid dispersions according to a General Factorial Design, in order to evaluate the statistical significance of two formulation (X(1) - type of poloxamer in SD and X(2) - poloxamer ratio in SD) and one process variable (X(3) - compression force) on the drug dissolution rate. It was found that desloratadine in SDs existed in the amorphous state, and that can be largely responsible for the enhanced intrinsic solubility, which was more pronounced in SDs containing poloxamer 188. Statistical analysis of the factorial design revealed that both investigated formulation variables exert a significant effect on the drug dissolution rate. Increased poloxamer ratio in SDs resulted in increased drug dissolution rate, with poloxamer 188 contributing to a faster dissolution rate than poloxamer 407, in accordance with the results of intrinsic dissolution tests. Moreover, there is a significant interaction between poloxamer ratio in SD and compression force. Higher poloxamer ratio in SDs and higher compression force results in a significant decrease of the drug dissolution rate, which can be attributed to the lower porosity of the tablets and more pronounced bonding between poloxamer particles. PMID:22772487

  13. Hydrocarbon-soluble low-melting corrosion inhibitor TAL-3

    SciTech Connect

    Nesterenko, S.A.; Sorokin, V.I.; Naumenko, O.V.

    1987-03-01

    The inhibitor TAL-3 is intended for the corrosion protection of metals that come into contact with two-phase systems of the hydrocarbon-water type. It is applicable to the service conditions of equipment and pipelines of the petroleum and petroleum refining industries. The purpose of this paper was to electrochemically assess its solubility in such systems and its inhibitory properties on samples of 08kp steel toward the effects of refinery and oil field waste water and process emulsions both on the laboratory scale and in field tests.

  14. Biological activities of water-soluble fullerene derivatives

    NASA Astrophysics Data System (ADS)

    Nakamura, S.; Mashino, T.

    2009-04-01

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C60-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C60-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC50 values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  15. Ultrasound influence on the solubility of solid dispersions prepared for a poorly soluble drug.

    PubMed

    Pereira, Simone Vieira; Colombo, Fábio Belotti; de Freitas, Luis Alexandre Pedro

    2016-03-01

    Solid dispersions have been successfully used to enhance the solubility of several poorly water soluble drugs. Solid dispersions are produced by melting hydrophilic carriers and mixing in the poorly water soluble drug. Supersaturation is obtained by quickly cooling the mixture until it solidifies, thereby entrapping the drug. The effects of using ultrasound to homogenize the molten carrier and drug mixture were studied. In particular, the increase in drug solubility for the resulting solid dispersions was analyzed. Piroxicam, which has very low water solubility, was used as a model drug. A full factorial design was used to analyze how sonication parameters affected the solubility and in vitro release of the drug. The results show that the use of ultrasound can significantly increase the solubility and dissolution rate of the piroxicam solid dispersion. Pure piroxicam presented a solubility of 13.3?g/mL. A maximum fourfold increase in solubility, reaching 53.8?g/mL, was observed for a solid dispersion sonicated at 19kHz for 10min and 475W. The in vitro dissolution rate test showed the sonicated solid dispersion reached a maximum rate of 18%/min, a sixfold increase over the piroxicam rate of 2.9%/min. Further solid state characterization by thermal, X-ray diffraction and Fourier transform infrared analyses also showed that the sonication process, in the described conditions, did not adversely alter the drug or significantly change its polymorphic form. Ultrasound is therefore an interesting technique to homogenize drug/carrier mixtures with the objective of increasing the solubility of drugs with poor water solubility. PMID:26548840

  16. Redefining solubility parameters: the partial solvation parameters.

    PubMed

    Panayiotou, Costas

    2012-03-21

    The present work reconsiders a classical and universally accepted concept of physical chemistry, the solubility parameter. Based on the insight derived from modern quantum chemical calculations, a new definition of solubility parameter is proposed, which overcomes some of the inherent restrictions of the original definition and expands its range of applications. The original single solubility parameter is replaced by four partial solvation parameters reflecting the dispersion, the polar, the acidic and the basic character of the chemical compounds as expressed either in their pure state or in mixtures. Simple rules are adopted for the definition and calculation of these four parameters and their values are tabulated for a variety of common substances. In contrast, however, to the well known Hansen solubility parameters, their design and evaluation does not rely exclusively on the basic rule of "similarity matching" for solubility but it makes also use of the other basic rule of compatibility, namely, the rule of "complementarity matching". This complementarity matching becomes particularly operational with the sound definition of the acidic and basic components of the solvation parameter based on the third ?-moments of the screening charge distributions of the quantum mechanics-based COSMO-RS theory. The new definitions are made in a simple and straightforward manner, thus, preserving the strength and appeal of solubility parameter stemming from its simplicity. The new predictive method has been applied to a variety of solubility data for systems of pharmaceuticals and polymers. The results from quantum mechanics calculations are critically compared with the results from Abraham's acid/base descriptors. PMID:22327537

  17. Identification of BMP and activin membrane-bound inhibitor (BAMBI), an inhibitor of transforming growth factor-beta signaling, as a target of the beta-catenin pathway in colorectal tumor cells.

    PubMed

    Sekiya, Takashi; Adachi, Shungo; Kohu, Kazuyoshi; Yamada, Tatsuya; Higuchi, Osamu; Furukawa, Yoichi; Nakamura, Yusuke; Nakamura, Tsutomu; Tashiro, Kousuke; Kuhara, Satoru; Ohwada, Susumu; Akiyama, Tetsu

    2004-02-20

    The Wnt signaling pathway is activated in most human colorectal tumors. Mutational inactivation in the tumor suppressor adenomatous polyposis coli (APC), as well as activation of beta-catenin, causes the accumulation of beta-catenin, which in turn associates with the T cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors and activates transcription of their target genes. Here we show that beta-catenin activates transcription of the BMP and activin membrane-bound inhibitor (BAMBI)/NMA gene. The expression level of BAMBI was found to be aberrantly elevated in most colorectal and hepatocellular carcinomas relative to the corresponding non-cancerous tissues. Expression of BAMBI in colorectal tumor cell lines was repressed by a dominant-negative mutant of TCF-4 or by an inhibitor of beta-catenin-TCF interaction, suggesting that beta-catenin is responsible for the aberrant expression of BAMBI in colorectal tumor cells. Furthermore, overexpression of BAMBI inhibited the response of tumor cells to transforming growth factor-beta signaling. These results suggest that beta-catenin interferes with transforming growth factor-beta-mediated growth arrest by inducing the expression of BAMBI, and this may contribute to colorectal and hepatocellular tumorigenesis. PMID:14660579

  18. Apparent Benzene Solubility in Tetraphenylborate Slurries

    SciTech Connect

    Swingle, R.F.; Peterson, R.A.; Crawford, C.L.

    1997-11-01

    Personnel conducted testing to determine the apparent solubility of benzene in potassium tetraphenylborate (KTPB) slurries. The lack of benzene vapor pressure suppression in these tests indicate that for a 6.5 wt percent solids KTPB slurry in 4.65 M Na+ salt solution at approximately 25 degrees Celsius, no significant difference exists between the solubility of benzene in the slurry and the solubility of benzene in salt solution without KTPB solids. The work showed similar results in slurry with 6,000 mg/L sludge and 2,000 mg/L monosodium titanate added. Slurries containing tetraphenylborate decomposition intermediates (i.e., 4,200 mg/L triphenylboron (3PB), 510 mg/L diphenylborinic acid (2PB) and 1,500 mg/L phenylboric acid (1PB) or 100 mg/L tri-n-butylphosphate (TBP)) also showed no significant difference in benzene solubility form filtrate containing no KTPB solids. Slurry containing 2,000 mg/L Surfynol 420 did exhibit significant additional benzene solubility, as did irradiated slurries. The vapor pressure depression in the irradiated slurries presumably results from dissolution of biphenyl and other tetraphenylborate irradiation products in the benzene.

  19. Influence of Polymer Molecular Weight on Drug-Polymer Solubility: A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer.

    PubMed

    Knopp, Matthias Manne; Olesen, Niels Erik; Holm, Per; Langguth, Peter; Holm, René; Rades, Thomas

    2015-09-01

    In this study, the influence of polymer molecular weight on drug-polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31-0.32 g/g) were found to be lower than those experimentally determined in PVP (0.38-0.40 g/g). Nevertheless, the similarity between the values indicates that the analogue solubility can provide valuable indications on the solubility in the polymer. Hence, if a drug is soluble in an analogue of the polymer, it is most likely also soluble in the polymer. In conclusion, the solubility of a given drug-polymer system is determined by the strength of the drug-polymer interactions rather than the molecular weight of the polymer. Therefore, during the first screenings for drug solubility in polymers, only one representative molecular weight per polymer is needed. PMID:25740567

  20. Improvement in solubility of poor water-soluble drugs by solid dispersion

    PubMed Central

    Sareen, Swati; Mathew, George; Joseph, Lincy

    2012-01-01

    This article is intended to combine recent literature on solid dispersion technology for solubility enhancement with special emphasis on mechanism responsible for the same by solid dispersion, various preparation methods, and evaluation parameters. Solubility behavior is the most challenging aspect for various new chemical entities as 60% of the new potential products possess solubility problems. This is the biggest reason for new drug molecules not reaching to the market or not reaches to full potential. There are various techniques to enhance the drug solubility such as particle size reduction, nanosuspension, use of surfactants, salt formation, solid dispersion, etc. From this article it may be concluded that solid dispersion is an important approach for improvement of bioavailability of poor water-soluble drugs. PMID:23071955

  1. Optimization of single-walled carbon nanotube solubility by noncovalent PEGylation using experimental design methods

    PubMed Central

    Hadidi, Naghmeh; Kobarfard, Farzad; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

    2011-01-01

    In this study, noncovalent functionalization of single-walled carbon nanotubes (SWCNTs) with phospholipid-polyethylene glycols (Pl-PEGs) was performed to improve the solubility of SWCNTs in aqueous solution. Two kinds of PEG derivatives, ie, Pl-PEG 2000 and Pl-PEG 5000, were used for the PEGylation process. An experimental design technique (D-optimal design and second-order polynomial equations) was applied to investigate the effect of variables on PEGylation and the solubility of SWCNTs. The type of PEG derivative was selected as a qualitative parameter, and the PEG/SWCNT weight ratio and sonication time were applied as quantitative variables for the experimental design. Optimization was performed for two responses, aqueous solubility and loading efficiency. The grafting of PEG to the carbon nanostructure was determined by thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy. Aqueous solubility and loading efficiency were determined by ultraviolet-visible spectrophotometry and measurement of free amine groups, respectively. Results showed that Pl-PEGs were grafted onto SWCNTs. Aqueous solubility of 0.84 mg/mL and loading efficiency of nearly 98% were achieved for the prepared Pl-PEG 5000-SWCNT conjugates. Evaluation of functionalized SWCNTs showed that our noncovalent functionalization protocol could considerably increase aqueous solubility, which is an essential criterion in the design of a carbon nanotube-based drug delivery system and its biodistribution. PMID:21556348

  2. Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS).

    PubMed

    Xu, Linfeng; Lee, Hun; Jetta, Deekshitha; Oh, Kwang W

    2015-10-21

    Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems. PMID:26329518

  3. [Soluble nitrogen and soluble phosphorus dynamics during foliar litter decomposition in winter in alinine forest streams].

    PubMed

    Zhang, Chuan; Yang, Wan-qin; Yue, Kai; Huang, Chun-ping; Peng, Yan; Wu, Fu-zhong

    2015-06-01

    In order to understand the dynamic pattern of soluble nitrogen and soluble phosphorus in the headwater streams during the process of litter decomposition in winter, a field experiment using litterbag method was conducted in an alpine forest in Western Sichuan, China. The foliar litter of two dominant canopy trees (Sabina saltuaria, and Larix mastersiana) and two shrubs (Salix paraplesia and Rhododendron lapponicum) were selected. The litterbags were placed in a headwater stream, river, riparian zone and closed canopy, and sampled in different freezing-thawing periods of winter (pre-freezing period, freezing period and thawing period). The results indicated that the soluble nitrogen content of foliar litter showed little changes over a whole winter decomposition regardless of species. In contrast, the soluble phosphorus content displayed the order as river < stream < riparian zone < closed canopy, and showed a decrease tendency in stream, river and riparian, although little changes under closed canopy over a whole winter decomposition. Correlation analysis suggested that the dynamics of soluble phosphorus content significantly correlated to the average temperature, positive accumulated temperature, negative accumulated temperature and flow velocity during the decomposition in winter. The dynamics of soluble nitrogen content only exhibited significant correlations with positive accumulated temperature. Additionally, litter quality (species) also controlled the dynamics of soluble nitrogen and soluble phosphorus content as litter decomposition proceeded. The results implied that soluble phosphorus could be more liable to loss in streams and rivers during litter decomposition compared with soluble nitrogen, which could further provide some new ideas in understanding nitrogen and phosphorus cycling in this alpine forest. PMID:26572009

  4. Gaseous Sulfate Solubility in Glass: Experimental Method

    SciTech Connect

    Bliss, Mary

    2013-11-30

    Sulfate solubility in glass is a key parameter in many commercial glasses and nuclear waste glasses. This report summarizes key publications specific to sulfate solubility experimental methods and the underlying physical chemistry calculations. The published methods and experimental data are used to verify the calculations in this report and are expanded to a range of current technical interest. The calculations and experimental methods described in this report will guide several experiments on sulfate solubility and saturation for the Hanford Waste Treatment Plant Enhanced Waste Glass Models effort. There are several tables of sulfate gas equilibrium values at high temperature to guide experimental gas mixing and to achieve desired SO3 levels. This report also describes the necessary equipment and best practices to perform sulfate saturation experiments for molten glasses. Results and findings will be published when experimental work is finished and this report is validated from the data obtained.

  5. Diffusion and solubility of oxygen in silver

    NASA Technical Reports Server (NTRS)

    Eichenauer, W.; Miller, G.

    1985-01-01

    The diffusion and solubility of oxygen in Ag in the temperature range between 412 and 862 C was determined. The following interpolation formula was found for the solubility: L = 8.19.1/100.exp(-11 860/RT)Mol O2/g.At.Ag.at 1/.5. The process obeys the Sieverts square root law within the limits of error. The dissolution of oxygen in Ag may be accompanied by the dissociation of the oxygen molecules into atoms. The tests on Ag-foils reveal that below a temperature of about 500 C a higher solubility is simulated by the adsorption of oxygen. The diffusion coefficient of oxygen in silver obeys the following equation: D = 2.72.1/100.exp(-11 000/RT)sq cm/s. The relatively low activation energy of 11 kcal/g.At suggests that the diffusion of oxygen takes places over interstitial sites.

  6. Redispersity/Solubility of nanopowder in solvents.

    PubMed

    Zhao, Yunan; Wang, Minmin; Liu, Yan; Cui, Hongtao

    2014-01-01

    Because of the high surface energy, nanoparticles show strong tendency to agglomeration or aggregation during preparations and applications, which thus greatly deteriorate their performance. Investigations have proven that redispersible nanoparticles can exhibit enhanced performances or be used in new technical applications as compared with the non-redispersible nanoparticles. The redispersity or solubility of particles is defined as their ability for re-forming colloid-like suspension after they are redispersed in solvent. The redispersity/solubility of particles can be obtained by establishing compatibility between particles and solvent through various techniques. In this review, we will give summary descriptions about related methods and their mechanism for the fabrication of redispersible or soluble particles. Also, outlook for the development and applications in this area will be given. PMID:24635206

  7. AN-107 entrained solids - Solubility versus temperature

    SciTech Connect

    GJ Lumetta; RC Lettau

    2000-03-31

    This report describes the results of a test conducted by Battelle to assess the solubility of the solids entrained in the diluted AN-107 low-activity waste (LAW) sample. BNFL requested Battelle to dilute the AN-107 sample using sodium hydroxide and de-ionized water to mimic expected plant operating conditions. BNFL further requested Battelle to assess the solubility of the solids present in the diluted AN-107 sample versus temperature conditions of 30, 40, and 50 C. BNFL requested these tests to assess the composition of the LAW supernatant and solids versus expected plant-operating conditions.

  8. Connecting the solubility and CCN activation of complex organic aerosols: a theoretical study using solubility distributions

    NASA Astrophysics Data System (ADS)

    Riipinen, I.; Rastak, N.; Pandis, S. N.

    2015-06-01

    We present a theoretical study investigating the cloud activation of multicomponent organic particles. We modeled these complex mixtures using solubility distributions (analogous to volatility distributions in the VBS, i.e., volatility basis set, approach), describing the mixture as a set of surrogate compounds with varying water solubilities in a given range. We conducted Köhler theory calculations for 144 different mixtures with varying solubility range, number of components, assumption about the organic mixture thermodynamics and the shape of the solubility distribution, yielding approximately 6000 unique cloud condensation nucleus (CCN)-activation points. The results from these comprehensive calculations were compared to three simplifying assumptions about organic aerosol solubility: (1) complete dissolution at the point of activation; (2) combining the aerosol solubility with the molar mass and density into a single effective hygroscopicity parameter ?; and (3) assuming a fixed water-soluble fraction ϵeff. The complete dissolution was able to reproduce the activation points with a reasonable accuracy only when the majority (70-80%) of the material was dissolved at the point of activation. The single-parameter representations of complex mixture solubility were confirmed to be powerful semi-empirical tools for representing the CCN activation of organic aerosol, predicting the activation diameter within 10% in most of the studied supersaturations. Depending mostly on the condensed-phase interactions between the organic molecules, material with solubilities larger than about 0.1-100 g L-1 could be treated as soluble in the CCN activation process over atmospherically relevant particle dry diameters and supersaturations. Our results indicate that understanding the details of the solubility distribution in the range of 0.1-100 g L-1 is thus critical for capturing the CCN activation, while resolution outside this solubility range will probably not add much information except in some special cases. The connections of these results to the previous observations of the CCN activation and the molecular properties of complex organic mixture aerosols are discussed. The presented results help unravel the mechanistic reasons behind observations of hygroscopic growth and CCN activation of atmospheric secondary organic aerosol (SOA) particles. The proposed solubility distribution framework is a promising tool for modeling the interlinkages between atmospheric aging, volatility and water uptake of atmospheric organic aerosol.

  9. Novel Mitochondria-Targeted Heat-Soluble Proteins Identified in the Anhydrobiotic Tardigrade Improve Osmotic Tolerance of Human Cells

    PubMed Central

    Tanaka, Sae; Tanaka, Junko; Miwa, Yoshihiro; Horikawa, Daiki D.; Katayama, Toshiaki; Arakawa, Kazuharu; Toyoda, Atsushi; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Tardigrades are able to tolerate almost complete dehydration through transition to a metabolically inactive state, called “anhydrobiosis”. Late Embryogenesis Abundant (LEA) proteins are heat-soluble proteins involved in the desiccation tolerance of many anhydrobiotic organisms. Tardigrades, Ramazzottius varieornatus, however, express predominantly tardigrade-unique heat-soluble proteins: CAHS (Cytoplasmic Abundant Heat Soluble) and SAHS (Secretory Abundant Heat Soluble) proteins, which are secreted or localized in most intracellular compartments, except the mitochondria. Although mitochondrial integrity is crucial to ensure cellular survival, protective molecules for mitochondria have remained elusive. Here, we identified two novel mitochondrial heat-soluble proteins, RvLEAM and MAHS (Mitochondrial Abundant Heat Soluble), as potent mitochondrial protectants from Ramazzottius varieornatus. RvLEAM is a group3 LEA protein and immunohistochemistry confirmed its mitochondrial localization in tardigrade cells. MAHS-green fluorescent protein fusion protein localized in human mitochondria and was heat-soluble in vitro, though no sequence similarity with other known proteins was found, and one region was conserved among tardigrades. Furthermore, we demonstrated that RvLEAM protein as well as MAHS protein improved the hyperosmotic tolerance of human cells. The findings of the present study revealed that tardigrade mitochondria contain at least two types of heat-soluble proteins that might have protective roles in water-deficient environments. PMID:25675104

  10. Novel mitochondria-targeted heat-soluble proteins identified in the anhydrobiotic Tardigrade improve osmotic tolerance of human cells.

    PubMed

    Tanaka, Sae; Tanaka, Junko; Miwa, Yoshihiro; Horikawa, Daiki D; Katayama, Toshiaki; Arakawa, Kazuharu; Toyoda, Atsushi; Kubo, Takeo; Kunieda, Takekazu

    2015-01-01

    Tardigrades are able to tolerate almost complete dehydration through transition to a metabolically inactive state, called "anhydrobiosis". Late Embryogenesis Abundant (LEA) proteins are heat-soluble proteins involved in the desiccation tolerance of many anhydrobiotic organisms. Tardigrades, Ramazzottius varieornatus, however, express predominantly tardigrade-unique heat-soluble proteins: CAHS (Cytoplasmic Abundant Heat Soluble) and SAHS (Secretory Abundant Heat Soluble) proteins, which are secreted or localized in most intracellular compartments, except the mitochondria. Although mitochondrial integrity is crucial to ensure cellular survival, protective molecules for mitochondria have remained elusive. Here, we identified two novel mitochondrial heat-soluble proteins, RvLEAM and MAHS (Mitochondrial Abundant Heat Soluble), as potent mitochondrial protectants from Ramazzottius varieornatus. RvLEAM is a group3 LEA protein and immunohistochemistry confirmed its mitochondrial localization in tardigrade cells. MAHS-green fluorescent protein fusion protein localized in human mitochondria and was heat-soluble in vitro, though no sequence similarity with other known proteins was found, and one region was conserved among tardigrades. Furthermore, we demonstrated that RvLEAM protein as well as MAHS protein improved the hyperosmotic tolerance of human cells. The findings of the present study revealed that tardigrade mitochondria contain at least two types of heat-soluble proteins that might have protective roles in water-deficient environments. PMID:25675104

  11. Solubilities of significant compounds in HLW tank supernate solutions - FY 1996 progress report

    SciTech Connect

    Barney, G.S.

    1996-09-30

    The solubilities of two sodium salts of organic acids that are thought to exist in high-level waste at the Hanford Site were measured in tank supernate simulant solutions during FY1996 This solubility information will be used to determine if these organic salts could exist in solid phases (saltcake or sludges) in the waste where they might react violently with the nitrate or nitrite salts present in the tanks. Solubilities of sodium butyrate and trisodium N-(2-hydroxyethyl)ethylenediaminetriacetate were measured in simulated waste supernate solutions at 25 {degrees}C, 30 {degrees}C, 40 {degrees}C, and 50 {degrees}C. The organic compounds were selected because they are expected to exist in relatively high concentrations in the tanks. Two types of tank supernate simulants were used - a 4.O M sodium nitrate - 0.97 M sodium nitrite solution with sodium hydroxide concentrations ranging from O.00003 M to 2.O M and a 2.O M sodium nitrite solution saturated with crystalline sodium nitrate with sodium hydroxide concentrations ranging from 0.1 M to 2. 0 M. The solubilities of sodium butyrate and trisodium N-(2-hydroxyethyl)ethylene- diaminetriacetate in both types of HLW tank supernate solutions were high over the temperature and sodium hydroxide concentration ranges expected in the tanks. The solubilities of these compounds are similar (in terms of total organic carbon) to sodium glycolate, succinate, caproate, dibutylphosphate, citrate, formate, ethylenediaminetetraacetate, and nitrilotriacetate which were measured previously. High solubilities will prevent solid sodium salts of these organic acids from precipitating from tank supernate solutions. The total organic carbon concentrations (TOC) of actual tank supernates are generaly much lower than the TOC ranges for the simulated supernate solutions saturated (at the solubility limit) with the organic salts. This is true even if all the dissolved carbon in a given tank supernate is due to only one of these eight soluble compounds (an unlikely situation). Solubilities of all the organic salts decrease with increasing sodium hydoxide and sodium nitrate concentration because of the common ion effect of Na{sup +}. Increasing temperatures has little effect on the solubilities of sodium butyrate and trisodium N-(2-hydroxyethyl)ethylenediaminetriacetate.

  12. Prevention of obesity relatred metabolic diseases by processed foods containing soluble dietary fibers and flavonoids (abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Asians and other non-caucasians are generally more susceptible to obesity related chronic diseases such as type 2 diabetes and cardiovascular disease. Viscous soluble dietary fibers such as cereal beta-glucans and psyllium reduce plasma cholesterol and postprandial glycemia in humans. We have stud...

  13. Antibodies to Conformational Epitopes of Soluble Liver Antigen Define a Severe Form of Autoimmune

    E-print Network

    and clinical relevance of antibodies to soluble liver antigen (tRNP(Ser)Sec/SLA) in autoimmune hepatitis (AIH implication of this autoantibody in autoimmune liver disease. By using eukaryotically expressed tRNP(Ser)Sec/SLA as target in a radioligand assay (RLA), 81 patients with autoimmune liver disease (AILD) (33 type 1 AIH, 31

  14. Water-soluble carbon nanotube compositions for drug delivery and medicinal applications

    DOEpatents

    Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dmitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jr., Jodie L.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Mason, Kathy A.; Milas, Luka

    2014-07-22

    Compositions comprising a plurality of functionalized carbon nanotubes and at least one type of payload molecule are provided herein. The compositions are soluble in water and PBS in some embodiments. In certain embodiments, the payload molecules are insoluble in water. Methods are described for making the compositions and administering the compositions. An extended release formulation for paclitaxel utilizing functionalized carbon nanotubes is also described.

  15. Water-soluble constituents of amomum seed.

    PubMed

    Kitajima, Junichi; Ishikawa, Toru

    2003-07-01

    From the water-soluble portion of the methanolic extract of the amomum seed (seed of Amomum xanthioides WALL.), which has been used as a medicine for stomachic and digestive disorders, ten compounds, including two new and three newly isolated monoterpenoid glucosides and a newly isolated octane-tetrol, were isolated. Their structures were determined by spectral investigation. PMID:12843607

  16. Water-soluble polymers and compositions thereof

    DOEpatents

    Smith, Barbara F. (Los Alamos, NM); Robison, Thomas W. (Los Alamos, NM); Gohdes, Joel W. (Los Alamos, NM)

    2002-01-01

    Water-soluble polymers including functionalization from the group of amino groups, carboxylic acid groups, phosphonic acid groups, phosphonic ester groups, acylpyrazolone groups, hydroxamic acid groups, aza crown ether groups, oxy crown ethers groups, guanidinium groups, amide groups, ester groups, aminodicarboxylic groups, permethylated polvinylpyridine groups, permethylated amine groups, mercaptosuccinic acid groups, alkyl thiol groups, and N-alkylthiourea groups are disclosed.

  17. Water-soluble polymers and compositions thereof

    DOEpatents

    Smith, Barbara F. (Los Alamos, NM); Robison, Thomas W. (Los Alamos, NM); Gohdes, Joel W. (Los Alamos, NM)

    1999-01-01

    Water-soluble polymers including functionalization from the group of amino groups, carboxylic acid groups, phosphonic acid groups, phosphonic ester groups, acylpyrazolone groups, hydroxamic acid groups, aza crown ether groups, oxy crown ethers groups, guanidinium groups, amide groups, ester groups, aminodicarboxylic groups, permethylated polyvinylpyridine groups, permethylated amine groups, mercaptosuccinic acid groups, alkyl thiol groups, and N-alkylthiourea groups are disclosed.

  18. A new expanded solubility parameter approach.

    PubMed

    Stefanis, Emmanuel; Panayiotou, Costas

    2012-04-15

    The partial or Hansen solubility parameters (HSP) are important properties of the various substances and very useful tools for the selection of their solvents or the prediction of their behaviour in numerous applications. Their design and evaluation relies on the basic rule of "similarity matching" for solubility. The present work attempts to enhance the capacity of HSPs by incorporating into their evaluation the other basic rule of solubility, namely, the rule of "complementarity matching". This is done in a simple and straightforward manner by splitting the hydrogen bonding HSP into its acidic or proton donor component and its basic or proton acceptor one. The splitting is based on the third ?-moments of the screening charge distributions or sigma profiles of the quantum-mechanics based COSMO-RS theory. The whole development and application does not involve any sophisticated calculations or any strong specific background. The new method has been applied to a variety of solubility data for systems of pharmaceutical interest in order to verify the significant improvement over the classical HSP approach. The application of the new method requires, of course, the knowledge of the HSPs. For this reason, in Appendix A is presented an updated version of a robust and reliable group-contribution method for the calculation of the HSPs. The key features of this combined tool are critically discussed. PMID:22260970

  19. Soluble Mn(III) in Suboxic Zones

    NASA Astrophysics Data System (ADS)

    Trouwborst, Robert E.; Clement, Brian G.; Tebo, Bradley M.; Glazer, Brian T.; Luther, George W.

    2006-09-01

    Soluble manganese(III) [Mn(III)] has been thought to disproportionate to soluble Mn(II) and particulate MnIVO2 in natural waters, although it persists as complexes in laboratory solutions. We report that, in the Black Sea, soluble Mn(III) concentrations were as high as 5 micromolar and constituted up to 100% of the total dissolved Mn pool. Depth profiles indicated that soluble Mn(III) was produced at the top of the suboxic zone by Mn(II) oxidation and at the bottom of the suboxic zone by MnIVO2 reduction, then stabilized in each case by unknown natural ligands. We also found micromolar concentrations of dissolved Mn(III) in the Chesapeake Bay. Dissolved Mn(III) can maintain the existence of suboxic zones because it can act as either an electron acceptor or donor. Our data indicate that Mn(III) should be ubiquitous at all water column and sediment oxic/anoxic interfaces in the environment.

  20. Water-soluble polymers and compositions thereof

    DOEpatents

    Smith, B.F.; Robison, T.W.; Gohdes, J.W.

    1999-04-06

    Water-soluble polymers including functionalization from the group of amino groups, carboxylic acid groups, phosphonic acid groups, phosphonic ester groups, acylpyrazolone groups, hydroxamic acid groups, aza crown ether groups, oxy crown ethers groups, guanidinium groups, amide groups, ester groups, aminodicarboxylic groups, permethylated polyvinylpyridine groups, permethylated amine groups, mercaptosuccinic acid groups, alkyl thiol groups, and N-alkylthiourea groups are disclosed.

  1. Anhydrite solubility in differentiated arc magmas

    NASA Astrophysics Data System (ADS)

    Masotta, M.; Keppler, H.

    2015-06-01

    The solubility of anhydrite in differentiated arc magmas was experimentally studied at 200 MPa and 800-1000 °C over a range of oxygen fugacities, from 0.5 log units above the Ni-NiO buffer to the hematite-magnetite buffer. Anhydrite is stable only at oxidizing conditions (fO2 ? Re-ReO2), whereas sulfides only form under reducing conditions. The solubility of anhydrite in the melt ultimately regulates the amount of sulfur available to partition between melt and fluid phase during the eruption. At oxidizing conditions, the solubility product of anhydrite increases with temperature, nbo/t and melt water content. We provide a new calibration of the anhydrite solubility product (KSP = XCaO * XSO3), which reproduces all available experimental data with greatly improved accuracy: In this equation, the molar fractions XCaO and XSO3 in the melt as well as the number of non-bridging oxygen atoms per tetrahedron (nbo/t) are calculated on an anhydrous basis (H2O refers to the melt water content, T is temperature in Kelvin). We apply our model to estimate the sulfur yield of some recent volcanic eruptions and we show that the sulfur yield of the 1991 Mt. Pinatubo dacite eruption was unusually large, because only a small fraction of the sulfur was locked up in anhydrite. In general, high sulfur yields are expected when anhydrite solubility in the melt is high, i.e. for somewhat depolymerized melts. For rhyolitic systems, most of the available sulfur will be locked up in anhydrite, so that even very large eruptions may only have a small effect on global surface temperatures. Our model therefore allows improved predictions of the environmental impact of explosive volcanic eruptions.

  2. Solubility Diagram of a Fullerenol-d-NaCl-H2O System at 25°C

    NASA Astrophysics Data System (ADS)

    Semenov, K. N.; Charykov, N. A.

    2012-10-01

    Solubility in a ternary fullerenol-d-NaCl-H2O system is studied at 25°C with the use of isothermal saturation. It is established that the solubility diagram is composed of two branches that are responsible for the crystallization of fullerenol-d crystallohydrate and anhydrous sodium chloride, and it contains one invariant eutonic-type point that corresponds to cosaturation by the above two solid phases. The so-called salting-out effect was observed on the branch of the crystallization of fullerenol-d, while salting in was observed on the branch of the crystallization of sodium chloride.

  3. Solubility Enhancement of a Poorly Water Soluble Drug by Forming Solid Dispersions using Mechanochemical Activation

    PubMed Central

    Rojas-Oviedo, I.; Retchkiman-Corona, B.; Quirino-Barreda, C. T.; Cárdenas, J.; Schabes-Retchkiman, P. S.

    2012-01-01

    Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drug-carrier mixtures and the formation of noncovalent interactions (hydrogen bonds) between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to improve its solubility and dissolution rate. Samples of indomethacin and a physical mixture with a weight ratio of 1:1 of indomethacin and lactose were ground using a high speed vibrating ball mill. Particle size was determined by electron microscopy, the reduction of crystallinity was determined by calorimetry and transmission electron microscopy, infrared spectroscopy was used to find evidence of any interactions between the drug and the carrier and the determination of apparent solubility allowed for the corroboration of changes in solubility. Before grinding, scanning electron microscopy showed the drug and lactose to have an average particle size of around 50 and 30 ?m, respectively. After high speed grinding, indomethacin and the mixture had a reduced average particle size of around 5 and 2 ?m, respectively, showing a morphological change. The ground mixture produced a solid dispersion that had a loss of crystallinity that reached 81% after 30 min of grinding while the drug solubility of indomethacin within the solid dispersion increased by 2.76 fold as compared to the pure drug. Drug activation due to hydrogen bonds between the carboxylic group of the drug and the hydroxyl group of lactose as well as the decrease in crystallinity of the solid dispersion and the reduction of the particle size led to a better water solubility of indomethacin. PMID:23798775

  4. Solubility Enhancement of a Poorly Water Soluble Drug by Forming Solid Dispersions using Mechanochemical Activation.

    PubMed

    Rojas-Oviedo, I; Retchkiman-Corona, B; Quirino-Barreda, C T; Cárdenas, J; Schabes-Retchkiman, P S

    2012-11-01

    Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drug-carrier mixtures and the formation of noncovalent interactions (hydrogen bonds) between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to improve its solubility and dissolution rate. Samples of indomethacin and a physical mixture with a weight ratio of 1:1 of indomethacin and lactose were ground using a high speed vibrating ball mill. Particle size was determined by electron microscopy, the reduction of crystallinity was determined by calorimetry and transmission electron microscopy, infrared spectroscopy was used to find evidence of any interactions between the drug and the carrier and the determination of apparent solubility allowed for the corroboration of changes in solubility. Before grinding, scanning electron microscopy showed the drug and lactose to have an average particle size of around 50 and 30 ?m, respectively. After high speed grinding, indomethacin and the mixture had a reduced average particle size of around 5 and 2 ?m, respectively, showing a morphological change. The ground mixture produced a solid dispersion that had a loss of crystallinity that reached 81% after 30 min of grinding while the drug solubility of indomethacin within the solid dispersion increased by 2.76 fold as compared to the pure drug. Drug activation due to hydrogen bonds between the carboxylic group of the drug and the hydroxyl group of lactose as well as the decrease in crystallinity of the solid dispersion and the reduction of the particle size led to a better water solubility of indomethacin. PMID:23798775

  5. The P23T Cataract Mutation Causes Loss of Solubility of Folded gD-Crystallin

    E-print Network

    Wallace, Bonnie Ann

    The P23T Cataract Mutation Causes Loss of Solubility of Folded gD-Crystallin P. Evans1 , K. Wyatt2 linked to several types of congenital cataracts. In particular, the Pro23 to Thr (P23T) mutation of human cataracts. We have expressed and purified wild-type human gD, P23T, and the Pro23 to Ser23 (P23S) mutant

  6. Water-soluble block polycations as carriers for oligonucleotide delivery.

    PubMed

    Kabanov, A V; Vinogradov, S V; Suzdaltseva, Y G; Alakhov VYu

    1995-01-01

    Water-soluble, block copolymeric carriers consisting of polyoxyethylene (PEO) and polyspermine (PS) chains have been developed for the delivery of antisense oligonucleotides (oligo) into the target cells. These copolymers spontaneously form complexes with oligos in aqueous solutions. The PS block electrostatically binds to the oligo, and as a result, the stability of the oligo is increased. Similarly, the polar PEO block provides for the aqueous solubility of the complex. This paper (i) reports the synthesis of the diblock PEO-PS copolymer and (ii) evaluates the effects of the complexes formed between this copolymer and phosphodiester oligo, complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5, on the reproduction of this virus in Vero cells. Infectious titer data 22 and 39 h post infection indicates that the copolymer-oligo complex inhibits the reproduction of the virus beyond the detection limit. Conversely, the free oligo inhibits the reproduction of the virus only 22 h postinfection, while 39 h postinfection significant virus titers are observed. The results of this study suggest that the copolymer complex increases the sequence-specific inhibition effect of oligo on the virus reproduction. PMID:8608176

  7. Hansen solubility parameter as a tool to predict cocrystal formation.

    PubMed

    Mohammad, Mohammad Amin; Alhalaweh, Amjad; Velaga, Sitaram P

    2011-04-01

    The objective of this study was to investigate whether the miscibility of a drug and coformer, as predicted by Hansen solubility parameters (HSPs), can indicate cocrystal formation and guide cocrystal screening. It was also our aim to evaluate various HSPs-based approaches in miscibility prediction. HSPs for indomethacin (the model drug) and over thirty coformers were calculated according to the group contribution method. Differences in the HSPs between indomethacin and each coformer were then calculated using three established approaches, and the miscibility was predicted. Subsequently, differential scanning calorimetry was used to investigate the experimental miscibility and cocrystal formation. The formation of cocrystals was also verified using liquid-assisted grinding. All except one of the drug-coformers that were predicted to be miscible were confirmed experimentally as miscible. All tested theoretical approaches were in agreement in predicting miscibility. All systems that formed cocrystals were miscible. Remarkably, two new cocrystals of indomethacin were discovered in this study. Though it may be necessary to test this approach in a wide range of different coformer and drug compound types for accurate generalizations, the trends with tested systems were clear and suggest that the drug and coformer should be miscible for cocrystal formation. Thus, predicting the miscibility of cocrystal components using solubility parameters can guide the selection of potential coformers prior to exhaustive cocrystal screening work. PMID:21256944

  8. Isothermal absorption of soluble gases by atmospheric nanoaerosols

    NASA Astrophysics Data System (ADS)

    Elperin, T.; Fominykh, A.; Krasovitov, B.; Lushnikov, A.

    2013-01-01

    We investigate mass transfer during the isothermal absorption of atmospheric trace soluble gases by a single droplet whose size is comparable to the molecular mean free path in air at normal conditions. It is assumed that the trace reactant diffuses to the droplet surface and then reacts with the substances inside the droplet according to the first-order rate law. Our analysis applies a flux-matching theory of transport processes in gases and assumes constant thermophysical properties of the gases and liquids. We derive an integral equation of Volterra type for the transient molecular flux density to a liquid droplet and solve it numerically. Numerical calculations are performed for absorption of sulfur dioxide (SO2), dinitrogen trioxide (N2O3), and chlorine (Cl2) by liquid nanoaerosols accompanied by chemical dissociation reaction. It is shown that during gas absorption by nanoaerosols, the kinetic effects play a significant role, and neglecting kinetic effects leads to a significant overestimation of the soluble gas flux into a droplet during the entire period of gas absorption.

  9. Polydithiényléthylènes solubles dérivés de précurseurs à structure pontée

    NASA Astrophysics Data System (ADS)

    Verlhac, P.; Blanchard, P.; Brisset, H.; Roncali, J.

    1998-06-01

    New small bandgap soluble conjugated polymers have been synthesized chemically or electrochemically from rigidified dithienylethylenes. De nouveaux polymères conjugués solubles à faible bande interdite ont été synthétisés par voie chimique ou électrochimique à partir de dithiényléthylènes rigidifiés.

  10. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food...88d Amoxicillin trihydrate soluble powder. (a) Specifications. Each gram... Administer by drench or by mixing in milk. Treatment should be...

  11. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food...88d Amoxicillin trihydrate soluble powder. (a) Specifications. Each gram... Administer by drench or by mixing in milk. Treatment should be...

  12. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food...88d Amoxicillin trihydrate soluble powder. (a) Specifications. Each gram... Administer by drench or by mixing in milk. Treatment should be...

  13. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food...88d Amoxicillin trihydrate soluble powder. (a) Specifications. Each gram... Administer by drench or by mixing in milk. Treatment should be...

  14. IUPAC-NIST Solubility Data Series. 95. Alkaline Earth Carbonates in Aqueous Systems. Part 2. Ca

    SciTech Connect

    De Visscher, Alex; Vanderdeelen, Jan

    2012-06-15

    The alkaline earth carbonates are an important class of minerals. This article is part of a volume in the IUPAC-NIST Solubility Data Series that compiles and critically evaluates solubility data of the alkaline earth carbonates in water and in simple aqueous electrolyte solutions. Part 1 outlined the procedure adopted in this volume, and presented the beryllium and magnesium carbonates. Part 2, the current paper, compiles and critically evaluates the solubility data of calcium carbonate. The chemical forms included are the anhydrous CaCO{sub 3} types calcite, aragonite, and vaterite, the monohydrate monohydrocalcite (CaCO{sub 3}{center_dot} H{sub 2}O), the hexahydrate ikaite (CaCO{sub 3}{center_dot}6H{sub 2}O), and an amorphous form. The data were analyzed with two model variants, and thermodynamic data of each form consistent with each of the models and with the CODATA key values for thermodynamics are presented.

  15. Effects of soluble dietary fiber on low-density lipoprotein cholesterol and coronary heart disease risk.

    PubMed

    Bazzano, Lydia A

    2008-12-01

    Strong epidemiologic and experimental data suggest that increasing dietary fiber may help to lower low-density lipoprotein cholesterol (LDL-C) and decrease the risk of coronary heart disease. Recent studies have highlighted the role of dietary fiber, particularly water-soluble varieties, in decreasing the risk of cardiovascular disease. Several types of soluble fiber, including psyllium, beta-glucan, pectin, and guar gum, have been shown to decrease LDL-C in well-controlled intervention studies, whereas the soluble fiber content of legumes and vegetables has also been shown to decrease LDL-C. Current investigations continue to explore this area in depth and examine potential synergies between dietary fiber and other phytochemicals that may lower cholesterol. These studies, along with recent analyses of ongoing prospective cohort studies, have provided new insights into the probable protective role of dietary fiber in the development of coronary heart disease and other cardiovascular diseases. PMID:18937894

  16. Solubility Behavior and Phase Stability of Transition Metal Oxides in Alkaline Hydrothermal Environments

    SciTech Connect

    S.E. Ziemniak

    2000-05-18

    The solubility behavior of transition metal oxides in high temperature water is interpreted by recognizing three types of chemical reaction equilibria: metal oxide hydration/dehydration, metal oxide dissolution and metal ion hydroxocomplex formation. The equilibria are quantified using thermodynamic concepts and the thermochemical properties of the metal oxides/ions representative of the most common constituents of construction metal alloys, i.e., element shaving atomic numbers between Z = 22 (Ti) and Z = 30 (Zn), are summarized on the basis of metal oxide solubility studies conducted in the laboratory. Particular attention is devoted to the uncharged metal ion hydrocomplex, M{sup Z}(OH){sub Z}(aq), since its thermochemical properties define minimum solubilities of the metal oxide at a given temperature. Experimentally-extracted values of standard partial molal entropy (S{sup 0}) for the transition metal ion neutral hydroxocomplex are shown to be influenced by ligand field stabilization energies and complex symmetry.

  17. Pretreatment with soluble ST2 reduces warm hepatic ischemia/reperfusion injury

    SciTech Connect

    Yin Hui; Huang Baojun; Yang Heng; Huang Yafei; Xiong Ping; Zheng Fang; Chen Xiaoping; Chen Yifa . E-mail: yfchen@tjh.tjmu.edu.cn; Gong Feili . E-mail: flgong@163.com

    2006-12-29

    The interleukin-1 receptor-like protein ST2 exists in both membrane-bound (ST2L) and soluble form (sST2). ST2L has been found to play an important regulatory role in Th2-type immune response, but the function of soluble form of ST2 remains to be elucidated. In this study, we report the protective effect of soluble ST2 on warm hepatic ischemia/reperfusion injury. We constructed a eukaryotic expression plasmid, psST2-Fc, which expresses functional murine soluble ST2-human IgG1 Fc (sST2-Fc) fusion protein. The liver damage after ischemia/reperfusion was significantly attenuated by the expression of this plasmid in vivo. sST2-Fc remarkably inhibited the activation of Kupffer cells and the production of proinflammatory mediators TNF-{alpha} and IL-6. Furthermore, the levels of TLR4 mRNA and the nuclear translocation of NF-{kappa}B were also suppressed by pretreatment with sST2-Fc. These results thus identified soluble ST2 as a negative regulator in hepatic I/R injury, possibly via ST2-TLR4 pathway.

  18. Preparation of Soluble Proteins from Escherichia coli

    PubMed Central

    Wingfield, Paul T.

    2014-01-01

    Purification of human IL-1? is used in this unit as an example of the preparation of soluble proteins from E. coli. Bacteria containing IL-1? are lysed, and IL-1 ? in the resulting supernatant is purified by anion-exchange chromatography, salt precipitation and cation-exchange chromatography, and then concentrated. Finally, the IL-1 ? protein is applied to a gel-filtration column to separate it from remaining higher- and lower-molecular-weight contaminants, the purified protein is stored frozen or is lyophilized. The purification protocol described is typical for a protein that is expressed in fairly high abundance (i.e., >5% total protein) and accumulates in a soluble state. Also, the purification procedure serves as an example of how use classical protein purifications methods which may also be used in conjunction with the affinity-based methods now more commonly used. PMID:25367009

  19. Oil soluble antioxidant polymetharylates for lubricants

    SciTech Connect

    Shirodkar, S.M.; Benfaremo, N.; Skarlos, L.

    1994-08-01

    The evaluation of oil soluble, antioxidant bound polymethacrylates used as viscosity index improver lubricant additives, is described herein. They were synthesized by copolymerization of the antioxidant-dispersant monomer and alkyl methacrylates. Oxidative stability was determined by oxidative pressure differential scanning calorimetry, thin film oxidation uptake test and aluminum beaker oxidation text. These tests show that lubricants containing these polymers show performance advantages over commercial polymethacrylates, with additional benefits in other viscometric properties such as shear stability and Brookfield viscosity. The antioxidant monomer also serves as a dispersant moiety, thus improving the polymer disperancy. Binding the antioxidant to the polymer ensures the solubility of the antioxidant while eliminating the possibility of its volatilization in high temperature environments. The current results suggest that antioxidant-dispersant polymethacrylates have excellent potential as additives in lubricants such as automatic transmission fluids. 13 refs., 5 figs., 3 tabs.

  20. Nanoparticle Solubility in Liquid Crystalline Defects

    NASA Astrophysics Data System (ADS)

    Whitmer, Jonathan K.; Armas-Perez, Julio C.; Joshi, Abhijeet A.; Roberts, Tyler F.; de Pablo, Juan J.

    2013-03-01

    Liquid crystalline materials often incorporate regions (defects) where the orientational ordering present in the bulk phase is disrupted. These include point hedgehogs, line disclinations, and domain boundaries. Recently, it has been shown that defects will accumulate impurities such as small molecules, monomer subunits or nanoparticles. Such an effect is thought to be due to the alleviation of elastic stresses within the bulk phase, or to a solubility gap between a nematic phase and the isotropic defect core. This presents opportunities for encapsulation and sequestration of molecular species, in addition to the formation of novel structures within a nematic phase through polymerization and nanoparticle self-assembly. Here, we examine the solubility of nanoparticles within a coarse-grained liquid crystalline phase and demonstrate the effects of nanoparticle size and surface interactions in determining sequestration into defect regions.

  1. Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium.

    PubMed

    Li, Dong Xun; Jang, Ki-Young; Kang, Wonku; Bae, Kyoungjin; Lee, Mann Hyung; Oh, Yu-Kyoung; Jee, Jun-Pil; Park, Young-Joon; Oh, Dong Hoon; Seo, Youn Gee; Kim, Young Ran; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2010-01-01

    To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The sibutramine base-loaded solid dispersion gave two type forms. Like conventional solid dispersion system, one type appeared as a spherical shape with smooth surface, as the carriers and drug with relatively low melting point were soluble in water and formed it. The other appeared as an irregular form with relatively rough surface. Unlike conventional solid dispersion system, this type changed no crystalline form of drug. Our results suggested that this type was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting from changing the hydrophobic drug to hydrophilic form. The sibutramine-loaded solid dispersion at the weight ratio of sibutramine base/HPMC/poloxamer/citric acid of 5/3/3/0.2 gave the maximum drug solubility of about 3 mg/ml. Furthermore, it showed the similar plasma concentration, area under the curve (AUC) and C(max) of parent drug, metabolite I and II to the commercial product, indicating that it might give the similar drug efficacy compared to the sibutramine hydrochloride monohydrate-loaded commercial product in rats. Thus, this solid dispersion system would be useful to deliver poorly water-soluble sibutramine base with enhanced bioavailability. PMID:20118553

  2. SOLUBLE POLYMER-SUPPORTED CATALYSTS AND INITIATORS A Dissertation Presented

    E-print Network

    Venkataraman, Dhandapani "DV"

    SOLUBLE POLYMER-SUPPORTED CATALYSTS AND INITIATORS A Dissertation Presented by UCHE K. ANYANWU. Anyanwu 2005 All Rights Reserved #12;SOLUBLE POLYMER-SUPPORTED CATALYSTS AND INITIATORS A Dissertation it without you guys. Yes Oooh! #12;vi ABSTRACT SOLUBLE POLYMER-SUPPORTED CATALYSTS AND INITIATORS MAY 2005

  3. The Hildebrand Solubility Parameters of Ionic Liquids—Part 2

    PubMed Central

    Marciniak, Andrzej

    2011-01-01

    The Hildebrand solubility parameters have been calculated for eight ionic liquids. Retention data from the inverse gas chromatography measurements of the activity coefficients at infinite dilution were used for the calculation. From the solubility parameters, the enthalpies of vaporization of ionic liquids were estimated. Results are compared with solubility parameters estimated by different methods. PMID:21747694

  4. ACCELERATED COMMUNICATION Alterations in Detergent Solubility of Heterotrimeric G Proteins

    E-print Network

    Vogel, Zvi

    ACCELERATED COMMUNICATION Alterations in Detergent Solubility of Heterotrimeric G Proteins after Chronic Activation of Gi/o-Coupled Receptors: Changes in Detergent Solubility Are in Correlation leads to a decrease in cholate detergent solubility of G protein subunits, and that antagonist treatment

  5. Chukwuemeka I. Okoye Carbon Dioxide Solubility and Absorption Rate in

    E-print Network

    Rochelle, Gary T.

    Copyright by Chukwuemeka I. Okoye 2005 #12;Carbon Dioxide Solubility and Absorption Rate _______________________ Nicholas A. Peppas #12;Carbon Dioxide Solubility and Absorption Rate in Monoethanolamine/Piperazine/H2O for. #12;iii Carbon Dioxide Solubility and Absorption Rate in Monoethanolamine/Piperazine/H2O

  6. Murine lung immunity to a soluble antigen

    SciTech Connect

    Weissman, D.N.; Bice, D.E.; Siegel, D.W.; Schuyler, M.R. Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM )

    1990-01-01

    To test the hypothesis that soluble antigen triggers antigen-specific immunity in the respiratory tract in a fashion similar to that reported for particulate antigen, the authors examined the development of local and systemic immunity in C57BL/6 mice after intratracheal (i.t.) instillation of a soluble, large molecular weight protein neoantigen, keyhole limpet hemocyanin (KLH). Specific anti-KLH IgG and IgM first appeared in the sera of mice on day 7 after primary immunization by i.t. instillation of KLH, with specific serum antibody concentrations remaining elevated at day 11. Cultured spleen cells obtained from mice after primary immunization released only low levels of specific IgM, and no specific IgG. No specific antibody was released by cell populations derived from the lungs of animals undergoing primary immunization. When presensitized mice were given an i.t. challenge with KLH, responses differed markedly from those following primary immunization. Lung-associated lymph node cell populations from challenged mice released greater amounts of specific antibody earlier than did cell populations, which after primary immunization had not released detectable amounts of specific antibody in vitro, released easily detectable amounts of specific antibody after challenge. Thus, i.t. instillation of soluble KLH generates specific immunity in mice in a fashion similar to that reported for particulate antigen. Specific responses following primary immunization occur largely within draining lung-associated lymph nodes. In contrast, presensitized animals challenged i.t. with soluble KLH mount secondary antibody responses in both lung and lung-associated lymph nodes.

  7. Cure study of soluble aromatic polyimide films

    NASA Technical Reports Server (NTRS)

    Young, Philip R.; Chang, A. C.

    1987-01-01

    Several soluble aromatic poly(amic acid) films were staged at intervals to 325 C and characterized by IR spectroscopy and various solution property techniques. A series of films in which the polymer had been endcapped in an effort to control chain extension was also examined. Much of the behavior observed is consistent with an interpretation that a reduction in molecular weight occurred during cure before the ultimate molecular weight was achieved as a polyimide.

  8. Wormhole growth in soluble porous materials

    SciTech Connect

    Nilson, R.H.; Griffiths, S.K. )

    1990-09-24

    Analytical solutions are derived for the quasisteady shape and speed of a single wormhole resulting from the coupled processes of Darcian fluid motion and chemical dissolution in a soluble permeable material. For an initially unsaturated medium, two-dimensional solutions are obtained by addressing an inverted free-boundary problem in which the spatial coordinates are treated as dependent variables on the plane of a complex potential. For initially saturated materials, solutions are obtained by analogy to Ivantsov's problem of dendrite growth.

  9. Synergistic effect of hydrotrope and surfactant on solubility and dissolution of atorvastatin calcium: screening factorial design followed by ratio optimization.

    PubMed

    Patel, V F; Sarai, J

    2014-01-01

    The present study was aimed at investigating the effect of hydrotrope and surfactant on poor solubility of atorvastatin calcium. Excipients screening followed by factorial design was performed to study effect of excipients and manufacturing methods on solubility of drug. Three independent factors (carrier, surfactant and manufacturing method) were evaluated at two levels using solubility as a dependant variable. Solid-state characterisation was performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimised complex were incorporated into orally disintegrating micro tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and sodium dodecyl sulphate were emerged as promising excipients from excipient screening. General regression analysis revealed only the type of carrier has significantly enhanced (P<0.05) the solubility of drug while other factors were found to be nonsignificant. Ratio optimisation trial revealed that drug to nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold increases in solubility compared to pure drug) in comparison to drug-surfactant ratio; however the presence of surfactant deemed essential. Significantly higher rate and extent of dissolution was observed from solid dispersion complex and tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope and surfactant have synergistic effect on solubility and dissolution of atorvastatin calcium and this can be explored further. PMID:25593381

  10. Synergistic Effect of Hydrotrope and Surfactant on Solubility and Dissolution of Atorvastatin Calcium: Screening Factorial Design Followed by Ratio Optimization

    PubMed Central

    Patel, V. F.; Sarai, J.

    2014-01-01

    The present study was aimed at investigating the effect of hydrotrope and surfactant on poor solubility of atorvastatin calcium. Excipients screening followed by factorial design was performed to study effect of excipients and manufacturing methods on solubility of drug. Three independent factors (carrier, surfactant and manufacturing method) were evaluated at two levels using solubility as a dependant variable. Solid-state characterisation was performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimised complex were incorporated into orally disintegrating micro tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and sodium dodecyl sulphate were emerged as promising excipients from excipient screening. General regression analysis revealed only the type of carrier has significantly enhanced (P<0.05) the solubility of drug while other factors were found to be nonsignificant. Ratio optimisation trial revealed that drug to nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold increases in solubility compared to pure drug) in comparison to drug-surfactant ratio; however the presence of surfactant deemed essential. Significantly higher rate and extent of dissolution was observed from solid dispersion complex and tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope and surfactant have synergistic effect on solubility and dissolution of atorvastatin calcium and this can be explored further. PMID:25593381

  11. Fluorite solubility equilibria in selected geothermal waters

    USGS Publications Warehouse

    Nordstrom, D.K.; Jenne, E.A.

    1977-01-01

    Calculation of chemical equilibria in 351 hot springs and surface waters from selected geothermal areas in the western United States indicate that the solubility of the mineral fluorite, CaF2, provides an equilibrium control on dissolved fluoride activity. Waters that are undersaturated have undergone dilution by non-thermal waters as shown by decreased conductivity and temperature values, and only 2% of the samples are supersaturated by more than the expected error. Calculations also demonstrate that simultaneous chemical equilibria between the thermal waters and calcite as well as fluorite minerals exist under a variety of conditions. Testing for fluorite solubility required a critical review of the thermodynamic data for fluorite. By applying multiple regression of a mathematical model to selected published data we have obtained revised estimates of the pK (10,96), ??Gof (-280.08 kcal/mole), ??Hof (-292.59 kcal/mole), S?? (16.39 cal/deg/mole) and CoP (16.16 cal/deg/mole) for CaF2 at 25??C and 1 atm. Association constants and reaction enthalpies for fluoride complexes with boron, calcium and iron are included in this review. The excellent agreement between the computer-based activity products and the revised pK suggests that the chemistry of geothermal waters may also be a guide to evaluating mineral solubility data where major discrepancies are evident. ?? 1977.

  12. Aluminum Solubility in Complex Electrolytes - 13011

    SciTech Connect

    Agnew, S.F.; Johnston, C.T.

    2013-07-01

    Predicting aluminum solubility for Hanford and Savannah River waste liquids is very important for their disposition. It is a key mission goal at each Site to leach as much aluminum as practical from sludges in order to minimize the amount of vitrified high level waste. And it is correspondingly important to assure that any soluble aluminum does not precipitate during subsequent decontamination of the liquid leachates with ion exchange. This report shows a very simple and yet thermodynamic model for aluminum solubility that is consistent with a wide range of Al liquors, from simple mixtures of hydroxide and aluminate to over 300 Hanford concentrates and to a set of 19 Bayer liquors for temperatures from 20-100 deg. C. This dimer-dS{sub mix} (DDS) model incorporates an ideal entropy of mixing along with previous reports for the Al dimer, water activities, gibbsite, and bayerite thermodynamics. We expect this model will have broad application for nuclear wastes as well as the Bayer gibbsite process industry. (authors)

  13. The solubilities of significant organic compounds in HLW tanks upernate solutions - FY 1997 progress report

    SciTech Connect

    Barney, G.S.

    1997-09-16

    The solubilities of seven sodium salts of organic acids that are thought to exist in high-level waste at the Hanford Site were measured in tank supernatant simulant solutions during FY 1997. This solubility information will be used to determine if these organic salts could exist in solid phases (saltcake or sludges) in the waste where they might react violently with the nitrate or nitrite salts present in the tanks. The solubility of sodium acetate was measured in simulated waste supernate solutions at 25C, 30C, 40C, and 50C that were both unsaturated and saturated with sodium nitrate. Solubilities of sodium glycolate, citrate, ethylenediaminetetraacetate (EDTA), nitrilotriacetate (NTA), formate, and oxalate were measured in simulated waste supernate solutions that were saturated with sodium nitrate. In addition, solubilities of sodium EDTA, citrate, glycolate, and NTA were measured in a complex waste matrix. The organic compounds were selected because they are expected to exist in relatively high concentrations in the tanks. The solubilities of sodium glycolate citrate, EDTA, NTA, and formate were high over the temperature and sodium hydroxide concentration ranges expected in the tanks. The solubility of sodium oxalate in solutions saturated with sodium nitrate were quite low. The presence of additional sodium in the waste simulant solutions that were saturated with sodium nitrate slightly lowered the solubilities of each of the organic salts. Solubilities were, however, high enough to prevent solid sodium salts of all the organic acids from precipitating from tank supernate solutions, except for sodium oxalate. The total organic carbon concentrations (TOC) of actual tank supernates are generally much lower than the TOC ranges for the simulated supernate solutions saturated (at the solubility limit) with the organic salts. This is true even if all the dissolved carbon in a given tank supernate is due to only one of these soluble compounds (an unlikely situation). Solubilities of all the organic salts, except for glycolate, decrease with increasing sodium hydroxide and sodium nitrate concentration because of the common ion effect of Na+. Sodium glycolate solubility increased with increasing hydroxide concentration. The complex waste solutions had sodium ion concentrations 3.4 to 7. 0 molar higher than unsaturated solutions. This caused a significant lowering of the solubilities of the organic sodium salts due to the common ion effect of sodium. Results of EDTA adsorption measurements show that EDTA or EDTA-metal complexes can be adsorbed onto hydrous metal oxides (that make up the sludge layers in the tanks) under conditions simulating the high-level waste tanks. The extent of adsorption is not large and depends on the concentration of hydroxide in the waste solutions. Higher hydroxide concentrations lower adsorption of EDTA. Adsorption also depends on the type of metal hydrous oxide present. Adsorption data for Fe(III), Cr(III), and NI(IV) hydrous oxides show that chromium(III) hydrous oxide adsorbs EDTA most effectively.

  14. Illinois basin coal fly ashes. 1. Chemical characterization and solubility

    USGS Publications Warehouse

    Roy, W.R.; Griffin, R.A.; Dickerson, D.R.; Schuller, R.M.; Martin, S.M.C.

    1984-01-01

    Twelve precipitator-collected fly ash samples (nine derived from high-sulfur Illinois Basin coals and three from Western U.S. coals) were found to contain a variety of paraffins, aryl esters, phenols, and polynuclear aromatic hydrocarbons including phenanthrene, pyrene, and chrysene but all at very low concentrations. Less than 1% of the organic carbon in the samples was extractable into benzene. Solubility studies with a short-term (24-h) extraction procedure and a long-term (20-week) procedure indicate that the inorganic chemical composition of some types of fly ash effluent is time dependent and may be most toxic to aquatic ecosystems when initially mixed with water and pumped to disposal ponds. Some acidic, high-Cd fly ashes would be classified as hazardous wastes if coal ash was included in this waste category by future RCRA revisions. ?? 1984 American Chemical Society.

  15. Phenol-soluble modulins – critical determinants of staphylococcal virulence

    PubMed Central

    Cheung, Gordon Y. C.; Joo, Hwang-Soo; Chatterjee, Som S.; Otto, Michael

    2014-01-01

    Phenol-soluble modulins (PSMs) are a recently discovered family of amphipathic, alpha-helical peptides that have multiple roles in staphylococcal pathogenesis and contribute to a large extent to the pathogenic success of virulent staphylococci, such as Staphylococcus aureus. PSMs may cause lysis of many human cell types including leukocytes and erythrocytes, stimulate inflammatory responses, and contribute to biofilm development. PSMs appear to have an original role in the commensal lifestyle of staphylococci, where they facilitate growth and spreading on epithelial surfaces. Aggressive, cytolytic PSMs seem to have evolved from that original role and are mainly expressed in highly virulent S. aureus. Here we will review the biochemistry, genetics and role of PSMs in the commensal and pathogenic lifestyles of staphylococci, discuss how diversification of PSMs defines the aggressiveness of staphylococcal species, and evaluate potential avenues to target PSMs for drug development against staphylococcal infections. PMID:24372362

  16. Reactivity of Metal Ions Bound to Water-Soluble Polymers

    SciTech Connect

    Sauer, N.N.; Watkins, J.G.; Lin, M.; Birnbaum, E.R.; Robison, T.W.; Smith, B.F.; Gohdes, J.W.; McDonald, J.G.

    1999-06-29

    The intent of this work is to determine the effectiveness of catalysts covalently bound to polymers and to understand the consequences of supporting the catalysts on catalyst efficiency and selectivity. Rhodium phosphine complexes with functional groups for coupling to polymers were prepared. These catalyst precursors were characterized using standard techniques including IR, NMR, and elemental analysis. Studies on the modified catalysts showed that they were still active hydrogenation catalysts. However, tethering of the catalysts to polyamines gave systems with low hydrogenation activity. Analogous biphasic systems were also explored. Phosphine ligands with a surfactant-like structure have been synthesized and used to prepare catalytically active complexes of palladium. The palladium complexes were utilized in Heck-type coupling reactions (e.g. coupling of iodobenzene and ethyl acrylate to produce ethyl cinnamate) under vigorously stirred biphasic reaction conditions, and were found to offer superior performance over a standard water-soluble palladium catalyst under analogous conditions.

  17. IUPAC-NIST Solubility Data Series 70. The Solubility of Gases in Glassy Polymers

    NASA Astrophysics Data System (ADS)

    Paterson, Russell; Yampol'Skii, Yuri P.; Fogg, Peter G. T.; Bokarev, Alexandre; Bondar, Valerii; Ilinich, Oleg; Shishatskii, Sergey

    1999-09-01

    Solubility of gases in polymers is an important property of polymeric materials relevant to many practical applications. Sorption of small molecules in polymers is a fundamental concern in such areas as food packaging, beverage storage, and polymer processing. However, by far the main interest in the solubility of gases in polymers, and especially in glassy polymers, is related to development of novel advanced materials for gas separation membranes. This is because the concentration gradient of a dissolved gas is the driving force of membrane processes. Development of these novel separation methods resulted in a rapid accumulation, in the recent literature, of thermodynamic data related to the solubility of gases in polymers at different temperatures and pressures. Polymers can be regarded as special cases of media intermediate between liquids and solids. As a consequence, modeling of gas sorption in polymers is very difficult and presents a permanent challenge to theoreticians and experimenters. The collection and critical evaluation of solubility data for various gas-polymer systems is relevant to both practical aspects of polymer applications and to fundamental studies of polymer behavior. This volume of the IUPAC-NIST Solubility Data Series summarizes the compilations and critical evaluations of the data on solubility of gases in glassy polymers. It is implied in this edition that "gases" are the components that are either permanent gases (supercitical fluids) or have saturated vapor pressure more than 1 atm at ambient conditions (298 K). The polymeric components of compilations and critical evaluations are primarily high molecular mass, amorphous, linear (noncross-linked) compounds that have the glass transition temperatures above ambient temperature. The data for each gas-polymer system have been evaluated, if the results of at least three independent and reliable studies have been reported. Where the data of sufficient accuracy and reliability are available, values are recommended, and in some cases smoothing equations are given to represent variations of solubility with changes in gas pressure and temperature. Referenced works are presented in the standard IUPAC-NIST Solubility Data Series format. Depending on the gas-polymer system, reported data are given in tabular form or in the form of sorption isotherms. The data included in the volume comprise solubilities of 30 different gases in more than 80 primarily amorphous homo and copolymers. Where available, the compilation or critical evaluation sheets include enthalpies of sorption and parameters for sorption isotherms. Throughout the volume, SI conventions have been employed as the customary units in addition to the units used in original publications.

  18. Warmer and wetter climate: More soluble pollutants

    NASA Astrophysics Data System (ADS)

    Fang, Y.; Fiore, A. M.; Horowitz, L. W.

    2010-12-01

    While the IPCC AR4 models indicate a global increase of total precipitation in a future climate, simulated precipitation changes exhibit strong regional and seasonal variability, likely affecting the distributions of soluble pollutants that are primarily removed by wet scavenging. We conduct a pair of 20-year simulations in the GFDL AM3 global climate model to examine the impact of climate change on pollutant distributions from 1981-2000 (present-day) to 2081-2100 (future). The present-day simulation is driven by a 20-year mean climatology of monthly mean observed sea surface temperatures and sea ice. The future simulation is driven by this observed climatology plus the 19-model (from IPCC AR4) ensemble mean difference of 20-year average values (separately for each month) from present-day to future, and by long-lived greenhouse gases under the SRES A1B scenario. To isolate the impact of precipitation change on the wet deposition of soluble pollutants, we implement a simple carbon monoxide (CO)-like tracer (COt) with CO emissions from the RETRO and GFED v2 inventories for 2001 and a fixed 25-day lifetime. We also implement a soluble version of that tracer (SAt) with wet deposition of sulfate. In the future, reduced lower tropospheric ventilation contributes to a degradation of surface air quality for COt, but horizontal circulation patterns and the corresponding spatial distribution of COt are relatively unchanged from the present-day simulation. Despite higher global precipitation, soluble pollutant concentrations near the surface increase more than for insoluble pollutants, reflecting weaker wet deposition. It is thus misleading to use the total global precipitation change alone to predict the response of soluble pollutants in a future climate. The zonal mean annual wet deposition change can be explained mainly by the zonal mean of large-scale (LS) precipitation change since LS precipitation dominates wet deposition in our model. Over some regions such as North America, differences in the seasonality of LS precipitation and tracer burdens must be considered. The spatial pattern of changes in LS precipitation weighted by present-day tracer burden is well correlated with that of wet deposition change. We thus develop a diagnosed precipitation impact (DPI) index as the global mean of LS precipitation change weighted by present-day tracer burden, divided by the global mean of LS precipitation weighted by present-day tracer burden. This DPI index captures well the relative change of wet deposition in the future annually and in July. It enables us to directly infer the global soluble pollutant wet deposition changes from the LS precipitation changes in the future and the present-day pollutant burden. We will explore the applicability of DPI to black carbon, sulfate and organic matter. Considering the wide range in the relative importance of LS versus convective precipitation across models, observational constraints are needed to confirm our finding that LS precipitation dominates wet deposition. Our results imply that a warmer, wetter climate degrades air quality and that tighter emission regulations may be required for both insoluble and soluble pollutants to obtain a desired level of air quality.

  19. Hansen solubility parameters for polyethylene glycols by inverse gas chromatography.

    PubMed

    Adamska, Katarzyna; Voelkel, Adam

    2006-11-01

    Inverse gas chromatography (IGC) has been applied to determine solubility parameter and its components for nonionic surfactants--polyethylene glycols (PEG) of different molecular weight. Flory-Huggins interaction parameter (chi) and solubility parameter (delta(2)) were calculated according to DiPaola-Baranyi and Guillet method from experimentally collected retention data for the series of carefully selected test solutes. The Hansen's three-dimensional solubility parameters concept was applied to determine components (delta(d), delta(p), delta(h)) of corrected solubility parameter (delta(T)). The molecular weight and temperature of measurement influence the solubility parameter data, estimated from the slope, intercept and total solubility parameter. The solubility parameters calculated from the intercept are lower than those calculated from the slope. Temperature and structural dependences of the entopic factor (chi(S)) are presented and discussed. PMID:16920129

  20. PETROLEUM RESIDUA SOLUBILITY PARAMETER/POLARITY MAP: STABILITY STUDIES OF RESIDUA PYROLYSIS

    SciTech Connect

    John F. Schabron; A. Troy Pauli; Joseph F. Rovani, Jr.

    1999-04-30

    A new molecular weight/polarity map based on the Scatchard-Hildebrand solubility equation has been developed for petroleum residua. A series of extractions are performed with solvents of increasing solubility parameter, and the fractions are analyzed by vapor pressure osmometry for number average molecular weight and by analytical-scale size exclusion chromatography for molecular weight spread. Work was performed for a heavy oil material subjected to three increasing severities of thermal treatment prior to and through the onset of coke formation. The results are diagnostic of the layers of solvations by resin-type molecules around a central asphaltene core. Two additional stability diagnostic methods were also used. These were the Heithaus titration ''P-index'' and Gaestel ''G'' index, which have been applied to paving asphalts for decades. The Heithaus titration involves the titration of three toluene solutions of a residuum at three concentrations with a poor solvent, such as isooctane, to the point of asphaltene flocculation. In the present work, the significance of the data are developed in terms of the Hildebrand solubility parameter. The Heithaus results are combined with data from the new molecular weight/polarity map. The solubility parameters for the toluene-soluble asphaltene components are measured, and the solubility parameters of the maltenes can be calculated. As thermal treatment progresses, the solubility parameters of asphaltene materials increase and the molecular weights decrease. A new coking index is proposed based on Heithaus titration data. Preliminary results suggest that an alternative, simpler coking index may be developed by measuring the weight percent of cyclohexane solubles in heptane asphaltenes. Coking onset appears to coincide with the depletion of these resin-type asphaltene solubilizing components of residua. The objective of the present study was to develop a mapping tool that will enhance understanding of the changes that occur in residua during upgrading and support the industry-sponsored work in which Western Research Institute is engaged. WRI performs proprietary industry-sponsored residua and heavy oil upgrading process development and optimization research. The new mapping tool can be used for evaluating heavy oils and residua in both upstream and downstream operations.

  1. Monazite solubility in hydrous silicic melts at high pressure conditions relevant to subduction zone metamorphism

    NASA Astrophysics Data System (ADS)

    Skora, Susanne; Blundy, Jon

    2012-03-01

    Critical to any application of accessory phase stability to subduction zone thermal structure and processes is knowledge of the thermodynamic stability of these minerals in different types of subducted rock, their solubility in the presence of fluids, and the extent to which they fractionate trace element ratios of interest. This study focuses on monazite, which is the principal carrier of light rare earth elements (LREE) and thorium (Th) in CaO-poor subducted sediments. Relatively little is known about the mechanism of monazite dissolution in high-pressure hydrous melts (or supercritical fluids), yet monazite and allanite (the principal carrier of LREE and Th in oceanic basalts and some CaO-rich sediments) solubility has been used recently to quantify subducted slab-top temperatures (Plank, T., Cooper, L.B., Manning, C.E., 2009. Emerging geothermometers for estimating slab surface temperatures. Nature Geosci. 2, 611-615). We have studied monazite solubility at subduction zone conditions (3 GPa, T ? 800 °C) in hydrous sediment-melting experiments. Experimental results highlight the important role that phosphorous exerts on monazite solubility in hydrous silicic melts at high pressure. Thermodynamically this corresponds to a case where monazite dissolves predominantly as its dissociated constituent ions (LREE3 + and PO43 -). This is in contrast to monazite solubility in granitic melts at low pressures (0.2 GPa) where it appears to dissolve predominantly as associate LREEPO4 species, such that its solubility is essentially independent of dissolved phosphorous. Our results have implications for monazite-based thermometry, as the error introduced by not taking phosphorous into account in high-pressure fluids can amount to > 100 °C.

  2. Soluble N-Substituted Organosilane Polybenzimidazoles

    SciTech Connect

    Klaehn, J. R.; Luther, T. A.; Orme, C. J.; Jones, M. G.; Wertsching, A. K.; Peterson, E. S.

    2007-10-01

    Six organosilane derivatives were synthesized, and are more soluble in common organic solvents (tetrahydrofuran and chloroform) than the parent polybenzimidazole. Our polymer modification pathway provides a straightforward synthesis that can be carried out at room temperature and give reasonable yields. Solution 1H NMR spectra of both the parent and deprotonated polybenzimidazoles are reported. Based upon the NMR analysis in CDCl3, nearly all of the benzimidazole N-H positions are substituted by the organosilane moieties. Some of the modified polymers have similar thermal properties compared to the parent polymer, and the average molecular weights are higher for the substituted polybenzimidazoles than the parent PBI.

  3. Water-soluble titanium alkoxide material

    DOEpatents

    Boyle, Timothy J.

    2010-06-22

    A water soluble, water stable, titanium alkoxide composition represented by the chemical formula (OC.sub.6H.sub.6N).sub.2Ti(OC.sub.6H.sub.2(CH.sub.2N(CH.sub.3).sub.2).sub- .3-2,4,6).sub.2 with a theoretical molecular weight of 792.8 and an elemental composition of 63.6% C, 8.1% H, 14.1% N, 8.1% O and 6.0% Ti.

  4. [Novel Water-Soluble Substrate for Silicateins].

    PubMed

    Povarova, N V; Baranov, M S; Kovalchuk, S N; Semiletova, I V; Lukyanov, K A; Kozhemyak, V B

    2015-01-01

    We suggested to use tetrakis(2-hydroxyethyl)orthosilicate (THEOS) as a substrate for silicateins--an enzyme family playing a key role in formation of skeleton in marine sponges. We compared THEOS with tetraethylorthosilicate (TEOS)--a commonly used substrate for silicateins. These substrates were tested in reaction of amorphous silica formation in vitro catalyzed by silicatein Al from sponge Latrunculia oparinae. It was found that reaction with THEOS occurs more efficiently than with TEOS, probably due to high water solubility and higher hydrolysis rate of THEOS. PMID:26502615

  5. Exactly soluble quantum wormhole in two dimensions

    SciTech Connect

    Kim, Won Tae; Son, Edwin J.; Yoon, Myung Seok

    2004-11-15

    We are presenting a quantum traversable wormhole in an exactly soluble two-dimensional model. This is different from previous works since the exotic negative energy that supports the wormhole is generated from the quantization of classical energy-momentum tensors. This explicit illustration shows the quantum-mechanical energy can be used as a candidate for the exotic source. As for the traversability, after a particle travels through the wormhole, the static initial wormhole geometry gets a back reaction which spoils the wormhole structure. However, it may still maintain the initial structure along with the appropriate boundary condition.

  6. The Marangoni flow of soluble amphiphiles

    E-print Network

    Roché, Matthieu; Griffiths, Ian M; Roux, Sébastien Le; Cantat, Isabelle; Saint-Jalmes, Arnaud; Stone, Howard A

    2013-01-01

    Surfactant distribution heterogeneities at a fluid/fluid interface trigger the Marangoni effect, i.e. a bulk flow due to a surface tension gradient. The influence of surfactant solubility in the bulk on these flows remains incompletely characterized. Here we study Marangoni flows sustained by injection of hydrosoluble surfactants at the air/water interface. We show that the flow extent increases with a decrease of the critical micelle concentration, i.e. the concentration at which these surfactants self-assemble in water. We document the universality of the surface velocity field and predict scaling laws based on hydrodynamics and surfactant physicochemistry that capture the flow features.

  7. Classic and Atypical FOP Phenotypes are Caused by Mutations in the BMP Type I Receptor ACVR1

    PubMed Central

    Kaplan, Frederick S.; Xu, Meiqi; Seemann, Petra; Connor, Michael; Glaser, David L.; Carroll, Liam; Delai, Patricia; Fastnacht-Urban, Elisabeth; Forman, Stephen J.; Gillessen-Kaesbach, Gabriele; Hoover-Fong, Julie; Köster, Bernhard; Pauli, Richard M.; Reardon, William; Zaidi, Syed-Adeel; Zasloff, Michael; Morhart, Rolf; Mundlos, Stefan; Groppe, Jay; Shore, Eileen M.

    2010-01-01

    Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant human disorder of bone formation that causes developmental skeletal defects and extensive debilitating bone formation within soft connective tissues (heterotopic ossification) during childhood. All patients with classic clinical features of FOP (great toe malformations and progressive heterotopic ossification) have previously been found to carry the same heterozygous mutation (c.617G>A; p.R206H) in the GS activation domain of activin A type I receptor/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor. Among patients with FOP-like heterotopic ossification and/or toe malformations, we identified patients with clinical features unusual for FOP. These atypical FOP patients form two classes: FOP-plus (classic defining features of FOP plus one or more atypical features) and FOP variants (major variations in one or both of the two classic defining features of FOP). All patients examined have heterozygous ACVR1 missense mutations in conserved amino acids. While the recurrent c.617G>A; p.R206H mutation was found in all cases of classic FOP and most cases of FOP-plus, novel ACVR1 mutations occur in the FOP variants and two cases of FOP-plus. Protein structure homology modeling predicts that each of the amino acid substitutions activates the ACVR1 protein to enhance receptor signaling. We observed genotype-phenotype correlation between some ACVR1 mutations and the age of onset of heterotopic ossification or on embryonic skeletal development. PMID:19085907

  8. U solubility in the core of Earth

    E-print Network

    Bao, X; Bao, Xuezhao; Secco, Richard A.

    2006-01-01

    Uranium is the most important heat producing element in the Earth. The presence of an appreciable amount of U in the core of Earth would have an important influence on geodynamics. In this study, the solubility of U in Fe-10wt% S and in Fe-35wt% S was measured by partitioning experiments with a mixture of peridotite, uraninite, Fe and FeS powder at pressure (P) of 0-9 GPa and temperature (T) of 1500-2200 oC. Comparisons with the run products containing pure Fe as the metal phase in our previous study and re-analysis of run products were made in this study. We found that in all run products, including Fe-10wt% S, Fe-35wt% S and pure Fe groups, the solubility and partitioning of U in the pure metal or metal-sulfide phase relative to the silicate phase (DU) increases with increasing P and T. With a molten silicate phase, DU is generally 3-6 times larger than with a solid silicate phase. While DU has a positive dependence on S concentration of the metal-sulfide phase, there is a negative correlation between Ca an...

  9. Water soluble fraction of Asian dust particles

    NASA Astrophysics Data System (ADS)

    Osada, Kazuo

    2013-04-01

    The volume fraction (?) of water soluble material in atmospheric aerosol particles is an important parameter related to their hygroscopicity and activation processes to form cloud and ice particles. To estimate ? of coarse dust particles, confocal scanning laser microscope was applied to measure the volume difference of individual particles before and after water dialysis directly. Individual particles (sphere equivalent diameter approx. 1-8 ?m) of Asian reference dusts (CJ1 and CJ2) and atmospheric coarse particles during four Asian dust events were analyzed to ascertain ?. Median values of ? for CJ1 and CJ2 were, respectively, 29% and 13% with no size trend. Median values of ? for coarse aerosol particles during four dust events were 18-42%, which show nearly pure (low ?) to aged (higher ? possibly attributable to addition of sea salts and other water soluble salts) Asian dust. Dust particles with high ? are potentially important for acting as giant CCN. Therefore the aging of dust particles during transport might enhance the number of giant CCN over the North Pacific.

  10. Selective Water-Soluble Gelatinase Inhibitor Prodrugs

    PubMed Central

    Gooyit, Major; Lee, Mijoon; Schroeder, Valerie A.; Ikejiri, Masahiro; Suckow, Mark A.; Mobashery, Shahriar; Chang, Mayland

    2011-01-01

    SB-3CT (1), a selective and potent thiirane-based gelatinase inhibitor, is effective in animal models of cancer metastasis and stroke; however, it is limited by poor aqueous solubility and extensive metabolism. We addressed these issues by blocking the primary site of metabolism and capitalizing on a prodrug strategy to achieve >5000-fold increased solubility. The amide prodrugs were quantitatively hydrolyzed in human blood to a potent gelatinase inhibitor, ND-322 (3). The arginyl amide prodrug (ND-478, 5d) was metabolically stable in mouse, rat, and human liver microsomes. Both 5d and 3 were non-mutagenic in the Ames II mutagenicity assay. The prodrug 5d showed moderate clearance of 0.0582 L/min/kg, remained mostly in the extracellular fluid compartment (Vd = 0.0978 L/kg), and had a terminal half-life of >4 h. The prodrug 5d had superior pharmacokinetic properties than 3, making the thiirane class of selective gelatinase inhibitors suitable for intravenous administration in treatment of acute gelatinase-dependent diseases. PMID:21866961

  11. Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility

    E-print Network

    Hammock, Bruce D.

    and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties such as arachidonic acid,1 linoleic acid,2 and other lipid epoxides.3 Epoxides of arachidonic acid (epoxyeicosatrienoic acids or EETs) are known as effective modulators of blood pressure.4 However, hy- drolyzed

  12. Optimization of Amide-Based Inhibitors of Soluble Epoxide Hydrolase with Improved Water Solubility

    PubMed Central

    Kim, In-Hae; Heirtzler, Fenton R.; Morisseau, Christophe; Nishi, Kosuke; Tsai, Hsing-Ju; Hammock, Bruce D.

    2006-01-01

    Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group on the right side of carbonyl group of the amide pharmacophore substituted with an adamantyl group (such as compound 14) and a methylene carbon present between the adamantyl and amide groups were essential to produce potent inhibition of sEH. The resulting amide inhibitors have 10–30-fold better solubility and lower melting point than the corresponding urea compounds. These findings will facilitate synthesis of sEH inhibitors that are easier to formulate and more bioavailable. PMID:15887969

  13. Soluble phosphate fertilizer production using acid effluent from metallurgical industry.

    PubMed

    Mattiello, Edson M; Resende Filho, Itamar D P; Barreto, Matheus S; Soares, Aline R; Silva, Ivo R da; Vergütz, Leonardus; Melo, Leônidas C A; Soares, Emanuelle M B

    2016-01-15

    Preventive and effective waste management requires cleaner production strategies and technologies for recycling and reuse. Metallurgical industries produce a great amount of acid effluent that must be discarded in a responsible manner, protecting the environment. The focus of this study was to examine the use of this effluent to increase reactivity of some phosphate rocks, thus enabling soluble phosphate fertilizer production. The effluent was diluted in deionized water with the following concentrations 0; 12.5; 25; 50; 75% (v v(-1)), which were added to four natural phosphate rocks: Araxá, Patos, Bayovar and Catalão and then left to react for 1 h and 24 h. There was an increase in water (PW), neutral ammonium citrate (PNAC) and citric acid (PCA) soluble phosphorus fractions. Such increases were dependent of rock type while the reaction time had no significant effect (p < 0.05) on the chemical and mineralogical phosphate characteristics. Phosphate fertilizers with low toxic metal concentrations and a high level of micronutrients were produced compared to the original natural rocks. The minimum amount of total P2O5, PNAC and PW, required for national legislation for phosphate partially acidulated fertilizer, were met when using Catalão and the effluent at the concentration of 55% (v v(-1)). Fertilizer similar to partially acidulated phosphate was obtained when Bayovar with effluent at 37.5% (v v(-1)) was used. Even though fertilizers obtained from Araxá and Patos did not contain the minimum levels of total P2O5 required by legislation, they can be used as a nutrient source and for acid effluent recycling and reuse. PMID:26496844

  14. Prediction of the solubility in lipidic solvent mixture: Investigation of the modeling approach and thermodynamic analysis of solubility.

    PubMed

    Patel, Shruti V; Patel, Sarsvatkumar

    2015-09-18

    Self-micro emulsifying drug delivery system (SMEDDS) is one of the methods to improve solubility and bioavailability of poorly soluble drug(s). The knowledge of the solubility of pharmaceuticals in pure lipidic solvents and solvent mixtures is crucial for designing the SMEDDS of poorly soluble drug substances. Since, experiments are very time consuming, a model, which allows for solubility predictions in solvent mixtures based on less experimental data is desirable for efficiency. Solvents employed were Labrafil® M1944CS and Labrasol® as lipidic solvents; Capryol-90®, Capryol-PGMC® and Tween®-80 as surfactants; Transcutol® and PEG-400 as co-solvents. Solubilities of both drugs were determined in single solvent systems at temperature (T) range of 283-333K. In present study, we investigated the applicability of the thermodynamic model to understand the solubility behavior of drugs in the lipiodic solvents. By using the Van't Hoff and general solubility theory, the thermodynamic functions like Gibbs free energy, enthalpy and entropy of solution, mixing and solvation for drug in single and mixed solvents were understood. The thermodynamic parameters were understood in the framework of drug-solvent interaction based on their chemical similarity and dissimilarity. Clotrimazole and Fluconazole were used as active ingredients whose solubility was measured in single solvent as a function of temperature and the data obtained were used to derive mathematical models which can predict solubility in multi-component solvent mixtures. Model dependent parameters for each drug were calculated at each temperature. The experimental solubility data of solute in mixed solvent system were measured experimentally and further correlated with the calculates values obtained from exponent model and log-linear model of Yalkowsky. The good correlation was observed between experimental solubility and predicted solubility. PMID:26092370

  15. Selection of solubility parameters for characterization of pharmaceutical excipients.

    PubMed

    Adamska, Katarzyna; Voelkel, Adam; Héberger, Károly

    2007-11-01

    The solubility parameter (delta(2)), corrected solubility parameter (delta(T)) and its components (delta(d), delta(p), delta(h)) were determined for series of pharmaceutical excipients by using inverse gas chromatography (IGC). Principal component analysis (PCA) was applied for the selection of the solubility parameters which assure the complete characterization of examined materials. Application of PCA suggests that complete description of examined materials is achieved with four solubility parameters, i.e. delta(2) and Hansen solubility parameters (delta(d), delta(p), delta(h)). Selection of the excipients through PCA of their solubility parameters data can be used for prediction of their behavior in a multi-component system, e.g. for selection of the best materials to form stable pharmaceutical liquid mixtures or stable coating formulation. PMID:17931639

  16. Transport of soluble species in backfill and rock

    SciTech Connect

    Chambre, P.L.; Lee, W.W.L.; Light, W.B.; Pigford, T.H.

    1992-03-01

    In this report we study the release and transport of soluble species from spent nuclear fuel. By soluble species we mean a fraction of certain fission product species. Our previously developed methods for calculating release rates of solubility-limited species need to be revised for these soluble species. Here we provide methods of calculating release rates of soluble species directly into rock and into backfill and then into rock. Section 2 gives a brief discussion of the physics of fission products dissolution from U0{sub 2} spent fuel. Section 3 presents the mathematics for calculating release rates of soluble species into backfill and then into rock. The calculation of release rates directly into rock is a special case. Section 4 presents numerical illustrations of the analytic results.

  17. Rational formulation development and in vitro assessment of SMEDDS for oral delivery of poorly water soluble drugs.

    PubMed

    Sprunk, Angela; Strachan, Clare J; Graf, Anja

    2012-08-15

    The aims of this study were to formulate a self-microemulsifying drug delivery system (SMEDDS) by a rational formulation approach using mixture experimental design and to derive general concepts that make the development of such systems more feasible. Various types of oils and surfactants were systematically combined and the phase behaviour upon dilution with simulated gastric fluid examined by construction of phase diagrams. The systems solubilising the highest amount of simulated gastric fluid in the continuous microemulsion area were selected for investigation and optimisation of drug solubility. Simvastatin was added as a poorly water-soluble, lipophilic model drug. Two different mixture experimental designs using D-optimal design were set up and used to investigate the solubility of simvastatin in the SMEDDS before and after dilution with simulated gastric fluid respectively. The solubility in each mixture region was analysed by fitting quadratic models using partial least squares analysis. The established models revealed the influence of mixture components on phase behaviour and drug solubility and gave the rationale for formulation optimisation. This study demonstrated that the development of complex self-emulsifying formulations with sufficient solubilisation capacity for poorly water-soluble drugs upon oral administration can be more feasible when using experimental design. PMID:22521277

  18. Isolation and characterization of acid-soluble collagen from the scales of marine fishes from Japan and Vietnam.

    PubMed

    Minh Thuy, Le Thi; Okazaki, Emiko; Osako, Kazufumi

    2014-04-15

    Acid-soluble collagen (ASC) was successfully extracted from the scales of lizard fish (Saurida spp.) and horse mackerel (Trachurus japonicus) from Japan and Vietnam and grey mullet (Mugil cephalis), flying fish (Cypselurus melanurus) and yellowback seabream (Dentex tumifrons) from Japan. ASC yields were about 0.43-1.5% (on a dry weight basis), depending on the species. The SDS-PAGE profile showed that the ASCs were type I collagens, and consisted of two different ? chains, ?1 and ?2, as well as a ? component. ASC of horse mackerel from Vietnam contained a higher imino acid level than that from Japan. ASC denaturation temperature (Td) ranged from 26 to 29 °C, depending on fish species and imino acid content (p<0.01). Maximal solubility of individual collagens was observed at pHs 1-3. Collagen solubility decreased sharply at NaCl concentrations >0.4M, regardless of fish type. PMID:24295705

  19. Stearic acid solubility and cubic phase volume.

    PubMed

    Schmidt, Walter F; Barone, Justin R; Francis, Barry; Reeves, James B

    2006-07-01

    Stearic acid (SA) is highly soluble in structurally diverse solvents. SA/solvent packing within a (24.8 A)3 cubic volume explains the stoichiometry of SA solubility at multiple temperatures in multiple solvents. In the absence of solvent, the cubic volume contains 25 molecules at van der Waals distances from each other. At 55 degrees C, SA occupied half the cubic volume in saturated solution of four structurally diverse solvents. Below 4% SA/volume (e.g. in acetonitrile), the head and foot of each SA molecules on average is more than one solvent molecule away from the head and foot of a neighboring SA molecule. At 50% SA/cubic volume, -CH2- groups on SA molecules are separated from neighboring -CH2- groups on SA molecules by a monolayer of solvent molecules. Lowering the temperature from 55 to 25 degrees C, the volume fraction of SA decreased by a factor of 2 (or more) for every 6 degrees C. Lowering temperature increased the relative number of column of solvent molecules in the cubic phase, and correspondingly, the distance between SA molecules within the cubic volume increased. In three of five solvents, molecular mechanics calculations demonstrated the van der Waals stabilization that occurs from SA/SA affinity in the absence of solvent is similar in magnitude to the van der Waals stabilization from SA/solvent affinity. Methyl-t-butyl ether was less stabilized than hexane, acetone or methanol because the more bulky molecules packed less efficiently within the cubic volume. The most efficient/most stable packing however was still as columns of solvent between columns of SA. The efficiency and stability of SA and solvent packing optimal within the (24.8 A)3 cubic volume. Between 100 and 8% SA, multiple SA molecules present within the cubic volume function as SA aggregates. Both inter- and intra-cubic (phase) volume properties of SA aggregates coexist. Although acetonitrile and SA at the molecular level are both rod shaped, acetonitrile disrupted the packing of SA molecules within the cubic phase. The disrupted packing explains the much lower solubility of SA in acetonitrile than in the other solvents. The same molecular structures (e.g. methanol) can either stabilize or disrupt the packing of aggregated SA molecules, depending upon temperature. The mechanisms of aggregation within cubic volumes could also occur with structurally more complicated lipids. Aggregation and dispersion from such cubic phases could also be present in more complex chemical and/or macromolecular environments. PMID:16616908

  20. Are soluble and membrane-bound rat brain acetylcholinesterase different

    SciTech Connect

    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. )

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  1. Method of increasing biodegradation of sparingly soluble vapors

    DOEpatents

    Cherry, Robert S. (Idaho Falls, ID)

    2000-01-01

    A method for increasing biodegradation of sparingly soluble volatile organic compounds (VOCs) in a bioreactor is disclosed. The method comprises dissolving in the aqueous phase of the bioreactor a water soluble, nontoxic, non-biodegradable polymer having a molecular weight of at least 500 and operable for decreasing the distribution coefficient of the VOCs. Polyoxyalkylene alkanols are preferred polymers. A method of increasing the growth rate of VOC-degrading microorganisms in the bioreactor and a method of increasing the solubility of sparingly soluble VOCs in aqueous solution are also disclosed.

  2. MgO Solubility in Steelmaking Slags

    NASA Astrophysics Data System (ADS)

    Tayeb, Mohammed A.; Assis, Andre N.; Sridhar, Seetharaman; Fruehan, Richard J.

    2015-04-01

    A predominantly liquid and MgO-saturated slag is preferred in EAF and BOF steelmaking. Fully liquid slag provides a better environment for faster mass transfer due to lower bulk viscosities and larger liquid slag volume and these help dephosphorization and desulfurization. Also, an MgO-saturated slag would be preferable in order to increase the lifetime of furnace refractory lining by reducing the extent of dissolution. This article will demonstrate the factors that would influence MgO saturation, which includes FeO, CaO, P2O5, and Al2O3 contents and temperature. In addition, this paper comments on the applicability and accuracy of FactSage prediction, which are compared to laboratory experiments. The results indicate that FactSage may underestimate MgO solubility by up to 2.5 wt pct at higher basicities while there is reasonable agreement with current measurements at lower basicities.

  3. Communication: Epistructural thermodynamics of soluble proteins

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    2012-03-01

    The epistructural tension of a soluble protein is defined as the reversible work per unit area required to span the interfacial solvent envelope of the protein structure. It includes an entropic penalty term to account for losses in hydrogen-bonding coordination of interfacial water and is determined by a scalar field that indicates the expected coordination of a test water molecule at any given spatial location. An exhaustive analysis of structure-reported monomeric proteins reveals that disulfide bridges required to maintain structural integrity provide the thermodynamic counterbalance to the epistructural tension, yielding a tight linear correlation. Accordingly, deviations from the balance law correlate with the thermal denaturation free energies of proteins under reducing conditions. The picomolar-affinity toxin HsTX1 has the highest epistructural tension, while the metastable cellular form of the human prion protein PrPC represents the least tension-balanced protein.

  4. Solubility of magnesium carbonate in natural waters

    USGS Publications Warehouse

    Wells, R.C.

    1915-01-01

    (1) Under atmospheric conditions it appears possible to attain practically the same state in a solution saturated with MgCO33H2O, whether one starts with a solution containing an excess of magnesium bicarbonate or with the pure trihydrate and water, but the adjustment occurs very slowly. The solution finally contains 0.36 g. magnesium and 1.01 g. carbon dioxide per liter at 20??. (2) The solubility found for magnesite, however, is much smaller, viz., 0.02 g. magnesium and 0.07 g. carbon dioxide per liter. (3) Certain natural waters, freely exposed to the atmosphere, appear to be supersaturated with respect to magnesite but none approaches very closely to the point of saturation of the trihydrate MgCO3.3H2O.

  5. Polymerized soluble venom--human serum albumin

    SciTech Connect

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-03-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

  6. DEVELOPMENT OF PETROLUEM RESIDUA SOLUBILITY MEASUREMENT METHODOLOGY

    SciTech Connect

    Per Redelius

    2006-03-01

    In the present study an existing spectrophotometry system was upgraded to provide high-resolution ultraviolet (UV), visible (Vis), and near infrared (NIR) analyses of test solutions to measure the relative solubilities of petroleum residua dissolved in eighteen test solvents. Test solutions were prepared by dissolving ten percent petroleum residue in a given test solvent, agitating the mixture, followed by filtration and/or centrifugation to remove insoluble materials. These solutions were finally diluted with a good solvent resulting in a supernatant solution that was analyzed by spectrophotometry to quantify the degree of dissolution of a particular residue in the suite of test solvents that were selected. Results obtained from this approach were compared with spot-test data (to be discussed) obtained from the cosponsor.

  7. Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs.

    PubMed

    Khadra, Ibrahim; Zhou, Zhou; Dunn, Claire; Wilson, Clive G; Halbert, Gavin

    2015-01-25

    A drug's solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain and highly variable, which has led to the development of multiple simulated intestinal fluid (SIF) recipes. Using a statistical design of experiment (DoE) technique this paper has investigated the effects and interactions on equilibrium drug solubility of seven typical SIF components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pH, pancreatin and sodium oleate) within concentration ranges relevant to human intestinal fluid values. A range of poorly soluble drugs with acidic (naproxen, indomethacin, phenytoin, and piroxicam), basic (aprepitant, carvedilol, zafirlukast, tadalafil) or neutral (fenofibrate, griseofulvin, felodipine and probucol) properties have been investigated. The equilibrium solubility results determined are comparable with literature studies of the drugs in either HIF or SIF indicating that the DoE is operating in the correct space. With the exception of pancreatin, all of the factors individually had a statistically significant influence on equilibrium solubility with variations in magnitude of effect between the acidic and basic or neutral compounds and drug specific interactions were evident. Interestingly for the neutral compounds pH was the factor with the second largest solubility effect. Around one third of all the possible factor combinations showed a significant influence on equilibrium solubility with variations in interaction significance and magnitude of effect between the acidic and basic or neutral compounds. The least number of significant media component interactions were noted for the acidic compounds with three and the greatest for the neutral compounds at seven, with again drug specific effects evident. This indicates that a drug's equilibrium solubility in SIF is influenced depending upon drug type by between eight to fourteen individual or combinations of media components with some of these drug specific. This illustrates the complex nature of these fluids and provides for individual drugs a visualisation of the possible solubility envelope within the gastrointestinal tract, which may be of importance for modelling in vivo behaviour. In addition the results indicate that the design of experiment approach can be employed to provide greater detail of drug solubility behaviour, possible drug specific interactions and influence of variations in gastrointestinal media components due to disease. The approach is also feasible and amenable to adaptation for high throughput screening of drug candidates. PMID:25444845

  8. U solubility in the core of Earth

    E-print Network

    Xuezhao Bao; Richard A. Secco

    2006-06-29

    Uranium is the most important heat producing element in the Earth. The presence of an appreciable amount of U in the core of Earth would have an important influence on geodynamics. In this study, the solubility of U in Fe-10wt% S and in Fe-35wt% S was measured by partitioning experiments with a mixture of peridotite, uraninite, Fe and FeS powder at pressure (P) of 0-9 GPa and temperature (T) of 1500-2200 oC. Comparisons with the run products containing pure Fe as the metal phase in our previous study and re-analysis of run products were made in this study. We found that in all run products, including Fe-10wt% S, Fe-35wt% S and pure Fe groups, the solubility and partitioning of U in the pure metal or metal-sulfide phase relative to the silicate phase (DU) increases with increasing P and T. With a molten silicate phase, DU is generally 3-6 times larger than with a solid silicate phase. While DU has a positive dependence on S concentration of the metal-sulfide phase, there is a negative correlation between Ca and U. According to our calculations based on these experimental results, if the core has formed from a magma ocean at a P of 26 GPa at its base and the core contained 10wt% S, then it could have incorporated at least 10 ppb U. Alternatively, if the core formed by percolation and contained 10wt% S, then it could have incorporated 5-22 ppb U. The geophysical implications of U in the core of Earth are discussed.

  9. A Path to Soluble Molecularly Imprinted Polymers

    PubMed Central

    Verma, Abhilasha; Murray, George M.

    2011-01-01

    Molecular imprinting is a technique for making a selective binding site for a specific chemical. The technique involves building a polymeric scaffold of molecular complements containing the target molecule. Subsequent removal of the target leaves a cavity with a structural “memory” of the target. Molecularly imprinted polymers (MIPs) can be employed as selective adsorbents of specific molecules or molecular functional groups. In addition, sensors for specific molecules can be made using optical transduction through lumiphores residing in the imprinted site. We have found that the use of metal ions as chromophores can improve selectivity due to selective complex formation. The combination of molecular imprinting and spectroscopic selectivity can result in sensors that are highly sensitive and nearly immune to interferences. A weakness of conventional MIPs with regard to processing is the insolubility of crosslinked polymers. Traditional MIPs are prepared either as monoliths and ground into powders or are prepared in situ on a support. This limits the applicability of MIPs by imposing tedious or difficult processes for their inclusion in devices. The size of the particles hinders diffusion and slows response. These weaknesses could be avoided if a means were found to prepare individual macromolecules with crosslinked binding sites with soluble linear polymeric arms. This process has been made possible by controlled free radical polymerization techniques that can form pseudo-living polymers. Modern techniques of controlled free radical polymerization allow the preparation of block copolymers with potentially crosslinkable substituents in specific locations. The inclusion of crosslinkable mers proximate to the binding complex in the core of a star polymer allows the formation of molecularly imprinted macromolecules that are soluble and processable. Due to the much shorter distance for diffusion, the polymers exhibit rapid responses. This paper reviews the methods that have been employed for the trace determination of organophosphates in real world samples using MIPs. PMID:24956512

  10. Study of isopropyl myristate microemulsion systems containing cyclodextrins to improve the solubility of 2 model hydrophobic drugs.

    PubMed

    Nandi, Indranil; Bari, Mohammad; Joshi, Hemant

    2003-01-01

    The objectives of this project were to evaluate the effect of alkanols and cyclodextrins on the phase behavior of an isopropyl myristate microemulsion system and to examine the solubility of model drugs. Triangular phase diagrams were developed for the microemulsion systems using the water titration method, and the solubility values of progesterone and indomethacin were determined using a conventional shake-flask method. The water assimilation capacities were determined to evaluate the effective microemulsion formation in different systems. The alkanols showed higher microemulsion formation rates at higher concentrations. A correlation between the carbon numbers of the alkanol and water assimilation capacity in the microemulsions studied was observed; isobutanol and isopentanol produced the best results. The addition of cyclodextrins showed no effect or had a negative effect on the microemulsion formation based on the type of cyclodextrin used. Isopropyl myristate-based microemulsion systems alone could increase the solubility values of progesterone and indomethacin up to 3300-fold and 500-fold, respectively, compared to those in water. However, the addition of cyclodextrins to the microemulsion systems did not show a synergistic effect in increasing the solubility values of the model drugs. In conclusion, microemulsion systems improve the solubility of progesterone and indomethacin. But the two types of cyclodextrins studied affected isopropyl myristate-based microemulsion systems negatively and did not improve the solubilization of 2 model drugs. PMID:12916919

  11. The use of the solubility domain approach for the modeling of the hydroxide precipitation of lead from wastewater

    SciTech Connect

    Baltpurvins, K.A.; Burns, R.C.; Lawrance, G.A.; Stuart, A.D.

    1996-11-01

    One of the principal sources of heavy metal pollution is discharge from industrial operations. In response to this, industry has developed a number of specialized treatment processes for the removal of the heavy metals prior to their discharge into the environment. Of all such processes, heavy metal hydroxide precipitation is the most commonly employed due to its low cost and simplicity. In order for hydroxide precipitation to be considered as an effective treatment option the residual heavy metal ion concentrations after treatment must be below those deemed permissible for discharge by the authorities. One method which appears to be potentially useful for the prediction of effluent composition effects employs the use of the solubility domain concept. This involves the calculation of the treatment efficiency in terms of residual metal ion concentration versus pH for the chemical extremes of the potential effluent compositions. Providing that these boundaries represent the treatment efficiency extremes, the experimentally observed precipitation profiles will be encompassed within the defined solubility domain. Thus, the solubility domain provides a convenient representation of the potential treatment efficiency ranges likely to be encountered for an effluent type. The purpose of this study is to develop and illustrate the use of the solubility domain approach for the overall prediction of hydroxide treatment efficiencies for the precipitation of lead using lime as a precipitant for effluents of various electrolyte types. Accommodation of multiple components in developing solubility domain models represents an important extrapolation from earlier work.

  12. ChrR, a Soluble Quinone Reductase of Pseudomonas putida That Defends against H2O2*

    E-print Network

    Matin, A.C.

    ChrR, a Soluble Quinone Reductase of Pseudomonas putida That Defends against H2O2* Received semiquinone in- termediates and producing quinols that promote toler- ance of H2O2. Expression of chrR was induced by H2O2, and levels of chrR expression in overexpressing, wild type, and knock-out mutant strains

  13. TitaniQ in reverse: backing out the equilibrium solubility of titanium in quartz

    NASA Astrophysics Data System (ADS)

    Thomas, J. B.

    2014-12-01

    There is close agreement among three of the four experimental studies that have 'calibrated' the P-T dependencies of Ti-in-quartz solubility. New experiments were conducted to identify potential experimental disequilibrium, and determine which Ti-in-quartz solubility calibration is most accurate. Quartz and rutile were synthesized from SiO2- and TiO2saturated aqueous fluids in a forward-type experiment at 925°C and 10 kbar in a piston-cylinder apparatus. A range of crystal sizes was examined to determine if growth rate affected Ti incorporation in quartz. Cathodoluminescence (CL) images and electron microprobe measurements show that intercrystalline and intracrystalline variations in Ti concentrations are remarkably small regardless of crystal size. The average Ti-in-quartz concentration from the forward-type experiment is 392±1 ppm Ti, which is within 95% confidence interval of data from the 10 kbar isobar of Wark and Watson (2006) and Thomas et al. (2010). Quartz from the forward-type experiment was used as starting material for reversal-type experiments. The high-Ti quartz starting material was recrystallized at 925°C and 20 kbar to reduce the solubility of Ti in recrystallized quartz to the equilibrium solubility concentration of the reversed P-T condition. The 'dry' and 'wet' reversal experiments produced polycrystalline quartzites. Rutile occurs as inclusions in quartz, and as individual crystals dispersed along quartz/quartz grain boundaries. Quartz that recrystallized during the reversal-type experiment has substantially lower Ti concentrations than the quartz starting material because Ti solubility at 20 kbar is significantly lower than at 10 kbar. Dark cathodoluminescent quartz with low Ti concentrations shows that extensive quartz recrystallization occurred at the reversal P-T condition. The average Ti concentration in quartz from reversal experiments is 94±2 ppm Ti, which is within the 95% confidence interval of a linear fit to the 20 kbar data of Thomas et al. (2010). Thomas JB, Watson EB, Spear FS, Shemella FS, Nayak SK, Lanzirotti A (2010) Contrib Mineral Petrol 160:743-759 Wark DA, Watson EB (2006) Contrib Mineral Petrol 152:743-754

  14. Increased expression of cytokines, soluble cytokine receptors, soluble apoptosis ligand and apoptosis in dengue.

    PubMed

    Arias, Julia; Valero, Nereida; Mosquera, Jesús; Montiel, Milagros; Reyes, Eduardo; Larreal, Yraima; Alvarez-Mon, Melchor

    2014-03-01

    Several studies have been performed to determine biomarkers that define the risk factors to developing severe forms of dengue. In this study, the levels of TNF-?, IL-6, IL-1, IL-17, soluble interleukin-1 receptor like 1 protein (sST2), soluble TNF-related apoptosis-inducing ligand (sTRAIL), IL-12 and soluble receptors for TNF (sTNF-RI and sTNF-RII) were determined by ELISA in dengue patients and monocyte/macrophage cultures. Dengue was classified as dengue without warning symptoms (DNWS), with warning symptoms (DWWS) and severe dengue (SD). High values of IL-6, sTNFRI, sTNFRII and sST2 were observed in DWWS and/or SD and IL-12 and sTRAIL in DNWS. TNF-? and IL-17 were increased not associated to the disease severity. High production of TNF-?, IL-1?, IL-12, IL-17, sST2 and sTRAIL and apoptosis expression were observed in dengue monocyte/macrophage cultures. This study shows that beneficial or deleterious biomarkers can be present in dengue regardless the disease severity and that monocytes may be in part the source of studied molecules. PMID:24606681

  15. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine

    PubMed Central

    Belhekar, Mahesh N.; Pai, Sarayu; Tayade, Parimal; Dalwadi, Pradip; Munshi, Renuka; Varthakavi, Prema

    2015-01-01

    Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control. PMID:25878390

  16. 21 CFR 520.44 - Acetazolamide sodium soluble powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Acetazolamide sodium soluble powder. 520.44... Acetazolamide sodium soluble powder. (a) Specifications. The drug is in a powder form containing acetazolamide sodium, USP equivalent to 25 percent acetazolamide activity. (b) Sponsor. See No. 053501 in §...

  17. 21 CFR 520.44 - Acetazolamide sodium soluble powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Acetazolamide sodium soluble powder. 520.44... Acetazolamide sodium soluble powder. (a) Specifications. The drug is in a powder form containing acetazolamide sodium, USP equivalent to 25 percent acetazolamide activity. (b) Sponsor. See No. 053501 in §...

  18. Water-Soluble Organometallic Catalysts from Carbohydrates. 1.

    E-print Network

    RajanBabu, T. V. "Babu"

    Water-Soluble Organometallic Catalysts from Carbohydrates. 1. Diphosphinite-Rh Complexes Seunghoon carbohydrates are the most abundantly available water-soluble natural products, and their use as ligand precursors for asymmetric synthesis has been on the rise.3 In previous work, we have shown that carbohydrate

  19. Peptidyl-urea based inhibitors of soluble epoxide hydrolases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We prepared a series of amino acid derived cyclohexyl and adamantyl ureas and tested them as inhibitors of the human soluble epoxide hydrolase, and obtained very potent compounds (K(I)=15nM) that are >10-fold more soluble than previously described sEH inhibitors. While our lead compound 2 showed low...

  20. Apparatus automatically measures soluble residue content of volatile solvents

    NASA Technical Reports Server (NTRS)

    Oswalt, F. W.

    1969-01-01

    Solvent Purity Meter /SPM/ automatically measures the soluble residue in volatile solvents used in cleaning or extraction of oils, greases, and other nonvolatile materials. The SPM gives instantaneous and continuous readout of soluble contaminant residues in concentrations as low as one part per million of solution.

  1. 21 CFR 524.1580c - Nitrofurazone soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Nitrofurazone soluble powder. 524.1580c Section 524.1580c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1580c Nitrofurazone soluble powder....

  2. 21 CFR 520.44 - Acetazolamide sodium soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Acetazolamide sodium soluble powder. 520.44 Section 520.44 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.44 Acetazolamide sodium soluble powder. (a)...

  3. 21 CFR 520.2087 - Roxarsone soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Roxarsone soluble powder. 520.2087 Section 520.2087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2087 Roxarsone soluble powder. (a) Specifications. Each ounce...

  4. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88d Amoxicillin trihydrate soluble powder....

  5. 21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1263c Lincomycin hydrochloride soluble powder....

  6. 21 CFR 520.44 - Acetazolamide sodium soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Acetazolamide sodium soluble powder. 520.44 Section 520.44 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.44 Acetazolamide sodium soluble powder. (a)...

  7. 21 CFR 524.1580c - Nitrofurazone soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Nitrofurazone soluble powder. 524.1580c Section 524.1580c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1580c Nitrofurazone soluble powder....

  8. 21 CFR 520.2087 - Roxarsone soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Roxarsone soluble powder. 520.2087 Section 520.2087 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2087 Roxarsone soluble powder. (a) Specifications. Each ounce...

  9. 21 CFR 520.88d - Amoxicillin trihydrate soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin trihydrate soluble powder. 520.88d Section 520.88d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.88d Amoxicillin trihydrate soluble powder....

  10. 21 CFR 520.1263c - Lincomycin hydrochloride soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Lincomycin hydrochloride soluble powder. 520.1263c Section 520.1263c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1263c Lincomycin hydrochloride soluble powder....

  11. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...2012-04-01 2012-04-01 false Bacitracin zinc soluble powder. 520.154c Section...ANIMAL DRUGS § 520.154c Bacitracin zinc soluble powder. (a) Specifications...perfringens susceptible to bacitracin zinc. (B) Limitations . Prepare a...

  12. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...2011-04-01 2011-04-01 false Bacitracin zinc soluble powder. 520.154c Section...ANIMAL DRUGS § 520.154c Bacitracin zinc soluble powder. (a) Specifications...perfringens susceptible to bacitracin zinc. (B) Limitations . Prepare a...

  13. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Bacitracin zinc soluble powder. 520.154c Section...ANIMAL DRUGS § 520.154c Bacitracin zinc soluble powder. (a) Specifications...perfringens susceptible to bacitracin zinc. (B) Limitations . Prepare a...

  14. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Bacitracin zinc soluble powder. 520.154c Section...ANIMAL DRUGS § 520.154c Bacitracin zinc soluble powder. (a) Specifications...perfringens susceptible to bacitracin zinc. (B) Limitations. Prepare a...

  15. Temperature-dependent solubility of wax compounds in ethanol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of ethanol to dissolve wax compounds was investigated as an alternative to traditional lipid solvents. The solubility of fatty esters with carbon chain lengths between 46 and 54 was measured in ethanol at elevated temperatures. The greatest increase in solubility was observed between 40°...

  16. Facilitating protein solubility by use of peptide extensions

    SciTech Connect

    Freimuth, Paul I; Zhang, Yian-Biao; Howitt, Jason

    2013-09-17

    Expression vectors for expression of a protein or polypeptide of interest as a fusion product composed of the protein or polypeptide of interest fused at one terminus to a solubility enhancing peptide extension are provided. Sequences encoding the peptide extensions are provided. The invention further comprises antibodies which bind specifically to one or more of the solubility enhancing peptide extensions.

  17. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...2010-04-01 2010-04-01 false Bacitracin zinc soluble powder. 520.154c Section...ANIMAL DRUGS § 520.154c Bacitracin zinc soluble powder. (a) Specifications...perfringens susceptible to bacitracin zinc. (B) Limitations . Prepare a...

  18. Intraluminal zinc bioavailability - effect of amino acids on zinc solubility

    SciTech Connect

    Jacobs, F.A.; Nelson, L.S. Jr.; Brushmiller, J.G.

    1986-03-01

    Human and bovine milks and simple solutions modeled after milks (milk models) have been used in the development of an intraluminal system involves subjecting a food, i.e., milk, to the pH range encountered in the digestive tract, and measuring the amount of soluble minerals at various pH's. With this system the authors have demonstrated that co-precipitation of zinc with calcium phosphate is a key factor modulating the solubility of zinc in milks and in milk models. Since a mineral must be soluble in order to be bioavailable, and since free amino acids have been suggested to increase the solubility of zinc by adding various amino acids. Of the amino acids, aspartate, glutamate, histidine, and phosphoserine, only histidine (10 mM) increased the solubility of zinc in a milk model, albeit slightly. Supplementation of bovine milk with 10 mM histidine also resulted in a slight increase in zinc solubility. No increase in zinc solubility was observed at a physiologic histidine level. Free amino acids at physiologic concentrations do not increase zinc solubility in milks, and therefore, do not seem to contribute to zinc bioavailability.

  19. The Differential Cytotoxicity of Water-Soluble Fullerenes

    E-print Network

    Natelson, Douglas

    The Differential Cytotoxicity of Water-Soluble Fullerenes Christie M. Sayes, John D. Fortner, Wenh, 2004 ABSTRACT We show that the cytotoxicity of water-soluble fullerene species is a sensitive function of surface derivatization; in two different human cell lines, the lethal dose of fullerene changed over 7

  20. Leaching behavior of water-soluble carbohydrates from almond hulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over 58% of the dry matter content of the hulls from the commercial almond (Prunus dulcis (Miller) D.A. Webb) is soluble in warm water (50-70°C) extraction. The water-soluble extractables include useful amounts of fermentable sugars (glucose, fructose, sucrose), sugar alcohols (inositol and sorbito...

  1. A Lab Experiment to Introduce Gas/Liquid Solubility

    ERIC Educational Resources Information Center

    Fonsecaa, I. M. A.; Almeida, J. P. B.; Fachada, H. C.

    2008-01-01

    A simplified version of a volumetric apparatus for gas/liquid solubility measurements is proposed. The procedure familiarizes undergraduate students with the experimental study of the solubility of a gas in a liquid and contributes to the understanding of this important phase equilibrium concept. The experimental results report the determination…

  2. Genetic Analyses of Soluble Carbohydrate Concentrations in Onion Bulbs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fructans are the primary soluble carbohydrate in onion (Allium cepa L.) bulbs and show significant correlations with dry weights and pungency. In this research, we estimated the genetic effects and interactions between two chromosome regions associated with higher amounts of soluble carbohydrates i...

  3. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin zinc soluble powder. 520.154c Section... zinc soluble powder. (a) Specifications. Each pound contains the equivalent of not less than 5 grams of... susceptible to bacitracin zinc. (B) Limitations. Prepare a fresh solution daily. (ii) Amount. 200 to...

  4. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Bacitracin zinc soluble powder. 520.154c Section... zinc soluble powder. (a) Specifications. Each pound contains the equivalent of not less than 5 grams of... susceptible to bacitracin zinc. (B) Limitations. Prepare a fresh solution daily. (ii) Amount. 200 to...

  5. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Bacitracin zinc soluble powder. 520.154c Section... zinc soluble powder. (a) Specifications. Each pound contains the equivalent of not less than 5 grams of... susceptible to bacitracin zinc. (B) Limitations. Prepare a fresh solution daily. (ii) Amount. 200 to...

  6. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Bacitracin zinc soluble powder. 520.154c Section... zinc soluble powder. (a) Specifications. Each pound contains the equivalent of not less than 5 grams of... susceptible to bacitracin zinc. (B) Limitations. Prepare a fresh solution daily. (ii) Amount. 200 to...

  7. 21 CFR 520.154c - Bacitracin zinc soluble powder.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Bacitracin zinc soluble powder. 520.154c Section... zinc soluble powder. (a) Specifications. Each pound contains the equivalent of not less than 5 grams of... susceptible to bacitracin zinc. (B) Limitations. Prepare a fresh solution daily. (ii) Amount. 200 to...

  8. High throughput solubility measurement in drug discovery and development.

    PubMed

    Alsenz, Jochem; Kansy, Manfred

    2007-07-30

    Measurement of drug solubility in various solvents is one of the key elements of compound characterization during the whole discovery and development process. This review summarizes current experimental approaches and addresses recent advances in the experimental methods used to determine drug solubility in drug discovery and early development. This paper focuses on high throughput methods designed to determine kinetic and thermodynamic (equilibrium) solubility but traditional methods are also presented. The focus, positioning, experimental setup, pros and cons, and limitations of individual assays are discussed and differences in solubility studies in discovery and development environments are highlighted. Finally, future needs and trends in solubility assay development designed to overcome current bottlenecks and trade-offs between speed and quality/quantity of measurements are addressed. PMID:17604872

  9. The removal of soluble species by warm stratiform clouds

    NASA Technical Reports Server (NTRS)

    Qin, YU; Chameides, W. L.

    1986-01-01

    The development of a one-dimensional, time-dependent model to study the removal of soluble gases from a warm, precipitating stratiform cloud is reported. The model calculates the distributions of water vapor and condensed water, in the form of cloud drops and raindrops, as well as the in-cloud concentration of a soluble species in the gas and aqueous phases for a specified profile of pressure and temperature and an assumed updraft velocity. Highly soluble gases are found to be rapidly dissolved into cloud droplets and then slowly incorporated into raindrops as cloudwater is converted to rainwater. The rainout rate for highly soluble species is found to be ultimately limited by the rate at which new gaseous material can be transferred from the cloud-free air into the cloud. The model calculations indicate that turbulence represents an important mechanism by which highly soluble gases are transported into stratiform clouds.

  10. Total and soluble oxalate content of some Indian spices.

    PubMed

    Ghosh Das, Sumana; Savage, G P

    2012-06-01

    Spices, such as cinnamon, cloves, cardamom, garlic, ginger, cumin, coriander and turmeric are used all over the world as flavouring and colouring ingredients in Indian foods. Previous studies have shown that spices contain variable amounts of total oxalates but there are few reports of soluble oxalate contents. In this study, the total, soluble and insoluble oxalate contents of ten different spices commonly used in Indian cuisine were measured. Total oxalate content ranged from 194 (nutmeg) to 4,014 (green cardamom) mg/100 g DM, while the soluble oxalate contents ranged from 41 (nutmeg) to 3,977 (green cardamom) mg/100 g DM. Overall, the percentage of soluble oxalate content of the spices ranged from 4.7 to 99.1% of the total oxalate content which suggests that some spices present no risk to people liable to kidney stone formation, while other spices can supply significant amounts of soluble oxalates and therefore should be used in moderation. PMID:22492273

  11. Increasing the solubility enhancement of anionic DOWFAX surfactants

    SciTech Connect

    Carter, T.; Wu, B.; Sabatini, D.A.; Harwell, J.H.

    1998-11-01

    Previous research has demonstrated the robust nature of DOWFAX surfactants for enhanced subsurface remediation. However, these surfactants are not as effective as others in enhancing contaminant solubility. A series of experiments evaluated various methods of increasing the solubility enhancement of the DOWFAX components (i.e., using a cosurfactant, adding an electrolyte, and forming middle-phase microemulsions). Results demonstrate that while increasing the alkyl chain produced slight increases in contaminant solubility, middle-phase microemulsions produced the greatest enhancements. Middle-phase microemulsions were produced using an electrolyte, isobutanol, a cosurfactant, and one of the DOWFAX components. Middle-phase microemulsions increased contaminant solubilities by one to two orders of magnitude over DOWFAX surfactants alone, and by three to four orders of magnitude relative to water. Thus, DOWFAX-based microemulsion systems have the potential to significantly enhance contaminant solubility and expedite environmental remediation.

  12. Sparingly soluble pesticide dissolved in ionic liquid aqueous.

    PubMed

    Fan, Tengfei; Wu, Xuemin; Peng, Qingrong

    2014-10-01

    Ionic liquids may be considered as "environment-friendly solvents" for sparingly soluble pesticides. In this study, a series of aqueous ionic liquids (ILs) with different cations and different anions was used as environment-friendly alternative to harmful organic solvents sparingly dissolved in soluble pesticides (metolachlor, acetochlor, clethodim, thiamethoxam, and prochloraz). The aggregation behavior of aqueous ILs was investigated through surface tension measurement. Minimum area per IL molecule (Amin) values from the surface tension measurement showed that alkyl chain length and the halide anions strongly affect the aggregation behavior of ILs and the solubilization of pesticides. The solubility of metolachlor, acetochlor, clethodim, thiamethoxam, nitenpyram, and prochloraz in aqueous ILs increased. More importantly, the solubility of prochloraz in [C10mim][I] became 5771-fold higher than that in pure water. The substantially enhanced solubility of the above pesticides proved that aqueous ILs are promising environment-friendly solvents for pesticides that are commercially processed in emulsifiable concentrate (EC) formulation. PMID:25222470

  13. Metal solubility enhancing peptides derived from barley protein.

    PubMed

    Eckert, Ewelina; Bamdad, Fatemeh; Chen, Lingyun

    2014-09-15

    Mineral supplements are required to be soluble as their bioavailability is highly correlated to their solubility in body fluids. In this study, metal binding capacity of barley protein hydrolysates and their purified fractions was investigated and expressed as increase in solubility of metal ions. Metal ions in the presence of hydrolysates exhibited a remarkable increase in solubility: 118, 32, 10, 29 and 35-fold for Fe(2+), Fe(3+), Ca(2+), Cu(2+) and Zn(2+), respectively. A mixture of low molecular weight peptides possesses a synergistic combination of both charged and hydrophobic residues and achieves the best binding metal ions. Electrostatic interactions via charged side chains and coordination binding with His and Cys, initially attract the metal ions and, afterward, hydrophobic interactions and aromatic ring stacking stabilize the positioning of metal ions in the structure of the peptide. Barley hordein hydrolysates show potential as dietary supplements that enhance both mineral solubility and bioavailability. PMID:24767088

  14. Tetragonal Chicken Egg White Lysozyme Solubility in Sodium Chloride Solutions

    NASA Technical Reports Server (NTRS)

    Forsythe, Elizabeth L.; Judge, Russell A.; Pusey, Marc L.

    1998-01-01

    The solubility of chicken egg white lysozyme, crystallized in the tetragonal form was measured in sodium chloride solutions from 1.6 to 30.7 C, using a miniature column solubility apparatus. Sodium chloride solution concentrations ranged from 1 to 7% (w/v). The solutions were buffered with 0.1 M sodium acetate buffer with the solubility being measured at pH values in 0.2 pH unit increments in the range pH 4.0 to 5.4, with data also included at pH 4.5. Lysozyme solubility was found to increase with increases in temperature and decreasing salt concentration. Solution pH has a varied and unpredictable effect on solubility.

  15. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    PubMed

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability. PMID:26593522

  16. A literature review of interaction of oxidized uranium species and uranium complexes with soluble organic matter

    USGS Publications Warehouse

    Jennings, Joan K.; Leventhal, J.S.

    1978-01-01

    Organic material is commonly found associated with uranium ores in sandstone-type deposits. This review of the literature summarizes the classes and separations of naturally occurring organic material but the emphasis is on soluble organic species. The main class of materials of interest is humic substances which are high-molecular-weight complex molecules that are soluble in alkaline solution. These humic substances are able to solubilize (make soluble) minerals and also to complex [by ion exchange and (or) chelation] many cations. The natural process of soil formation results in both mineral decomposition and element complexing by organic species. Uranium in solution, such as ground water, can form many species with other elements or complexes present depending on Eh and pH. In natural systems (oxidizing Eh, pH 5-9) the uranium is usually present as a complex with hydroxide or carbonate. Thermodynamic data for these species are presented. Interacting metals and organic materials have been observed in nature and studied in the laboratory by many workers in diverse scientific disciplines. The results are not easily compared. Measurements of the degree of complexation are reported as equilibrium stability constant determinations. This type of research has been done for Mn, Fe, Cu, Zn, Pb, Ni, Co, Mg, Ca, Al, and to a limited degree for U. The use of Conditional Stability Constants has given quantitative results in some cases. The methods utilized in experiments and calculations are reviewed.

  17. Discordant effects of a soluble VEGF receptor on wound healing and angiogenesis.

    PubMed

    Jacobi, Johannes; Tam, Betty Y Y; Sundram, Uma; von Degenfeld, Georges; Blau, Helen M; Kuo, Calvin J; Cooke, John P

    2004-02-01

    Soluble receptors to vascular endothelial growth factor (VEGF) can inhibit its angiogenic effect. Since angiogenesis is involved in wound repair, we hypothesized that adenovirus-mediated gene transfer of a soluble form of VEGF receptor 2 (Flk-1) would attenuate wound healing in mice. C57Bl/6J and genetically diabetic (db/db) mice (each n=20) received intravenous (i.v.) injections of recombinant adenoviruses (10(9) PFU) encoding the ligand-binding ectodomain of VEGF receptor 2 (Flk-1) or cDNA encoding the murine IgG2alpha Fc fragment (each n=10). At 4 days after gene transfer, two full-thickness skin wounds (0.8 cm) were created on the dorsum of each animal. Wound closure was measured over 9-14 days after which wounds were resected for histological analysis. Prior to killing, fluorescent microspheres were systemically injected for quantitation of wound vascularity. Single i.v. injections of adenoviruses encoding soluble Flk-1 significantly decreased wound angiogenesis in both wild-type and diabetic mice. Fluorescence microscopy revealed a 2.0-fold (wild type) and 2.9-fold (diabetic) reduction in wound vascularity in Flk-1-treated animals (p<0.05). Impairment of angiogenesis was confirmed by CD31 immunohistochemistry. Interestingly, despite significant reductions in wound vascularity, wound closure was not grossly delayed. Our data indicates that while VEGF function is essential for optimal wound angiogenesis, it is not required for wound closure. PMID:14737090

  18. Biological significance of soluble IL-2 receptor

    PubMed Central

    Candore, Giuseppina; Cigna, Diego; Colucci, Antonio Tobia; Modica, Maria Assunta

    1993-01-01

    A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC) activation and interleukin-2 receptor (IL-2R) expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R) is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting findings are discussed in the light of the data showing that sIL-2R production correlates with IL-2 production. PMID:18475497

  19. Ion Association versus Ion Interaction Models in Examining Electrolyte Solutions: Application to Calcium Hydroxide Solubility Equilibrium

    ERIC Educational Resources Information Center

    Menéndez, M. Isabel; Borge, Javier

    2014-01-01

    The heterogeneous equilibrium of the solubility of calcium hydroxide in water is used to predict both its solubility product from solubility and solubility values from solubility product when inert salts, in any concentration, are present. Accepting the necessity of including activity coefficients to treat the saturated solution of calcium…

  20. Illustrating the Concept of Sparingly Soluble Salts Using Various Copper Compounds: A Classroom Demonstration

    ERIC Educational Resources Information Center

    O'Sullivan, Daniel W.; Crouch, Collier C.

    2009-01-01

    Many students in general and advanced chemistry courses have difficulty understanding differences in solubility by inspecting changing values of the solubility product constants for sparingly soluble salts. In this demonstration, the concepts involved in understanding the solubility of sparingly soluble salts are illustrated visually. Utilizing…

  1. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    PubMed Central

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  2. Small acid soluble proteins for rapid spore identification.

    SciTech Connect

    Branda, Steven S.; Lane, Todd W.; VanderNoot, Victoria A.; Jokerst, Amanda S.

    2006-12-01

    This one year LDRD addressed the problem of rapid characterization of bacterial spores such as those from the genus Bacillus, the group that contains pathogenic spores such as B. anthracis. In this effort we addressed the feasibility of using a proteomics based approach to spore characterization using a subset of conserved spore proteins known as the small acid soluble proteins or SASPs. We proposed developing techniques that built on our previous expertise in microseparations to rapidly characterize or identify spores. An alternative SASP extraction method was developed that was amenable to both the subsequent fluorescent labeling required for laser-induced fluorescence detection and the low ionic strength requirements for isoelectric focusing. For the microseparations, both capillary isoelectric focusing and chip gel electrophoresis were employed. A variety of methods were evaluated to improve the molecular weight resolution for the SASPs, which are in a molecular weight range that is not well resolved by the current methods. Isoelectric focusing was optimized and employed to resolve the SASPs using UV absorbance detection. Proteomic signatures of native wild type Bacillus spores and clones genetically engineered to produce altered SASP patterns were assessed by slab gel electrophoresis, capillary isoelectric focusing with absorbance detection as well as microchip based gel electrophoresis employing sensitive laser-induced fluorescence detection.

  3. Hansen solubility parameter analysis on the dispersion of zirconia nanocrystals.

    PubMed

    Wang, Sho-Hsun; Liu, Jia-Hong; Pai, Chin-Tung; Chen, Chien-Wei; Chung, Pao-Tang; Chiang, Anthony Shiaw-Tseh; Chang, Shinn-Jen

    2013-10-01

    Nanoparticle dispersible in a broad range of solvents is desirable when preparing an organic/inorganic nanocomposite. In this report, the dispersion behavior of carboxylate-grafted zirconia nanoparticle in 25 solvents covering a wide range of polarity was analyzed based on their Hansen solubility parameters (HSP). Particles grafted with alkyl-chain longer than four carbons could only be dispersed in non-polar solvents, while that grafted with acetic acid was dispersible in polar ones. However, particle modified with methacrylic acid (MA) was compatible with both types of solvents, which was rather unexpected. Further NMR analysis showed that the carboxylate-grafted samples contained a trace amount of triethanolamine (TEA) due to the particular ZrO2 synthesis process employed. The combination of the hydrophilic TEA ligand with the short hydrophobic tail of methacrylate broadened the range of compatible solvents from benzene to methanol. Such an extended solvent compatibility was observed previously only for nanoparticles covered with large polymer surfactants having both hydrophilic and hydrophobic groups. Achieving this with two small molecules having separate functional groups is crucial when one needs to maximize the inorganic content in a composite. PMID:23906862

  4. Soluble epoxide hydrolase inhibitory activity of anthraquinone components from Aloe.

    PubMed

    Sun, Ya Nan; Kim, Jang Hoon; Li, Wei; Jo, A Reum; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

    2015-10-15

    Aloe is a short-stemmed succulent herb widely used in traditional medicine to treat various diseases and as raw material in cosmetics and heath foods. In this study, we isolated and identified two new anthraquinone derivatives, aloinoside C (6) and aloinoside D (7), together with six known compounds from an aqueous dissolved Aloe exudate. Their structures were identified by spectroscopic analysis. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were evaluated. Compounds 1-8 inhibited sEH activity potently, with IC50 values ranging from 4.1±0.6 to 41.1±4.2?M. A kinetic analysis of compounds 1-8 revealed that the inhibitory actions of compounds 1, 6 and 8 were non-competitive, whereas those of compounds 2-5 and 7 were the mixed-type. Molecular docking increases our understanding of receptor-ligand binding of all compounds. These results demonstrate that compounds 1-8 from Aloe are potential sEH inhibitors. PMID:26372074

  5. Expression and regulation of soluble epoxide hydrolase in adipose tissue.

    PubMed

    De Taeye, Bart M; Morisseau, Christophe; Coyle, Julie; Covington, Joseph W; Luria, Ayala; Yang, Jun; Murphy, Sheila B; Friedman, David B; Hammock, Bruce B; Vaughan, Douglas E

    2010-03-01

    Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a "western diet." sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a "western diet," total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity. PMID:19644452

  6. Activin Receptor Signaling Regulates Prostatic Epithelial

    E-print Network

    Wisconsin at Madison, University of

    and neuroblastoma cells grown in FBS. Suppression of ActRII signaling in PCC and neuroblastoma cells did not induce metastasis. These findings indicate that ActRII signaling is required for PCC and neuroblastoma cell

  7. Activin/Nodal signalling in stem cells

    E-print Network

    Pauklin, Siim; Vallier, Ludovic

    2015-02-15

      acetyltransferase   CBP/p300   or   histone   deacetylases   HDAC1-­?6,   respectively.   Smad2/3   can   also   cooperate   with   co-­? regulators   SWI/SNF,   MEDIATOR/ARC105   and   NuRD   in   inducing   or   repressing...

  8. Solubility of Lysozyme in Polyethylene Glycol-Electrolyte Mixtures: The Depletion Interaction and Ion-Specific Effects

    PubMed Central

    Bon?ina, Matjaž; Reš?i?, Jurij; Vlachy, Vojko

    2008-01-01

    The solubility of aqueous solutions of lysozyme in the presence of polyethylene glycol and various alkaline salts was studied experimentally. The protein-electrolyte mixture was titrated with polyethylene glycol, and when precipitation of the protein occurred, a strong increase of the absorbance at 340 nm was observed. The solubility data were obtained as a function of experimental variables such as protein and electrolyte concentrations, electrolyte type, degree of polymerization of polyethylene glycol, and pH of the solution; the last defines the net charge of the lysozyme. The results indicate that the solubility of lysozyme decreases with the addition of polyethylene glycol; the solubility is lower for a polyethylene glycol with a higher degree of polymerization. Further, the logarithm of the protein solubility is a linear function of the polyethylene glycol concentration. The process is reversible and the protein remains in its native form. An increase of the electrolyte (NaCl) concentration decreases the solubility of lysozyme in the presence and absence of polyethylene glycol. The effect can be explained by the screening of the charged amino residues of the protein. The solubility experiments were performed at two different pH values (pH = 4.0 and 6.0), where the lysozyme net charge was +11 and +8, respectively. Ion-specific effects were systematically investigated. Anions such as Br?, Cl?, F?, and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{H}}_{2}{\\mathrm{PO}}_{4}^{-}\\end{equation*}\\end{document} (all in combination with Na+), when acting as counterions to a protein with positive net charge, exhibit a strong effect on the lysozyme solubility. The differences in protein solubility for chloride solutions with different cations Cs+, K+, and Na+ (coions) were much smaller. The results at pH = 4.0 show that anions decrease the lysozyme solubility in the order \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{F}}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{H}}_{2}{\\mathrm{PO}}_{4}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{Cl}}^{-}\\hspace{.167em}<\\hspace{.167em}{\\mathrm{Br}}^{-}\\end{equation*}\\end{document} (the inverse Hofmeister series), whereas cations follow the direct Hofmeister series (Cs+ < K+ < Na+) in this situation. PMID:18441020

  9. Development of an ALK2-biased BMP type I receptor kinase inhibitor.

    PubMed

    Mohedas, Agustin H; Xing, Xuechao; Armstrong, Kelli A; Bullock, Alex N; Cuny, Gregory D; Yu, Paul B

    2013-01-01

    The bone morphogenetic protein (BMP) signaling pathway has essential functions in development, homeostasis, and the normal and pathophysiologic remodeling of tissues. Small molecule inhibitors of the BMP receptor kinase family have been useful for probing physiologic functions of BMP signaling in vitro and in vivo and may have roles in the treatment of BMP-mediated diseases. Here we describe the development of a selective and potent inhibitor of the BMP type I receptor kinases, LDN-212854, which in contrast to previously described BMP receptor kinase inhibitors exhibits nearly 4 orders of selectivity for BMP versus the closely related TGF-? and Activin type I receptors. In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity, and function. LDN-212854 potently inhibits heterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva. These findings represent a significant step toward developing selective inhibitors targeting individual members of the highly homologous BMP type I receptor family. Such inhibitors would provide greater resolution as probes of physiologic function and improved selectivity against therapeutic targets. PMID:23547776

  10. Soluble ST2 in heart failure.

    PubMed

    Dieplinger, Benjamin; Mueller, Thomas

    2015-03-30

    In addition to routine clinical laboratory tests (including natriuretic peptides and cardiac troponins), other biomarkers are gaining attention for their utility in heart failure (HF) management. Among them, soluble ST2 (sST2) a novel biomarker integrating inflammation, fibrosis, and cardiac stress has been included in the 2013 ACCF/AHA guideline for additive risk stratification of patients with acute and chronic HF. sST2 is an interleukin-1 (IL-1) receptor family member, is secreted into the circulation and functions as a "decoy" receptor for IL-33, inhibiting IL-33/ST2 signaling. Blood concentrations of sST2 are increased in various diseases such as inflammatory diseases and heart diseases and are considered a valuable prognostic marker in both conditions. sST2 lacks disease specificity and, therefore, is not a valuable marker for the diagnosis of HF. In acute and chronic HF, however, sST2 is strongly associated with measures of HF severity and poor outcome. Several studies in patients with HF indicate that serial measurement of sST2 has prognostic value and could have a potential role in future biomarker-directed therapy. In this review, the role of sST2 as a HF biomarker will be discussed, specifically addressing analytical considerations of measuring sST2 as well as the clinical applications of measurement of sST2 for the diagnosis, prognosis and monitoring of acute and chronic HF. PMID:25269091

  11. Sodium tetraphenylborate solubility and dissolution rates

    SciTech Connect

    Barnes, M.J.; Peterson, R.A.; Swingle, R.F.; Reeves, C.T.

    1995-12-31

    The rate of solid sodium tetraphenylborate (NaTPB) dissolution in In-Tank Precipitation salt solutions has been experimentally determined. The data indicates that the dissolution rate of solid NaTPB is a minor contributor the lag time experienced in the 1983 Salt Decontamination Demonstration Test and should not be considered as the rate determining step. Current analytical models for predicting the time to reach the composite lower flammability limit assume that the lag time is not more than 6 hours, and the data supports this assumption (i.e., dissolution by itself requires much less than 6 hours). The data suggests that another step--such as mass transport, the reaction of a benzene precursor or the mixing behavior--is the rate determining factor for benzene release to the vapor space in Tank 48H. In addition, preliminary results from this program show that the degree of agitation employed is not a significant parameter in determining the rate of NaTPB dissolution. As a result of this study, an improved equation for predicting equilibrium tetraphenylborate solubility with respect to temperature and sodium ion concentration has been determined.

  12. Solubility of H2O in rhyolitic melts at low pressures and a new empirical model for mixed H2OCO2 solubility in rhyolitic melts

    E-print Network

    Zhang, Youxue

    Solubility of H2O in rhyolitic melts at low pressures and a new empirical model for mixed H2O­CO2: H2O solubility; H2O­CO2 solubility; solubility model; exsolution enthalpy; volcanic eruption@geosci.uchicago.edu (Y. Liu). Journal of Volcanology and Geothermal Research 143 (2005) 219­235 www

  13. Rationally Designed, Nontoxic, Nonamyloidogenic Analogues of Human Islet Amyloid Polypeptide with Improved Solubility

    PubMed Central

    2015-01-01

    Human islet amyloid polypeptide (hIAPP or amylin) is a polypeptide hormone produced in the pancreatic ?-cells that plays a role in glycemic control. hIAPP is deficient in type 1 and type 2 diabetes and is a promising adjunct to insulin therapy. However, hIAPP rapidly forms amyloid, and its strong tendency to aggregate limits its usefulness. The process of hIAPP amyloid formation is toxic to cultured ?-cells and islets, and islet amyloid formation in vivo has been linked to ?-cell death and islet graft failure. An analogue of hIAPP with a weakened tendency to aggregate, denoted pramlintide (PM), has been approved for clinical applications, but suffers from poor solubility, particularly at physiological pH, and its unfavorable solubility profile prevents coformulation with insulin. We describe a strategy for rationally designing analogues of hIAPP with improved properties; key proline mutations are combined with substitutions that increase the net charge of the molecule. An H18R/G24P/I26P triple mutant and an H18R/A25P/S28P/S29P quadruple mutant are significantly more soluble at neutral pH than hIAPP or PM. They are nonamyloidogenic and are not toxic to rat INS ?-cells. The approach is not limited to these examples; additional analogues can be designed using this strategy. To illustrate this point, we show that an S20R/G24P/I26P triple mutant and an H18R/I26P double mutant are nonamyloidogenic and significantly more soluble than human IAPP or PM. These analogues and second-generation derivatives are potential candidates for the coformulation of IAPP with insulin and other polypeptides. PMID:25140605

  14. A Strategy for Increasing Drug Solubility and Efficacy through Covalent Attachment to Polyvalent DNA-Nanoparticle Conjugates

    PubMed Central

    Zhang, Xue-Qing; Xu, Xiaoyang; Lam, Robert; Giljohann, David; Ho, Dean; Mirkin, Chad A.

    2011-01-01

    Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50 fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA-nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media. PMID:21812457

  15. Solubility properties of synthetic and natural meta-torbernite

    NASA Astrophysics Data System (ADS)

    Cretaz, Fanny; Szenknect, Stéphanie; Clavier, Nicolas; Vitorge, Pierre; Mesbah, Adel; Descostes, Michael; Poinssot, Christophe; Dacheux, Nicolas

    2013-11-01

    Meta-torbernite, Cu(UO2)2(PO4)2?8H2O, is one of the most common secondary minerals resulting from the alteration of pitchblende. The determination of the thermodynamic data associated to this phase appears to be a crucial step toward the understanding the origin of uranium deposits or to forecast the fate and transport of uranium in natural media. A parallel approach based on the study of both synthetic and natural samples of meta-torbernite (H3O)0.4Cu0.8(UO2)2(PO4)2?7.6H2O was set up to evaluate its solubility constant. The two solids were first thoroughly characterized and compared by means of XRD, SEM, X-EDS analyses, Raman spectroscopy and BET measurements. The solubility constant was then determined in both under- and supersaturated conditions: the obtained value appeared close to logKs,0°(298 K) = -52.9 ± 0.1 whatever the type of experiment and the sample considered. The joint determination of Gibbs free energy (?RG°(298 K) = 300 ± 2 kJ mol-1) then allowed the calculation of ?RH°(298 K) = 40 ± 3 kJ mol-1 and ?RS°(298 K) = -879 ± 7 J mol-1 K-1. From these values, the thermodynamic data associated with the formation of meta-torbernite (H3O)0.4Cu0.8(UO2)2(PO4)2?7.6H2O were also evaluated and found to be consistent with those previously obtained by calorimetry, showing the reliability of the method developed in this work. Finally, the obtained data were implemented in a calculation code to determine the conditions of meta-torbernite formation in environmental conditions typical of a former mining site. SI=log({Q}/{Ks}) with Q=?i( where ?i is the stoichiometric coefficient (algebraic value) of species i and ai the nonequilibrium activity of i.

  16. Solubility of simvastatin: A theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Aceves-Hernández, Juan M.; Hinojosa-Torres, Jaime; Nicolás-Vázquez, Inés; Ruvalcaba, Rene Miranda; García, Rosa María Lima

    2011-05-01

    Solubility experimental data from Simvastatin in a family of alcohols were obtained at different temperatures. Simvastatin was characterized by using thermal analysis and X-ray diffraction. From the experimental solubility data an anomalous behavior was observed, since an increase the number of alcohol carbon atoms shows an increase in solubility only for the three first alcohols, ethanol, 1-propanol and 1-butanol. A decrease in solubility was obtained for 1-pentanol, 1-hexanol and 1-octanol. Van't·Hoff equation was used to obtain the theoretical solubility value and the ideal activity coefficient. Experimental error was very low and does not affect the plots and equations used. No polymorphic phenomenon was found from the Simvastatin characterization. Theoretical calculations were carried out in order to corroborate the experimental solubility data. Trends and results are similar in both cases. The geometry optimizations of Simvastatin was carried out using density functional theory with Becke's three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-311++G?? basis set. The solvent effect was treated using a continuum model as modeled in water, methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol and 1-octanol. Moreover, dielectric constant, dipolar moment and solubility in the solvents were obtained for explaining the former behavior.

  17. Uranium (VI) solubility in carbonate-free ERDA-6 brine

    SciTech Connect

    Lucchini, Jean-francois; Khaing, Hnin; Reed, Donald T

    2010-01-01

    When present, uranium is usually an element of importance in a nuclear waste repository. In the Waste Isolation Pilot Plant (WIPP), uranium is the most prevalent actinide component by mass, with about 647 metric tons to be placed in the repository. Therefore, the chemistry of uranium, and especially its solubility in the WIPP conditions, needs to be well determined. Long-term experiments were performed to measure the solubility of uranium (VI) in carbonate-free ERDA-6 brine, a simulated WIPP brine, at pC{sub H+} values between 8 and 12.5. These data, obtained from the over-saturation approach, were the first repository-relevant data for the VI actinide oxidation state. The solubility trends observed pointed towards low uranium solubility in WIPP brines and a lack of amphotericity. At the expected pC{sub H+} in the WIPP ({approx} 9.5), measured uranium solubility approached 10{sup -7} M. The objective of these experiments was to establish a baseline solubility to further investigate the effects of carbonate complexation on uranium solubility in WIPP brines.

  18. CCN activation of fumed silica aerosols mixed with soluble pollutants

    NASA Astrophysics Data System (ADS)

    Dalirian, M.; Keskinen, H.; Ahlm, L.; Ylisirniö, A.; Romakkaniemi, S.; Laaksonen, A.; Virtanen, A.; Riipinen, I.

    2014-09-01

    Particle-water interactions of completely soluble or insoluble particles are fairly well understood but less is known of aerosols consisting of mixtures of soluble and insoluble components. In this study, laboratory measurements were performed to investigate cloud condensation nuclei (CCN) activity of silica particles coated with ammonium sulphate (a salt), sucrose (a sugar) and bovine serum albumin known as BSA (a protein). In addition, the agglomerated structure of the silica particles was investigated by estimating the surface equivalent diameter based on measurements with a Differential Mobility Analyzer (DMA) and an Aerosol Particle Mass Analyzer (APM). By using the surface equivalent diameter the non-sphericity of the particles containing silica was accounted for when estimating CCN activation. Furthermore, characterizing critical supersaturations of particles consisting of pure soluble on insoluble compounds using existing frameworks showed that the CCN activation of single component particles was in good agreement with Köhler and adsorption theory based models when the agglomerated structure was accounted for. For mixed particles the CCN activation was governed by the soluble components, and the soluble fraction varied considerably with particle size for our wet-generated aerosols. Our results confirm the hypothesis that knowing the soluble fraction is the key parameter needed for describing the CCN activation of mixed aerosols, and highlight the importance of controlled coating techniques for acquiring a detailed understanding of the CCN activation of atmospheric insoluble particles mixed with soluble pollutants.

  19. CCN activation of fumed silica aerosols mixed with soluble pollutants

    NASA Astrophysics Data System (ADS)

    Dalirian, M.; Keskinen, H.; Ahlm, L.; Ylisirniö, A.; Romakkaniemi, S.; Laaksonen, A.; Virtanen, A.; Riipinen, I.

    2015-04-01

    Particle-water interactions of completely soluble or insoluble particles are fairly well understood but less is known of aerosols consisting of mixtures of soluble and insoluble components. In this study, laboratory measurements were performed to investigate cloud condensation nuclei (CCN) activity of silica particles mixed with ammonium sulfate (a salt), sucrose (a sugar) and bovine serum albumin known as BSA (a protein). The agglomerated structure of the silica particles was investigated using measurements with a differential mobility analyser (DMA) and an aerosol particle mass analyser (APM). Based on these data, the particles were assumed to be compact agglomerates when studying their CCN activation capabilities. Furthermore, the critical supersaturations of particles consisting of pure and mixed soluble and insoluble compounds were explored using existing theoretical frameworks. These results showed that the CCN activation of single-component particles was in good agreement with Köhler- and adsorption theory based models when the agglomerated structure was accounted for. For mixed particles the CCN activation was governed by the soluble components, and the soluble fraction varied considerably with particle size for our wet-generated aerosols. Our results confirm the hypothesis that knowing the soluble fraction is the key parameter needed for describing the CCN activation of mixed aerosols, and highlight the importance of controlled coating techniques for acquiring a detailed understanding of the CCN activation of atmospheric insoluble particles mixed with soluble pollutants.

  20. Solubilities of nitrogen and noble gases in basalt melt

    NASA Technical Reports Server (NTRS)

    Miyazaki, A.; Hiyagon, H.; Sugiura, N.

    1994-01-01

    Nitrogen and noble gases are important tracers in geochemistry and chosmochemistry. Compared to noble gases, however, physicochemical properties of nitrogen, such as solubility in melt or melt/silicate partition, are not well known. Solubility of nitrogen in basalt melt depends on redox condition of the atmosphere. For example, solubility of nitrogen in E chondrite melt under reducing conditions is as high as 2 mol percent at 1500 C, suggesting that nitrogen is chemically dissolved in silicate melts, i.e., being dissolved as free anions or replacing oxygen sites in silicate network. However, the solubility and the dissolution mechanism of nitrogen under oxidizing conditions are not well investigated. To obtain nitrogen solubility in silicate melts under various redox conditions and to understand its mechanism, we are conducting experiments by using (15)N(15)N-labeled nitrogen gas. This makes it easy to distinguish dissolved nitrogen from later contamination of atmospheric nitrogen, and hence enables us to measure the nitrogen solubility accurately. As a preliminary experiment, we have measured solubility of nitrogen in basalt melt under the atmospheric oxygen pressure.

  1. The solubility of hydrogen in rhodium, ruthenium, iridium and nickel.

    NASA Technical Reports Server (NTRS)

    Mclellan, R. B.; Oates, W. A.

    1973-01-01

    The temperature variation of the solubility of hydrogen in rhodium, ruthenium, iridium, and nickel in equilibrium with H2 gas at 1 atm pressure has been measured by a technique involving saturating the solvent metal with hydrogen, quenching, and analyzing in resultant solid solutions. The solubilities determined are small (atom fraction of H is in the range from 0.0005 to 0.00001, and the results are consistent with the simple quasi-regular model for dilute interstitial solid solutions. The relative partial enthalpy and excess entropy of the dissolved hydrogen atoms have been calculated from the solubility data and compared with well-known correlations between these quantities.

  2. The solubility of hen egg-white lysozyme

    NASA Technical Reports Server (NTRS)

    Howard, Sandra B.; Twigg, Pamela J.; Baird, James K.; Meehan, Edward J.

    1988-01-01

    The equilibrium solubility of chicken egg-white lysozyme in the presence of crystalline solid state was determined as a function of NaCl concentration, pH, and temperature. The solubility curves obtained represent a region of the lysozyme phase diagram. This diagram makes it possible to determine the supersaturation of a given set of conditions or to achieve identical supersaturations by different combinations of parameters. The temperature dependence of the solubility permits the evaluation of Delta-H of crystallization. The data indicate a negative heat of crystallization for the tetragonal crystal form but a positive heat of crystallization for the high-temperature orthorhombic form.

  3. Solubility and diffusion coefficients of gaseous formaldehyde in polymers.

    PubMed

    Hennebert, P

    1988-03-01

    The solubility and diffusion (desorption) coefficients of gaseous formaldehyde in 14 materials have been measured at different temperatures. Cellulose, paper, polyamide (Nylon 6), polyester and natural rubber (latex) show very high values of formaldehyde solubility and very low diffusion coefficients, with a weak or inversed influence of the temperature, leading to the conclusion that a chemical reaction occurs with the formaldehyde. The behaviour of the other polymers follows the classical laws of solubility and diffusion of gases except for silicone rubber which shows two-phase desorption curves. PMID:3370284

  4. Soluble epoxide hydrolase inhibitors and heart failure.

    PubMed

    Qiu, Hong; Li, Ning; Liu, Jun-Yan; Harris, Todd R; Hammock, Bruce D; Chiamvimonvat, Nipavan

    2011-04-01

    Cardiovascular disease remains one of the leading causes of death in the Western societies. Heart failure (HF) is due primarily to progressive myocardial dysfunction accompanied by myocardial remodeling. Once HF develops, the condition is, in most cases, irreversible and is associated with a very high mortality rate. Soluble epoxide hydrolase (sEH) is an enzyme that catalyzes the hydrolysis of epoxyeicosatrienoic acids (EETs), which are lipid mediators derived from arachidonic acid through the cytochrome P450 epoxygenase pathway. EETs have been shown to have vasodilatory, antiinflammatory, and cardioprotective effects. When EETs are hydrolyzed by sEH to corresponding dihydroxyeicosatrienoic acids, their cardioprotective activities become less pronounced. In line with the recent genetic study that has identified sEH as a susceptibility gene for HF, the sEH enzyme has received considerable attention as an attractive therapeutic target for cardiovascular diseases. Indeed, sEH inhibition has been demonstrated to have antihypertensive and antiinflammatory actions, presumably due to the increased bioavailability of endogenous EETs and other epoxylipids, and several potent sEH inhibitors have been developed and tested in animal models of cardiovascular disease including hypertension, cardiac hypertrophy, and ischemia/reperfusion injury. sEH inhibitor treatment has been shown to effectively prevent pressure overload- and angiotensin II-induced cardiac hypertrophy and reverse the pre-established cardiac hypertrophy caused by chronic pressure overload. Application of sEH inhibitors in several cardiac ischemia/reperfusion injury models reduced infarct size and prevented the progressive cardiac remodeling. Moreover, the use of sEH inhibitors prevented the development of electrical remodeling and ventricular arrhythmias associated with cardiac hypertrophy and ischemia/reperfusion injury. The data published to date support the notion that sEH inhibitors may represent a promising therapeutic approach for combating detrimental cardiac remodeling and HF. PMID:20433684

  5. Soluble Fibrin Monomer Complex and Cardiopulmonary Bypass

    PubMed Central

    Bonk, Ryan; Trowbridge, Cody; Stammers, Alfred; Klayman, Myra; Marko, Molly; Brindisi, Nicholas; Pezzuto, James

    2009-01-01

    Abstract: Soluble fibrin monomer complexes (SFMCs) are precursors of fibrin polymer formation. Laboratory tests can be used to detect SFMCs in plasma. The purpose of this study was to determine whether a positive SFMC test is associated with pre-operative, intra-operative, and post-operative variables for patients that have undergone cardiopulmonary bypass (CPB). Pre-operative, operative, post-operative, and laboratory data from 120 consecutive adults patients (July 3, 2006 to June 29, 2007) that had undergone cardiac surgery with the use of CPB were obtained from a prospective quality control database. Two groups were created. Group 1 was all negative (NEG). This group had no SFMC test with a positive result (n = 60) and no positive SFMCs (POS, n = 60). Group 2 was any positive (POS). This group had at least one positive SFMC test (n = 60). The POS group had more patients with endocarditis (11.7% vs. 3.3%, p < .001), chronic obstructive pulmonary disease (COPD) (18% vs. 8.3%, p = .005), longer CPB time (172 ± 64 vs. 151 ± 53 minutes, p = .047), and fewer minimally invasive procedures (31.7% vs. 51.7%, p = .002). The POS group required intraoperative (70.0% vs. 53.3%, p = .010) and post-operative (75.5% vs. 45.0%, p < .001) transfusions more frequently than the NEG group, despite similar amounts of blood loss. SFMC tests in CPB may be associated with patient pre-operative status and an increase in transfusion requirements. PMID:19806798

  6. Expression and identification of recombinant soluble single-chain variable fragment of monoclonal antibody MC3

    PubMed Central

    He, Feng-Tian; Nie, Yong-Zhan; Chen, Bao-Jun; Qiao, Tai-Dong; Fan, Dai-Ming; Li, Rong-Fen; Kang, Yun-Sheng; Zhang, Yan

    2002-01-01

    AIM: To generate soluble single chain variable fragments (ScFv) of monoclonal antibody MC3 recognizing colorectal and gastric carcinomas. METHODS: mRNA was isolated from the hybridoma cell line producing MC3 and the DNAs encoding variable domains of heavy and light chains (VH and VL) of the antibody were amplified separately by RT-PCR and assembled into ScFv DNA with a linker DNA.The ScFv DNA was ligated into the phagemid vector pCANTAB5E and the ligated sample was transformed into E. coli TG1.The transformed cells were infected with M13KO7 helper phage to yield recombinant phages. After two rounds of panning with gastric carcinoma cell line AGS highly expressing MC3-binding antigen, the phage clones displaying ScFv fragments of the antibody were selected by ELISA. 4 phage clones showing strong signal in ELISA were used to infect E. coli HB2151 to express soluble ScFvs. The soluble ScFvs were identified by Dot blot and Western blot, and their antigen-binding activity was assayed by ELISA. The VH and VL DNAs of the ScFv DNA derived from phage clone 19 were sequenced. RESULTS: The VH, VL and ScFv DNAs were about 340 bp, 320 bp and 750 bp respectively. After two rounds of panning to the recombinant phages, 18 antigen-positive phage clones were selected from 30 preselected phage clones by ELISA. All the soluble ScFvs derived from the 4 out of the 18 antigen-positive phage clones were about Mr32000 and concentrated in periplasmatic space under the given culture condition. The soluble ScFvs could bind the antigen, and they shared the same binding site with MC3. The sequences of the VH and VL DNAs of the MC3 ScFv showed that the variable antibody genes belonged to the IgG1 subgroup, ?-type. CONCLUSION: The soluble ScFv of MC3 is successfully produced, which not only provides a possible novel targeting vehicle for in vivo and in vitro study on associated cancers, but also offers the anuibody a stable genetic source. PMID:11925603

  7. Solubility of Aragonite in Aqueous Fluids at High Pressure and High Temperature

    NASA Astrophysics Data System (ADS)

    Facq, Sébastien; Daniel, Isabelle; Petitgirard, Sylvain; Cardon, Hervé; Sverjensky, Dimitri

    2014-05-01

    Deep crustal and mantle aqueous fluids play a crucial role in geologic processes occurring in the Earth's interior, especially at high PT conditions. Dissolved carbon appears to be a major element constituting these aqueous fluids, occurring under the form of molecular species (CO2, CO, CH4), ionic species such as carbonate or bicarbonate ions or some more complex organic compounds [1]. However, the nature and the content of the chemical species constituting these C-bearing aqueous fluids may strongly be affected by the environmental geologic conditions such as the pressure and the temperature range. If fluid speciation and solubility of carbonate minerals are well characterized at HT and relatively low pressure, less is evident at pressure above 2 GPa where experimental challenges make trickier speciation and solubility measurements. Thanks to recent advances in theoretical aqueous geochemistry [1-3], combined experimental and theoretical efforts allow now the investigation of speciation and solubility of carbonate minerals with pure water at higher PT conditions than previously feasible [4]. However, direct measurements of solubility of carbonate minerals at HP-HT conditions are still needed to help to the development of quantitative models of carbon transport by aqueous fluids in subduction zones and validate existing aqueous speciation model. In this study, we present recent X-ray fluorescence measurements and thermodynamic model of solubility of carbonate in aqueous fluids at pressure up to 5 GPa. The amount of dissolved aragonite in the fluid has been measured from the intensity of the Ca K-lines at the ESRF-ID27 using an externally-heated membrane-type diamond anvil cell and an incident monochromatic focused X-Ray beam at 20 keV. The combination of the XRF data on dissolution of CaCO3mineral combined to previous speciation results permits now to calculate the solubility KS of aragonite a pressure in excess of 2 GPa. [1] Manning, C. E. et al., Review in Mineralogy & Geochemistry, 75, 109 (2013). [2] Sverjensky, D. A et al., Geochimica et Cosmochimica Acta (2014, in press). [3] Pan et al., Proceedings of the National Academy of Sciences, 110, 6646 (2013) [4] Facq et al, Geochimica et Cosmochimica Acta (2014, submitted).

  8. Acid soluble platelet aggregating material isolated from human umbilical cord

    SciTech Connect

    Schneider, M.D.

    1983-12-27

    An acid soluble, pepsin sensitive platelet aggregating material is isolated from human umbilical cord tissue by extraction with dilute aqueous acid. The method of isolation is disclosed and its use to control bleeding is described. 2 figs.

  9. Which Starch Fraction is Water-Soluble, Amylose or Amylopectin?

    ERIC Educational Resources Information Center

    Green, Mark M.; And Others

    1975-01-01

    A survey of 22 popular organic chemistry textbooks showed that only four correctly stated that of the two components of starch, amylopectin is the water-soluble, and amylose is the water-insoluble. (MLH)

  10. Combining insoluble and soluble factors to steer stem cell fate

    NASA Astrophysics Data System (ADS)

    Dingal, P. C. Dave P.; Discher, Dennis E.

    2014-06-01

    Materials-based control of stem cell fate is beginning to be rigorously combined with traditional soluble-factor approaches to better understand the cells' behaviour and maximize their potential for therapy.

  11. Improving tenoxicam solubility and bioavailability by cosolvent system.

    PubMed

    Yeh, Ming-Kung; Chang, Li-Chien; Chiou, Andy Hong-Jey

    2009-01-01

    The formulation study of tenoxicam, a poorly water-soluble drug, was developed by use of a ternary cosolvent system and has significantly enhanced the solubility. Additionally, the relative bioavailability of testing formulation was also evaluated by New Zealand rabbit with a single i.m. injection. The three-phase diagram for dimethylsulfoxide (DMSO)/propylene glycol/water, DMSO/ethanol/water, and DMSO/polyethoxylated castor oil/ethanol system was developed. The volume ratio of 5:4:1 in the DMSO/polyethoxylated castor oil/ethanol system resulted in a more suitable vehicle than other systems, with a high solubility (20.73 mg/ml) and low viscosity (10.0 Cp). A pharmacokinetic study of bioequivalence (F (rel) = 0.89) was also obtained. The present study not only provides a novel strategy improving tenoxicam solubility but also helps further scientific knowledge for the development of parenteral formulations. PMID:19224373

  12. Water-soluble dopamine-based polymers for photoacoustic imaging.

    PubMed

    Repenko, Tatjana; Fokong, Stanley; De Laporte, Laura; Go, Dennis; Kiessling, Fabian; Lammers, Twan; Kuehne, Alexander J C

    2015-04-11

    Here we present a facile synthetic method yielding a linear form of polydopamine via Kumada-coupling, which can be converted into water-soluble melanin, generating high contrast in photoacoustic imaging. PMID:25670068

  13. Relationships between octanol-water partition coefficient and aqueous solubility

    SciTech Connect

    Miller, M.M.; Waslk, S.P.; Huang, G.L.; Shiu, W.Y.; Mackay, D.

    1985-06-01

    The thermodynamic relationship between octanol-water partition coefficient and aqueous solubility is discussed in the light of recently measured data for highly hydrophobic chemicals. Experimental data indicate that the presence of dissolved octanol in water has little effect on the solubility of chemicals in water and that the presence of dissolved water in octanol has little effect on the solubility of chemicals in octanol. The activity coefficients of hydrophobic chemicals in aqueous solution and in octanol solution both increase with increased chemical molar volume. An approximately linear relationship between log activity coefficient and molar volume is suggested in both phases, a consequence of which is that a plot of log octanol-water partition coefficient vs. log liquid or subcooled liquid solubility has a slope of approximately -0.8. A molecular thermodynamic interpretation of the data is presented, and some environmental implications are discussed.

  14. Enhanced solubility and bioavailability of flurbiprofen by cycloamylose.

    PubMed

    Baek, Hyung Hee; Kwon, So Young; Rho, Shin-Joung; Lee, Won Seok; Yang, Ho-Joon; Hah, Jung-Mi; Choi, Han-Gon; Kim, Yong-Ro; Yong, Chul Soon

    2011-03-01

    The effect of cycloamylose on the aqueous solubility of flurbiprofen was investigated. To improve the solubility and bioavailability of flurbiprofen (poor water solubility), a solid dispersion was spray dried with a solution of flurbiprofen and cycloamylose at a weight ratio of 1:1. The physicochemical properties of solid dispersions were investigated using SEM, DSC, and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with a commercial product. Cycloamylose increased solubility of flurbiprofen approximately 12-fold and dissolution of it by 2-fold. Flurbiprofen was present in an unchanged crystalline state, and cycloamylose was a solubilizing agent for flurbiprofen in this solid dispersion. Furthermore, the dispersion gave higher AUC and C(max) values compared with the commercial product, indicating that it improved the oral bioavailability of flurbiprofen in rats. Thus, the solid dispersion may be useful to deliver flurbiprofen with enhanced bioavailability without changes in crystalline structure. PMID:21547670

  15. Anomalous solubility behavior of mixed monolayer protected metal nanoparticles

    E-print Network

    Myerson, Jacob W

    2005-01-01

    The solubility of mixed monolayer protected gold nanoparticles was studied. Monolayer protected metal nanoparticles are attractive materials because of the optical and electronic properties of their metal cores and because ...

  16. Actinide (III) solubility in WIPP Brine: data summary and recommendations

    SciTech Connect

    Borkowski, Marian; Lucchini, Jean-Francois; Richmann, Michael K.; Reed, Donald T.

    2009-09-01

    The solubility of actinides in the +3 oxidation state is an important input into the Waste Isolation Pilot Plant (WIPP) performance assessment (PA) models that calculate potential actinide release from the WIPP repository. In this context, the solubility of neodymium(III) was determined as a function of pH, carbonate concentration, and WIPP brine composition. Additionally, we conducted a literature review on the solubility of +3 actinides under WIPP-related conditions. Neodymium(III) was used as a redox-invariant analog for the +3 oxidation state of americium and plutonium, which is the oxidation state that accounts for over 90% of the potential release from the WIPP through the dissolved brine release (DBR) mechanism, based on current WIPP performance assessment assumptions. These solubility data extend past studies to brine compositions that are more WIPP-relevant and cover a broader range of experimental conditions than past studies.

  17. Designing phase selective soluble polymers for applications in organic chemistry 

    E-print Network

    Li, Chunmei

    2004-09-30

    Soluble polymers as supports are gaining more attention now. Developing new polymers, new reagents and catalysts, new separation systems are thus of great interest as these sorts of materials' applications in synthesis and catalysis increase...

  18. SOLUBILITY AND MOBILITY OF TOXIC METALS UNDER COMPLEX CONDITIONS

    EPA Science Inventory

    EPA Identifier: F8P11069
    Title: Solubility and Mobility of Toxic Metals Under Complex Conditions
    Fellow (Principal Investigator): Brandi N. Clark
    Institution: University of Missouri - Rolla
    EPA GRANT Representative: Georgette Bod...

  19. The solubility of gold in silicate melts: First results

    NASA Technical Reports Server (NTRS)

    Borisov, A.; Palme, H.; Spettel, B.

    1993-01-01

    The effects of oxygen fugacity and temperature on the solubility of Au in silicate melts were determined. Pd-Au alloys were equilibrated with silicate of anorthite-diopside eutectic composition at different T-fO2 conditions. The behavior of Au was found to be similar to that of Pd reported recently. Au solubilities for alloys with 30 to 40 at. percent Au decrease at 1400 C from 12 ppm in air to 160 ppb at a log fO2 = -8.7. The slope of the log(Me-solubility) vs. log(fO2) curve is close to 1/4 for Au and the simultaneously determined Pd suggesting a formal valence of Au and Pd of 1+. Near the IW buffer Pd and Au solubilities become even less dependent on fO2 perhaps reflecting the presence of some metallic Au and Pd.

  20. ORIGINAL ARTICLE Inhibition of Soluble Epoxide Hydrolase Limits

    E-print Network

    Hammock, Bruce D.

    ;60:70­75) INTRODUCTION Nicotinic acid, or niacin, is a water-soluble B vitamin that, in high doses, is effective metabolized by 2 other enzymatic routes, the lipoxygenase and cytochrome P450 (cyp450) enzymes to leukotrienes

  1. Solid-state characterization and solubility of a genistein-caffeine cocrystal

    NASA Astrophysics Data System (ADS)

    Sowa, Micha?; ?lepokura, Katarzyna; Matczak-Jon, Ewa

    2014-11-01

    Combination of genistein and caffeine leads to a 1:1 cocrystalline phase, which was identified by means of a solvent-drop grinding experiment and isolated afterwards in a solution-evaporation approach. Obtained cocrystal was characterized by X-ray single-crystal and powder diffraction as well as investigated in terms of thermal stability and Hirshfeld surfaces. A scale-up procedure was provided by slurry technique, enabling solubility determination. Neutral forms of both compounds cocrystallize in a common P21/c space group of the monoclinic crystal system. Analysis of packing and interactions in the crystal lattice reveals formation of molecular layers, formed by O-H⋯O, O-H⋯N and C-H⋯O-type contacts between genistein and caffeine molecules, whereas stabilization of the three-dimensional crystal lattice is provided by ?⋯? interactions. Dissolution studies in a 50:50 v/v ethanol-water medium revealed that the maximum solubility of the cocrystalline phase reached 0.861 mg/mL after 8 h, revealing some degree of enhancement as compared to parent genistein, maximum solubility of which was also reached after 8 h and equalled 0.588 mg/mL.

  2. Characterization of the water soluble component of inedible residue from candidate CELSS crops

    NASA Technical Reports Server (NTRS)

    Garland, Jay

    1992-01-01

    Recycling of inorganic nutrients required for plant growth will be a necessary component of a fully closed, bioregenerative life support system. This research characterized the recovery of plant nutrients from the inedible fraction of three crop types (wheat, potato, and soybean) by soaking, or leaching, in water. A considerable portion of the dry weight of the inedible biomass was readily soluble (29 percent for soybean, 43 percent for wheat, and 52 percent for potato). Greater weight loss from potato was a result of higher tissue concentrations of potassium, nitrate, and phosphate. Approximately 25 percent of the organic content of the biomass was water soluble, while the majority of most inorganic nutrients, except for calcium and iron, were recovered in the leachate. Direct use of the leachates in hydroponic media could provide between 40-90 percent of plant nutrient demands for wheat, and 20-50 percent of demand for soybean and potato. Further evaluation of leaching as a component of resource recovery scheme in a bioregenerative system requires study of (1) utilization of plant leachates in hydroponic plant culture; and (2) conversion of organic material (both soluble and insoluble) into edible, or other useful, products.

  3. Elemental Solubility Tendency for the Phases of Uranium by Classical Models Used to Predict Alloy Behavior

    SciTech Connect

    Van Blackwood; Travis Koenig; Saleem Drera; Brajenda Mishra; Davis Olson; Doug Porter; Robert Mariani

    2012-03-01

    Traditional alloy theory models, specifically Darken-Gurry and Miedema’s analyses, that characterize solutes in solid solvents relative to physical properties of the elements have been used to assist in predicting alloy behavior. These models will be applied relative to the three solid phases of uranium: alpha (orthorhombic), beta (tetragonal), and gamma (bcc). These phases have different solubilities for specific alloy additions as a function of temperature. The Darken-Gurry and Miedema models, with modifications based on concepts of Waber, Gschneider, and Brewer will be used to predict the behavior of four types of solutes: 1) Transition metals that are used for various purposes associated with the containment as alloy additions in the uranium fuel 2) Transuranic elements in the uranium 3) Rare earth fission products (lanthanides) 4) Transition metals and other fission products Using these solute map criteria, elemental behavior will be predicted as highly soluble, marginally soluble, or immiscible (compound formers) and will be used to compare solute effects during uranium phase transformations. The overlapping of these solute maps are convenient first approximation tools for predicting alloy behavior.

  4. In vitro analysis of zinc solubility in breakfast cereals

    SciTech Connect

    Woodhouse, L.R.; Carlson, M.S.; King, J.C. )

    1991-03-15

    Breakfast cereals are often fortified with zinc (Zn), as well as other minerals. The purpose of this study was to determine to what extent the grain matrix of the cereal affects the solubility of the Zn. Ten whole or mixed-grain cereals were analyzed for Zn content by AAS, and Zn solubility was assessed by an in vitro digestion method. Cereals used were fortified with Zn to 100% US RDA, 25% US RDA, and non-fortified . An in vitro digestion method was developed using pepsin and pancreatin, followed by a filtration step, in order to determine the percent of Zn released from the matrix, defined as Zn solubility. The 100% fortified cereals yielded 19-35% soluble Zn, the 25% fortified cereals yielded 6-25% soluble Zn, and the non-fortified cereals yielded 0-17% soluble Zn. Those fortified cereals containing corn, rice, oat, or wheat as the primary ingredient showed decreasing Zn solubility values of 31-35%, 25%, 23%, and 6-20%, respectively. Theoretically, only the soluble Zn would be available for absorption, suggesting that these results may give a rough estimation of Zn bioavailability. In general, a 100% Zn-may give a rough estimation of Zn bioavailability. In general, a 100% Zn-fortified cereal will provide more available Zn than a 25% or non-fortified cereal, and the extent of availability depends in part on the grain matrix of the cereal. Those Zn-fortified cereals containing grains other than wheat may provide a more absorbable Zn source.

  5. Solubility series of methanofullerenes in concentrated sulfuric acid

    NASA Astrophysics Data System (ADS)

    Biglova, Yu. N.; Kolesov, S. V.; Biglova, R. Z.; Kraikin, V. A.

    2015-12-01

    A spectroscopic study of the dissolution of C60 and its monosubstituted derivatives methanofullerenes in 98% sulfuric acid revealed that methanofullerenes dissolved in sulfuric acid much better than the starting C60. A solubility series of functionalized fullerenes was obtained, which did not change during the extraction of methanofullerenes with sulfuric acid from benzene solutions. An effective methods was developed for separating methanofullerenes, which is based on the difference between the solubilities of the starting and functionalized fullerenes in concentrated sulfuric acid.

  6. Atmospheric Deposition of Soluble Organic Nitrogen due to Biomass Burning

    NASA Astrophysics Data System (ADS)

    Ito, A.; Lin, G.; Penner, J. E.

    2014-12-01

    Atmospheric deposition of reactive nitrogen (N) species from large fires may contribute to enrichment of nutrients in aquatic ecosystems. Here we use an atmospheric chemistry transport model to investigate the supply of soluble organic nitrogen (ON) from open biomass burning to the ocean. The model results show that the annual deposition rate of soluble ON to the oceans is increased globally by 13% with the increase being particularly notable over the coastal water downwind from the source regions. The estimated deposition of soluble ON due to haze events from the secondary formation is more than half of that from the primary sources. We examine the secondary formation of particulate C-N compounds (e.g., imidazole) from the reactions of glyoxal and methylglyoxal with atmospheric ammonium in wet aerosols and upon cloud evaporation. These ON sources result in a significant contribution to the open ocean, suggesting that atmospheric processing in aqueous phase may have a large effect. We compare the soluble ON concentration in aerosols with and without open biomass burning as a case study in Singapore. The model results demonstrate that the soluble ON concentration in aerosols is episodically enriched during the fire events, compared to the without smoke simulations. However, the model results show that the daily soluble ON concentration can be also enhanced in the without smoke simulations during the same period, compared to the monthly averages. This indicates that care should be taken when using in-situ observations to constrain the soluble ON source strength from biomass burning. More accurate quantification of the soluble ON burdens with no smoke sources is therefore needed to assess the effect of biomass burning on bioavailable ON input to the oceans.

  7. Dioxygen activation in soluble methane monooxygenase.

    PubMed

    Tinberg, Christine E; Lippard, Stephen J

    2011-04-19

    The controlled oxidation of methane to methanol is a chemical transformation of great value, particularly in the pursuit of alternative fuels, but the reaction remains underutilized industrially because of inefficient and costly synthetic procedures. In contrast, methane monooxygenase enzymes (MMOs) from methanotrophic bacteria achieve this chemistry efficiently under ambient conditions. In this Account, we discuss the first observable step in the oxidation of methane at the carboxylate-bridged diiron active site of the soluble MMO (sMMO), namely, the reductive activation of atmospheric O(2). The results provide benchmarks against which the dioxygen activation mechanisms of other bacterial multicomponent monooxygenases can be measured. Molecular oxygen reacts rapidly with the reduced diiron(II) cen-ter of the hydroxylase component of sMMO (MMOH). The first spectroscopically characterized intermediate that results from this process is a peroxodiiron(III) species, P*, in which the iron atoms have identical environments. P* converts to a second peroxodiiron(III) unit, H(peroxo), in a process accompanied by the transfer of a proton, probably with the assistance of a residue near the active site. Proton-promoted O-O bond scission and rearrangement of the diiron core then leads to a diiron(IV) unit, termed Q, that is directly responsible for the oxidation of methane to methanol. In one section of this Account, we provide a detailed discussion of these processes, with particular emphasis on possible structures of the intermediates. The geometries of P* and H(peroxo) are currently unknown, and recent synthetic modeling chemistry has highlighted the need for further structural characterization of Q, currently assigned as a di(?-oxo)diiron(IV) "diamond core." In another section of the Account, we discuss in detail proton transfer during the O(2) activation events. The role of protons in promoting O-O bond cleavage, thereby initiating the conversion of H(peroxo) to Q, was previously a controversial topic. Recent studies of the mechanism, covering a range of pH values and in D(2)O instead of H(2)O, confirmed conclusively that the transfer of protons, possibly at or near the active site, is necessary for both P*-to-H(peroxo) and H(peroxo)-to-Q conversions. Specific mechanistic insights into these processes are provided. In the final section of the Account, we present our view of experiments that need to be done to further define crucial aspects of sMMO chemistry. Here our goal is to detail the challenges that we and others face in this research, particularly with respect to some long-standing questions about the system, as well as approaches that might be used to solve them. PMID:21391602

  8. Soluble guanylate cyclase stimulators in pulmonary hypertension.

    PubMed

    Stasch, Johannes-Peter; Evgenov, Oleg V

    2013-01-01

    Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating pulmonary vascular tone is demonstrated by the dysregulation of NO production, sGC activity and cGMP degradation in pulmonary hypertension (PH). The sGC stimulators are novel pharmacological agents that directly stimulate sGC, both independently of NO and in synergy with NO. Optimisation of the first sGC stimulator, YC-1, led to the development of the more potent and more specific sGC stimulators, BAY 41-2272, BAY 41-8543 and riociguat (BAY 63-2521). Other sGC stimulators include CFM-1571, BAY 60-4552, vericiguat (BAY 1021189), the acrylamide analogue A-350619 and the aminopyrimidine analogues. BAY 41-2272, BAY 41-8543 and riociguat induced marked dose-dependent reductions in mean pulmonary arterial pressure and vascular resistance with a concomitant increase in cardiac output, and they also reversed vascular remodelling and right heart hypertrophy in several experimental models of PH. Riociguat is the first sGC stimulator that has entered clinical development. Clinical trials have shown that it significantly improves pulmonary vascular haemodynamics and increases exercise ability in patients with pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH associated with interstitial lung disease. Furthermore, riociguat reduces mean pulmonary arterial pressure in patients with PH associated with chronic obstructive pulmonary disease and improves cardiac index and pulmonary vascular resistance in patients with PH associated with left ventricular systolic dysfunction. These promising results suggest that sGC stimulators may constitute a valuable new therapy for PH. Other trials of riociguat are in progress, including a study of the haemodynamic effects and safety of riociguat in patients with PH associated with left ventricular diastolic dysfunction, and long-term extensions of the phase 3 trials investigating the efficacy and safety of riociguat in patients with PAH and chronic thromboembolic PH. Finally, sGC stimulators may also have potential therapeutic applications in other diseases, including heart failure, lung fibrosis, scleroderma and sickle cell disease. PMID:24092345

  9. Determination of solubility parameters for poly(3-hydroxyalkanoates).

    PubMed

    Terada, M; Marchessault, R H

    1999-01-01

    The three dimensional solubility parameters defined by Hansen are based on dispersion forces between structural units, interaction between polar groups and hydrogen bonding. For polar polymers such as poly(3-hydroxyalkanoates), P(3HA), this approach was used to obtain the three coordinates of a solubility parameter in terms of: a dispersion part, a polar part and a hydrogen bonding part. Thirty-eight different solvents for poly(3-hydroxybutyrate), PHB, which are mentioned in the literature are examined by this method and the theoretical predictions are compared with the experimental reports. Another overall comparison between PHA polymers provides their Hansen and Hildebrand parameters for side chain lengths up to C13. In this series a linear progression in calculated solubility parameters with side chain length was found. An Appendix provides information and data on calculation of the solubility parameters. While the solubility information is limited and only covers homopolymers, it should help to highlight some of the contradictions regarding PHB solubility. This semi-empirical approach is only valid for amorphous polymers hence crystallinity effects, which are important with PHB, as well as molecular weight effects still require analysis. PMID:10416669

  10. The Effects of Acetate Buffer Concentration on Lysozyme Solubility

    NASA Technical Reports Server (NTRS)

    Forsythe, Elizabeth L.; Pusey, Marc L.

    1996-01-01

    The micro-solubility column technique was employed to systematically investigate the effects of buffer concentration on tetragonal lysozyme solubility. While keeping the NaCl concentrations constant at 2%, 3%, 4%, 5% and 7%, and the pH at 4.0, we have studied the solubility of tetragonal lysozyme over an acetate buffer concentration range of 0.01M to 0.5M as a function of temperature. The lysozyme solubility decreased with increasing acetate concentration from 0.01M to 0.1M. This decrease may simply be due to the net increase in solvent ionic strength. Increasing the acetate concentration beyond 0.1M resulted in an increase in the lysozyme solubility, which reached a peak at - 0.3M acetate concentration. This increase was believed to be due to the increased binding of acetate to the anionic binding sites of lysozyme, preventing their occupation by chloride. In keeping with the previously observed reversal of the Hoffmeister series for effectiveness of anions in crystallizing lysozyme, acetate would be a less effective precipitant than chloride. Further increasing the acetate concentration beyond 0.3M resulted in a subsequent gradual decrease in the lysozyme solubility at all NaCl concentrations.

  11. Optimization of Trichloroethylene Degradation Using Soluble Methane

    E-print Network

    Wood, Thomas K.

    and by supplementing with an iron source (3.6 pM of ferrous ammonium sulfate). Using chemostat-grown f.putida Fl- type strainisknowntobe regulated by the concentration of copper ions [sMMOis expressed at copper sMMO expression was ~bserved.'~In this recombinant system, copper repression, competitive inhibition

  12. THE EFFECT OF FLUORIDE ON LEAD SOLUBILITY

    EPA Science Inventory

    Difficulties in predicting and controlling lead corrosion are encountered by hundreds of water systems across the country. Inorganic carbonate, sulfate, silicate, orthophosphate, pH, total organic carbon, temperature and the type/amount of chlorine residual are all known factors ...

  13. Soluble cysteine-rich tick saliva proteins Salp15 and Iric-1 from E. coli

    PubMed Central

    Kolb, Philipp; Vorreiter, Jolanta; Habicht, Jüri; Bentrop, Detlef; Wallich, Reinhard; Nassal, Michael

    2014-01-01

    Ticks transmit numerous pathogens, including borreliae, which cause Lyme disease. Tick saliva contains a complex mix of anti-host defense factors, including the immunosuppressive cysteine-rich secretory glycoprotein Salp15 from Ixodes scapularis ticks and orthologs like Iric-1 from Ixodesricinus. All tick-borne microbes benefit from the immunosuppression at the tick bite site; in addition, borreliae exploit the binding of Salp15 to their outer surface protein C (OspC) for enhanced transmission. Hence, Salp15 proteins are attractive targets for anti-tick vaccines that also target borreliae. However, recombinant Salp proteins are not accessible in sufficient quantity for either vaccine manufacturing or for structural characterization. As an alternative to low-yield eukaryotic systems, we investigated cytoplasmic expression in Escherichia coli, even though this would not result in glycosylation. His-tagged Salp15 was efficiently expressed but insoluble. Among the various solubility-enhancing protein tags tested, DsbA was superior, yielding milligram amounts of soluble, monomeric Salp15 and Iric-1 fusions. Easily accessible mutants enabled epitope mapping of two monoclonal antibodies that, importantly, cross-react with glycosylated Salp15, and revealed interaction sites with OspC. Free Salp15 and Iric-1 from protease-cleavable fusions, despite limited solubility, allowed the recording of 1H–15N 2D NMR spectra, suggesting partial folding of the wild-type proteins but not of Cys-free variants. Fusion to the NMR-compatible GB1 domain sufficiently enhanced solubility to reveal first secondary structure elements in 13C/15N double-labeled Iric-1. Together, E. coli expression of appropriately fused Salp15 proteins may be highly valuable for the molecular characterization of the function and eventually the 3D structure of these medically relevant tick proteins. PMID:25628987

  14. Calcium-dependent Dimerization of Human Soluble Calcium Activated Nucleotidase: Characterization of the Dimer Interface

    SciTech Connect

    Yang,M.; Horii, K.; Herr, A.; Kirley, T.

    2006-01-01

    Mammals express a protein homologous to soluble nucleotidases used by blood-sucking insects to inhibit host blood clotting. These vertebrate nucleotidases may play a role in protein glycosylation. The activity of this enzyme family is strictly dependent on calcium, which induces a conformational change in the secreted, soluble human nucleotidase. The crystal structure of this human enzyme was recently solved; however, the mechanism of calcium activation and the basis for the calcium-induced changes remain unclear. In this study, using analytical ultracentrifugation and chemical cross-linking, we show that calcium or strontium induce noncovalent dimerization of the soluble human enzyme. The location and nature of the dimer interface was elucidated using a combination of site-directed mutagenesis and chemical cross-linking, coupled with crystallographic analyses. Replacement of Ile{sup 170}, Ser{sup 172}, and Ser{sup 226} with cysteine residues resulted in calcium-dependent, sulfhydryl-specific intermolecular cross-linking, which was not observed after cysteine introduction at other surface locations. Analysis of a super-active mutant, E130Y, revealed that this mutant dimerized more readily than the wild-type enzyme. The crystal structure of the E130Y mutant revealed that the mutated residue is found in the dimer interface. In addition, expression of the full-length nucleotidase revealed that this membrane-bound form can also dimerize and that these dimers are stabilized by spontaneous oxidative cross-linking of Cys{sup 30}, located between the single transmembrane helix and the start of the soluble sequence. Thus, calcium-mediated dimerization may also represent a mechanism for regulation of the activity of this nucleotidase in the physiological setting of the endoplasmic reticulum or Golgi.

  15. Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

    PubMed Central

    2010-01-01

    Background Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. Methods Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. Results Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes. Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients. In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. Conclusions Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. PMID:20307269

  16. Preparation of heme-free soluble guanylate cyclase.

    PubMed

    Schmidt, Peter; Schramm, Matthias; Schröder, Henning; Stasch, Johannes Peter

    2003-09-01

    Soluble guanylate cyclase (sGC), a heterodimer consisting of alpha- and beta-subunit, is the key enzyme of the NO/cGMP signaling pathway. The heme moiety ligated to the beta-subunit via His(105) is crucial for the activation of the enzyme by NO. In addition to this NO binding capability, the heme status of the enzyme influences the activity of non-NO sGC activators and sGC inhibitors. Different sGC activity profiles were observed in the presence, absence, or the oxidized form of heme. Modulating the heme status is therefore crucial for the investigation of the mechanism of sGC activation. Here, we present a simple and reliable procedure for the removal of the heme moiety of sGC that is capable of eliminating any traces of unbound heme and detergent from the sample mixture in one single step. Samples containing 15 microg sGC and the non-ionic detergent Tween 20 (2%) were incubated at 37 degrees C for 10 min and loaded onto centrifugal ion exchange columns. After centrifugation, heme was bound entirely to the ion exchanger and could not be eluted, even after incubation with 1M NaCl. Tween 20 was found completely within the flowthrough. Heme-free sGC was eluted from the ion exchanger after application of 300 mM NaCl. The absence of the heme moiety was confirmed by UV/Vis spectra and determination of the enzymatic activity. In summary, the described procedure is suitable for the preparation of very small amounts of highly purified heme-free sGC for the investigation of the mechanism of action of different types of sGC activators. PMID:12963339

  17. Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice

    PubMed Central

    Qin, Jun; Sun, Dong; Jiang, Houli; Kandhi, Sharath; Froogh, Ghezal; Hwang, Sung Hee; Hammock, Bruce D; Wolin, Michael S; Thompson, Carl I; Hintze, Thomas H; Huang, An

    2015-01-01

    Roles of soluble epoxide hydrolase (sEH), the enzyme responsible for hydrolysis of epoxyeicosatrienoic acids (EETs) to their diols (DHETs), in the coronary circulation and cardiac function remain unknown. We tested the hypothesis that compromising EET hydrolysis/degradation, via sEH deficiency, lowers the coronary resistance to promote cardiac perfusion and function. Hearts were isolated from wild type (WT), sEH knockout (KO) mice and WT mice chronically treated with t-TUCB (sEH inhibitor), and perfused with constant flow at different pre-loads. Compared to WT controls, sEH-deficient hearts required significantly greater basal coronary flow to maintain the perfusion pressure at 100 mmHg and exhibited a greater reduction in vascular resistance during tension-induced heart work, implying a better coronary perfusion during cardiac performance. Cardiac contractility, characterized by developed tension in response to changes in preload, was potentially increased in sEH-KO hearts, manifested by an enlarged magnitude at each step-wise increase in end-diastolic to peak-systolic tension. 14,15-EEZE (EET antagonist) prevented the adaptation of coronary circulation in sEH null hearts whereas responses in WT hearts were sensitive to the inhibition of NO. Cardiac expression of EET synthases (CYP2J2/2C29) was comparable in both genotypic mice whereas, levels of 14,15-, 11,12- and 8,9-EETs were significantly higher in sEH-KO hearts, accompanied with lower levels of DHETs. In conclusion, the elevation of cardiac EETs, as a function of sEH deficiency, plays key roles in the adaptation of coronary flow and cardiac function. PMID:26071213

  18. Inhibition of soluble epoxide hydrolase increases coronary perfusion in mice.

    PubMed

    Qin, Jun; Sun, Dong; Jiang, Houli; Kandhi, Sharath; Froogh, Ghezal; Hwang, Sung Hee; Hammock, Bruce D; Wolin, Michael S; Thompson, Carl I; Hintze, Thomas H; Huang, An

    2015-06-01

    Roles of soluble epoxide hydrolase (sEH), the enzyme responsible for hydrolysis of epoxyeicosatrienoic acids (EETs) to their diols (DHETs), in the coronary circulation and cardiac function remain unknown. We tested the hypothesis that compromising EET hydrolysis/degradation, via sEH deficiency, lowers the coronary resistance to promote cardiac perfusion and function. Hearts were isolated from wild type (WT), sEH knockout (KO) mice and WT mice chronically treated with t-TUCB (sEH inhibitor), and perfused with constant flow at different pre-loads. Compared to WT controls, sEH-deficient hearts required significantly greater basal coronary flow to maintain the perfusion pressure at 100 mmHg and exhibited a greater reduction in vascular resistance during tension-induced heart work, implying a better coronary perfusion during cardiac performance. Cardiac contractility, characterized by developed tension in response to changes in preload, was potentially increased in sEH-KO hearts, manifested by an enlarged magnitude at each step-wise increase in end-diastolic to peak-systolic tension. 14,15-EEZE (EET antagonist) prevented the adaptation of coronary circulation in sEH null hearts whereas responses in WT hearts were sensitive to the inhibition of NO. Cardiac expression of EET synthases (CYP2J2/2C29) was comparable in both genotypic mice whereas, levels of 14,15-, 11,12- and 8,9-EETs were significantly higher in sEH-KO hearts, accompanied with lower levels of DHETs. In conclusion, the elevation of cardiac EETs, as a function of sEH deficiency, plays key roles in the adaptation of coronary flow and cardiac function. PMID:26071213

  19. Soluble guanylate cyclase modulates alveolarization in the newborn lung

    PubMed Central

    Bachiller, Patricia R.; Cornog, Katherine H.; Kato, Rina; Buys, Emmanuel S.

    2013-01-01

    Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely through stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating pulmonary development, we tested whether decreased sGC activity reduces alveolarization in the normal and injured newborn lung. For these studies, mouse pups with gene-targeted sGC-?1 subunit truncation were used because we determined that they have decreased pulmonary sGC enzyme activity. sGC-?1 knockout (KO) mouse pups were observed to have decreased numbers of small airway structures and lung volume compared with wild-type (WT) mice although lung septation and body weights were not different. However, following mild lung injury caused by breathing 70% O2, the sGC-?1 KO mouse pups had pronounced inhibition of alveolarization, as evidenced by an increase in airway mean linear intercept, reduction in terminal airway units, and decrease in lung septation and alveolar openings, as well as reduced somatic growth. Because cGMP regulates SMC phenotype, we also tested whether decreased sGC activity reduces lung myofibroblast differentiation. Cellular markers revealed that vascular SMC differentiation decreased, whereas myofibroblast activation increased in the hyperoxic sGC-?1 KO pup lung. These results indicate that lung development, particularly during hyperoxic injury, is impaired in mouse pups with diminished sGC activity. These studies support the investigation of sGC-targeting agents as therapies directed at improving development in the newborn lung exposed to injury. PMID:23934926

  20. Effects of polarity, hydrophobicity, and density of ionic liquids on cellulose solubility.

    PubMed

    Abe, Mitsuru; Kuroda, Kosuke; Sato, Daiki; Kunimura, Haruhito; Ohno, Hiroyuki

    2015-12-01

    We have synthesised novel ionic liquids (ILs) to show both cellulose dissolution ability and LCST-type phase transition after mixing with water. To realise both polar and hydrophobic properties, tetraalkylphosphonium cations and a series of carboxylate anions were employed to assume hydrophobic and highly polar properties, respectively. Effects of their alkyl chain length on the water compatibility and cellulose solubility of the corresponding ILs were systematically examined. We succeeded in synthesising novel ILs which dissolve cellulose and separable with water at moderate temperature. Through the present study, we have clarified that not only polarity but also density of ILs is an important factor in designing the ILs for cellulose dissolution. PMID:26583649

  1. [Good laboratory practice of equilibrium solubility measurement II. Study of pH-dependent solubility of ionizable compounds].

    PubMed

    Völgyi, Gergely; Baka, Edit; Kovács, Márta; Takácsné, Novák Krisztina

    2011-01-01

    In this paper the pH-equilibrium solubility profiles of ionizable drugs are presented. The aim of the present work was to study the validity of the Henderson-Hasselbalch (HH) relationship in the case of structurally diverse weak bases. In the case of monoprotic bases, namely papaverine, promethazine and propafenone the experimental equilibrium solubility data precisely follow the theoretical HH curve until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. It is critical that the pKa value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs. PMID:21800714

  2. GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

    SciTech Connect

    Pierce, R. A.

    2012-03-12

    HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into the H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 °C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. At 25 °C, for 6 M HNO{sub 3}, 11 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2.5 g/L and 0.8 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}. The solubility of Gd in 4 M HNO{sub 3} with 0.15 M oxalate at 10 °C is about 1.5 g/L. For 6 M HNO{sub 3} with 0.15 M oxalate, the solubility of Gd at 10 °C is about 10 g/L. Gadolinium nitrate is very soluble in HNO{sub 3}. The solubility of Gd is linear as a function of HNO{sub 3} from 343 g/L Gd in 2.88 M HNO{sub 3} to 149 g/L in 8.16 M HNO{sub 3}. Below 2.88 M HNO{sub 3}, the solubility of Gd approaches a limit of about 360 g/L. However, there are no data available below 1.40 M HNO{sub 3}, which has a Gd solubility of 353 g/L.

  3. Filter Cake Formation of Water Soluble Polymers

    NASA Astrophysics Data System (ADS)

    Wang, Jeanlynn K.

    1995-01-01

    A filter cake consisting of either a gel layer or a non-aggregated polarized layer can be formed at a membrane surface during ultrafiltration. The mechanism of formation involves the solvent flux through the membrane which concentrates polymer molecules at the membrane surface. The formation of filter cakes of water soluble polymers was measured and modeled in this thesis. The polymers used were hydroxy propyl guar, guar, and dextran. Previous models of filter cake formation have only been tested against predictions of the overall solvent flux versus the transmembrane pressure (pressure drop) or the solvent flux versus the transverse flow rate. We performed in situ measurements of the concentration profile in the filter cake layer using an optical fiber probe detector. An optical fiber probe detector based on laser -fluorescence was used in ultrafiltration experiments to measure the polymer concentration profile in the filter cake. The experiments were performed in a rectangular, channel flow cell. The polymer was fluorescently tagged with DTAF (dichlorotriazinyl aminofluorescein). The height of the flow gap was scanned by a single 100 mu m optical fiber that delivered the excitation light at 488 nm and received the emitted fluorescence at 518 nm. The detected fluorescence signal is a function of the polymer concentration; however, it is a non-linear dependence. A mathematical model was developed to deconvolute the fluorescence intensity to obtain the concentration profile within the flow gap. In this study, we have developed a new model of filter cake formation by polymers. The polymer physical properties that enter the model, i.e. the osmotic pressure and permeability, were measured independently as a function of the polymer concentration. The solvent velocity through the polymer filter cakes during ultrafiltration was measured at different transmembrane pressures and transverse flow rates. The thickness of the filter cake was measured from the laser-fluorescence experiments. These four measured values were used in the model for filter cake formation to obtain the concentration profile within the filter cakes. Simulations were done to test the model. For guar and HPG, the concentrations at the membrane that were obtained from the simulations were 1.4 to 6 times higher than the results from the deconvolution of the laser -fluorescence experiments. For dextran, the concentrations at the membrane from the simulations were 4.2 to 10 times higher but the masses in the polarized layers were only 0.9 to 4.0 times higher in the simulations than in the experiment. The mass of polymer on the membrane obtained from the simulations and the deconvolution differed only by a factor of one to four for the low shear rate experiments and by a factor of four to ten for the HPG high shear rate experiments.

  4. Effervescence Assisted Fusion Technique to Enhance the Solubility of Drugs.

    PubMed

    Alam, Mohd Aftab; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Ali, Raisuddin

    2015-12-01

    The solubility of five poorly soluble drugs was enhanced by using an effervescence assisted solid dispersion (EASD) technique. EASDs were prepared by using modified fusion method. Drug and hydrophilic carrier were melted, and in this molten mixture, effervescence was generated by adding effervescence couple comprising organic acid (citric acid) and carbonic base (sodium bicarbonate). Solubility of drug powders, solid dispersions, and EASDs was determined at 25°C using shake flask method. Atorvastatin calcium, cefuroxime axetil, clotrimazole, ketoconazole, and metronidazole benzoate were estimated using a spectrophotometer at 246, 280, 260, 230, and 232 nm (? max), respectively. Solubility of atorvastatin calcium (from 100 to 345 ?g/ml), cefuroxime axetil (from 441 to 1948 ?g/ml), clotrimazole (from 63 to 677 ?g/ml), ketoconazole (from 16 to 500 ?g/ml), and metronidazole benzoate (from 112 to 208 ?g/ml) in EASDs was enhanced by 3.45-, 4.4-, 10.7-, 31.2-, and 1.8-fold, respectively. Scanning electron micrographs of drug powder, solid dispersion, and EASDs were compared. Scanning electron micrographs of EASDs showed a uniform distribution of drug particles in the carrier matrix. Morphology (size and shape) of cefuroxime axetil particles was altered in solid dispersion as well as in EASD. EASDs showed better solubility enhancement than conventional solid dispersions. The present technique is better suitable for drugs having a low melting point or melt without charring. Effervescence assisted fusion technique of preparing solid dispersions can be employed for enhancing solubility, dissolution, and bioavailability of poorly soluble drugs. PMID:26265190

  5. A New Soluble Gelatin Sponge for Transcatheter Hepatic Arterial Embolization

    SciTech Connect

    Takasaka, Isao; Kawai, Nobuyuki; Sato, Morio Sahara, Shinya; Minamiguchi, Hiroyuki; Nakai, Motoki; Ikoma, Akira; Nakata, Kouhei; Sonomura, Tetsuo

    2010-12-15

    To prepare a soluble gelatin sponge (GS) and to explore the GS particles (GSPs) that inhibit development of collateral pathways when transcatheter hepatic arterial embolization is performed. The approval of the Institutional Committee on Research Animal Care of our institution was obtained. By means of 50 and 100 kDa of regenerative medicine-gelatin (RM-G), RM-G sponges were prepared by freeze-drying and heating to temperatures of 110-150{sup o}C for cross-linkage. The soluble times of RM-GSPs were measured in vitro. Eight swine for transcatheter hepatic arterial embolization were assigned into two groups: six received 135{sup o}C/50RM-GSPs, 125{sup o}C/100RM-GSPs, and 138{sup o}C/50RM-GSPs, with soluble time of 48 h or more in vitro; two swine received Gelpart GSPs (G-GSPs) with insoluble time of 14 days as a control. Transarterial chemoembolization was performed on two branches of the hepatic artery per swine. RM-GSPs heated at temperatures of 110-138{sup o}C were soluble. Mean soluble times of the RM-GSPs increased with higher temperature. Hepatic branches embolized with G-GSP remained occluded after 6 days, and development of collateral pathways was observed after 3 days. Hepatic branches embolized with 135{sup o}C/50RM-GSP and 125{sup o}C/100RM-GSP remained occluded for 4 h, and recanalization was observed after 1 day. Hepatic branches embolized with 138{sup o}C/50RM-GS remained occluded for 1 day, and recanalization was observed after 2 days with no development of collateral pathways. In RM-GSs with various soluble times that were prepared by modulating the heating temperature, 138{sup o}C/50RM-GSP was the soluble GSP with the longest occlusion time without inducing development of collateral pathways.

  6. The temperature dependence of water solubility in enstatite

    NASA Astrophysics Data System (ADS)

    Mierdel, Katrin; Keppler, Hans

    2004-11-01

    The solubility of water in pure enstatite was measured on samples synthesized under water-saturated conditions at 15 kbar and temperatures ranging from 700 to 1,100°C. Polarized FTIR measurements on millimetre-sized, clear crystals showed that water solubility increases strongly with temperature, from 101 ppm by weight at 700°C to 269 ppm by weight at 1,100°C. The position and shape of the infrared bands hardly changes with temperature, with one notable exception: a band close to 3,380 cm-1 is present in samples synthesized between 700 and 1,000°C, while this band is absent from samples synthesized at 1,100°C. This effect appears to be very reproducible and points towards a slight change in the crystal structure of enstatite between 1,000 and 1,100°C at 15 kbar. The water solubility data of this study as well as those of Rauch and Keppler (Contrib Mineral Petrol 143:525 536, 2002) can be reproduced by the equation K = Af_{{{H}}_2 {{O}}} exp ( - ? H^{1 {{bar}}} /RT)exp ( - ? V^{{{solid}}} P/RT), where K is water solubility, f_{{text{H}}_2 {text{O}}} is water fugacity, A is 0.01354 ppm/bar, ?Vsolid=12.1 cm3/mol is the volume change of enstatite during incorporation of water, and ?H1 bar=-4,563 J/mol is the reaction enthalpy at 1 bar. This equation predicts the following behaviour of water solubility in enstatite as a function of pressure and temperature: (1) water solubility increases with pressure up to a maximum around 80 kbar; (2) water solubility decreases with temperature at 1 bar; and (3) water solubility increases with temperature between 10 and 100 kbar. If the observed temperature dependence for enstatite were representative for other upper mantle minerals as well, it would have the following implications: (1) Lateral temperature gradients in the upper mantle could cause major variations in water contents at the same depth; in particular, hot mantle plumes may scavenge water from the surrounding shallow upper mantle. (2) The scavenging of water by hot plumes could be a major factor in increasing the mobility of plumes. (3) The predicted temperature dependence of water solubility at the base of the upper mantle may allow plumes to bypass the transition zone water filter postulated by Bercovici and Karato (Nature 425:39 44, 2003).

  7. Partial-solubility parameters of naproxen and sodium diclofenac.

    PubMed

    Bustamante, P; Peña, M A; Barra, J

    1998-09-01

    The expanded Hansen method was tested for determination of the solubility parameters of two non-steroidal anti-inflammatory drugs, naproxen and sodium diclofenac. This work describes for the first time the application of the method to the sodium salt of a drug. The original dependent variable of the expanded Hansen method, involving the activity coefficient of the drug, was compared with the direct use of the logarithm of the mole fraction solubility 1nX2 in the solubility models. The solubility of both drugs was measured in pure solvents of several chemical classes and the activity coefficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid phase that might change the value of the activity coefficient. The molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained with the dependent variable 1nX2 in association with the four-parameter model which includes the acidic and basic partial-solubility parameters delta(a) and delta(b) instead of the Hansen hydrogen bonding parameter delta(h). Because the dispersion parameter does not vary greatly from one drug to another, the variation of solubility among solvents is largely a result of the dipolar and hydrogen-bonding parameters, a fact that is being consistently found for other drugs of small molecular weight. These results support earlier findings with citric acid and paracetamol that the expanded Hansen approach is suitable for determining partial-solubility parameters. The modification introduced in the expanded Hansen method, i.e. the use of 1nX2 as the dependent variable, provides better results than the activity coefficient used in the original method. This is advantageous for drugs such as sodium diclofenac for which the ideal solubility cannot be estimated. This paper shows for the first time that the method is suitable for determination of the partial-solubility parameters of a sodium salt of a drug, sodium diclofenac. PMID:9811157

  8. Inter-subject variability in intestinal drug solubility.

    PubMed

    Rabbie, Sarit Cohen; Flanagan, Talia; Martin, Paul D; Basit, Abdul W

    2015-05-15

    Variability in oral drug absorption is a well-known phenomenon, but it is often overlooked for its potential effects in oral drug delivery. Understanding the mechanisms behind absorption variability is crucial to understanding and predicting drug pharmacokinetics. In this study, the solubility of furosemide and dipyridamole - drugs known to have highly variable oral bioavailabilities - was investigated in individual ileostomy fluids from 10 subjects with ulcerative colitis. For comparison, drug solubility was also determined in pooled upper gastrointestinal fluids from healthy human subjects and simulated intestinal fluids. Ileostomy fluid characterization revealed high variability in buffer capacity and to a lesser degree for pH. Drug solubility in ileostomy fluids showed high variability. Correlation analysis revealed that dipyridamole solubility in these fluids is pH-dependent, whereas furosemide solubility was highly correlated to buffer capacity and pH. The implications of these results might partly explain the high variability in bioavailability in vivo, assuming that most of the observed variability is due to the absorption, and not the elimination, process. PMID:25758158

  9. Transformation of acidic poorly water soluble drugs into ionic liquids.

    PubMed

    Balk, Anja; Wiest, Johannes; Widmer, Toni; Galli, Bruno; Holzgrabe, Ulrike; Meinel, Lorenz

    2015-08-01

    Poor water solubility of active pharmaceutical ingredients (API) is a major challenge in drug development impairing bioavailability and therapeutic benefit. This study is addressing the possibility to tailor pharmaceutical and physical properties of APIs by transforming these into tetrabutylphosphonium (TBP) salts, including the generation of ionic liquids (IL). Therefore, poorly water soluble acidic APIs (Diclofenac, Ibuprofen, Ketoprofen, Naproxen, Sulfadiazine, Sulfamethoxazole, and Tolbutamide) were converted into TBP ILs or low melting salts and compared to the corresponding sodium salts. Free acids and TBP salts were characterized by NMR and IR spectroscopy, DSC and XRPD, DVS and dissolution rate measurements, release profiles, and saturation concentration measurements. TBP salts had lower melting points and glass transition temperatures and dissolution rates were improved up to a factor of 1000 as compared to the corresponding free acid. An increase in dissolution rates was at the expense of increased hygroscopicity. In conclusion, the creation of TBP ionic liquids or solid salts from APIs is a valuable concept addressing dissolution and solubility challenges of poorly water soluble acidic compounds. The data suggested that tailor-made counterions may substantially expand the formulation scientist's armamentarium to meet challenges of poorly water soluble drugs. PMID:25976317

  10. Solubility improvement of drugs using N-methyl pyrrolidone.

    PubMed

    Sanghvi, Ritesh; Narazaki, Ryuichi; Machatha, Stephen G; Yalkowsky, Samuel H

    2008-01-01

    The solubilization efficiency of N-methyl pyrrolidone (NMP) has been determined and compared to that of ethanol and propylene glycol for 13 poorly soluble drugs. NMP is found to be a more efficient solubilizer for all the drugs studied. The solubility enhancement as high as about 800-fold is obtained in 20% v/v NMP solution as compared to water. The mechanism of drug solubilization by NMP has also been investigated. It is proposed that NMP enhances drug solubility by simultaneously acting as a cosolvent and a complexing agent. A mathematical model is used to estimate the drug solubility in NMP-water mixture, according to which the total solubility enhancement is a sum of the two effects. This model describes the experimental data well and is more accurate than other models. A large and uniform reduction in the surface tension of water as a function of NMP concentration demonstrates its cosolvent effect. The complexation is supported by the fact that it's strength is affected by the temperature and the polarity of the medium. A strong correlation exists between log K (ow) of the drugs and the cosolvency coefficients. The correlation between log K (ow) and the complexation coefficients is weak suggesting that factors such as molecular shape and aromaticity of the drug molecule are significant in determining the complexation strength. This has been confirmed by the absence of a significant complexation between NMP and linear drug-like solutes. PMID:18431671

  11. Cyclodextrin-mediated enhancement of riboflavin solubility and corneal permeability.

    PubMed

    Morrison, Peter W J; Connon, Che J; Khutoryanskiy, Vitaliy V

    2013-02-01

    Cyclodextrins are water-soluble cyclic oligosaccharides consisting of six, seven, and eight ?-(1,4)-linked glucopyranose subunits. This study reports the use of different cyclodextrins in eye drop formulations to improve the aqueous solubility and corneal permeability of riboflavin. Riboflavin is a poorly soluble drug with a solubility up to 0.08 mg mL(-1) in deionized water. It is used as a drug topically administered to the eye to mediate UV-induced corneal cross-linking in the treatment of keratoconus. Aqueous solutions of ?-cyclodextrin (10-30 mg mL(-1)) can enhance the solubility of riboflavin up to 0.12-0.19 mg mL(-1), whereas the higher concentration of ?-cyclodextrin (100 mg mL(-1)) achieved a lower level of enhancement of 0.11 mg mL(-1). The other oligosaccharides were found to be inefficient for this purpose. In vitro diffusion experiments performed with fresh and cryopreserved bovine cornea have demonstrated that ?-cyclodextrin enhances riboflavin permeability. The mechanism of this enhancement was examined through microscopic histological analysis of the cornea and is discussed in this paper. PMID:23294178

  12. Synthesis and application of widely soluble graphene sheets.

    PubMed

    Li, Fenghua; Bao, Yu; Chai, Jia; Zhang, Qixian; Han, Dongxue; Niu, Li

    2010-07-20

    A widely soluble graphene sheet/Congo red (GSCR) composite was synthesized and applied to prepare GSCR/Au hybrid materials. UV-vis absorption, Fourier transform infrared, Raman, and X-ray photoelectron spectra revealed that Congo red (CR) is successfully coupled on graphene sheets. The morphology of GSCR was studied by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. The dispersion behavior of the GSCR composite was also studied in 18 different solvents, and the digital images indicate that it is soluble both in water and in a variety of organic solvents. The GSCR nanosheets are still single layers or bilayers in water and individual from one to another after 100 days of storage. Furthermore, the mechanism of GSCR's good solubility was successfully explained by the Hansen solubility parameters. The four standard probe result shows that the GSCR films have a bulk conductivity of approximately 6850 S m(-1). The wide solubility and long lifetime of GSCR solutions are absolutely necessary for further treatment. As an example, Au nanoparticles densely decorated CR-functionalized graphene sheets through electrostatic interaction. PMID:20536161

  13. An emulsion polymerization process for soluble and electrically conductive polyaniline

    SciTech Connect

    Kinlen, P.J.; Ding, Y.; Graham, C.R.; Liu, J.; Remsen, E.E.

    1998-07-01

    A new emulsion process has been developed for the direct synthesis of the emeraldine salt of polyaniline (PANI) that is soluble in organic solvents. The process entails forming an emulsion composed of water, a water soluble organic solvent (e.g., 2-butoxyethanol), a water insoluble organic acid (e.g., dinonylnaphthalene sulfonic acid) and aniline. Aniline is protonated by the organic acid to form a salt which partitions into the organic phase. As oxidant (ammonium peroxydisulfate) is added, PANI salt forms in the organic phase and remains soluble. As the reaction proceeds, the reaction mixture changes from an emulsion to a two phase system, the soluble PANI remaining in the organic phase. With dinonylnaphthalene sulfonic acid (DNNSA) as the organic acid, the resulting product is truly soluble in organic solvents such as xylene and toluene (not a dispersion), of high molecular weight (M{sub w} > 22,000), film forming and miscible with many polymers such as polyurethanes, epoxies and phenoxy resins. As cast, the polyaniline film is only moderately conductive, (10{sup {minus}5} S/cm), however treatment of the film with surfactants such as benzyltriethylammonium chloride (BTEAC) or low molecular weight alcohols and ketones such as methanol and acetone increases the conductivity 2--3 orders of magnitude.

  14. Solubility of Two Resin Composites in Different Mouthrinses

    PubMed Central

    Ozer, Sezin; Sen Tunc, Emine; Tuloglu, Nuray; Bayrak, Sule

    2014-01-01

    Aim. This study aimed to compare the solubility of a universal restorative resin composite (Filtek Z250; FZ250) and a silorane-based resin composite (Filtek Silorane; FS) after immersion in alcohol-containing mouthrinse, alcohol-free mouthrinse, and artificial saliva. Methods. 30 discs (10?mm?×?1?mm) were prepared from each material and desiccated until a constant mass was obtained. Specimens were immersed in the test solutions for two days and desiccated again. Solubility was calculated based on the change in weight of each specimen before and after immersion. Data was analyzed using two-way ANOVA and Tukey's Post Hoc test (P < 0.05). Results. Solubility values for both resin composites were the highest in the alcohol-containing mouthrinse. FZ250 showed greater solubility than FS; the difference was only significant in artificial saliva. Conclusion. Both resin-composite materials tested exhibited some degree of solubility in each of the test solutions. The use of an alcohol-free mouthrinse may be preferable for patients with extensive composite restorations. PMID:24809053

  15. The Relationship between Solubility and Transdermal Absorption of Tadalafil

    PubMed Central

    Hamishehkar, Hamed; Khoshbakht, Mehdi; Jouyban, Abolghasem; Ghanbarzadeh, Saeed

    2015-01-01

    Purpose: The aim of this study was to find a relationship between drug solubility and its transdermal permeation and find the best vehicle composition to improve transdermal permeation of Tadalafil. Methods: Pure or binary mixtures of commonly used solvents in pharmaceutical sciences including ethanol, glycerin, N-methyl pyrrolidone (NMP), polyethylene glycol (PEG) 400 and propylene glycol (PG) were evaluated for drug solubility and transdermal delivery through the exercised rat skin employing Franz diffusion cells. Results: Tadalafil showed higher solubility in NMP compared to the other solvents. The amount of Tadalafil permeation from the pure vehicles was ranked as follow: Ethanol >glycerin >NMP>PEG 400 >PG. Furthermore, the solubility and transdermal delivery from binary mixtures of NMP and PG were higher than that obtained from pure PG, and accordingly, both increased with increasing NMP concentration in the binary solvent mixtures. The Flux values were determined as following order for Ethanol>NMP>glycerin>PG>PEG 400. Conclusion: Generally, increase in Tadalafil solubility resulted in a decrease in its skin penetration rate and amount. However, NMP exhibited substantial drug skin penetration rate and amount accompanying with appropriate drug solvency. In conclusion, the results of this study introduced NMP as a solvent suitable for application in the formulation of topically applied drug delivery systems. PMID:26504764

  16. Determination of solubility profiles of eflucimibe polymorphs: experimental and modeling.

    PubMed

    Teychene, S; Autret, J M; Biscans, B

    2006-04-01

    This work presents the determination of the phase diagram of two polymorphs of Eflucimibe in pure solvents and solvent mixtures at different temperatures. Solid phase changes were analysed by Differential Scanning Calorimetry. Solubility measurements show that the solubility of the two forms are very similar. Experimental data obtained in ethanol, reported in a Van t'Hoff plot, exhibit a transition temperature around 265 K. A single maximum is observed when solubility is plotted against the solubility parameters of solvents or solvent mixture and it is not related to a solid phase change. This phenomenon, known as a positive synergetic effect, has been explained in term of evolution of solute-solvents polar interactions. Several thermodynamics models (UNIFAC, UNIQUAC, Wilson, Scatchard Hildebrand ... ) were tested in order to predict the Liquid-Solid Equilibrium for this system. The semi empirical model UNIQUAC gives the best fit. The results obtained are in good agreement with the experimental data (mean deviation lower than 5%) and the solubility maximum found experimentally for each polymorph is also well described. PMID:16489606

  17. Identifying protein domains by global analysis of soluble fragment data.

    PubMed

    Bulloch, Esther M M; Kingston, Richard L

    2014-11-15

    The production and analysis of individual structural domains is a common strategy for studying large or complex proteins, which may be experimentally intractable in their full-length form. However, identifying domain boundaries is challenging if there is little structural information concerning the protein target. One experimental procedure for mapping domains is to screen a library of random protein fragments for solubility, since truncation of a domain will typically expose hydrophobic groups, leading to poor fragment solubility. We have coupled fragment solubility screening with global data analysis to develop an effective method for identifying structural domains within a protein. A gene fragment library is generated using mechanical shearing, or by uracil doping of the gene and a uracil-specific enzymatic digest. A split green fluorescent protein (GFP) assay is used to screen the corresponding protein fragments for solubility when expressed in Escherichia coli. The soluble fragment data are then analyzed using two complementary approaches. Fragmentation "hotspots" indicate possible interdomain regions. Clustering algorithms are used to group related fragments, and concomitantly predict domain location. The effectiveness of this Domain Seeking procedure is demonstrated by application to the well-characterized human protein p85?. PMID:25016192

  18. Soluble N-cadherin in human biological fluids.

    PubMed

    Derycke, Lara; De Wever, Olivier; Stove, Veronique; Vanhoecke, Barbara; Delanghe, Joris; Depypere, Herman; Bracke, Marc

    2006-12-15

    Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that mediate cell-cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P- or N-cadherin ectodomains. Circulating soluble E- and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The N-cadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons. PMID:16998833

  19. Soluble biglycan as a biomarker of inflammatory renal diseases

    PubMed Central

    Hsieh, Louise Tzung-Harn; Nastase, Madalina-Viviana; Zeng-Brouwers, Jinyang; Iozzo, Renato V.; Schaefer, Liliana

    2014-01-01

    Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Liberated SLRPs can then bind to and activate Toll-like receptors, thus modulating downstream inflammatory signaling. Preclinical animal models and human studies have recently identified soluble biglycan as a key initiator and regulator of various inflammatory renal diseases. Biglycan, generated by activated macrophages, can enter the circulation and its elevated levels in plasma and renal parenchyma correlate with unfavorable renal function and outcome. In this review, we will focus on the critical role of soluble biglycan in inflammatory signaling in various renal disorders. Moreover, we will provide new data implicating proinflammatory effects of soluble decorin in unilateral ureteral obstruction. Finally, we will critically evaluate the potential application of soluble biglycan vis-à-vis other SLRPs (decorin, lumican and fibromodulin) as a promising target and novel biomarker of inflammatory renal diseases. PMID:25091702

  20. Soluble biglycan as a biomarker of inflammatory renal diseases.

    PubMed

    Hsieh, Louise Tzung-Harn; Nastase, Madalina-Viviana; Zeng-Brouwers, Jinyang; Iozzo, Renato V; Schaefer, Liliana

    2014-09-01

    Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Liberated SLRPs can then bind to and activate Toll-like receptors, thus modulating downstream inflammatory signaling. Preclinical animal models and human studies have recently identified soluble biglycan as a key initiator and regulator of various inflammatory renal diseases. Biglycan, generated by activated macrophages, can enter the circulation and its elevated levels in plasma and renal parenchyma correlate with unfavorable renal function and outcome. In this review, we will focus on the critical role of soluble biglycan in inflammatory signaling in various renal disorders. Moreover, we will provide new data implicating proinflammatory effects of soluble decorin in unilateral ureteral obstruction. Finally, we will critically evaluate the potential application of soluble biglycan vis-à-vis other SLRPs (decorin, lumican and fibromodulin) as a promising target and novel biomarker of inflammatory renal diseases. PMID:25091702

  1. Soluble Extract from Moringa oleifera Leaves with a New Anticancer Activity

    PubMed Central

    Jung, Il Lae

    2014-01-01

    Moringa oleifera has been regarded as a food substance since ancient times and has also been used as a treatment for many diseases. Recently, various therapeutic effects of M. oleifera such as antimicrobial, anticancer, anti-inflammatory, antidiabetic, and antioxidant effects have been investigated; however, most of these studies described only simple biological phenomena and their chemical compositions. Due to the increasing attention on natural products, such as those from plants, and the advantages of oral administration of anticancer drugs, soluble extracts from M. oleifera leaves (MOL) have been prepared and their potential as new anticancer drug candidates has been assessed in this study. Here, the soluble cold Distilled Water extract (4°C; concentration, 300 µg/mL) from MOL greatly induced apoptosis, inhibited tumor cell growth, and lowered the level of internal reactive oxygen species (ROS) in human lung cancer cells as well as other several types of cancer cells, suggesting that the treatment of cancer cells with MOL significantly reduced cancer cell proliferation and invasion. Moreover, over 90% of the genes tested were unexpectedly downregulated more than 2-fold, while just below 1% of the genes were upregulated more than 2-fold in MOL extract-treated cells, when compared with nontreated cells. Since severe dose-dependent rRNA degradation was observed, the abnormal downregulation of numerous genes was considered to be attributable to abnormal RNA formation caused by treatment with MOL extracts. Additionally, the MOL extract showed greater cytotoxicity for tumor cells than for normal cells, strongly suggesting that it could potentially be an ideal anticancer therapeutic candidate specific to cancer cells. These results suggest the potential therapeutic implications of the soluble extract from MOL in the treatment of various types of cancers. PMID:24748376

  2. Soluble extract from Moringa oleifera leaves with a new anticancer activity.

    PubMed

    Jung, Il Lae

    2014-01-01

    Moringa oleifera has been regarded as a food substance since ancient times and has also been used as a treatment for many diseases. Recently, various therapeutic effects of M. oleifera such as antimicrobial, anticancer, anti-inflammatory, antidiabetic, and antioxidant effects have been investigated; however, most of these studies described only simple biological phenomena and their chemical compositions. Due to the increasing attention on natural products, such as those from plants, and the advantages of oral administration of anticancer drugs, soluble extracts from M. oleifera leaves (MOL) have been prepared and their potential as new anticancer drug candidates has been assessed in this study. Here, the soluble cold Distilled Water extract (4°C; concentration, 300 µg/mL) from MOL greatly induced apoptosis, inhibited tumor cell growth, and lowered the level of internal reactive oxygen species (ROS) in human lung cancer cells as well as other several types of cancer cells, suggesting that the treatment of cancer cells with MOL significantly reduced cancer cell proliferation and invasion. Moreover, over 90% of the genes tested were unexpectedly downregulated more than 2-fold, while just below 1% of the genes were upregulated more than 2-fold in MOL extract-treated cells, when compared with nontreated cells. Since severe dose-dependent rRNA degradation was observed, the abnormal downregulation of numerous genes was considered to be attributable to abnormal RNA formation caused by treatment with MOL extracts. Additionally, the MOL extract showed greater cytotoxicity for tumor cells than for normal cells, strongly suggesting that it could potentially be an ideal anticancer therapeutic candidate specific to cancer cells. These results suggest the potential therapeutic implications of the soluble extract from MOL in the treatment of various types of cancers. PMID:24748376

  3. Constraints on core formation from molybdenum solubility in silicate melts at high pressure

    NASA Astrophysics Data System (ADS)

    Burkemper, Laura K.; Agee, Carl B.; Garcia, Kody A.

    2012-06-01

    We report results from 43 new molybdenum solubility experiments performed in order to test molybdenum's compatibility with the magma ocean hypothesis for core formation. A Walker-type multi-anvil press was used for all experiments and we investigated the pressure range of 2.5-12 GPa and temperature range of 1585-2200 °C. Eight different silicate compositions were also employed. Our data show that increasing temperature causes solubility to increase, whereas pressure has a negligible effect over the range investigated here. In general, increasing silicate melt polymerization causes solubility to decrease; however, the effect of silicate composition is best addressed by looking at the effects of individual oxides versus a universal melt parameter such as NBO/T (ratio of non-bridging oxygens to tetrahedrally coordinated oxygens). From our solubility data, we calculated metal-silicate partition coefficients at infinite iron dilution. Parameterization of our data plus data from the literature shows that there is no discrepancy between partition coefficients determined directly from experiments and those calculated from solubility data, so long as all variables are taken into account, i.e. changes in metal phase composition. Additionally, most of the experiments in the literature were conducted at pressures below 2 GPa, therefore the addition of our high pressure data set makes extrapolations to deep magma ocean conditions more accurate. We determined that the observed mantle abundance of Mo can be explained by both single-stage and multi-stage magma ocean models. Previous siderophile element studies have suggested a wide range of possible single-stage core formation conditions, from 10 to 60 GPa along the peridotite liquidus. Our results narrowed this range by constraining the P-T conditions to 40-54 GPa and 3050-3400 K. Our results also further constrained the multi-stage core formation models by limiting the depth of metal-silicate equilibration during the final impacts of accretion to 31-42% of the core-mantle boundary depth.

  4. Human alpha-galactosidase A: glycosylation site 3 is essential for enzyme solubility.

    PubMed Central

    Ioannou, Y A; Zeidner, K M; Grace, M E; Desnick, R J

    1998-01-01

    Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the homodimeric glycoprotein that hydrolyses the terminal alpha-galactosyl moieties from glycolipids and glycoproteins. The type, site occupancy and function of the N-linked oligosaccharide chains on this lysosomal hydrolase were determined. Endoglycosidase treatment of the purified recombinant enzyme and mutagenesis studies indicated that three (Asn-139, Asn-192 and Asn-215) of the four potential N-glycosylation consensus sequences were occupied by complex, high-mannose and hybrid-type oligosaccharides respectively. When expressed in COS-1 cells, glycoforms with glycosylation site 1 or 2 obliterated had more than 70% of wild-type activity, and both glycoforms were secreted. In contrast, the glycoform with only site 3 eliminated had decreased activity (less than 40%); little, if any, was secreted. Expressed mutant glycoforms in which site 3 and site 1 or 2 were obliterated had little, if any, intracellular or secreted enzymic activity, and immunofluorescence microscopy revealed that the expressed mutant glycoforms were retained in the endoplasmic reticulum, presumably where they were degraded. Thus glycosylation at site 3 was crucial to the formation of soluble, active enzyme, as well as transport to the lysosome. Absence of the site 3 hybrid-type oligosaccharide exposed an adjacent, normally protected, hydrophobic region, resulting in aggregation of the enzyme polypeptide in the endoplasmic reticulum. In support of this concept, endoglycosidase H-treated enzyme or mannose-terminated enzyme expressed in Autographa californica cells also aggregated when concentrated, emphasizing that site 3 occupancy by a hybrid-type oligosaccharide was required for enzyme solubility. PMID:9620884

  5. A Soluble Adenylyl Cyclase Form Targets to Axonemes and Rescues Beat Regulation in Soluble Adenylyl Cyclase Knockout Mice

    PubMed Central

    Chen, Xi; Baumlin, Nathalie; Buck, Jochen; Levin, Lonny R.; Fregien, Nevis

    2014-01-01

    Ciliary beating is important for effective mucociliary clearance. Soluble adenylyl cyclase (sAC) regulates ciliary beating, and a roughly 50-kD sAC variant is expressed in axonemes. Normal human bronchial epithelial (NHBE) cells express multiple sAC splice variants: full-length sAC; variants with catalytic domain 1 (C1) deletions; and variants with partial C1. One variant, sACex5v2-ex12v2, contains two alternative splices creating new exons 5 (ex5v2) and 12 (ex12v2), encoding a roughly 45-kD protein. It is therefore similar in size to ciliary sAC. The variant increases in expression upon ciliogenesis during differentiation at the air–liquid interface. When expressed in NHBE cells, this variant was targeted to cilia. Exons 5v2–7 were important for ciliary targeting, whereas exons 2–4 prevented it. In vitro, cytoplasmic sACex2-ex12v2 (containing C1 and C2) was the only variant producing cAMP. Ciliary sACex5v2-ex12v2 was not catalytically active. Airway epithelial cells isolated from wild-type mice revealed sAC-dependent ciliary beat frequency (CBF) regulation, analogous to NHBE cells: CBF rescue from HCO3?/CO2–mediated intracellular acidification was sensitive to the sAC inhibitor, KH7. Compared with wild type, sAC C2 knockout (KO) mice revealed lower CBF baseline, and the HCO3?/CO2–mediated CBF decrease was not inhibited by KH7, confirming lack of functional sAC. Human sACex5v2-ex12v2 was targeted to cilia and sACex2-ex12v2 to the cytoplasm in these KO mice. Introduction of the ciliary sACex5v2-ex12v2 variant, but not the cytoplasmic sACex2-ex12v2, restored functional sAC activity in C2 KO mice. Thus, we show, for the first time, a mammalian axonemal targeting sequence that localizes a sAC variant to cilia to regulate CBF. PMID:24874272

  6. Credit for soluble boron in the spent-fuel pool

    SciTech Connect

    Newmyer, W.D.; Hill, D.J.

    1996-12-31

    A Westinghouse owners group (WOG) program to take analytical credit for the soluble boron contained in the spent-fuel pool (SFP) water in the SFP rack criticality analyses was recently submitted to the U.S. Nuclear Regulatory Commission for review and approval. Current SFP rack criticality analyses do not take credit for the soluble boron based on the requirements in Sec. III.2.a of Standard Review Plan 9.1.2, which states that criticality analyses must show that the fuel rack array is maintained in a subcritical condition when fully loaded and flooded with nonborated water. Nuclear plant owners are facing increasing fuel assembly enrichments, spent-fuel assembly burnup limitations, SFP storage cell restrictions (checkerboards), and problems with SFP fixed neutron absorber (Boraflex) degradation, all of which are challenging their traditional criticality analyses. The credit for soluble boron in the spent-fuel pool criticality analysis offers a solution to these concerns.

  7. Process for Preparing a Tough, Soluble, Aromatic, Thermoplastic Copolyimide

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor)

    1997-01-01

    A process for preparing a tough, soluble, aromatic, thermoplastic copolyimide is provided. The process comprises the steps of (a) providing 4.4'-oxydiphthalic anhydride to 3,4,3',4'-biphenyltetracarboxylic dianhydride at a mole ratio ranging from about 25 mole percent to 75 mole percent to 75 mole percent to about 25 mole percent; (b) adding 3,4'-oxydianiline to form a mixture; (c) adding a polar aprotic or polar protic solvent to the mixture to form a solution having a percentage of solids capable of maintaining polymer solubility; (d) stirring the solution to allow it to react; (e) adding an azeotropic solvent to the solution and heating to remove water; (f) cooling the solution of step (e) to room temperature and recovering the tough, soluble, aromatic, thermoplastic copolyimide.

  8. Improvement in solubility and bioavailability of puerarin by mechanochemical preparation.

    PubMed

    Xie, Jie; Yang, Fan; Shi, Xiangjun; Zhu, Xingyi; Su, Weike; Wang, Ping

    2013-06-01

    An efficient and solvent-free procedure was developed to improve the solubility and bioavailability of the poorly water-soluble drug puerarin by mechanochemical technology. The stable inclusion complex of puerarin and 2-hydroxypropyl-?-cyclodextrin (HPCD) was prepared by a ball mill under the following conditions: equimolar ratio of puerarin to HPCD; rotational speed of 250 rpm; milling time of 90 min; steel balls of 22 mm diameter. The solid complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD), and fourier transformation-infrared spectroscopy (FT-IR). Mechanochemical action could result in enhanced molecular encapsulation, homogeneous distribution and amorphization of the drug. In comparison to puerarin, a 1.64-fold increase in absolute bioavailability was obtained. The solubility of the inclusion complex was 25.33-fold higher and the drug release amount reached 79.44% at 15 min, 2.76-fold higher. PMID:22591175

  9. Overcoming solubility limits in overloaded gradient hydrophobic interaction chromatography.

    PubMed

    Poplewska, Izabela; Pi?tkowski, Wojciech; Antos, Dorota

    2015-03-20

    The impact of the solubility limits on the performance of gradient protein chromatography has been studied. As a case study elution of model protein, i.e., lysozyme, on hydrophobic interaction media has been selected. A dependence of the protein solubility and crystallization kinetics on the content of cosmotropic salt in the mobile phase has been determined. Moreover, adsorption properties of the protein versus the mobile phase composition have been quantified. A model of chromatographic column dynamics has been developed which incorporated the mass transport kinetics accompanying both adsorption and crystallization processes. The model was used to study the influence of operating parameters such as flowrate and concentration loading on the solubility pattern inside the column and the separation performance. The analysis performed indicated existence of supersaturation regions for which, due to slow kinetics of crystallization, chromatographic process could be performed under conditions of strong concentration overloading while avoiding undesirable effects of flow blockage in chromatographic systems. PMID:25687455

  10. SOLUBLE CD40 LIGAND IN DEMENTIA

    PubMed Central

    Giunta, B.; Figueroa, K.P.; Town, T.; Tan, J.

    2009-01-01

    Some 15–20% of the population over the age of 65 years suffer from dementia, currently one of the leading causes of death behind cardiovascular diseases, cancer and cerebrovascular diseases. The major forms of dementia share in common overactivation of the CD40-CD40-L complex, leading to high levels of proinflammatory cytokine production by immune cells of the central nervous system (CNS), including microglia and astrocytes. Consequently, both neuronal survival and signaling are negatively affected, leading to the characteristic progressive loss of higher cortical functions. We have reviewed the literature concerning the involvement of this complex in the pathology of three major forms of dementia: Alzheimer's-type, HIV-associated and vascular dementia. This is followed by a discussion of current preclinical and clinical therapies that may influence this interaction, and thus point the way toward a future neuroimmunological approach to inhibiting the effects of CD40-CD40-L in neuropsychiatric disease. PMID:19777117

  11. Toxicity of the crude oil water-soluble fraction and kaolin-adsorbed crude oil on Daphnia magna (Crustacea: Anomopoda).

    PubMed

    Martínez-Jerónimo, F; Villaseñor, R; Ríos, G; Espinosa-Chavez, F

    2005-05-01

    Crude oil is a complex mixture of hydrocarbons entering aquatic environments from accidental or normal marine and transportation activities. Toxicologic crude oil analysis is usually performed on the basis of the water-soluble fraction. However, this yields only a partial estimate of the damage caused by these contaminants because a substantial hydrophobic amount can be adsorbed onto suspended solids (biotic and abiotic), which directly affects filter-feeding species and permits bioaccumulation through trophic relationships. This study determined the acute toxic damage sustained after 48 hours caused by seven types of crude oil from Tabasco, Mexico on the cladoceran Daphnia magna. Comparisons were documented based on the responses of D. magna from application of the water-soluble fraction and exposure to entire crude oil samples adsorbed on kaolin clay. Oil-sorbed kaolin was more toxic than the water-soluble fraction in acute exposure. This confirms that tests of the water-soluble fraction tend to underestimate the toxic damage that can be produced in natural environments. Furthermore, chronic toxicity (21 days) was evaluated for crude oil samples adsorbed on kaolin at sublethal concentrations as established from Application Factors (AF) criteria. Results showed that in most cases, it is impossible to predict safe concentrations on the basis of LC(50) values because samples with lower acute toxicity exercised a greater influence on D. magna reproduction and survival when subjected to chronic exposure. PMID:15883675

  12. Lipid nanoparticles with no surfactant improve oral absorption rate of poorly water-soluble drug.

    PubMed

    Funakoshi, Yuka; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2013-07-15

    A pharmacokinetic study was performed in rats to evaluate the oral absorption ratios of nanoparticle suspensions containing the poorly water-soluble compound nifedipine (NI) and two different types of lipids, including hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol. NI-lipid nanoparticle (LN) suspensions with a mean particle size of 48.0 nm and a zeta potential of -57.2 mV were prepared by co-grinding combined with a high-pressure homogenization process. The oral administration of NI-LN suspensions to rats led to a significant increase in the NI plasma concentration, and the area under the curve (AUC) value was found to be 108 min ?g mL?¹, indicating a 4-fold increase relative to the NI suspensions. A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions. These results therefore indicated that lipid nanoparticles prepared using only two types of phospholipid with a mean particle size of less than 50 nm could improve the absorption of the poorly water-soluble drug. PMID:23624178

  13. Correlation of octanol/water solubility ratios and partition coefficients

    SciTech Connect

    Pinsuwan, S.; Li, A.; Yalkowsky, S.H.

    1995-05-01

    The partition coefficient between octanol and water in an important physicochemical parameter for characterizing the lipophilicity or hydrophobicity of a compound and it is used in many fields, especially in the environmental and pharmaceutical sciences. The octanol/water solubility ratio (S{sub o}/S{sub W}) was found to be highly correlated with the octanol/water partition coefficient (K{sub ow}) of 82 pharmaceutically and environmentally relevant compounds. The solubility ratio gives comparable estimates to that of the group contribution (log P(calcd)) method for estimating the partition coefficient of the compounds used in this study.

  14. Supersymmetry, shape invariance and the solubility of the hypergeometric equation

    NASA Astrophysics Data System (ADS)

    Das, Ashok K.; Kalauni, Pushpa

    2015-02-01

    It has been shown earlier [D. Bazeia and A. K. Das, Phys. Lett. B 715, 256 (2012)] that the solubility of the Legendre and the associated Legendre equations can be understood as a consequence of an underlying supersymmetry and shape invariance. We have extended this result to the hypergeometric equation. Since the hypergeometric equation as well as the hypergeometric function reduce to various orthogonal polynomials, this study shows that the solubility of all such systems can also be understood as a consequence of an underlying supersymmetry and shape invariance. Our analysis leads naturally to closed form expressions (Rodrigues' formula) for the orthogonal polynomials.

  15. GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

    SciTech Connect

    Pierce, R.

    2012-02-22

    HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into the H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. For 6 M HNO{sub 3}, 10.5 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2 g/L and 0.25 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}.

  16. Rocky core solubility in Jupiter and giant exoplanets.

    PubMed

    Wilson, Hugh F; Militzer, Burkhard

    2012-03-16

    Gas giants are believed to form by the accretion of hydrogen-helium gas around an initial protocore of rock and ice. The question of whether the rocky parts of the core dissolve into the fluid H-He layers following formation has significant implications for planetary structure and evolution. Here we use ab initio calculations to study rock solubility in fluid hydrogen, choosing MgO as a representative example of planetary rocky materials, and find MgO to be highly soluble in H for temperatures in excess of approximately 10,000 K, implying the potential for significant redistribution of rocky core material in Jupiter and larger exoplanets. PMID:22540454

  17. Characterization of a thermally imidized soluble polyimide film

    NASA Technical Reports Server (NTRS)

    Young, Philip R.; Davis, Judith R. J.; Chang, A. C.; Richardson, John N.

    1989-01-01

    A soluble aromatic poly(amic acid) film was converted to a soluble polyimide by staging at 25 deg intervals to 325 C and characterized at each interval by several analytical methods. The behavior observed was consistent with an interpretation that a reduction occurred in molecular weight of the poly(amic acid) during the initial stages of cure before the ultimate molecular weight was achieved as a polyimide. This interpretation was supported by the results of solution viscosity, gel permeation chromatography, low angle laser light scattering photometry and infrared spectroscopy analysis. The results serve to increase the fundamental understanding of how polyimides are thermally formed from poly(amic acids).

  18. Characterization of a thermally imidized soluble polyimide film

    SciTech Connect

    Young, P.R.; Davis, J.R.J.; Chang, A.C.; Richardson, J.N. )

    1990-01-01

    A soluble aromatic poly(amic acid) film was converted to a soluble polyimide by staging at 25 deg intervals to 325 C and characterized at each interval by several analytical methods. The behavior observed was consistent with an interpretation that a reduction occurred in molecular weight of the poly(amic acid) during the initial stages of cure before the ultimate molecular weight was achieved as a polyimide. This interpretation was supported by the results of solution viscosity, gel permeation chromatography, low angle laser light scattering photometry and infrared spectroscopy analysis. The results serve to increase the fundamental understanding of how polyimides are thermally formed from poly(amic acids). 42 refs.

  19. Characterization of a thermally imidized soluble polyimide film

    NASA Technical Reports Server (NTRS)

    Young, Philip R.; Davis, Judith R. J.; Chang, A. C.; Richardson, John N.

    1990-01-01

    A soluble aromatic poly(amic acid) film was converted to a soluble polyimide by staging at 25 deg intervals to 325 C and characterized at each interval by several analytical methods. The behavior observed was consistent with an interpretation that a reduction occurred in molecular weight of the poly(amic acid) during the initial stages of cure before the ultimate molecular weight was achieved as a polyimide. This interpretation was supported by the results of solution viscosity, gel permeation chromatography, low angle laser light scattering photometry and infrared spectroscopy analysis. The results serve to increase the fundamental understanding of how polyimides are thermally formed from poly(amic acids).

  20. Potential of freezing in wastewater treatment: soluble pollutant applications.

    PubMed

    Lorain, O; Thiebaud, P; Badorc, E; Aurelle, Y

    2001-02-01

    When wastewater containing only soluble pollutants is frozen gradually, ice crystals grow from the pure water only, while pollutants are rejected into the liquid phase thus increasing their concentration. In this way, pure water can be removed from various wastewaters. Two kinds of wastewater were studied: synthetic wastewater containing water and one or more soluble pollutants, and industrial wastewaters (urban wastewater and cutting oil wastewater). In most cases, separation efficiency close to 100% was achieved. A large range of pollutant concentrations was studied in order to determine the limits of freezing separation. PMID:11229009

  1. In Vitro Solubility and Wear Rates of Silorane and Dimethacrylate Resin Based Composite Restorative Materials under Different pH Conditions

    PubMed Central

    Soliman, Tarek A; Tubaigy, Khalid M; Raffat, Eman M; Al-Agha, Ebaa I

    2015-01-01

    Background: The purpose of this study was to evaluate the effect of different pH solutions on the solubility and wear resistance of Silorane and dimethacrylate resin based composite restorative materials. Materials and Methods: Two different resin based restorative materials (Filtek Silorane P90 and hybrid composite Z100) were tested. Different pH solutions (2.5 and 5) also were used. A total of 60 samples of each type of selected composite were prepared. Specimens were immersed in each type of pH solutions (2.5 and 5) and distilled water as a control group for 24 h then the specimens was subjected to the required mechanical tests. Results: Significant statistical differences were observed regarding water solubility and wear values in different pH solutions. Filtek Silorane presented the smallest values of water solubility and wear values. Conclusion: Under tested experimental conditions, the pH solutions used in this study showed pronounced effect on water solubility and wear values of both two restorative materials. Finally, within the limitation of this study we recommended to use Filtek Silorane (P90) instead of hybrid (Z100) due to its low solubility values under different pH solutions. PMID:26225097

  2. Designing a highly active soluble PQQ-glucose dehydrogenase for efficient glucose biosensors and biofuel cells

    SciTech Connect

    Durand, Fabien; Stines-Chaumeil, Claire; Flexer, Victoria; Andre, Isabelle; CNRS, UMR5504, F-31400 Toulouse; INRA, UMR 792 Ingenierie des Systemes Biologiques et des Procedes, F-31400 Toulouse ; Mano, Nicolas

    2010-11-26

    Research highlights: {yields} A new mutant of PQQ-GDH designed for glucose biosensors application. {yields} First mutant of PQQ-GDH with higher activity for D-glucose than the Wild type. {yields} Position N428 is a key point to increase the enzyme activity. {yields} Molecular modeling shows that the N428 C mutant displays a better interaction for PQQ than the WT. -- Abstract: We report for the first time a soluble PQQ-glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to a better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells.

  3. Quantitative Analysis of Snake Venoms Using Soluble Polymer-based Isotope Labeling*S?

    PubMed Central

    Galan, Jacob A.; Guo, Minjie; Sanchez, Elda E.; Cantu, Esteban; Rodriguez-Acosta, Alexis; Perez, John C.; Tao, W. Andy

    2008-01-01

    We present the design and synthesis of a new quantitative strategy termed soluble polymer-based isotope labeling (SoPIL) and its application as a novel and inclusive method for the identification and relative quantification of individual proteins in complex snake venoms. The SoPIL reagent selectively captures and isolates cysteine-containing peptides, and the subsequent tagged peptides are released and analyzed using nanoflow liquid chromatography-tandem mass spectrometry. The SoPIL strategy was used to quantify venom proteins from two pairs of venomous snakes: Crotalus scutulatus scutulatus type A, C. scutulatus scutulatus type B, Crotalus oreganus helleri, and Bothrops colombiensis. The hemorrhagic, hemolytic, clotting ability, and fibrinogenolytic activities of crude venoms were measured and correlated with difference in protein abundance determined by the SoPIL analysis. The SoPIL approach could provide an efficient and widely applicable tool for quantitative proteomics. PMID:18089550

  4. PLUTONIUM SOLUBILITY IN SIMULATED SAVANNAH RIVER SITE WASTE SOLUTIONS

    SciTech Connect

    Rudisill, T.; Hobbs, D.; Edwards, T.

    2010-09-27

    To address the accelerated disposition of the supernate and salt portions of Savannah River Site (SRS) high level waste (HLW), solubility experiments were performed to develop a predictive capability for plutonium (Pu) solubility. A statistically designed experiment was used to measure the solubility of Pu in simulated solutions with salt concentrations and temperatures which bounded those observed in SRS HLW solutions. Constituents of the simulated waste solutions included: hydroxide (OH{sup -}), aluminate (Al(OH){sub 4}{sup -}), sulfate (SO{sub 4}{sup 2-}), carbonate (CO{sub 3}{sup 2-}), nitrate (NO{sub 3}{sup -}), and nitrite (NO{sub 2}{sup -}) anions. Each anion was added to the waste solution in the sodium form. The solubilities were measured at 25 and 80 C. Five sets of samples were analyzed over a six month period and a partial sample set was analyzed after nominally fifteen months of equilibration. No discernable time dependence of the measured Pu concentrations was observed except for two salt solutions equilibrated at 80 C which contained OH{sup -} concentrations >5 mol/L. In these solutions, the Pu solubility increased with time. This observation was attributed to the air oxidation of a portion of the Pu from Pu(IV) to the more soluble Pu(V) or Pu(VI) valence states. A data driven approach was subsequently used to develop a modified response surface model for Pu solubility. Solubility data from this study and historical data from the literature were used to fit the model. The model predicted the Pu solubility of the solutions from this study within the 95% confidence interval for individual predictions and the analysis of variance indicated no statistically significant lack of fit. The Savannah River National Laboratory (SRNL) model was compared with predicted values from the Aqueous Electrolyte (AQ) model developed by OLI Systems, Inc. and a solubility prediction equation developed by Delegard and Gallagher for Hanford tank waste. The agreement between measured or values predicted by the SRNL model and values predicted by the OLI AG model was very poor. The much higher predicted concentrations by the OLI AQ model appears to be the result of the model predicting the predominate Pu oxidation state is Pu(V) which is reported as unstable below sodium hydroxide (NaOH) concentrations of 6 M. There was very good agreement between the predicted Pu concentrations using the SRNL model and the model developed by Delegard and Gallagher with the exception of solutions that had very high OH{sup -} (15 M) concentrations. The lower Pu solubilities in these solutions were attributed to the presence of NO{sub 3}{sup -} and NO{sub 2}{sup -} which limit the oxidation of Pu(IV) to Pu(V).

  5. Three bisphosphonate ligands improve the water solubility of quantum dots.

    PubMed

    Abdul Ghani, Siti Fatimah; Wright, Michael; Paramo, Juan Gallo; Bottrill, Melanie; Green, Mark; Long, Nicholas; Thanou, Maya

    2014-01-01

    Synthesised Quantum Dots (QDs) require surface modification in order to improve their aqueous dispersion and biocompatibility. Here, we suggest bisphosphonate molecules as agents to modify the surface of QDs for improved water solubility and biocompatibility. QDs_TOPO (CdSe/ZnS-trioctylphosphine oxide) were synthesised following modification of the method of Bawendi et al. (J. Phys. Chem. B, 1997, 101, 9463-9475). QDs surface modification is performed using a ligand exchange reaction with structurally different bisphosphonates (BIPs). The BIPs used were ethylene diphosphonate (EDP), methylenediphosphonate (MDP) and imidodiphosphonate (IDP). After ligand exchange, the QDs were extensively purified using centrifugation, PD-10 desalting columns and mini dialysis filters. Transmission electron microscopy (TEM) and fluorescent spectroscopy have been used to characterise the size and optical properties of the QDs. Cell toxicity was investigated using MTT (tetrazolium salt) and glutathione assays and intracellular uptake was imaged using confocal laser scanning microscopy and assessed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). QDs_TOPO and QDs-capped with BIPs (QDs_BIPs) were successfully synthesised. TEM showed the size and morphology of the QDs to be 5-7 nm with spherical shape. The stabilised QDs_BIPs showed significantly improved dispersion in aqueous solutions compared to QDs_TOPO. The cytotoxicity studies showed very rapid cell death for cells treated by QDs_TOPO and a minor effect on cell viability when QDs_BIPs were applied to the cells. Both EDP- and MDP-modified QDs did not significantly increase the intracellular levels of glutathione. In contrast, IDP-modified QDs substantially increased the intracellular glutathione levels, indicating potential cadmium leakage and inability of IDP to adequately cap and stabilise the QDs. EDP- and MDP-modified QDs were taken up by IGROV-1 (ovarian cancer) cells as shown by fluorescence microscopy, however, the IDP-modified QD signal was not clearly visible in the cells. Cellular uptake measured by intracellular cadmium levels using ICP-MS showed significant uptake of all three BIPs QDs. The structure of BIPs appears to play a significant role in the ability of these molecules to act as capping agents. Our findings demonstrate a novel approach to produce water-dispersible QDs through ligand exchange with certain types of BIPs molecules that can find application in bioimaging. PMID:25318058

  6. Precipitation of sparingly soluble salts in packed sandbeds

    NASA Astrophysics Data System (ADS)

    Pavlakou, Efstathia I.; Sygouni, Varvara; Paraskeva, Christakis A.

    2015-04-01

    One of the main problems encountered by the oil extraction industry, is the reduction of the local permeability of the rock formation near the extraction wells because of salt deposition in the pores of the rocks during the injection of brine water to displace the trapped oil ganglia within the oil formations. This phenomenon makes the oil recovery less efficient and under extreme cases the well is abandoned with a large amount of oil entrapped. Several detailed studies have been conducted in the past concerning sand bed consolidation using sparingly soluble salts for varying conditions (e.g. temperature, grain size, sand type, salt concentrations etc) and various salts [1]. Nevertheless, salt precipitation in the rock formation pores under the presence of other miscible or immiscible substances with water has not been investigated in details yet. In the present study, salt (CaCO3) precipitation experiments were performed in small beds packed with sea sand mixed with a low amount of CaCO3 seed grains. The experiments were performed using pure solutions (NaHCO3, CaCl2.2H2O) and solutions mixed with Ethylene Glycol in sand beds. Additionally, precipitation experiments were performed using pure solutions in sand beds saturated with oil phase (n-dodecane) for a wide range of solution supersaturation. During the experiments the ionic strength was kept constant. pH and concentration values of calcium ion of the effluent were measured and the precipitated salt crystals were identified using X-ray Diffraction (XRD) method. At the end of each experiment Scanning Electron Microscope (SEM) was conducted using a sample of the precipitated sand to identify the morphology of the precipitated crystals and their cohesion with sand grains. Acknowledgments This research was partially funded by the European Union (European Social Fund-ESF) and Greek National Funds through the Operational program "Education and Lifelong Learning" under the action Aristeia II (Code No 4420). References [1] Paraskeva C. A., Charalampous P. C., Stokka L. E., Klepetsanis P. G., Koutsoukos P. G., Read P., Ostvold, T. and Payatakes A. C. (2000), ''Sandbed Consolidation with Mineral Precipitation'', Journal of Colloid and Interface Science, 232, 326-339.

  7. ADMINISTRATION OF A SUBSTITUTED ADAMANTLY-UREA INHIBITOR OF THE SOLUBLE EPOXIDE HYDROLASE PROTECTS THE KIDNEY FROM DAMAGE IN HYPERTENSIVE GOTO-KAKIZAKI RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hypertension and type II diabetes are co-morbid diseases that lead to the development of nephropathy. Soluble epoxide hydrolase (sEH) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) protects ...

  8. FACTORS AFFECTING WATER SOLUBLE P IN ANIMAL WASTES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water-soluble phosphorus (WSP) in animal wastes has received recent attention because phosphorus extraction by water may closely simulate extraction by rainfall and runoff water in the field. However, no comprehensive study has been conducted on WSP extraction from animal waste. In preliminary work ...

  9. Developing Worksheet Based on Science Process Skills: Factors Affecting Solubility

    ERIC Educational Resources Information Center

    Karsli, Fethiye; Sahin, Cigdem

    2009-01-01

    The purpose of this study is to develop a worksheet about the factors affecting solubility, which could be useful for the prospective science teachers (PST) to remind and regain their science process skills (SPS). The pilot study of the WS was carried out with 32 first grade PST during the 2007-2008 academic year in the education department at…

  10. Flowability Properties of Commercial Distillers Dried Grains with Solubles (DDGS)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Distillers dried grains with solubles (DDGS), the major coproduct from the corn-based fuel ethanol industry, is primarily used as livestock feed. Due to high protein, fiber, and energy contents, there is a high demand for DDGS. Flowability of DDGS is often hindered due the phenomenon of “caking”. S...

  11. Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines.

    PubMed

    Liu, Wei; Jensen, Timothy J; Fronczek, Frank R; Hammer, Robert P; Smith, Kevin M; Vicente, M Graça H

    2005-02-24

    Water-soluble phthalocyanines are promising photosensitizers for application in cancer therapy and in the photoinactivation of viruses. The water-soluble zinc(II) phthalocyanines 5 and 6 were synthesized by converting the corresponding ester derivative 4 into the sodium carboxylate and carboxylic acid species. Compound 5 can be solubilized in water as a monomeric species, as demonstrated by UV/vis and fluorescence spectroscopy. These compounds were characterized by analytical and spectroscopic methods and, in the case of 4, by X-ray crystallography. The water-soluble phthalocyanines were found to have low dark cytotoxicity toward V79 hamster fibroblasts and human HEp2 cells, to be phototoxic at low light and drug doses, to be taken up by cells in culture, and to localize intracellularly, mainly in the cell lysosomes. Conjugation of the anionic phthalocyanines with positively charged LipoGen liposomes resulted in effective delivery of these compounds into the nuclei of cells. It is concluded that these highly water-soluble phthalocyanines are promising sensitizers for the photodynamic therapy of tumors. PMID:15715471

  12. Minimalist design of water-soluble cross-? architecture

    PubMed Central

    Biancalana, Matthew; Makabe, Koki; Koide, Shohei

    2010-01-01

    Demonstrated successes of protein design and engineering suggest significant potential to produce diverse protein architectures and assemblies beyond those found in nature. Here, we describe a new class of synthetic protein architecture through the successful design and atomic structures of water-soluble cross-? proteins. The cross-? motif is formed from the lamination of successive ?-sheet layers, and it is abundantly observed in the core of insoluble amyloid fibrils associated with protein-misfolding diseases. Despite its prominence, cross-? has been designed only in the context of insoluble aggregates of peptides or proteins. Cross-?’s recalcitrance to protein engineering and conspicuous absence among the known atomic structures of natural proteins thus makes it a challenging target for design in a water-soluble form. Through comparative analysis of the cross-? structures of fibril-forming peptides, we identified rows of hydrophobic residues (“ladders”) running across ?-strands of each ?-sheet layer as a minimal component of the cross-? motif. Grafting a single ladder of hydrophobic residues designed from the Alzheimer’s amyloid-? peptide onto a large ?-sheet protein formed a dimeric protein with a cross-? architecture that remained water-soluble, as revealed by solution analysis and x-ray crystal structures. These results demonstrate that the cross-? motif is a stable architecture in water-soluble polypeptides and can be readily designed. Our results provide a new route for accessing the cross-? structure and expanding the scope of protein design. PMID:20133689

  13. INVITED REVIEW The Soluble Epoxide Hydrolase as a Pharmaceutical

    E-print Network

    Hammock, Bruce D.

    INVITED REVIEW The Soluble Epoxide Hydrolase as a Pharmaceutical Target for Hypertension Nipavan-inflammatory drugs (NSAIDs) in reducing PGE2 in inflammation models, they strongly synergize with NSAIDs, and appearTM 2007;50:225­237) NEED FOR NEW ANTIHYPERTENSIVE DRUGS A large number of classes of antihypertensive

  14. Solubility of nonelectrolytes: a first-principles computational approach.

    PubMed

    Jackson, Nicholas E; Chen, Lin X; Ratner, Mark A

    2014-05-15

    Using a combination of classical molecular dynamics and symmetry adapted intermolecular perturbation theory, we develop a high-accuracy computational method for examining the solubility energetics of nonelectrolytes. This approach is used to accurately compute the cohesive energy density and Hildebrand solubility parameters of 26 molecular liquids. The energy decomposition of symmetry adapted perturbation theory is then utilized to develop multicomponent Hansen-like solubility parameters. These parameters are shown to reproduce the solvent categorizations (nonpolar, polar aprotic, or polar protic) of all molecular liquids studied while lending quantitative rigor to these qualitative categorizations via the introduction of simple, easily computable parameters. Notably, we find that by monitoring the first-order exchange energy contribution to the total interaction energy, one can rigorously determine the hydrogen bonding character of a molecular liquid. Finally, this method is applied to compute explicitly the Flory interaction parameter and the free energy of mixing for two different small molecule mixtures, reproducing the known miscibilities. This methodology represents an important step toward the prediction of molecular solubility from first principles. PMID:24773531

  15. Application of the Hansen solubility Parameters theory to carbon nanotubes.

    PubMed

    Detriche, S; Zorzini, G; Colomer, J F; Fonseca, A; Nagy, J B

    2008-11-01

    Carbon nanotubes (CNT) are very promising nano-objects due to their exceptional properties. However, their tendency to form bundles as well as their insolubility in common solvents makes them difficult to handle. The main way to solve the problem is chemical or physical CNTs functionalisations, with all the problems inherent to the methods. In this contribution, we present a new approach that allows predicting the solubility of carbon nanotubes in many solvents but also predicting the most appropriate solvents to use for given samples of CNTs. Solubilisation and dispersion being directly connected, the present approach of solubilisation proves also to be efficient in dispersing the CNTs bundles. This contribution is a first step toward the control of carbon nanotube's dispersion in polymers and their homogenous functionalisation. Moreover, we also report here a new method, based on solvents, to separate carbon nanotubes by size, the use of mixture of non-solvents in order to obtain good solvents and the use of mixture of good solvents to obtain higher solubility. The use of mixture of good solvents allowed us to obtain high solubility, up to three times higher then that reported in literature. We have also measured and analysed the solubility of some functionalised carbon nanotubes. PMID:19198349

  16. RESPONSE OF LEAD SOLUBILITY TO DISSOLVED CARBONATE IN DRINKING WATER

    EPA Science Inventory

    A model is presented showing the detailed response of the theoretical solubility curves for lead to changes in dissolved inorganic carbonate concentration (TIC) and pH at 25 C. Aqueous Pb(II) ion, lead carbonate complexes, lead hydroxide monomers and polymers, and the solids lead...

  17. A molecular study of gas solubility in nitrile rubber

    NASA Astrophysics Data System (ADS)

    Khawaja, Musab; Mostofi, Arash; Sutton, Adrian

    2015-03-01

    One of the most important uses of elastomers in the oil industry is for seals to encase and protect sensitive monitoring equipment from contamination by gases and liquids at the high pressures and temperatures in the well. Failure of such seals sometimes occurs on decompression when they are returned to the surface. The conditions in the well lead to gases being absorbed by Nitrile rubber (NBR) seals. NBR exhibits a strong permselectivity towards CO2 compared to other gases; something attributed experimentally to the enhanced solubility of CO2. In this study an explanation is sought at the molecular level for this phenomenon. A series of molecular mechanics calculations are performed to compute solubilities of different gases in NBR. The effect of acrylonitrile content on their solubilities is studied for the first time by simulation, and we discuss the important issue of convergence with respect to the sampling of different elastomer configurations. It is observed that the presence of cyano groups has a marked impact on the solubility of CO2 and an explanation is offered.

  18. Atmospheric Processing Outside Clouds Increases Soluble Iron in Mineral Dust

    E-print Network

    Benning, Liane G.

    Atmospheric Processing Outside Clouds Increases Soluble Iron in Mineral Dust Zongbo Shi,*, Michael in many parts of the global ocean. Dust deposition is an important source of Fe to the surface ocean, but most of this Fe is biologically unavailable. Atmospheric processing and reworking of Fe in dust aerosol

  19. Battle of the starches: Insoluble versus soluble at the refinery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study using the USDA starch research method has been conducted to evaluate the effects of total, insoluble, and soluble starch on raw sugar filterability and viscosity in international carbonatation refineries. Raw sugar qualities, i.e., pol, color, % invert, ash, and dextran, were also studied in...

  20. Phase selectively soluble polymer supports to facilitate homogeneous catalysis 

    E-print Network

    Ortiz-Acosta, Denisse

    2009-05-15

    (N-n-octadecylacrylamide-co-N-n-butylacrylamide) copolymers’ phase selective solubility is equally dependant of the polar n-butyl and nonpolar n-octadecyl groups on the copolymers. Dye-labeled poly(N,N-dialkylacrylamide)s prepared by the polymerization of N,N-dialkylacrylamides monomers with methyl, ethyl...